Cell Biology: Mitochondria and Pyruvate Dehydrogenase
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Questions and Answers

What part of the coenzyme is primarily involved in catalysis?

  • The thiazole ring (correct)
  • The carbonyl group
  • The nitrogen atom
  • The hydroxyl group

    • Which atom in the thiazole ring serves as the functional site of catalysis?

  • Carbon atom at the top of the thiazole ring (correct)
  • Nitrogen atom
  • Carbon atom at the bottom of the thiazole ring
  • Sulfur atom

    • What occurs when the upper thiazole carbon is deprotonated?

  • It forms a pyruvyl-thiamine complex
  • It acquires two unpaired electrons (correct)
  • It releases carbon dioxide
  • It generates hydroxyl ions

    • What bond forms between the thiazole carbon and the carbonyl carbon of pyruvate?

    <p>Covalent bond</p> Signup and view all the answers

    What happens to the carbonyl oxygen after the bond with thiazole carbon forms?

    <p>It becomes negatively charged</p> Signup and view all the answers

    In the reaction involving pyruvyl-thiamine pyrophosphate, what is released?

    <p>Carbon dioxide</p> Signup and view all the answers

    What type of intermediate is formed after the decarboxylation of pyruvyl-thiamine pyrophosphate?

    <p>Hydroxyethyl-thiamine pyrophosphate</p> Signup and view all the answers

    What is transferred to lipoamide in the next step of the pyruvate dehydrogenase mechanism?

    <p>Two carbon intermediate</p> Signup and view all the answers

    What is the primary function of acetylCoA in the TCA cycle?

    <p>To convert two carbon atoms into carbon dioxide</p> Signup and view all the answers

    What is the anionic form of acetic acid called?

    <p>Acetate ion</p> Signup and view all the answers

    What is produced alongside carbon dioxide in one round of the TCA cycle?

    <p>One NADH and one FADH2</p> Signup and view all the answers

    How is the acetyl group introduced into the TCA cycle?

    <p>By the condensation with oxaloacetate</p> Signup and view all the answers

    Which carbon atoms are lost as carbon dioxide during the TCA cycle?

    <p>Initially from oxaloacetate in the first round</p> Signup and view all the answers

    Which statement about the structure of acetylCoA is correct?

    <p>It consists of a two-carbon acetyl group attached to coenzyme A.</p> Signup and view all the answers

    What type of reaction occurs during the rearrangement of citrate in the TCA cycle?

    <p>β-cleavage reaction</p> Signup and view all the answers

    What type of group is an acetyl group classified as?

    <p>Acyl group</p> Signup and view all the answers

    What is the primary function of the pyruvate dehydrogenase complex?

    <p>To transform pyruvate into acetyl-CoA</p> Signup and view all the answers

    Where is the pyruvate dehydrogenase complex located in eukaryotic cells?

    <p>In the mitochondrial matrix</p> Signup and view all the answers

    Which of the following products is generated during the reaction facilitated by the pyruvate dehydrogenase complex?

    <p>Acetyl-CoA</p> Signup and view all the answers

    What is the role of NADH produced in the pyruvate dehydrogenase reaction?

    <p>It serves as an electron donor for oxidative phosphorylation.</p> Signup and view all the answers

    Which cofactor involves thiamine and is essential for the pyruvate dehydrogenase reaction?

    <p>Thiamine pyrophosphate (TPP)</p> Signup and view all the answers

    What happens to lipoate during the pyruvate dehydrogenase reaction?

    <p>It is reduced and then reoxidized by FAD.</p> Signup and view all the answers

    How many subunits make up the pyruvate dehydrogenase complex, and what types of proteins does it contain?

    <p>96 subunits with three types of proteins</p> Signup and view all the answers

    What is the initial step of the reaction catalyzed by pyruvate dehydrogenase?

    <p>Attachment of pyruvate to thiamine pyrophosphate</p> Signup and view all the answers

    What is the primary substrate for the reaction catalyzed by citrate synthase?

    <p>AcetylCoA</p> Signup and view all the answers

    Which product is formed after the reaction catalyzed by aconitase?

    <p>Isocitrate</p> Signup and view all the answers

    What key process occurs during the citrate synthase reaction that helps drive it towards product formation?

    <p>Release of CoA group</p> Signup and view all the answers

    What unintended result could occur if the aconitase reaction were conducted chemically without an enzyme?

    <p>Random placement of the hydroxyl group</p> Signup and view all the answers

    What type of molecular reaction occurs during the aconitase catalyzed process before the generation of isocitrate?

    <p>Dehydration</p> Signup and view all the answers

    Which statement accurately describes the role of citrate in foods and beverages?

    <p>It imparts tartness.</p> Signup and view all the answers

    During the citrate synthase reaction, what occurs to the electrons from the carbonyl double bond?

    <p>They jump onto the carbonyl oxygen.</p> Signup and view all the answers

    What aspect of citrate synthase's mechanism makes it energetically favorable?

    <p>Cleavage of the thioester linkage</p> Signup and view all the answers

    What is the role of succinate dehydrogenase in the TCA cycle?

    <p>It catalyzes the oxidation of succinate to fumarate.</p> Signup and view all the answers

    Which enzyme is responsible for converting fumarate to L-malate?

    <p>Fumarase</p> Signup and view all the answers

    What is a distinguishing feature of the oxidation reaction catalyzed by succinate dehydrogenase?

    <p>It is a membrane-bound reaction.</p> Signup and view all the answers

    What type of bond is formed during the conversion of succinate to fumarate?

    <p>A double bond</p> Signup and view all the answers

    Which product is formed from the reaction catalyzed by L-malate dehydrogenase?

    <p>Oxaloacetate</p> Signup and view all the answers

    What is the relationship between FADH2 and NADH regarding their ATP-producing potential?

    <p>NADH has a higher potential than FADH2.</p> Signup and view all the answers

    What type of chemical reaction is used by fumarase?

    <p>Hydration</p> Signup and view all the answers

    What characteristic does L-malate possess that is not found in fumarate?

    <p>A hydroxyl group on one carbon</p> Signup and view all the answers

    What distinguishes isocitrate from its precursor citrate in terms of molecular structure?

    <p>Isocitrate is asymmetrical with a chiral center.</p> Signup and view all the answers

    What role does the thiazole ring play in the catalytic process?

    <p>It is involved in the formation of covalent bonds with substrates.</p> Signup and view all the answers

    What is the result of the deprotonation of the upper thiazole carbon during the reaction?

    <p>The thiazole carbon acquires two unpaired electrons.</p> Signup and view all the answers

    In the reaction catalyzed by isocitrate dehydrogenase, what is produced alongside the conversion of isocitrate?

    <p>NADH</p> Signup and view all the answers

    Which process occurs after the formation of the pyruvyl-thiamine pyrophosphate intermediate?

    <p>Formation of carbon dioxide and a hydroxyethyl derivative.</p> Signup and view all the answers

    What is the significance of β-keto acids in the context of the reactions described?

    <p>They facilitate the release of carbon dioxide through decarboxylation.</p> Signup and view all the answers

    During the reaction catalyzed by α-ketoglutarate dehydrogenase, what is released alongside succinyl-CoA?

    <p>Carbon dioxide</p> Signup and view all the answers

    What happens to the carboxyl group of pyruvate during the reaction?

    <p>It is released as carbon dioxide in the decarboxylation step.</p> Signup and view all the answers

    What reaction does succinyl-CoA synthase perform with respect to high-energy bonds?

    <p>It breaks the thioester bond to release energy for ATP formation.</p> Signup and view all the answers

    What structural change occurs in the thiazole nitrogen after the formation of the carbon bond?

    <p>The nitrogen experiences a loss of electron density.</p> Signup and view all the answers

    What is a key feature of the hydroxyethyl-thiamine pyrophosphate intermediate?

    <p>It contains a hydroxyl group at the C-2 carbon.</p> Signup and view all the answers

    How many points of attachment between substrate and enzyme does an enzyme require to effectively discriminate between symmetrical compounds?

    <p>Three</p> Signup and view all the answers

    Which of the following statements correctly describes the product of the oxidative decarboxylation reaction involving isocitrate?

    <p>It generates a five-carbon product called α-ketoglutarate.</p> Signup and view all the answers

    In the mechanism described, what role does the solvent play during the reaction?

    <p>It neutralizes negative charges produced during the process.</p> Signup and view all the answers

    Which electron movement occurs during the decarboxylation of pyruvyl-thiamine pyrophosphate?

    <p>Electrons are transferred from the hydroxyl carbon to the carbonyl carbon.</p> Signup and view all the answers

    Which component of the TCA cycle is predominantly responsible for producing NADH as a result of its enzymatic action?

    <p>α-Ketoglutarate dehydrogenase</p> Signup and view all the answers

    What is the primary product of the reaction catalyzed by citrate synthase?

    <p>Citrate</p> Signup and view all the answers

    Which statement accurately describes the role of aconitase in the TCA cycle?

    <p>It facilitates a two-step process involving dehydration and rehydration.</p> Signup and view all the answers

    What initiates the formation of citrate during the citrate synthase reaction?

    <p>Nucleophilic attack by the methyl group of acetylCoA</p> Signup and view all the answers

    During which phase of the aconitase-catalyzed reaction is water removed?

    <p>During the dehydration reaction step</p> Signup and view all the answers

    In citrate synthase's mechanism, what role does the CoA group play?

    <p>It provides energy for the reaction via thioester cleavage.</p> Signup and view all the answers

    Why is citrate considered a symmetrical compound during enzymatic reactions?

    <p>The new hydroxyl group has equal likelihood of attachment to different carbons.</p> Signup and view all the answers

    What distinguishes the mechanistic pathway of the citrate synthase reaction from a non-enzymatic reaction?

    <p>Specificity in substrate orientation and bond formation.</p> Signup and view all the answers

    What is the overall thermodynamic balance achieved in the citrate synthase reaction?

    <p>Release of energy upon CoA cleavage drives product formation.</p> Signup and view all the answers

    What is produced alongside the conversion of α-ketoglutarate in the TCA cycle?

    <p>Carbon dioxide</p> Signup and view all the answers

    What distinguishes the oxidation reaction performed by succinate dehydrogenase from other reactions in the TCA cycle?

    <p>It uses FAD as the oxidant instead of NAD+.</p> Signup and view all the answers

    Which of the following compounds enters the TCA cycle to provide a carbon source?

    <p>AcetylCoA</p> Signup and view all the answers

    Which product results from the hydration of fumarate by fumarase?

    <p>L-malate</p> Signup and view all the answers

    Which of the following cofactors is utilized in one complete cycle of the TCA cycle?

    <p>NAD+</p> Signup and view all the answers

    What type of enzyme is fumarase classified as?

    <p>Lyase</p> Signup and view all the answers

    What is mainly generated from the TCA cycle that is further used in oxidative phosphorylation?

    <p>NADH and FADH2</p> Signup and view all the answers

    What is the significance of the L-configuration of L-malate produced in the TCA cycle?

    <p>It indicates the presence of a chiral center.</p> Signup and view all the answers

    Which enzyme converts citrate into isocitrate in the TCA cycle?

    <p>Aconitase</p> Signup and view all the answers

    What is the final product formed after the oxidation of L-malate by L-malate dehydrogenase?

    <p>Oxaloacetate</p> Signup and view all the answers

    What is the net carbon input of the TCA cycle?

    <p>2 carbons as AcetylCoA and 4 carbons as Oxaloacetate</p> Signup and view all the answers

    How does the reducing potential of FADH2 compare to that of NADH in terms of ATP yield?

    <p>FADH2 yields slightly less ATP than NADH.</p> Signup and view all the answers

    Which product of the TCA cycle is regenerated to continue the cycle?

    <p>Oxaloacetate</p> Signup and view all the answers

    What is the result of the oxidation of succinate in the TCA cycle?

    <p>Loss of two protons and two electrons.</p> Signup and view all the answers

    What role does the proton gradient play in the context of oxidative phosphorylation?

    <p>It drives the synthesis of ATP from ADP and inorganic phosphate.</p> Signup and view all the answers

    What property of fumarate is important during its conversion in the TCA cycle?

    <p>It has a trans double bond.</p> Signup and view all the answers

    What occurs to the hydrogen atom on the thiazole carbon due to the delocalized aromatic nature of the ring system?

    <p>It becomes more acidic than usual.</p> Signup and view all the answers

    Which atom connects the thiazole ring with the carbonyl group of pyruvate during the reaction?

    <p>The carbon atom at the top of the thiazole ring.</p> Signup and view all the answers

    What happens to the carboxylate anion after the formation of pyruvyl-thiamine pyrophosphate?

    <p>It releases carbon dioxide.</p> Signup and view all the answers

    What is the resulting intermediate when pyruvyl-thiamine pyrophosphate undergoes decarboxylation?

    <p>Hydroxyethyl-thiamine pyrophosphate.</p> Signup and view all the answers

    Which role does the thiazole nitrogen play after the formation of a covalent bond with pyruvate?

    <p>It neutralizes a positive charge.</p> Signup and view all the answers

    What occurs to the electrons after the release of carbon dioxide from pyruvyl-thiamine pyrophosphate?

    <p>They form a double bond with the hydroxyl carbon.</p> Signup and view all the answers

    What happens to the electrons between the carboxylate carbon and C-2 during the reaction?

    <p>They move to create a hydroxyethyl group.</p> Signup and view all the answers

    How does the interaction between the thiazole carbon and pyruvate contribute to the formation of a negatively charged intermediate?

    <p>By deprotonation of the thiazole carbon.</p> Signup and view all the answers

    What two compounds are condensed by citrate synthase to begin the TCA cycle?

    <p>AcetylCoA and Oxaloacetate</p> Signup and view all the answers

    What is produced alongside carbon dioxide during the decarboxylation of isocitrate?

    <p>α-ketoglutarate and NADH</p> Signup and view all the answers

    How many NAD+ molecules are utilized in one round of the TCA cycle?

    <p>3</p> Signup and view all the answers

    What intermediate does α-ketoglutarate convert into during its decarboxylation?

    <p>SuccinylCoA</p> Signup and view all the answers

    What is the relationship between the amount of carbon input and output in the TCA cycle?

    <p>Six carbons input, six carbons output</p> Signup and view all the answers

    Which molecule is primarily responsible for transferring electrons during the TCA cycle?

    <p>NADH</p> Signup and view all the answers

    What occurs during the oxidative phosphorylation process following the TCA cycle?

    <p>Electrons drive proton flow, creating a gradient for ATP synthesis</p> Signup and view all the answers

    What roles do the products of the TCA cycle primarily serve in the body?

    <p>Both energy production and substrates for biosynthesis</p> Signup and view all the answers

    What is the product of the reaction catalyzed by succinate dehydrogenase?

    <p>Fumarate</p> Signup and view all the answers

    Which enzyme is responsible for the conversion of fumarate to L-malate?

    <p>Fumarase</p> Signup and view all the answers

    What is the configuration of the double bond in fumarate?

    <p>Trans</p> Signup and view all the answers

    Which reducing agent is used in the oxidation of succinate to fumarate?

    <p>FAD</p> Signup and view all the answers

    What type of reaction does fumarase catalyze?

    <p>Hydration</p> Signup and view all the answers

    What is the final product formed by L-malate dehydrogenase during the TCA cycle?

    <p>Oxaloacetate</p> Signup and view all the answers

    What characteristic distinguishes the oxidation of succinate from the previous oxidation reactions in the TCA cycle?

    <p>It creates a double bond.</p> Signup and view all the answers

    What is the significance of the hydroxyl group added during the conversion of fumarate to L-malate?

    <p>It creates a chiral center.</p> Signup and view all the answers

    What product is formed when the hydroxyethyl group is passed from thiamine pyrophosphate to lipoamide?

    <p>Acetylthioester</p> Signup and view all the answers

    What structural change occurs to lipoamide when it is converted to its reduced form?

    <p>Addition of electrons and protons</p> Signup and view all the answers

    Which component is associated with the final step of the pyruvate dehydrogenase mechanism?

    <p>Dihydrolipoyltransacetylase</p> Signup and view all the answers

    What characterizes the acetyl group formed during the pyruvate dehydrogenase reaction?

    <p>It is a thioester derivative.</p> Signup and view all the answers

    What is the role of pantothenic acid in coenzyme A?

    <p>It acts as a structural element.</p> Signup and view all the answers

    What happens to lipoamide during the pyruvate dehydrogenase reaction?

    <p>It gains an acetyl group.</p> Signup and view all the answers

    What oxidation state is the hydroxyethyl group in when it is attached to thiamine pyrophosphate?

    <p>Aldehyde</p> Signup and view all the answers

    Which of the following best describes dihydrolipoamide during the pyruvate dehydrogenase reaction?

    <p>It has two reduced sulfur groups.</p> Signup and view all the answers

    What is the ultimate outcome of acetylCoA in the TCA cycle?

    <p>Two carbon atoms are oxidized entirely to carbon dioxide.</p> Signup and view all the answers

    What type of compound is formed when acetate is bonded to an organic group other than a hydroxyl group?

    <p>Acetyl group</p> Signup and view all the answers

    Which molecule initially contributes to the carbon atoms lost as carbon dioxide in the TCA cycle?

    <p>Oxaloacetate</p> Signup and view all the answers

    What is produced alongside the decarboxylation of pyruvate to form acetylCoA?

    <p>NADH</p> Signup and view all the answers

    During the TCA cycle, which process occurs after the production of citrate from acetylCoA?

    <p>Rearrangement of citrate for a β-cleavage reaction</p> Signup and view all the answers

    Which product is generated during the conversion of a C6 compound to a C5 compound in the TCA cycle?

    <p>Carbon dioxide</p> Signup and view all the answers

    What challenge arises when trying to cleave the carbons of acetylCoA?

    <p>The bond between the two carbons is very strong.</p> Signup and view all the answers

    In the TCA cycle, what is the net product produced in terms of electrons from one complete cycle?

    <p>8 electrons</p> Signup and view all the answers

    What is produced during one round of the TCA cycle in addition to carbon dioxide?

    <p>1 GTP</p> Signup and view all the answers

    How is the acetyl group initially introduced into the TCA cycle?

    <p>Condensation with oxaloacetate</p> Signup and view all the answers

    Which statement correctly describes the loss of carbon atoms in the TCA cycle?

    <p>The carbons lost initially come from oxaloacetate.</p> Signup and view all the answers

    What are the products formed during the conversion of a C5 compound to a C4 compound in the TCA cycle?

    <p>1 NADH and 1 carbon dioxide</p> Signup and view all the answers

    In the context of the TCA cycle, what happens to the acetylCoA carbons after the first round?

    <p>They are lost in subsequent rounds.</p> Signup and view all the answers

    Which of the following accurately describes an acetyl group?

    <p>It is a two-carbon fragment attached to another group.</p> Signup and view all the answers

    Which reaction step in the TCA cycle involves a β-cleavage?

    <p>Rearrangement of citrate</p> Signup and view all the answers

    What occurs to the hydrogen atom on the carbon at the top of the thiazole ring due to its delocalized aromatic nature?

    <p>It becomes more acidic than usual.</p> Signup and view all the answers

    Which intermediate is produced following pyruvate decarboxylation?

    <p>AcetylCoA</p> Signup and view all the answers

    What happens to the carboxyl group of pyruvate during the release of carbon dioxide?

    <p>It is released as carbon dioxide.</p> Signup and view all the answers

    What is the significance of the upper thiazole carbon becoming deprotonated?

    <p>It allows for the formation of unpaired electrons.</p> Signup and view all the answers

    What structural change occurs in the hydroxyethyl intermediate after the decarboxylation of pyruvyl-thiamine pyrophosphate?

    <p>It forms a double bond with the thiazole carbon.</p> Signup and view all the answers

    Which statement accurately describes the nature of the bond formed between the thiazole carbon and pyruvate's carbonyl carbon?

    <p>It is a covalent bond.</p> Signup and view all the answers

    What role does the hydroxyl group play after the attack of the thiazole carbon on pyruvate?

    <p>It neutralizes a negative charge formed during the reaction.</p> Signup and view all the answers

    What happens to the carboxylate anion of the pyruvyl-thiamine pyrophosphate intermediate during the reaction?

    <p>It releases carbon dioxide.</p> Signup and view all the answers

    What is the primary outcome of the interaction between electrons from the carboxylate carbon and hydroxyl carbon during the reaction?

    <p>It results in the release of carbon dioxide.</p> Signup and view all the answers

    What role does the sulfhydryl group in coenzyme A play?

    <p>It facilitates the formation of thioester bonds.</p> Signup and view all the answers

    What is produced when dihydrolipoamide is reoxidized?

    <p>FADH2</p> Signup and view all the answers

    Which element within FAD is involved in the catalysis during the oxidation of dihydrolipoamide?

    <p>Isoalloxazine ring</p> Signup and view all the answers

    Why is the citric acid cycle also known as the tricarboxylic acid cycle?

    <p>It involves three carboxyl groups.</p> Signup and view all the answers

    What happens to FADH2 after it is produced from the reoxidation of dihydrolipoamide?

    <p>It is oxidized back to FAD by transferring electrons to NAD+.</p> Signup and view all the answers

    Which component is crucial for converting dihydrolipoamide back to oxidized lipoamide?

    <p>Catalysis by dihydrolipoyl dehydrogenase</p> Signup and view all the answers

    What initial product of the citric acid cycle is formed from acetyl-CoA and oxaloacetate?

    <p>Citrate</p> Signup and view all the answers

    What distinguishes the role of Sir Hans Krebs in biochemistry?

    <p>He discovered both the citric acid cycle and the urea cycle.</p> Signup and view all the answers

    What product is formed as a result of the citrate synthase reaction?

    <p>Citrate</p> Signup and view all the answers

    Which reaction is catalyzed by aconitase?

    <p>Conversion of citrate to isocitrate</p> Signup and view all the answers

    What energy-related event occurs during the citrate synthase reaction?

    <p>Release of CoA</p> Signup and view all the answers

    What is the nucleophilic component involved in the citrate synthase mechanism?

    <p>Methyl group of acetylCoA</p> Signup and view all the answers

    What thermodynamic change helps drive the citrate synthase reaction towards product formation?

    <p>Cleavage of thioester linkage</p> Signup and view all the answers

    What is the consequence of conducting the aconitase reaction without the enzyme?

    <p>Random hydroxyl placement on citrate</p> Signup and view all the answers

    Which aspect of citrate contributes to its flavor in processed foods?

    <p>Its tartness</p> Signup and view all the answers

    What occurs during the hydration reaction in the aconitase-catalyzed process?

    <p>Addition of elements of water</p> Signup and view all the answers

    What is the role of succinate dehydrogenase in the TCA cycle?

    <p>It catalyzes the conversion of succinate to fumarate.</p> Signup and view all the answers

    Which enzyme is responsible for adding water to fumarate to produce L-malate?

    <p>Fumarase</p> Signup and view all the answers

    What distinguishes the oxidation of succinate to fumarate from previous oxidation reactions in the TCA cycle?

    <p>It produces FADH2 instead of NADH.</p> Signup and view all the answers

    What type of reaction does fumarase catalyze when converting fumarate to L-malate?

    <p>Hydration</p> Signup and view all the answers

    What is produced from the final reaction in the cycle involving L-malate?

    <p>Oxaloacetate</p> Signup and view all the answers

    Why is the removal of protons and electrons in the succinate dehydrogenase reaction significant?

    <p>It creates a double bond in fumarate.</p> Signup and view all the answers

    What characteristic does L-malate possess that distinguishes it from fumarate?

    <p>It has a hydroxyl group on a chiral carbon.</p> Signup and view all the answers

    What is the significance of FADH2 in comparison to NADH in oxidative phosphorylation?

    <p>FADH2 has a lower potential for ATP yield compared to NADH.</p> Signup and view all the answers

    What is the main product generated from the conversion of pyruvate by the pyruvate dehydrogenase complex?

    <p>AcetylCoA</p> Signup and view all the answers

    Which pathway is directly linked to the production of acetylCoA?

    <p>Beta-oxidation of fatty acids</p> Signup and view all the answers

    What percentage of the overall free energy change from glucose to carbon dioxide occurs during the conversion of pyruvate to acetylCoA?

    <p>20%</p> Signup and view all the answers

    Which process occurs within the mitochondria during the specific transformation of pyruvate?

    <p>Conversion to acetylCoA</p> Signup and view all the answers

    Which of the following statements correctly describes the role of acetylCoA in cellular metabolism?

    <p>It enters the citric acid cycle for oxidation.</p> Signup and view all the answers

    What is the approximate percentage of ATP equivalents produced during the conversion of pyruvate to acetylCoA?

    <p>17%</p> Signup and view all the answers

    What metabolic process is directly responsible for pyruvate being converted into acetylCoA?

    <p>Oxidative decarboxylation</p> Signup and view all the answers

    What role does pyruvate play in the metabolic pathways discussed?

    <p>It connects glycolysis and the citric acid cycle.</p> Signup and view all the answers

    What is the primary purpose of the pyruvate dehydrogenase complex in cellular metabolism?

    <p>It links glycolysis to the citric acid cycle.</p> Signup and view all the answers

    Which of the following accurately describes the inner membrane of mitochondria?

    <p>It contains the systems for electron transport and oxidative phosphorylation.</p> Signup and view all the answers

    Which cofactor is essential in the initial step of the pyruvate dehydrogenase reaction?

    <p>Thiamine pyrophosphate</p> Signup and view all the answers

    What are the products generated from the reaction catalyzed by pyruvate dehydrogenase complex?

    <p>NADH and acetyl-CoA</p> Signup and view all the answers

    What role does reduced lipoate play in the pyruvate dehydrogenase reaction?

    <p>It is reoxidized by FAD.</p> Signup and view all the answers

    Which process immediately follows the decarboxylation of pyruvate in the reaction mechanism?

    <p>The transfer of the acetyl group to coenzyme A.</p> Signup and view all the answers

    What is the significance of the convoluted structure of the inner membrane of mitochondria?

    <p>It increases the surface area for electron transport processes.</p> Signup and view all the answers

    How is thiamine relevant to the function of the pyruvate dehydrogenase complex?

    <p>It is converted to thiamine pyrophosphate to aid in catalysis.</p> Signup and view all the answers

    Which step of the TCA cycle is unique for being catalyzed by a membrane-bound enzyme complex?

    <p>Conversion of succinate to fumarate</p> Signup and view all the answers

    What is the primary oxidant utilized in the oxidation of succinate to fumarate?

    <p>FAD</p> Signup and view all the answers

    During the hydration of fumarate, what atoms are specifically added to produce L-malate?

    <p>Two hydrogens and one hydroxyl group</p> Signup and view all the answers

    What is the result of the reaction catalyzed by L-malate dehydrogenase?

    <p>Conversion of L-malate to oxaloacetate</p> Signup and view all the answers

    In terms of reducing potential, how does FADH2 compare to NADH in ATP production?

    <p>FADH2 has a lower potential than NADH</p> Signup and view all the answers

    What distinguishes fumarase's mechanism of action from other enzymes in the TCA cycle?

    <p>It adds water across a double bond</p> Signup and view all the answers

    The product of the reaction catalyzed by succinate dehydrogenase is specifically which compound?

    <p>Fumarate</p> Signup and view all the answers

    Which configuration of the double bond in fumarate is specified, and what significance does it have?

    <p>Cis configuration, it represents a different compound</p> Signup and view all the answers

    What is the primary role of the sulfhydryl group in coenzyme A?

    <p>To form thioester bonds with acyl groups</p> Signup and view all the answers

    During the reoxidation of dihydrolipoamide, which coenzyme is produced as a result of electron transfer?

    <p>FADH2</p> Signup and view all the answers

    What must occur to dihydrolipoamide before the oxidation-reduction reaction can be repeated?

    <p>It must be reoxidized to lipoamide</p> Signup and view all the answers

    Which of the following statements correctly describes FAD's chemical change during the dihydrolipoamide oxidation?

    <p>FAD is reduced to FADH2</p> Signup and view all the answers

    What is a defining characteristic of the citric acid cycle?

    <p>It is also referred to as the tricarboxylic acid cycle</p> Signup and view all the answers

    What type of bond is formed when the acetyl group links to the sulfur atom in acetylCoA?

    <p>Thioester bond</p> Signup and view all the answers

    Which coenzyme is involved in the transfer of protons during the conversion of FADH2 back to FAD?

    <p>NAD+</p> Signup and view all the answers

    What significant insight about Sir Hans Krebs is noted in relation to the citric acid cycle?

    <p>He is credited with the discovery of both the citric acid cycle and the urea cycle</p> Signup and view all the answers

    What process occurs when acetylCoA enters the TCA cycle?

    <p>It condenses with oxaloacetate to form citrate.</p> Signup and view all the answers

    What type of cleavage reaction is performed during the rearrangement of citrate?

    <p>β-cleavage reaction</p> Signup and view all the answers

    Where do the carbon atoms lost as carbon dioxide in a single round of the TCA cycle primarily originate from?

    <p>The oxaloacetate compound</p> Signup and view all the answers

    How does the TCA cycle process electrons during the transformation of succinyl-CoA?

    <p>Electrons are stored as NADH and FADH2.</p> Signup and view all the answers

    What characterizes an acetyl group when compared to an acetate ion?

    <p>It is covalently attached to another group.</p> Signup and view all the answers

    Which net products result from one complete round of the TCA cycle?

    <p>1 GTP, 2 carbon dioxide, and 8 electrons</p> Signup and view all the answers

    What makes the cleavage of acetic acid into its components easier compared to acetylCoA?

    <p>The cleavage between carbons in acetylCoA is harder.</p> Signup and view all the answers

    What is a significant step in the reaction catalyzed by citrate synthase?

    <p>Condensation of acetylCoA with oxaloacetate.</p> Signup and view all the answers

    What is the role of the sulfhydryl group in coenzyme A?

    <p>It activates various acyl groups through thioester bonds.</p> Signup and view all the answers

    What process occurs to reoxidize dihydrolipoamide?

    <p>It is converted back to lipoamide by dihydrolipoyl dehydrogenase.</p> Signup and view all the answers

    Which of the following describes the structure of FAD?

    <p>It includes adenosine diphosphate connected to ribitol and an isoalloxazine ring.</p> Signup and view all the answers

    What is a distinguishing feature of the citric acid cycle?

    <p>It begins with the formation of citric acid.</p> Signup and view all the answers

    How are electrons transferred during the oxidation of dihydrolipoamide?

    <p>Two electrons and two protons are transferred to FAD.</p> Signup and view all the answers

    What is required for converting FADH2 back to FAD?

    <p>Transfer of two protons and two electrons to NAD+.</p> Signup and view all the answers

    What is the ultimate fate of the proton released into the solvent during the conversion of FADH2?

    <p>It contributes to the acidity of the environment.</p> Signup and view all the answers

    What name is associated with the discoverer of the TCA cycle?

    <p>Sir Hans Krebs</p> Signup and view all the answers

    What distinguishes the oxidation reaction catalyzed by succinate dehydrogenase from other oxidation-reduction reactions in the TCA cycle?

    <p>It involves the formation of a double bond from a single bond.</p> Signup and view all the answers

    Which statement about the product of the succinate dehydrogenase reaction is correct?

    <p>Fumarate is hydrated by fumarase to form malate.</p> Signup and view all the answers

    What is the reason for the lower ATP yield from FADH2 compared to NADH in oxidative phosphorylation?

    <p>FADH2 donates electrons at a lower energy level in the electron transport chain.</p> Signup and view all the answers

    What characteristic of L-malate distinguishes it from fumarate?

    <p>L-malate has a hydroxyl group contributing to its chirality.</p> Signup and view all the answers

    What function does fumarase serve in the TCA cycle?

    <p>It catalyzes the hydration of fumarate to L-malate.</p> Signup and view all the answers

    Which of the following statements accurately describes NADH produced in the TCA cycle?

    <p>NADH is generated when the alcohol group in L-malate is oxidized.</p> Signup and view all the answers

    What is the role of the double bond in fumarate during its conversion to malate?

    <p>It serves as a site for hydroxyl group addition through hydration.</p> Signup and view all the answers

    What product is generated at the conclusion of the TCA cycle after L-malate is oxidized?

    <p>Oxaloacetate</p> Signup and view all the answers

    What is the effect of the aromatic nature of the thiazole ring on the hydrogen atom at the top carbon?

    <p>It makes the hydrogen atom more acidic than usual.</p> Signup and view all the answers

    What happens to the electrons after the bond forms between the thiazole carbon and the carbonyl carbon of pyruvate?

    <p>They move onto the carbonyl oxygen, making it negatively charged.</p> Signup and view all the answers

    During decarboxylation, what structural change occurs in the hydroxyethyl intermediate?

    <p>It loses a carbon atom as carbon dioxide.</p> Signup and view all the answers

    Which component is neutralized by the transfer of electrons from the thiazole nitrogen during the release of carbon dioxide?

    <p>The positive charge at the thiazole nitrogen.</p> Signup and view all the answers

    What is the primary reaction that occurs at the thiazole carbon during the formation of the pyruvyl-thiamine pyrophosphate intermediate?

    <p>Formation of a covalent bond with pyruvate.</p> Signup and view all the answers

    In the sequence of reactions, what role does the hydroxyl group play after the formation of the pyruvyl-thiamine pyrophosphate intermediate?

    <p>It participates in the decarboxylation process.</p> Signup and view all the answers

    What occurs immediately after the formation of the pyruvyl-thiamine pyrophosphate intermediate?

    <p>Electrons between the carboxylate carbon and C-2 move.</p> Signup and view all the answers

    What process follows the deprotonation of the upper thiazole carbon in the context of pyruvate?

    <p>Formation of a double bond with the carbonyl carbon.</p> Signup and view all the answers

    What happens to the carbon atoms from acetylCoA during a round of the TCA cycle?

    <p>One carbon is lost while the other is retained for recycling.</p> Signup and view all the answers

    Which compound is first formed when acetylCoA condenses with oxaloacetate in the TCA cycle?

    <p>Citrate</p> Signup and view all the answers

    What is the importance of having three points of attachment between substrate and enzyme in the reaction involving citrate?

    <p>It enables the differentiation between various parts of symmetrical compounds.</p> Signup and view all the answers

    Which of the following best describes the oxidative decarboxylation reaction catalyzed by isocitrate dehydrogenase?

    <p>It oxidizes a hydroxyl group of isocitrate and reduces NAD+ to NADH.</p> Signup and view all the answers

    Which of the following describes acetyl groups?

    <p>They are derived from acetic acid by attachment to organic groups.</p> Signup and view all the answers

    What characterizes β-keto acids in relation to the reactions described?

    <p>They are prone to decarboxylation and release carbon dioxide.</p> Signup and view all the answers

    What are the net products produced during one complete cycle of the TCA cycle?

    <p>2 CO2, 8 electrons, and 1 GTP</p> Signup and view all the answers

    What role does Coenzyme A play during the reaction catalyzed by α-ketoglutarate dehydrogenase?

    <p>It assists in the condensation of the four-carbon product.</p> Signup and view all the answers

    In the context of the TCA cycle, what is the main role of the citrate molecule during its rearrangement process?

    <p>To facilitate the β-cleavage reaction.</p> Signup and view all the answers

    How does succinyl-CoA synthase utilize the hydrolysis of a thioester bond?

    <p>It couples energy release to produce a GTP molecule.</p> Signup and view all the answers

    Which statement accurately reflects the process of carbon oxidation in the TCA cycle?

    <p>Each carbon is individually oxidized to carbon dioxide.</p> Signup and view all the answers

    Why is it easier to cleave between two carbons that are α and β to a carbonyl group during the TCA cycle?

    <p>The carbonyl group stabilizes the transition state.</p> Signup and view all the answers

    What is produced alongside NADH in the TCA cycle during the oxidative decarboxylation reactions?

    <p>Carbon dioxide and a ketone.</p> Signup and view all the answers

    What molecular structure does α-ketoglutarate share with pyruvate that is noted in the context of dehydrogenase reactions?

    <p>The lower three carbons of each molecule are similar.</p> Signup and view all the answers

    How many total electrons are generated from one complete round of the TCA cycle?

    <p>8 electrons total, including both NADH and FADH2.</p> Signup and view all the answers

    In the reaction involving the conversion of succinyl-CoA, what is the significance of the energy derived from hydrolysis?

    <p>It leads to the direct synthesis of GTP.</p> Signup and view all the answers

    What is the product formed when succinate is oxidized by succinate dehydrogenase?

    <p>Fumarate</p> Signup and view all the answers

    Which oxidant is used by succinate dehydrogenase in the TCA cycle?

    <p>FAD</p> Signup and view all the answers

    How is L-malate produced from fumarate?

    <p>By hydration</p> Signup and view all the answers

    What distinguishes the oxidation reaction of succinate dehydrogenase from other oxidation-reduction reactions in the TCA cycle?

    <p>It forms a double bond between carbons.</p> Signup and view all the answers

    What characteristic of L-malate contributes to its designation as such?

    <p>It contains a hydroxyl group.</p> Signup and view all the answers

    Which of the following statements is true about the product of the succinate dehydrogenase reaction?

    <p>It has a lower reducing potential than NADH.</p> Signup and view all the answers

    In which configuration does fumarate possess its double bond?

    <p>Trans configuration</p> Signup and view all the answers

    What is the final product of the conversion of L-malate in the TCA cycle?

    <p>Oxaloacetate</p> Signup and view all the answers

    What is released during the reaction catalyzed by citrate synthase?

    <p>CoA group</p> Signup and view all the answers

    Which compound is formed from the reaction catalyzed by aconitase?

    <p>Isocitrate</p> Signup and view all the answers

    What type of reaction occurs first in the two-step process catalyzed by aconitase?

    <p>Dehydration</p> Signup and view all the answers

    Why does the aconitase reaction favor the formation of isocitrate instead of allowing the hydroxyl group to end up randomly?

    <p>Enzymes have asymmetric binding sites.</p> Signup and view all the answers

    What aspect of the citrate synthase reaction contributes to its favorable thermodynamic balance?

    <p>Release of a CoA group</p> Signup and view all the answers

    What happens to the electrons from the bond between the carbonyl carbon and oxygen when pyruvate attaches to the thiazole carbon?

    <p>They transfer to the carbonyl oxygen, making it negatively charged.</p> Signup and view all the answers

    Which of the following accurately describes citrate?

    <p>It is found in high levels in processed foods.</p> Signup and view all the answers

    What role does the hydrogen atom play on the upper thiazole carbon?

    <p>It enhances the acidity of the thiazole carbon.</p> Signup and view all the answers

    What distinguishes the mechanism of citrate synthase from a chemical reaction conducted without an enzyme?

    <p>Enzymes provide substrate specificity and lower transition state energies.</p> Signup and view all the answers

    What occurs immediately after the formation of the covalent bond between the thiazole carbon and pyruvate?

    <p>A hydroxyl group forms through neutralization.</p> Signup and view all the answers

    How does citrate contribute to the taste of beverages and foods?

    <p>It imparts a pleasing tartness.</p> Signup and view all the answers

    Which of the following correctly describes the reaction involving pyruvyl-thiamine pyrophosphate?

    <p>Carbon dioxide is released as a result of decarboxylation.</p> Signup and view all the answers

    What ultimately happens to the carboxylate anion formed during the reaction?

    <p>It facilitates the release of carbon dioxide.</p> Signup and view all the answers

    What structural change occurs following deprotonation of the thiazole carbon during the reaction?

    <p>The thiazole carbon acquires unpaired electrons for activation.</p> Signup and view all the answers

    What type of intermediate is specifically mentioned as being formed after the decarboxylation of pyruvyl-thiamine pyrophosphate?

    <p>Hydroxyethyl-thiamine pyrophosphate</p> Signup and view all the answers

    What would happen to the thiazole nitrogen after forming the bond with pyruvate?

    <p>It neutralizes its positive charge.</p> Signup and view all the answers

    What is the net carbon input into the TCA cycle?

    <p>Four carbons from oxaloacetate and two from AcetylCoA</p> Signup and view all the answers

    Which compound is produced after the decarboxylation of α-ketoglutarate?

    <p>SuccinylCoA</p> Signup and view all the answers

    How many NAD+ molecules are utilized in one round of the TCA cycle?

    <p>3</p> Signup and view all the answers

    What is produced in the reaction catalyzed by isocitrate dehydrogenase?

    <p>α-Ketoglutarate</p> Signup and view all the answers

    What is primarily generated from the oxidation of NADH and FADH2 in oxidative phosphorylation?

    <p>ATP</p> Signup and view all the answers

    Which of the following statements is true regarding the production of NADH in the TCA cycle?

    <p>NADH is produced during the conversion of α-ketoglutarate to succinyl-CoA.</p> Signup and view all the answers

    Which enzyme catalyzes the conversion of citrate to isocitrate?

    <p>Aconitase</p> Signup and view all the answers

    What type of reaction does the enzyme α-ketoglutarate dehydrogenase catalyze?

    <p>Oxidative decarboxylation</p> Signup and view all the answers

    What process utilizes the products of the TCA cycle for biosynthesis?

    <p>Amino acid biosynthesis</p> Signup and view all the answers

    What is one of the key products formed during the conversion of succinylCoA back to oxaloacetate?

    <p>Carbon dioxide</p> Signup and view all the answers

    Which compound is formed after the decarboxylation of β-keto acids in the TCA cycle?

    <p>α-Ketoglutarate</p> Signup and view all the answers

    What is the significance of the thioester bond in succinyl-CoA during the reaction with succinyl-CoA synthase?

    <p>It provides energy for ATP synthesis.</p> Signup and view all the answers

    Which component of the TCA cycle is essential for creating a proton gradient during oxidative phosphorylation?

    <p>FADH2</p> Signup and view all the answers

    What happens to the hydroxyl group of isocitrate during the reaction catalyzed by isocitrate dehydrogenase?

    <p>It is converted to a carbonyl group.</p> Signup and view all the answers

    What characterizes β-keto acids in the context of their stability during the TCA cycle?

    <p>They are relatively unstable and prone to decarboxylation.</p> Signup and view all the answers

    What is the end product of the reaction catalyzed by succinyl-CoA synthetase?

    <p>GTP</p> Signup and view all the answers

    What occurs when the pyruvate molecule approaches the thiazole carbon?

    <p>A covalent bond forms with the thiazole carbon.</p> Signup and view all the answers

    Which sequence of events immediately follows the formation of the hydroxyl group in the reaction?

    <p>A double bond forms, releasing carbon dioxide.</p> Signup and view all the answers

    What effect does the delocalized aromatic nature of the thiazole ring have on the hydrogen atom on its carbon?

    <p>It makes the hydrogen more acidic than usual.</p> Signup and view all the answers

    What is the outcome of the interaction between unpaired electrons of the deprotonated thiazole carbon and the carbonyl carbon of pyruvate?

    <p>Formation of a covalent bond.</p> Signup and view all the answers

    What happens to the carboxylate anion after the carbon dioxide is released from the pyruvyl-thiamine pyrophosphate intermediate?

    <p>It moves between the hydroxyl carbon and the thiazole carbon.</p> Signup and view all the answers

    Which of the following best describes the structure formed after the decarboxylation of pyruvyl-thiamine pyrophosphate?

    <p>Hydroxyethyl-thiamine pyrophosphate.</p> Signup and view all the answers

    What is the immediate consequence of the bond formation between the thiazole carbon and the carbonyl carbon of pyruvate?

    <p>The carbonyl oxygen becomes negatively charged.</p> Signup and view all the answers

    What type of intermediate is produced during the transfer step after the formation of the hydroxyethyl-thiamine pyrophosphate?

    <p>Lipoamide complex.</p> Signup and view all the answers

    What characteristic of isocitrate distinguishes it from its symmetrical precursor, citrate?

    <p>It has a chiral center.</p> Signup and view all the answers

    What type of reaction is catalyzed by isocitrate dehydrogenase?

    <p>Oxidative decarboxylation</p> Signup and view all the answers

    What product is formed directly after the oxidative decarboxylation of isocitrate?

    <p>Oxalosuccinate</p> Signup and view all the answers

    What is the significance of NADH produced during the decarboxylation reactions in the TCA cycle?

    <p>It donates two electrons to the electron transport chain</p> Signup and view all the answers

    What determines the selectivity of enzymes towards distinguishing different parts of symmetrical compounds?

    <p>The number of attachment points between substrate and enzyme</p> Signup and view all the answers

    What structural feature of α-ketoglutarate is similar to pyruvate?

    <p>Their lower three carbon atoms mirror each other's structure.</p> Signup and view all the answers

    What is coenzyme A's role during the conversion of α-ketoglutarate?

    <p>It is condensed with the product to form succinyl-CoA.</p> Signup and view all the answers

    What type of energy transaction occurs during the reaction catalyzed by succinyl-CoA synthase?

    <p>It releases energy from hydrolysis of a thioester bond.</p> Signup and view all the answers

    What transformation occurs during the transfer of the hydroxyethyl group to lipoamide?

    <p>It is oxidized to an acetyl group.</p> Signup and view all the answers

    Which form of lipoamide contains a disulfide ring structure?

    <p>Oxidized lipoamide</p> Signup and view all the answers

    What is the significance of acetylCoA in metabolic pathways?

    <p>It acts as an active acetate for various carbon acceptor molecules.</p> Signup and view all the answers

    Which reaction produces dihydrolipoamide during the pyruvate dehydrogenase mechanism?

    <p>The transfer of two electrons and two protons from hydroxyethyl intermediate to lipoamide.</p> Signup and view all the answers

    What kind of intermediate is formed after the hydroxyethyl group is transferred from thiamine pyrophosphate?

    <p>Acetylthioester derivative</p> Signup and view all the answers

    Which component of coenzyme A must be obtained through the human diet?

    <p>Pantothenic acid</p> Signup and view all the answers

    During the reaction catalyzed by dihydrolipoyltransacetylase, which product is formed?

    <p>AcetylCoA</p> Signup and view all the answers

    What change occurs to the hydroxyethyl group when it is passed from thiamine pyrophosphate?

    <p>It loses electrons and protons.</p> Signup and view all the answers

    What is the product formed when α-ketoglutarate is decarboxylated?

    <p>SuccinylCoA</p> Signup and view all the answers

    Which cofactors are produced during one complete round of the TCA cycle?

    <p>3 NADH, 1 FADH2, 1 GTP</p> Signup and view all the answers

    How many carbon atoms are net input into the TCA cycle and what is their source?

    <p>Two carbons from AcetylCoA and four from oxaloacetate</p> Signup and view all the answers

    What role does the electron transport chain play in the energy balance of the TCA cycle?

    <p>It channels electrons to drive ATP formation.</p> Signup and view all the answers

    What is the consequence of the proton gradient created during oxidative phosphorylation?

    <p>It drives the flow of protons through the ATP synthase.</p> Signup and view all the answers

    What types of biosynthetic pathways are supported by intermediates of the TCA cycle?

    <p>Amino acid and nucleotide biosynthesis</p> Signup and view all the answers

    What significant change occurs when citrate is converted to isocitrate?

    <p>Rearrangement of the molecular structure</p> Signup and view all the answers

    Which component primarily carries energy from the TCA cycle to subsequent pathways?

    <p>NADH</p> Signup and view all the answers

    What type of bond connects the acetyl group to coenzyme A in acetylCoA?

    <p>Thioester bond</p> Signup and view all the answers

    Which enzyme is responsible for the oxidation of dihydrolipoamide to regenerate lipoamide?

    <p>Dihydrolipoyl dehydrogenase</p> Signup and view all the answers

    Which component is transferred during the conversion of FAD to FADH2 in the oxidation of dihydrolipoamide?

    <p>Two electrons and two protons</p> Signup and view all the answers

    Which name is not used to refer to the citric acid cycle?

    <p>Glycolytic cycle</p> Signup and view all the answers

    What characteristic of the isoalloxazine ring makes it essential for FAD's function in catalysis?

    <p>It is involved in electron transfer reactions</p> Signup and view all the answers

    How many protons are released into the solvent during the conversion of FADH2 back to FAD?

    <p>One proton</p> Signup and view all the answers

    What distinguishes the first product of the citric acid cycle?

    <p>It is a six-carbon molecule with multiple functional groups</p> Signup and view all the answers

    Which type of reaction is facilitated by the dihydrolipoyl dehydrogenase enzyme?

    <p>Oxidation-reduction</p> Signup and view all the answers

    What is formed when the hydroxyethyl group is transferred from thiamine pyrophosphate to lipoamide?

    <p>Acetylthioester</p> Signup and view all the answers

    Which chemical change occurs to lipoamide when it interacts with the hydroxyethyl intermediate?

    <p>It is reduced to dihydrolipoamide</p> Signup and view all the answers

    What aspect of acetylCoA contributes to its ability to transfer the acetyl group to other carbon acceptor molecules?

    <p>It is a thioester derivative</p> Signup and view all the answers

    What is the primary structural difference between oxidized and reduced forms of lipoamide?

    <p>Presence of a disulfide ring structure</p> Signup and view all the answers

    How is the conversion of lipoamide from oxidized to reduced form initiated?

    <p>Through the addition of electrons and protons to the oxidized form</p> Signup and view all the answers

    What role does coenzyme A play in the reaction catalyzed by dihydrolipoyltransacetylase?

    <p>It is the primary substrate converted to acetylCoA</p> Signup and view all the answers

    What feature of acetylCoA is significant for its biochemical function?

    <p>It has a high energy of hydrolysis</p> Signup and view all the answers

    Where is the vitamin component of coenzyme A derived from?

    <p>Pantothenic acid</p> Signup and view all the answers

    What role does the convoluted inner membrane of mitochondria play in cellular respiration?

    <p>It contains the ATP synthase used for ATP production.</p> Signup and view all the answers

    Which of the following statements about the pyruvate dehydrogenase complex is incorrect?

    <p>It converts acetyl-CoA directly into carbon dioxide.</p> Signup and view all the answers

    What is the function of FAD in the pyruvate dehydrogenase reaction?

    <p>It is reduced to FADH2 as it accepts electrons.</p> Signup and view all the answers

    Which statement about thiamine pyrophosphate (TPP) in the pyruvate dehydrogenase mechanism is true?

    <p>It must be obtained from the diet for proper enzyme function.</p> Signup and view all the answers

    Which of the following pathways does the pyruvate dehydrogenase complex directly connect?

    <p>Glycolysis to the citric acid cycle.</p> Signup and view all the answers

    What type of intermediate is produced when pyruvate is first attached to thiamine pyrophosphate?

    <p>A two-carbon hydroxyethyl intermediate.</p> Signup and view all the answers

    During the reaction catalyzed by the pyruvate dehydrogenase complex, which molecule serves as an electron donor?

    <p>NADH.</p> Signup and view all the answers

    What occurs to lipoate during the pyruvate dehydrogenase reaction?

    <p>It undergoes a cycle of reduction and reoxidation.</p> Signup and view all the answers

    Which statement best describes the role of citrate within the context of food and beverages?

    <p>It serves primarily as a flavor enhancer with a tart character.</p> Signup and view all the answers

    What advantage does the enzymatic reaction of aconitase provide over a chemical reaction conducted without an enzyme?

    <p>It allows for a better yield of isocitrate due to selective placement of the hydroxyl group.</p> Signup and view all the answers

    Which of the following correctly represents the primary thermodynamic factor in the citrate synthase reaction?

    <p>Release of CoA to favor product formation.</p> Signup and view all the answers

    During the synthesis of citrate, what occurs in terms of electron movement?

    <p>Electrons from the carbonyl double bond are transferred to carbonyl oxygen.</p> Signup and view all the answers

    What is the consequence of the CoA group being cleaved during the citrate synthase reaction?

    <p>It provides the necessary energy to drive the reaction forward.</p> Signup and view all the answers

    What type of reaction does aconitase perform to convert citrate to isocitrate?

    <p>A dehydration followed by a hydration reaction.</p> Signup and view all the answers

    What molecular characteristic differentiates citrate from isocitrate?

    <p>The presence of an additional hydroxyl group.</p> Signup and view all the answers

    What could potentially limit the efficiency of aconitase when conducting the reaction outside of a biological system?

    <p>Reduced specificity in the positioning of the hydroxyl group.</p> Signup and view all the answers

    What is the main reason why acetylCoA is first condensed with oxaloacetate in the TCA cycle?

    <p>To initiate the cycle with a six-carbon compound</p> Signup and view all the answers

    Which of the following statements about the loss of carbon atoms during the TCA cycle is true?

    <p>The two carbons lost as carbon dioxide come from both oxaloacetate and acetylCoA.</p> Signup and view all the answers

    What role does NADH play during the TCA cycle as it pertains to electron transfer?

    <p>It captures electrons during oxidation reactions</p> Signup and view all the answers

    Which of the following accurately describes the acetyl group in biochemical terms?

    <p>It is classified under the broader category of acyl groups.</p> Signup and view all the answers

    Which reaction occurs in the TCA cycle after the conversion of a C6 compound to a C5 compound?

    <p>NADH and carbon dioxide are removed.</p> Signup and view all the answers

    What distinguishes the cleavage between carbon atoms in acetylCoA during the TCA cycle?

    <p>Cleavage is favored between carbons α and β to a carbonyl group.</p> Signup and view all the answers

    Which of the following represents the net products of one complete round of the TCA cycle?

    <p>2 carbon dioxide, 6 electrons, and 1 GTP</p> Signup and view all the answers

    What structural change occurs to citrate during its rearrangement in the TCA cycle?

    <p>It undergoes β-cleavage.</p> Signup and view all the answers

    What is the net carbon input into the TCA cycle after one complete turn?

    <p>2 carbons from acetylCoA and 4 from oxaloacetate</p> Signup and view all the answers

    Which of the following best represents the products generated after one round of the TCA cycle?

    <p>3 NADH, 1 FADH2, 1 GTP, and 2 carbon dioxide</p> Signup and view all the answers

    What role do the electrons removed during the TCA cycle serve?

    <p>They enhance the respiratory chain and increase proton pumping.</p> Signup and view all the answers

    Which intermediates are generated during the conversion of citrate to α-ketoglutarate?

    <p>Citrate, isocitrate, and α-ketoglutarate</p> Signup and view all the answers

    How does the TCA cycle contribute to biosynthetic pathways?

    <p>By providing substrates necessary for amino acid and nucleotide synthesis.</p> Signup and view all the answers

    What is the final outcome regarding carbon atoms in the carbon cycle of the TCA cycle?

    <p>6 carbons enter and 4 carbons are lost as carbon dioxide.</p> Signup and view all the answers

    What distinguishes succinylCoA in the TCA cycle?

    <p>It carries a high-energy thioester bond.</p> Signup and view all the answers

    Which cofactors are primarily involved in the energy balance of the TCA cycle?

    <p>3 NAD+, 1 FAD, and 1 GDP</p> Signup and view all the answers

    What is produced during the conversion of pyruvate to acetylCoA?

    <p>AcetylCoA and carbon dioxide</p> Signup and view all the answers

    Where does the citric acid cycle (TCA cycle) take place in a eukaryotic cell?

    <p>Mitochondria</p> Signup and view all the answers

    What percentage of ATP equivalents is produced during the conversion of pyruvate to acetylCoA?

    <p>17%</p> Signup and view all the answers

    What is one of the primary substrates that enters the citric acid cycle after being generated by the pyruvate dehydrogenase complex?

    <p>AcetylCoA</p> Signup and view all the answers

    What compound is produced alongside carbon dioxide during the reaction of pyruvate conversion by the pyruvate dehydrogenase complex?

    <p>NADH</p> Signup and view all the answers

    Which of the following is an alternative source of acetylCoA apart from pyruvate?

    <p>Fatty acids</p> Signup and view all the answers

    What best describes the relationship between glycolysis and the TCA cycle?

    <p>Pyruvate links the two pathways.</p> Signup and view all the answers

    What is the overall effect of the processes involving pyruvate and acetylCoA on free energy?

    <p>They result in a loss of free energy.</p> Signup and view all the answers

    What happens to the hydrogen atom at the thiazole carbon during catalysis?

    <p>It becomes more acidic than usual.</p> Signup and view all the answers

    What results from the attack of the thiazole carbon on the carbonyl carbon of pyruvate?

    <p>Formation of a covalent bond.</p> Signup and view all the answers

    What happens to the carbon on the carboxyl group after the formation of pyruvyl-thiamine pyrophosphate?

    <p>It is released as carbon dioxide.</p> Signup and view all the answers

    Which intermediate is specifically formed following the decarboxylation of pyruvyl-thiamine pyrophosphate?

    <p>Hydroxyethyl-thiamine pyrophosphate.</p> Signup and view all the answers

    What structural change occurs to the thiazole nitrogen after carbon bond formation?

    <p>It is neutralized from a positive charge.</p> Signup and view all the answers

    What initiates the deprotonation of the upper thiazole carbon during catalysis?

    <p>Delocalization of electrons in the ring.</p> Signup and view all the answers

    What happens to electrons from the negative oxygen of the carboxylate anion in the subsequent steps?

    <p>They form a bond with C-2.</p> Signup and view all the answers

    What function does the hydroxyl group serve after its formation during the reaction?

    <p>It stabilizes the carbonyl compound.</p> Signup and view all the answers

    What are the two main products formed by the pyruvate dehydrogenase complex after the conversion of pyruvate?

    <p>Acetyl-CoA and NADH</p> Signup and view all the answers

    Which characteristic of the inner mitochondrial membrane contributes to its function in oxidative phosphorylation?

    <p>It is convoluted to increase surface area.</p> Signup and view all the answers

    What role does NADH play in relation to the pyruvate dehydrogenase reaction products?

    <p>NADH acts as an electron donor in oxidative phosphorylation.</p> Signup and view all the answers

    In which cellular compartment is the pyruvate dehydrogenase complex found in eukaryotic cells?

    <p>Mitochondrial matrix</p> Signup and view all the answers

    Which cofactor must be supplied through the diet for the proper functioning of pyruvate dehydrogenase?

    <p>Thiamine</p> Signup and view all the answers

    Which statement correctly describes the reaction mechanism of pyruvate dehydrogenase?

    <p>Thiamine pyrophosphate attaches to pyruvate forming a hydroxyethyl intermediate.</p> Signup and view all the answers

    What happens to lipoate during the reaction catalyzed by the pyruvate dehydrogenase complex?

    <p>Lipoate is reduced during the reaction.</p> Signup and view all the answers

    What is the total number of subunits in the pyruvate dehydrogenase complex, and what types of proteins does it consist of?

    <p>96 subunits consisting of three different protein types</p> Signup and view all the answers

    What activates various acyl groups in coenzyme A?

    <p>Sulfhydryl group</p> Signup and view all the answers

    Which enzyme catalyzes the reoxidation of dihydrolipoamide to lipoamide?

    <p>Dihydrolipoyl dehydrogenase</p> Signup and view all the answers

    What is formed when FAD is reduced during the reaction involving dihydrolipoamide?

    <p>FADH2</p> Signup and view all the answers

    Which of the following names refers to the citric acid cycle?

    <p>Krebs cycle</p> Signup and view all the answers

    What is the primary product of the citric acid cycle?

    <p>Citrate</p> Signup and view all the answers

    What is the significance of the isoalloxazine ring in FAD?

    <p>Involvement in catalysis</p> Signup and view all the answers

    What is the main role of NAD+ in the reactions described?

    <p>Electron acceptor</p> Signup and view all the answers

    Which coenzyme is essential for the conversion of dihydrolipoamide during the reaction?

    <p>Thiamine pyrophosphate</p> Signup and view all the answers

    What type of group is formed when acetate is attached to an organic or inorganic group other than a hydroxyl group?

    <p>Acetyl group</p> Signup and view all the answers

    During the TCA cycle, which molecule serves as the starting material that combines with acetylCoA?

    <p>Oxaloacetate</p> Signup and view all the answers

    What is removed from a C6 compound during the first conversion step in the TCA cycle?

    <p>NADH and carbon dioxide</p> Signup and view all the answers

    Which of the following represents the net products of one round of the TCA cycle?

    <p>2 carbon dioxide, 8 electrons, and 1 GTP</p> Signup and view all the answers

    What is the main challenge regarding the cleavage of acetylCoA in the TCA cycle?

    <p>It is hard to cleave the bond between the two carbon atoms.</p> Signup and view all the answers

    Which of the following describes what happens to the carbon atoms as they proceed through the TCA cycle?

    <p>Carbons are lost at different stages in each cycle round.</p> Signup and view all the answers

    What is the primary product of pyruvate decarboxylation?

    <p>AcetylCoA</p> Signup and view all the answers

    Which electrons are produced during the TCA cycle from oxidizing a C4 intermediate?

    <p>1 NADH and 1 FADH2</p> Signup and view all the answers

    What is the primary outcome of the pyruvate dehydrogenase complex catalyzing the breakdown of pyruvate?

    <p>Production of acetylCoA and carbon dioxide</p> Signup and view all the answers

    What percentage of the overall free energy change occurs during the conversion of pyruvate to acetylCoA?

    <p>20%</p> Signup and view all the answers

    Which pathways are metabolically linked by pyruvate?

    <p>Glycolysis and the citric acid cycle</p> Signup and view all the answers

    Which of the following accurately describes the location of glycolysis and the citric acid cycle in eukaryotic cells?

    <p>Glycolysis occurs in the cytoplasm, TCA cycle in the mitochondria</p> Signup and view all the answers

    What molecular product is generated alongside carbon dioxide during the conversion of pyruvate by the pyruvate dehydrogenase complex?

    <p>NADH</p> Signup and view all the answers

    Which substrate does acetylCoA serve as the end product for besides glycolysis?

    <p>Amino acid catabolism</p> Signup and view all the answers

    What is the total energy contribution from aerobic glycolysis to the overall ATP production?

    <p>17%</p> Signup and view all the answers

    Which process does acetylCoA undergo once it enters the citric acid cycle?

    <p>Oxidation into two molecules of carbon dioxide</p> Signup and view all the answers

    What role does the sulfhydryl group of coenzyme A play in metabolism?

    <p>It forms a thioester bond with acyl groups.</p> Signup and view all the answers

    What is the end product of the oxidation of dihydrolipoamide in the presence of FAD?

    <p>FADH2</p> Signup and view all the answers

    Which component must be reoxidized for the pyruvate dehydrogenase reaction cycle to continue?

    <p>Dihydrolipoamide</p> Signup and view all the answers

    Why is the TCA cycle also known as the Krebs cycle?

    <p>It was first discovered by Sir Hans Krebs.</p> Signup and view all the answers

    What is formed when FAD undergoes reduction during the oxidation of dihydrolipoamide?

    <p>FADH2</p> Signup and view all the answers

    What is the main role of the isoalloxazine ring in FAD?

    <p>To participate in oxidation-reduction reactions.</p> Signup and view all the answers

    During the conversion of FAD to FADH2, how many protons are involved?

    <p>Two protons</p> Signup and view all the answers

    Which B vitamin is associated with riboflavin, a component of FAD?

    <p>Vitamin B2</p> Signup and view all the answers

    What is the result of the covalent bond formation between the thiazole carbon and the carbonyl carbon of pyruvate?

    <p>The carboxyl group of pyruvate is converted into carbon dioxide.</p> Signup and view all the answers

    What role does the negatively charged carbonyl oxygen play after the bond forms with the thiazole carbon?

    <p>It is neutralized by a proton from the solvent.</p> Signup and view all the answers

    During the decarboxylation of pyruvyl-thiamine pyrophosphate, what is primarily released?

    <p>Carbon dioxide.</p> Signup and view all the answers

    What structural change occurs at the thiazole nitrogen after the carbon bond formation?

    <p>It becomes positively charged.</p> Signup and view all the answers

    Which of the following best describes the role of the aromatic nature of the thiazole ring?

    <p>It increases the nucleophilicity of the thiazole carbon.</p> Signup and view all the answers

    What type of interaction occurs between the electrons of the negative oxygen and the adjacent carbon in the pyruvyl-thiamine pyrophosphate intermediate?

    <p>Electron transfer to form a new carbon-carbon bond.</p> Signup and view all the answers

    What ultimately helps drive the reaction toward the formation of hydroxylethyl-thiamine pyrophosphate?

    <p>The release of carbon dioxide.</p> Signup and view all the answers

    Which component is transferred to lipoamide after the formation of the hydroxyethyl intermediate?

    <p>The acetyl group.</p> Signup and view all the answers

    What is produced when isocitrate undergoes oxidation by isocitrate dehydrogenase?

    <p>α-Ketoglutarate</p> Signup and view all the answers

    What type of reaction follows the decarboxylation of α-ketoglutarate?

    <p>Oxidative decarboxylation</p> Signup and view all the answers

    What is the primary transformation involving the carbons of acetylCoA during the TCA cycle?

    <p>Two carbons are oxidized to carbon dioxide, but originate from oxaloacetate.</p> Signup and view all the answers

    Which molecule is generated as a direct result of the hydrolysis of the thioester bond in succinyl-CoA?

    <p>GTP</p> Signup and view all the answers

    What distinguishes an acetyl group from an acetate ion?

    <p>An acetyl group is part of a larger molecular framework, while acetate is not.</p> Signup and view all the answers

    In what manner do the products of the TCA cycle relate to the initial input of acetylCoA?

    <p>The reduction of carbons originates exclusively from oxaloacetate.</p> Signup and view all the answers

    What characteristic does the chiral center of isocitrate have in relation to its structure?

    <p>It is derived from a symmetrical compound</p> Signup and view all the answers

    What mechanism allows for the synthesis of citrate from acetylCoA?

    <p>Condensation reaction with oxaloacetate.</p> Signup and view all the answers

    Which cofactor is involved in the reactions catalyzed by both α-ketoglutarate dehydrogenase and pyruvate dehydrogenase?

    <p>NAD+</p> Signup and view all the answers

    What is the net electron yield from one round of the TCA cycle?

    <p>8 electrons: 6 from NADH and 2 from FADH2.</p> Signup and view all the answers

    What type of compound is produced after the oxidative decarboxylation of isocitrate?

    <p>Beta-keto acid</p> Signup and view all the answers

    Which reaction occurs after the conversion of a C6 compound in the TCA cycle?

    <p>A β-cleavage reaction that reduces the carbon count.</p> Signup and view all the answers

    Which of the following statements is true regarding the energy dynamics of succinyl-CoA synthesis?

    <p>It involves the formation of a thioester bond.</p> Signup and view all the answers

    What challenge arises in cleaving the two carbons of acetylCoA during the cycle?

    <p>It involves a higher energy transition state than single carbon cleavage.</p> Signup and view all the answers

    What is the role of NADH produced during the TCA cycle?

    <p>To donate electrons to the electron transport system</p> Signup and view all the answers

    What is a defining feature of the transformation of C4 intermediates in the TCA cycle?

    <p>They undergo multiple oxidative reactions resulting in NADH and FADH2.</p> Signup and view all the answers

    What is formed when pyruvate's carbonyl carbon is attacked by the deprotonated thiazole carbon?

    <p>A covalent bond</p> Signup and view all the answers

    What occurs to the negative charge on the carbonyl oxygen after the bond with the thiazole carbon forms?

    <p>It is neutralized by a proton from the solvent</p> Signup and view all the answers

    Which intermediate is formed after the decarboxylation of pyruvyl-thiamine pyrophosphate?

    <p>Hydroxyethyl-thiamine pyrophosphate</p> Signup and view all the answers

    During the reaction leading to the formation of pyruvyl-thiamine pyrophosphate, what happens to the electrons from the carboxylate anion?

    <p>They move to the C-2 carbon</p> Signup and view all the answers

    What triggers the release of carbon dioxide from the pyruvyl-thiamine pyrophosphate intermediate?

    <p>Formation of a double bond with the hydroxyl carbon</p> Signup and view all the answers

    What is the role of the carbon atom at the top of the thiazole ring in catalysis?

    <p>It aids in binding pyruvate</p> Signup and view all the answers

    What process occurs after the formation of the hydroxyethyl-thiamine pyrophosphate intermediate?

    <p>Transfer to lipoamide</p> Signup and view all the answers

    What structural feature of the thiazole ring contributes to its catalytic properties?

    <p>The presence of an aromatic system</p> Signup and view all the answers

    What does the hydroxyethyl group resemble and what is its actual oxidation level when attached to thiamine pyrophosphate?

    <p>It resembles an alcohol but is at the oxidation level of an aldehyde.</p> Signup and view all the answers

    What is the form of lipoamide after the hydroxyethyl group is passed to it during the reaction?

    <p>It is converted to dihydrolipoamide, having reduced sulfur groups.</p> Signup and view all the answers

    What type of group is the acetyl group classified as before being transferred to coenzyme A?

    <p>Thioester group</p> Signup and view all the answers

    What is the significance of acetylCoA in metabolic processes?

    <p>It is involved in the synthesis of fatty acids and energy production.</p> Signup and view all the answers

    Which vitamin component is linked with coenzyme A and must be included in the human diet?

    <p>Pantothenic acid</p> Signup and view all the answers

    What is the mechanism that leads to the oxidation of the hydroxyethyl group during its transfer to lipoamide?

    <p>Oxidation with electron loss.</p> Signup and view all the answers

    What maintains the energetic potential for the transfer of the acetyl group from acetylCoA?

    <p>High energy of hydrolysis of acetylCoA.</p> Signup and view all the answers

    What is the primary product of the reaction catalyzed by citrate synthase?

    <p>Citrate</p> Signup and view all the answers

    What structural difference exists between the oxidized and reduced forms of lipoamide?

    <p>The oxidized form has a closed ring structure, while the reduced form is an open chain.</p> Signup and view all the answers

    Which step is essential for facilitating the citrate synthase reaction?

    <p>Cleavage of the thioester bond</p> Signup and view all the answers

    What is the type of reaction catalyzed by aconitase?

    <p>Dehydration followed by hydration</p> Signup and view all the answers

    How does citrate synthase differentiate between the symmetrical parts of citrate?

    <p>Using an asymmetric binding site</p> Signup and view all the answers

    Which molecule is released during the citrate synthase reaction?

    <p>CoA</p> Signup and view all the answers

    What occurs to the carbonyl oxygen in the citrate synthase reaction?

    <p>It becomes protonated to form a hydroxyl group.</p> Signup and view all the answers

    What is a potential outcome of conducting the aconitase reaction without an enzyme?

    <p>Random placement of the new hydroxyl group</p> Signup and view all the answers

    Which property of citrate contributes to its use in food and beverages?

    <p>The tartness it imparts</p> Signup and view all the answers

    What is the role of the sulfhydryl group in coenzyme A?

    <p>It helps in forming thioester bonds with acyl groups.</p> Signup and view all the answers

    Which enzyme is responsible for converting dihydrolipoamide back to oxidized lipoamide?

    <p>Dihydrolipoyl dehydrogenase</p> Signup and view all the answers

    What is produced when FAD is converted to FADH2 during the oxidation of dihydrolipoamide?

    <p>Two electrons and two protons</p> Signup and view all the answers

    Which of the following accurately describes the first product of the citric acid cycle?

    <p>Citrate</p> Signup and view all the answers

    What key function does FADH2 serve within metabolic pathways?

    <p>It functions as a reducing agent in electron transport.</p> Signup and view all the answers

    What distinguishes the tricarboxylic acid cycle from other metabolic cycles?

    <p>It involves three carboxyl groups in its initial products.</p> Signup and view all the answers

    Which component is required for the conversion of FADH2 back to FAD?

    <p>NAD+</p> Signup and view all the answers

    Who discovered the TCA cycle, which is also known as the Krebs cycle?

    <p>Sir Hans Krebs</p> Signup and view all the answers

    What is the significance of having at least three points of attachment in enzymatic reactions?

    <p>It enables the discrimination between symmetrical compounds.</p> Signup and view all the answers

    What product results from the oxidative decarboxylation of isocitrate catalyzed by isocitrate dehydrogenase?

    <p>α-Ketoglutarate</p> Signup and view all the answers

    What is a common outcome during both the pyruvate and α-ketoglutarate dehydrogenase reactions?

    <p>Production of CO2</p> Signup and view all the answers

    How does succinyl-CoA synthase generate energy during its reaction?

    <p>By hydrolysis of a thioester bond</p> Signup and view all the answers

    Which statement accurately describes the conversion process involving α-ketoglutarate?

    <p>It generates NADH and releases CO2.</p> Signup and view all the answers

    What happens to the hydroxyl group of isocitrate during the reaction with isocitrate dehydrogenase?

    <p>It gets converted to a carbonyl group.</p> Signup and view all the answers

    Why are β-keto acids susceptible to decarboxylation?

    <p>They have a carboxyl group adjacent to a carbonyl group.</p> Signup and view all the answers

    During which reaction is GTP produced in the TCA cycle?

    <p>Conversion of succinyl-CoA to succinate</p> Signup and view all the answers

    What is the primary function of the pyruvate dehydrogenase complex in cellular respiration?

    <p>Transforms pyruvate into acetyl-CoA</p> Signup and view all the answers

    Where is the pyruvate dehydrogenase complex located within eukaryotic cells?

    <p>In the mitochondrial matrix</p> Signup and view all the answers

    Which of the following best describes the role of acetyl-CoA within the TCA cycle?

    <p>It acts as a substrate for the conversion of citrate</p> Signup and view all the answers

    What cofactor must be supplied through the diet for the functioning of the pyruvate dehydrogenase complex?

    <p>Thiamin (Vitamin B1)</p> Signup and view all the answers

    During the reaction catalyzed by pyruvate dehydrogenase, which product serves as an electron donor for oxidative phosphorylation?

    <p>NADH</p> Signup and view all the answers

    Which intermediate is formed immediately after pyruvate is attached to thiamine pyrophosphate in the dehydrogenase reaction?

    <p>Hydroxyethyl intermediate</p> Signup and view all the answers

    What describes the general structure of a mitochondrion as observed through electron microscopy?

    <p>Double membrane with extensive folding</p> Signup and view all the answers

    What is the primary outcome of the reaction catalyzed by the pyruvate dehydrogenase complex?

    <p>Conversion of pyruvate to acetylCoA and carbon dioxide</p> Signup and view all the answers

    Under aerobic conditions, what is the fate of pyruvate after glycolysis?

    <p>It diffuses into the mitochondria to form acetylCoA</p> Signup and view all the answers

    What happens to the cofactor lipoate during the pyruvate dehydrogenase reaction?

    <p>It is reduced and then reoxidized</p> Signup and view all the answers

    Which of the following accurately describes how much free energy change occurs during the conversion of pyruvate to acetylCoA?

    <p>20% of the overall free energy change</p> Signup and view all the answers

    What percentage of ATP equivalents is produced from the conversion of pyruvate to acetylCoA?

    <p>17%</p> Signup and view all the answers

    What distinguishes the locations of glycolysis and the citric acid cycle?

    <p>Glycolysis occurs in the cytoplasm, while the citric acid cycle is located in the mitochondria.</p> Signup and view all the answers

    Which of these statements is true regarding the relationship between acetylCoA and other metabolic pathways?

    <p>AcetylCoA is also a major product of amino acid catabolism.</p> Signup and view all the answers

    What role does the pyruvate dehydrogenase complex play in metabolic pathways?

    <p>It links glycolysis to the citric acid cycle by converting pyruvate to acetylCoA.</p> Signup and view all the answers

    During which metabolic process is the majority of ATP equivalents produced after glycolysis?

    <p>Metabolism of acetylCoA in the citric acid cycle</p> Signup and view all the answers

    What is the primary role of succinate dehydrogenase in the TCA cycle?

    <p>It catalyzes the oxidation of succinate to fumarate.</p> Signup and view all the answers

    Which characteristic distinguishes fumarate from succinate?

    <p>Formation of a double bond between carbon atoms.</p> Signup and view all the answers

    What is the significance of the FADH2 produced during the oxidation of succinate?

    <p>It has a lower potential for ATP production in oxidative phosphorylation.</p> Signup and view all the answers

    Which enzyme is responsible for converting fumarate into L-malate?

    <p>Fumarase.</p> Signup and view all the answers

    What key feature does L-malate have that distinguishes it from fumarate?

    <p>It has a center of asymmetry.</p> Signup and view all the answers

    Which statement accurately describes the role of the enzyme fumarase?

    <p>It can add water to a double bond.</p> Signup and view all the answers

    What type of reaction is facilitated by L-malate dehydrogenase in the TCA cycle?

    <p>Oxidation of an alcohol to a ketone.</p> Signup and view all the answers

    How does the reducing potential of succinate oxidation compare to other reactions in the TCA cycle?

    <p>It is lower than the previous oxidation reactions.</p> Signup and view all the answers

    What is the role of the hydrogen atom on the upper thiazole carbon in the catalysis process?

    <p>It increases the acidity of the carbon atom.</p> Signup and view all the answers

    What occurs to the electrons from the carbonyl carbon of pyruvate during the formation of the covalent bond?

    <p>They become part of a hydroxyl group.</p> Signup and view all the answers

    In the reaction process, what is the order of events that occur after the bond formation between the thiazole carbon and pyruvate?

    <p>Covalent bond formation, hydroxyl group creation, carboxyl group release.</p> Signup and view all the answers

    Which chemical group is formed as a result of the decarboxylation process of pyruvyl-thiamine pyrophosphate?

    <p>Hydroxyethyl intermediate</p> Signup and view all the answers

    What happens to the electrons from the carboxylate anion after carbon dioxide is released?

    <p>They form a new double bond with the thiazole carbon.</p> Signup and view all the answers

    What type of intermediate forms as a result of the transfer to lipoamide in the pyruvate dehydrogenase mechanism?

    <p>Thioester intermediate</p> Signup and view all the answers

    Which factor affects the stability of the thiazole ring during catalysis?

    <p>The aromaticity of the thiazole structure.</p> Signup and view all the answers

    What role does the solvent play in the reaction after the formation of the covalent bond?

    <p>It neutralizes the negative charge on the carbonyl oxygen.</p> Signup and view all the answers

    What is the net carbon input into the TCA cycle?

    <p>2 carbons from acetylCoA and 4 carbons from oxaloacetate</p> Signup and view all the answers

    How many NADH are produced in one round of the TCA cycle?

    <p>3</p> Signup and view all the answers

    What products are generated from α-ketoglutarate after its decarboxylation?

    <p>SuccinylCoA and NADH</p> Signup and view all the answers

    What is a key role of the NADH and FADH2 produced in the TCA cycle?

    <p>Convert potential energy into ATP during oxidative phosphorylation</p> Signup and view all the answers

    Which substrates are utilized for amino acid biosynthesis that are derived from the TCA cycle?

    <p>Fumarate and α-ketoglutarate</p> Signup and view all the answers

    What is the total number of enzymes involved in the TCA cycle?

    <p>8</p> Signup and view all the answers

    What is the ultimate fate of the electrons removed in the TCA cycle?

    <p>Transferred to the electron transport chain</p> Signup and view all the answers

    What waste product is released during the conversion of isocitrate to α-ketoglutarate in the TCA cycle?

    <p>Carbon dioxide</p> Signup and view all the answers

    Study Notes

    Mitochondria

    • Mitochondria are organelles found in eukaryotic cells
    • They are characterized by a porous outer membrane and an impermeable convoluted inner membrane
    • The electron transport and oxidative phosphorylation systems are located in the inner membrane

    Pyruvate Dehydrogenase Complex

    • Pyruvate dehydrogenase complex transforms pyruvate into acetyl-CoA
    • Consists of 96 subunits and 3 types of proteins
    • Located in the mitochondrial matrix
    • Links glycolysis to the TCA cycle
    • Reaction produces NADH and acetyl-CoA
    • NADH is a donor for oxidative phosphorylation
    • Acetyl-CoA is a substrate for the TCA cycle

    Thiamine Pyrophosphate (TPP)

    • Thiamine pyrophosphate is a cofactor in the pyruvate dehydrogenase reaction
    • It is synthesized from thiamine, which is obtained from the diet.
    • The thiazole ring is the active part of TPP
    • Carbon atom at the top of the thiazole ring participates in catalysis.

    Steps of the Pyruvate Dehydrogenase Reaction

    • Pyruvate attaches to thiamine pyrophosphate
    • Pyruvate is converted to a two-carbon hydroxyethyl intermediate and releases carbon dioxide
    • Two-carbon intermediate is oxidized to an acetyl derivative
    • Acetyl group is transferred to coenzyme A
    • Lipoate is reduced during oxidation
    • Reduced lipoate is reoxidized by FAD.
      • FAD is converted to FADH2
      • FADH2 then transfers electrons to NAD+ forming NADH

    TCA Cycle Overview

    • Converts two carbons of acetyl-CoA into two molecules of carbon dioxide.
    • Net products are 2 carbon dioxide, 8 electrons (6 as NADH and 2 as FADH2), and 1 GTP.
    • Acetyl-CoA is condensed with oxaloacetate to form citrate
    • Citrate is rearranged to allow for β-cleavage reactions.

    TCA Cycle: Citrate Synthase

    • First reaction of the TCA cycle
    • Methyl carbon of acetyl-CoA condenses with the carbonyl carbon of oxaloacetate
    • CoA group is released
    • Cleavage of the thioester linkage in acetyl-CoA releases energy
    • Reaction product is citrate

    TCA Cycle: Aconitase

    • Catalyzes the second reaction of the TCA cycle
    • Involves a two-step process:
      • Dehydration reaction removes water to create a double bond
      • Hydration reaction adds water back to the double bond
    • Product of the reaction is isocitrate
    • Citrate is symmetrical, but aconitase discriminates between the upper and lower parts of the molecule due to its active site.

    TCA Cycle: Succinate Dehydrogenase

    • Catalyzes the first reaction involving four carbon intermediates
    • Succinate is oxidized to fumarate
    • The only reaction in the TCA cycle catalyzed by a membrane-bound enzyme complex
    • This is the third oxidation-reduction reaction in the TCA cycle, but it differs from the previous oxidation-reduction reactions in two ways:
      • It involves the removal of two protons and two electrons to create a double bond
      • It uses FAD as the oxidant instead of NAD+

    TCA Cycle: Fumarase

    • Catalyzes the hydration of fumarate to produce L-malate
    • Fumarase adds a hydroxyl group to one carbon and a hydrogen atom to the other carbon.
    • Fumarase is classified as a lyase because it can add water to a double bond.

    TCA Cycle: Malate Dehydrogenase

    • Catalyzes the oxidation of the alcohol group of L-malate to a ketone carbonyl group of oxaloacetate.
    • Produces the third and final NADH of the cycle.
    • The cycle returns to its starting material, oxaloacetate.

    Thiamine Pyrophosphate (TPP)

    • TPP is a coenzyme used in carbohydrate metabolism, especially in decarboxylation reactions.
    • The thiazole ring of TPP is the active site, with the carbon at the top of the ring being the attachment point for substrates.
    • This thiazole carbon is acidic due to the delocalized electrons in the ring system.

    Pyruvate Dehydrogenase Reaction

    • Pyruvate is decarboxylated to form a hydroxyethyl-TPP intermediate.
    • The carbonyl group of pyruvate attaches to the thiazole carbon of TPP.
    • The thiazole carbon attacks the carbonyl carbon of pyruvate, forming a covalent bond.
    • This results in the release of carbon dioxide and leaves a hydroxyethyl group attached to TPP.

    Citrate Synthase Reaction

    • The first reaction of the TCA cycle combines acetyl-CoA and oxaloacetate to form citrate.
    • Acetyl-CoA's methyl carbon attacks the carbonyl carbon of oxaloacetate.
    • The CoA group is released, providing energy to drive the reaction.

    Aconitase Reaction

    • Aconitase catalyzes the isomerization of citrate to isocitrate.
    • This involves a dehydration followed by a hydration reaction.
    • The hydroxyl group is moved from the middle carbon to the lower carbon.
    • The reaction produces isocitrate, which is asymmetric because aconitase creates a chiral center.

    Isocitrate Dehydrogenase

    • The enzyme catalyzes the oxidative decarboxylation of isocitrate to α-ketoglutarate.
    • The hydroxyl group is oxidized to a ketone, reducing NAD+ to NADH.
    • The β-keto acid intermediate then readily loses carbon dioxide to form α-ketoglutarate.

    α-Ketoglutarate Dehydrogenase

    • The enzyme catalyzes the oxidative decarboxylation of α-ketoglutarate to succinyl-CoA.
    • This reaction is similar to the pyruvate dehydrogenase reaction.
    • The lower three carbons of α-ketoglutarate resemble pyruvate's structure.
    • Carbon dioxide is released, and CoA is attached to the four-carbon product, succinyl-CoA.

    Succinyl-CoA Synthase Reaction

    • The enzyme uses the energy from hydrolyzing the thioester bond of succinyl-CoA to produce GTP.
    • Succinyl-CoA is converted to succinate.

    Succinate Dehydrogenase Reaction

    • Succinate is oxidized to fumarate, releasing FADH2.
    • This is the only TCA cycle reaction catalyzed by a membrane-bound enzyme complex.
    • The reaction uses FAD as the oxidant instead of NAD+.

    Fumarase Reaction

    • The enzyme catalyzes the hydration of fumarate to L-malate.
    • Water is added to the double bond of fumarate, creating a hydroxyl group.

    L-Malate Dehydrogenase Reaction

    • The enzyme oxidizes L-malate to oxaloacetate, regenerating the starting material of the cycle.
    • This reaction produces the third NADH molecule of the TCA cycle.

    TCA Cycle Summary

    • The cycle starts with a four-carbon molecule (oxaloacetate) and a two-carbon molecule (acetyl-CoA).
    • Two molecules of carbon dioxide are released for every turn of the cycle.
    • The cycle produces three molecules of NADH, one molecule of FADH2, and one molecule of GTP.
    • These reduced cofactors carry the energy from the cycle to the electron transport chain.

    Thiamine Pyrophosphate (TPP)

    • TPP's thiazole ring is the catalytic site.
    • The thiazole ring's carbon atom between nitrogen and sulfur is the functional site.
    • The ring's delocalized aromatic nature increases the hydrogen atom's acidity.

    Pyruvate Dehydrogenase Mechanism

    • Pyruvate interacts with the thiazole ring's carbon atom.
    • Deprotonated thiazole carbon attacks pyruvate's carbonyl carbon, forming a covalent bond.
    • This forms pyruvyl-thiamine pyrophosphate, with a negatively charged carbonyl oxygen.
    • The oxygen's negative charge is neutralized by a solvent proton, forming a hydroxyl group.
    • Electrons move between the carboxylate anion's oxygen and carbon, then between the carbon and C-2.
    • This releases carbon dioxide, neutralizing the thiazole nitrogen's positive charge.

    Hydroxyethyl-Thiamine Pyrophosphate

    • Forms when pyruvyl-thiamine pyrophosphate is decarboxylated.
    • Contains a two-carbon intermediate.
    • Transfered to lipoamide during the next step.

    Lipoamide

    • Covalently bound to the pyruvate dehydrogenase complex.
    • Exists in oxidized (disulfide ring structure) and reduced (open chain with two reduced sulfur groups) forms.
    • Conversion to the reduced form involves adding two electrons and two protons.
    • Reduced during the hydroxyethyl transfer, oxidizing the group to an acetyl group.

    AcetylCoA Production

    • Acetyl group is transferred from lipoamide to coenzyme A by dihydrolipoyltransacetylase.
    • AcetylCoA is the end product of the reaction sequence.
    • It's a thioester derivative with high energy of hydrolysis, facilitating transfer to carbon acceptor molecules.

    Coenzyme A Structure

    • Consists of adenosine diphosphate connected to pantothenic acid.
    • Pantothenic acid is a vitamin required in the human diet.

    TCA Cycle

    • Converts acetylCoA's two carbons into two carbon dioxide molecules.
    • Net products are two carbon dioxide, eight electrons (six as NADH, two as FADH2), and one GTP.

    TCA Cycle: Chemical Logic

    • AcetylCoA undergoes condensation with oxaloacetate to form citrate.
    • Citrate rearranges to allow for β-cleavage.

    TCA Cycle: Product Formation Sequence

    • NADH and carbon dioxide are removed in the conversion of a six-carbon compound to a five-carbon compound.
    • NADH and carbon dioxide are removed again during the conversion of the five-carbon compound to a four-carbon compound.
    • Oxidation reactions involving four-carbon intermediates produce one NADH, one FADH2, and one GTP.

    TCA Cycle: Carbon Loss

    • The two carbons lost as carbon dioxide in each cycle are not the carbons entering the cycle.
    • The lost carbons originate from oxaloacetate, while acetylCoA carbons are lost in subsequent cycles.

    TCA Cycle: Energy Balance

    • One TCA cycle round uses three NAD+, one FAD, and one GDP.
    • Produces three NADH, one FADH2, and one GTP.
    • Most energy from acetylCoA is stored in the reduced cofactors, converted to ATP during oxidative phosphorylation.

    TCA Cycle: Substrates for Biosynthetic Pathways

    • Provides starting materials for amino acid, purine, and pyrimidine biosynthesis.

    Thiamine Pyrophosphate and Pyruvate

    • Thiamine pyrophosphate (TPP) is a coenzyme that plays a key role in carbohydrate metabolism
    • The thiazole ring is the part of TPP involved in catalysis
    • The functional site of catalysis is the carbon atom at the top of the thiazole ring
    • The thiazole carbon becomes the point of attachment between thiazole ring and carbonyl group of pyruvate
    • When thiazole carbon is deprotonated, it attacks the carbonyl carbon of pyruvate forming a covalent bond
    • This results in the formation of a pyruvyl-thiamine pyrophosphate intermediate
    • The carboxyl group of pyruvate is released as carbon dioxide, leaving a hydroxyethyl-thiamine pyrophosphate intermediate

    Coenzyme A

    • Coenzyme A (CoA) is a coenzyme essential for many metabolic reactions
    • The sulfhydryl group at the end of CoA is involved in activating acyl groups through thioester bonds
    • AcetylCoA is a critical intermediate in the TCA cycle

    Pyruvate Dehydrogenase Mechanism

    • The oxidation of dihydrolipoamide to lipoamide is catalyzed by dihydrolipoyl dehydrogenase
    • This reaction involves the transfer of two electrons and two protons to FAD, forming FADH2
    • FADH2 is then oxidized back to FAD by transferring two electrons and one proton to NAD+, forming NADH

    FAD

    • FAD is a coenzyme essential for many metabolic reactions
    • FAD contains adenosine diphosphate connected to ribitol, which is connected to an isoalloxazine ring
    • Riboflavin is the ribitol-isoalloxazine pair, and is a B vitamin
    • The isoalloxazine ring is involved in FAD's catalytic activity
    • During the oxidation of dihydrolipoamide, FAD is converted to FADH2 by accepting two electrons and two protons
    • The electrons enter the isoalloxazine ring, and the protons attach to the nitrogen atoms

    Citric Acid Cycle

    • The Citric Acid Cycle (CAC) is a key metabolic pathway that converts acetylCoA into carbon dioxide, reducing equivalents (NADH and FADH2), and GTP
    • The CAC is also known as the tricarboxylic acid cycle and the Krebs cycle
    • The CAC starts with the condensation of acetylCoA with oxaloacetate to form citrate
    • Citrate is then rearranged to allow for β-cleavage reactions
    • The CAC produces 2 carbon dioxide, 8 electrons (6 as NADH and 2 as FADH2), and 1 GTP per cycle
    • The two carbons lost as carbon dioxide in each round of the CAC are not the same carbons that entered the cycle in that round

    Citrate Synthase

    • Citrate synthase catalyzes the first reaction of the CAC
    • The methyl carbon of acetylCoA condenses with the carbonyl carbon of oxaloacetate
    • The CoA group is released in the process
    • The reaction is driven by the energy released from the cleavage of the thioester bond of acetylCoA
    • Citrate is a common ingredient in processed foods and beverages, contributing a tart flavour

    Aconitase

    • Aconitase catalyzes the second reaction of the CAC
    • The reaction involves the isomerization of citrate to isocitrate
    • The hydroxyl group of citrate is moved from the middle carbon to the carbon below it
    • The reaction occurs in two steps: dehydration and hydration
    • Aconitase is an example of an enzyme that can discriminate between two parts of a symmetrical molecule

    Succinate Dehydrogenase

    • Succinate dehydrogenase catalyzes the oxidation of succinate to fumarate
    • This is the only reaction in the CAC that is catalyzed by a membrane-bound enzyme complex
    • This is the third redox reaction in the CAC, but it uses FAD instead of NAD+ as the oxidant
    • FADH2 produced in this reaction has a lower potential for yielding ATP compared to NADH

    Fumarase

    • Fumarase catalyzes the hydration of fumarate to L-malate
    • Fumarase adds water to a double bond, which is a characteristic of lyases

    L-Malate Dehydrogenase

    • L-malate dehydrogenase catalyzes the oxidation of L-malate to oxaloacetate
    • This reaction produces the third and final NADH of the CAC
    • This completes the cycle, returning to the starting four-carbon intermediate, oxaloacetate.

    Pyruvate Dehydrogenase Complex

    • Catalyzes the breakdown of pyruvate, the three-carbon product of glycolysis
    • Produces the two-carbon intermediate acetyl CoA plus carbon dioxide
    • Located in the mitochondrial matrix
    • Composed of three enzymes with 96 subunits total
    • Consists of three types of proteins

    Citric Acid Cycle (TCA Cycle)

    • Occurs in the mitochondria
    • Utilizes acetylCoA as a substrate
    • Converts the two carbons of acetylCoA into two molecules of carbon dioxide
    • Net products: 2 carbon dioxide, 8 electrons (6 as NADH and 2 as FADH2), 1 GTP
    • Named "citric acid cycle" because citric acid is the first product
    • Also called tricarboxylic acid cycle because citrate and isocitrate have three carboxyl groups
    • Also called the Krebs cycle after discoverer Sir Hans Krebs

    Thiamine Pyrophosphate (TPP)

    • First cofactor involved in pyruvate dehydrogenase reaction
    • Organic part of the cofactor is thiamine, which must be supplied in the diet
    • Humans can add the pyrophosphate group to thiamine to produce the functional cofactor

    Coenzyme A

    • Humans have the metabolic pathways to construct Coenzyme A from pantothenic acid
    • Working part of Coenzyme A is the sulfhydryl group at the end of the molecule
    • Sulfur connects and activates various acyl groups
    • Forms a thioester bond with acyl derivative

    Dihydrolipoyl Dehydrogenase

    • Catalyzes the reoxidation of dihydrolipoamide to lipoamide
    • Dihydrolipoamide is produced when the hydroxyethyl group is oxidized to an acetyl group
    • In the reoxidation of dihydrolipoamide, two electrons and two protons are transferred to FAD to form FADH2
    • FADH2 is then converted back to FAD when two electrons and one proton are transferred to NAD+ to form NADH

    Flavine Adenine Dinucleotide (FAD)

    • Contains adenosine diphosphate connected to ribitol, which in turn is connected to an isoalloxazine ring system
    • Riboflavin (the ribitol isoalloxazine pair) constitutes one of the B vitamins
    • Isoalloxazine ring is involved in catalysis

    Conversion of FAD to FADH2

    • FAD is converted to FADH2 during the oxidation of dihydrolipoamide
    • This involves the transfer of two electrons and two protons to FAD
    • The two electrons enter the isoalloxazine ring and the two protons sit on the two nitrogen atoms

    Chemical Logic of the TCA Cycle

    • Pyruvate decarboxylation yields acetylCoA, which contains two carbon molecules
    • The two carbons are oxidized to carbon dioxide in the TCA cycle
    • It is difficult to cleave between the two carbons of acetylCoA
    • It is easier to cleave between two carbons that are α and β to a carbonyl group
    • AcetylCoA is first condensed with oxaloacetate to make the six-carbon compound citrate
    • Citrate is then rearranged to perform a β-cleavage reaction

    Loss of Carbons in the TCA Cycle

    • The two carbons lost as carbon dioxide in each round are NOT the two that entered the cycle in that round
    • The carbons that are lost come initially from oxaloacetate
    • In succeeding rounds, the acetylCoA carbons will be lost

    Conversion of Succinate to Oxaloacetate

    • The next series of reactions involve four carbon intermediates and lead to the conversion of succinate back to oxaloacetate
    • Succinate is oxidized to fumarate by succinate dehydrogenase
    • This is the only reaction in the TCA cycle that is catalyzed by a membrane-bound enzyme complex
    • This is the third oxidation-reduction reaction in the TCA cycle
    • It differs from the previous oxidation-reduction reactions in two ways:
      • It involves the removal of two protons and two electrons from a carbon-carbon single bonded to create a double bond
      • It uses FAD as the oxidant instead of NAD+
    • The oxidation of a carbon-carbon single bond has a lower reducing potential than the previous oxidation reactions in the TCA cycle
    • FADH2 has a correspondingly lower potential than NADH for yielding ATP in oxidative phosphorylation
    • Fumarate is hydrated by the enzyme fumarase to produce L-malate
    • Fumarase is classified as a lyase because it can add water to a double bond
    • The product is designated as L-malate because it has a center of asymmetry and that chiral center is in the L-configuration
    • The final reaction in the cycle is catalyzed by L-malate dehydrogenase
    • The alcohol group of L-malate is oxidized to the ketone carbonyl group of oxaloacetate to produce the third NADH of the cycle
    • The reaction series has returned to the starting four carbon intermediate, oxaloacetate, and is ready to begin another cycle

    Pyruvate Dehydrogenase Mechanism

    • The part of the coenzyme involved in catalysis is the thiazole ring.
    • The functional site of catalysis is the carbon atom at the top of the thiazole ring that lies between a nitrogen atom and a sulfur atom.
    • The aromatic ring system makes the hydrogen atom on that carbon more acidic than usual.
    • Pyruvate approaches the carbon atom at the top of the thiazole ring.
    • This thiazole carbon becomes the point of attachment between the thiazole ring and the carbonyl group of pyruvate.
    • The thiazole carbon is deprotonated, resulting in two unpaired electrons that attack the carbonyl carbon of pyruvate.
    • A covalent bond forms between the thiazole carbon and pyruvate.
    • Two electrons from between the carbonyl carbon and oxygen move onto the carbonyl oxygen, making it negatively charged.
    • A proton from the solvent neutralizes this charge, producing a hydroxyl group.
    • The resulting pyruvyl-thiamine pyrophosphate intermediate is formed.
    • Electrons from the negative oxygen of the carboxylate anion of this intermediate move between that oxygen and the adjacent carbon.
    • Electrons between the carboxylate carbon and C-2 move down between the C-2 carbon and the thiazole carbon.
    • This releases carbon dioxide.
    • An electron pair from the double bond between the thiazole carbon and nitrogen moves onto the thiazole nitrogen and neutralizes its positive charge.
    • The carboxyl group of pyruvate is released as carbon dioxide.
    • An electron pair from that carboxyl group moves between the hydroxyl carbon and the thiazole carbon to form a double bond.
    • This hydroxyethyl intermediate is formed when pyruvyl-thiamine pyrophosphate is decarboxylated.
    • The hydroxyethyl-thiamine pyrophosphate is then transferred to lipoamide.
    • Humans have the metabolic pathways to construct coenzyme A from pantothenic acid.
    • The working part of coenzyme A is the sulfhydryl group at the end of the molecule.
    • This sulfur becomes connected to and activates various acyl groups by means of a thioester bond.
    • AcetylCoA has the acetyl group in thioester linkage to the sulfur group of coenzyme A.

    Reoxidation of Dihydrolipoamide

    • Dihydrolipoamide is produced when the hydroxyethyl group is oxidized to an acetyl group.
    • It needs to be converted back to oxidized lipoamide before the oxidation-reduction reaction can be repeated.
    • This conversion is catalyzed by dihydrolipoyl dehydrogenase.
    • In the reoxidation of dihydrolipoamide, two electrons and two protons are transferred to FAD to form FADH2.
    • The FADH2 is then converted back to FAD when two electrons and one proton are transferred to NAD+ to form NADH.

    Flavine Adenine Dinucleotide Structure

    • FAD contains the elements of adenosine diphosphate connected to ribitol, which in turn is connected to an isoalloxazine ring system.
    • The ribitol isoalloxazine pair, collectively known as riboflavin, constitutes one of the B vitamins.
    • The isoalloxazine ring is involved in catalysis.

    Conversion of FAD to FADH2

    • FAD is converted to FADH2 during the oxidation of dihydrolipoamide.
    • This reaction involves two electrons and two protons being transferred to FAD.
    • The two electrons enter the isoalloxazine ring and the two protons sit on the two nitrogen atoms.

    Citric Acid Cycle

    • The citric acid cycle is also called the tricarboxylic acid cycle because citrate and isocitrate have three carboxyl groups.
    • It is also called the Krebs cycle after its discoverer, Sir Hans Krebs.
    • AcetylCoA is the intermediate that enters the TCA cycle.
    • The TCA cycle converts the two carbons of acetylCoA into two molecules of carbon dioxide.
    • The net products of the TCA cycle are 2 carbon dioxide, 8 electrons (6 as NADH and 2 as FADH2), and 1 GTP.

    Chemical Logic of the TCA Cycle

    • Pyruvate decarboxylation yields acetylCoA, which contains two carbon molecules.
    • Each carbon will be oxidized all the way to carbon dioxide in the TCA cycle, but it is very hard to cleave between the two carbons of acetylCoA.
    • However, it is easier to cleave between two carbons that are α and β to a carbonyl group.
    • AcetylCoA is first condensed with oxaloacetate to make the six carbon compound citrate.
    • The citrate is then rearranged in order to perform a β-cleavage reaction.

    Sequence of TCA Cycle Product Formation

    • NADH (two electrons) and carbon dioxide are removed in the conversion of a C6 compound to a C5 compound.
    • NADH (two electrons) and carbon dioxide are removed in the subsequent conversion of a C5 compound to a C4 compound.
    • The cycle is completed by oxidation reactions involving C4 intermediates, which produce one NADH (two electrons), one FADH2 (two electrons), and one GTP.

    Loss of Carbons in the TCA Cycle

    • The two carbons lost as carbon dioxide in each round of the TCA cycle are NOT the two that entered the cycle in that round.
    • The carbons that are lost come initially from oxaloacetate.
    • In succeeding rounds, the acetylCoA carbons will be lost.

    TCA Cycle Selectivity

    • Enzymes that have at least three points of attachment are able to discriminate between different parts of symmetrical compounds.
    • The starting material, citrate, is a symmetrical compound, but the reaction product, isocitrate, is asymmetric with a chiral center.
    • The upper part of isocitrate that originated from acetylCoA does not carry the hydroxyl group.

    Isocitrate Dehydrogenase

    • The reaction catalyzed by isocitrate dehydrogenase involves an oxidative decarboxylation.
    • The hydroxyl group of isocitrate is oxidized to a ketone, coupled to the reduction on NAD+ to NADH.
    • This produces oxalosuccinate, which has a carboxyl group that is located β to a carbonyl group.
    • β-keto acids are relatively unstable and can be easily decarboxylated.
    • This decarboxylation reaction releases carbon dioxide and yields a five carbon product, α-ketoglutarate.
    • This is the first reaction in the TCA cycle in which NADH is produced.
    • The NADH will donate two electrons to the electron transport system that will lead to the production of ATP.

    α-Ketoglutarate Dehydrogenase

    • The next reaction is another oxidative decarboxylation, but in this reaction the product is also condensed with Coenzyme A.
    • This step, which is catalyzed by α-ketoglutarate dehydrogenase, should remind you of pyruvate dehydrogenase reaction.
    • The mechanism and cofactors are very similar for both reactions.
    • The lower three carbons of α-ketoglutarate mirror the structure of pyruvate.
    • In the decarboxylation phase of the reaction sequence, carbon dioxide is released.
    • The product succinyl-CoA now has four carbons.
    • This is the second reaction in the TCA cycle that produces NADH.

    Succinyl CoA Synthase

    • The energy from hydrolysis of a thioester bond is used to produce an ATP equivalent.
    • SuccinylCoA is a thioester, and such compounds have a very high standard state free energy of hydrolysis (ΔG0’).
    • The energy of hydrolysis from the release of CoA is coupled to the production of a GTP molecule.
    • The other product of the reaction is succinate, a four carbon dicarboxylic acid.

    Conversion of Succinate to Oxaloacetate

    • The next series of reactions all involve four carbon intermediates and lead to the conversion of succinate back to the starting material, oxaloacetate.
    • In the first step, succinate is oxidized to fumarate by succinate dehydrogenase.
    • This is the only reaction in the TCA cycle that is catalyzed by a membrane bound enzyme complex.
    • This is the third oxidation-reduction reaction in the TCA cycle, but it differs from the previous oxidation-reduction reactions in two ways: it involves the removal of two protons and two electrons from a carbon-carbon single bond to create a double bond, and it uses FAD as the oxidant instead of NAD+.
    • The oxidation of a carbon-carbon single bond has a lower reducing potential than the previous oxidation reactions in the TCA cycle.
    • FADH2 has a correspondingly lower potential than NADH for yielding ATP in oxidative phosphorylation.
    • The product of the succinate dehydrogenase reaction is fumarate, which is a four carbon dicarboxylic acid with a trans double bond between the central carbon atoms.
    • Fumarate is hydrated by the enzyme fumarase to produce L-malate.
    • The addition of water adds a hydroxyl group to one carbon and a hydrogen atom to the other carbon.
    • Fumarase is classified as a lyase because it can add water to a double bond.
    • The product is designated as L-malate because it has a center of asymmetry at the carbon atom bearing the hydroxyl group, and that chiral center is in the L-configuration.
    • The final reaction in the cycle is catalyzed by L-malate dehydrogenase, which catalyzes the oxidation of the alcohol group of L-malate to a form the ketone carbonyl group of oxaloacetate.
    • This reaction produces the third and final NADH of the cycle.
    • The reaction series has returned to the starting four carbon intermediate, oxaloacetate, and is ready to begin another cycle.

    TCA Cycle Compounds

    • The TCA cycle converts the two carbons of acetylCoA into two molecules of carbon dioxide.
    • The net products of the TCA cycle are 2 carbon dioxide, 8 electrons (6 as NADH and 2 as FADH2) and 1 GTP.

    Thiamine Pyrophosphate (TPP) and Pyruvate Decarboxylation

    • TPP is a coenzyme involved in the decarboxylation of pyruvate
    • The thiazole ring of TPP is involved in catalysis
    • The carbon atom at the top of the thiazole ring is the functional site of catalysis and becomes attached to the carbonyl group of pyruvate
    • The hydrogen atom on the thiazole carbon is acidic due to the delocalized aromatic system
    • The deprotonated thiazole carbon attacks the carbonyl carbon of pyruvate
    • This forms a covalent bond between the thiazole carbon and pyruvate
    • Two electrons from the carbonyl carbon and oxygen move onto the carbonyl oxygen, making it negatively charged.
    • A proton from the solvent neutralizes the negative charge, producing a hydroxyl group
    • This forms the pyruvyl-thiamine pyrophosphate intermediate
    • Electrons from the negative oxygen of the carboxylate anion of the pyruvyl-thiamine pyrophosphate intermediate move between that oxygen and the adjacent carbon
    • Electrons between the carboxylate carbon and C-2 move down between the C-2 carbon and the thiazole carbon
    • This releases carbon dioxide
    • An electron pair from the double bond between the thiazole carbon and nitrogen moves onto the thiazole nitrogen, neutralizing its positive charge
    • The carboxyl group of pyruvate is released as carbon dioxide
    • An electron pair from the carboxyl group moves between the hydroxyl carbon and the thiazole carbon forming a double bond
    • This creates a hydroxyethyl-thiamine pyrophosphate intermediate
    • The hydroxyethyl intermediate is transferred to lipoamide in the next step of the pyruvate dehydrogenase mechanism

    Citrate Synthase

    • Citrate synthase catalyzes the first reaction of the TCA cycle
    • The methyl carbon of acetyl CoA condenses with the carbonyl carbon of oxaloacetate forming a six-carbon molecule, citrate
    • The CoA group is released
    • The cleavage of the thioester linkage of acetyl CoA releases energy that helps drive the reaction towards product formation
    • Citrate is found in high levels in citrus fruits, processed foods, and drinks
    • The presence of citrate provides a tart flavor

    Mechanism of Citrate Synthase

    • The citrate synthase reaction involves a nucleophilic attack of a pair of electrons from the methyl group of acetyl CoA on the carbonyl carbon of oxaloacetate
    • A bond is formed between the two compounds, creating citrate
    • Two electrons from the carbonyl double bond jump onto the carbonyl oxygen
    • The oxygen is protonated by a hydrogen ion from the solvent, producing a hydroxyl group
    • During the reaction, the CoA group is cleaved, making the process thermodynamically favorable
    • The two carbons that originated from acetyl CoA are colored red to track their progression through the cycle

    Aconitase

    • Aconitase catalyzes the second reaction of the TCA cycle
    • Aconitase catalyzes a two-step process which relocates the hydroxyl group of citrate
    • The reaction involves a dehydration reaction, which removes water to create a double bond, followed by a hydration reaction that adds water back to the double bond, establishing a hydroxyl group on the lower carbon
    • The product of this isomerization sequence is isocitrate
    • Citrate is a symmetrical compound, and chemical reactions would not distinguish between the upper and lower part of the molecule
    • However, enzymes have asymmetric binding sites, so they often discriminate between two parts of a symmetrical molecule
    • The result is that, although the starting material, citrate, is symmetrical, the reaction product, isocitrate, is asymmetric with a chiral center
    • The upper part of isocitrate that originated from acetyl CoA does not carry the hydroxyl group

    Isocitrate Dehydrogenase

    • Isocitrate dehydrogenase catalyzes the next reaction
    • The reaction involves an oxidative decarboxylation
    • In the first step, the hydroxyl group of isocitrate is oxidized to a ketone, coupled to the reduction of NAD+ to NADH
    • This produces oxalosuccinate, which has a carboxyl group that is located β to a carbonyl group
    • β-keto acids are relatively unstable and can be easily decarboxylated
    • The decarboxylation reaction releases carbon dioxide and yields a five-carbon product, α-ketoglutarate
    • This is the first reaction in the TCA cycle in which NADH is produced
    • NADH will donate two electrons to the electron transport system, leading to the production of ATP

    α-Ketoglutarate Dehydrogenase

    • The next reaction is another oxidative decarboxylation, but in this reaction, the product is also condensed with Coenzyme A
    • This step, catalyzed by α-ketoglutarate dehydrogenase, is similar to the pyruvate dehydrogenase reaction
    • The mechanism and cofactors are very similar for both reactions
    • If you look at the structure of α-ketoglutarate, you will see that the lower three carbons mirror the structure of pyruvate
    • In the decarboxylation phase of the reaction sequence, carbon dioxide is released, and the product succinyl-CoA now has four carbons
    • This is the second reaction in the TCA cycle that produces NADH

    Succinyl CoA Synthase

    • Succinyl CoA synthase catalyzes a reaction that uses the energy from hydrolysis of a thioester bond to produce an ATP equivalent
    • Succinyl CoA is a thioester, and such compounds have a very high standard state free energy of hydrolysis (ΔG0’).
    • The energy of hydrolysis from the release of CoA is coupled to the production of a GTP molecule
    • GTP is energetically equivalent to ATP
    • The other product of the reaction is succinate, a four carbon dicarboxylic acid

    Conversion of Succinate to Oxaloacetate

    • The next series of reactions involve four-carbon intermediates, leading to the conversion of succinate back to the starting material, oxaloacetate
    • Succinate is oxidized to fumarate by succinate dehydrogenase
    • This is the only reaction in the TCA cycle that is catalyzed by a membrane-bound enzyme complex
    • This is the third oxidation-reduction reaction in the TCA cycle
    • It differs from the previous oxidation-reduction reactions in two ways:
      • It involves the removal of two protons and two electrons from a carbon-carbon single bond to create a double bond
      • It uses FAD as the oxidant instead of NAD+
    • The oxidation of a carbon-carbon single bond has a lower reducing potential than the previous oxidation reactions in the TCA cycle
    • FADH2 has a correspondingly lower potential than NADH for yielding ATP in oxidative phosphorylation
    • The product of the succinate dehydrogenase reaction is fumarate, a four-carbon dicarboxylic acid with a trans double bond between the central carbon atoms
    • Fumarate is hydrated by the enzyme fumarase to produce L-malate
    • The addition of water adds a hydroxyl group to one carbon and a hydrogen atom to the other carbon
    • Fumarase is classified as a lyase because it can add water to a double bond
    • The product is designated as L-malate because it has a center of asymmetry at the carbon atom bearing the hydroxyl group, and that chiral center is in the L-configuration
    • The final reaction in the cycle is catalyzed by L-malate dehydrogenase, which catalyzes the oxidation of the alcohol group of L-malate to a ketone carbonyl group of oxaloacetate
    • This reaction produces the third and final NADH of the cycle
    • At this point, the reaction series has returned to the starting four-carbon intermediate, oxaloacetate, and is ready to begin another cycle

    TCA Cycle Compounds

    • The first reaction catalyzed by citrate synthase results in the condensation of a two-carbon compound, Acetyl CoA, and a four-carbon compound, oxaloacetate, to yield a six-carbon product, citrate
    • Citrate is then converted to isocitrate, whose decarboxylation yields the five-carbon intermediate, α-ketoglutarate plus carbon dioxide
    • α-ketoglutarate is decarboxylated to the four-carbon compound succinyl CoA plus a second carbon dioxide
    • A series of reactions then gets the four-carbon intermediate, succinyl CoA, back to the starting four-carbon compound, oxaloacetate
    • The net carbon input into the cycle is two carbons in as acetyl CoA and four carbons in as oxaloacetate
    • The products of the cycle are two carbons released as carbon dioxide and four carbons regenerated as oxaloacetate—six carbons in and six carbons out!

    TCA Cycle Cofactors

    • One round of the TCA cycle uses 3 NAD+, 1 FAD, 1 GDP and produces 3 NADH, 1 FADH2, 1 GTP
    • Most of the energy from acetyl CoA is tied up in the reduced cofactors
    • In the next lectures, we will consider oxidative phosphorylation, in which the potential energy of NADH and FADH2 is converted into ATP

    TCA Cycle Enzymes

    • The TCA cycle has 8 enzymes
    • You should memorize the names of all of the TCA cycle enzymes

    Electrons from the TCA Cycle Energize Oxidative Phosphorylation

    • The electrons removed in the TCA cycle as NADH and FADH2 are channeled into oxidative phosphorylation
    • As the electrons pass through the electron transport chain, they drive the transmembrane flow of protons out of the mitochondrial matrix
    • This creates a proton gradient between the intermembrane space and the matrix
    • The downhill flow of electrons back into the matrix through the ATP synthase drives the formation of ATP from ADP and Pi

    TCA Cycle Provides Substrates for Biosynthetic Pathways

    • In addition to producing energy, the TCA cycle provides starting materials for a variety of biosynthetic pathways, for example, amino acid, purine, and pyrimidine biosynthesis.

    Pyruvate Dehydrogenase Mechanism

    • Thiamine pyrophosphate (TPP): The thiazole ring is the catalytic component and the thiazole carbon is the point of attachment to pyruvate.
    • Pyruvate binds to TPP: The carbonyl carbon of pyruvate forms a covalent bond with the thiazole carbon.
    • Decarboxylation: The carbon dioxide is released, leaving a hydroxyethyl intermediate bound to TPP.
    • Hydroxyethyl group transfer: The hydroxyethyl group is transferred to lipoamide and oxidized to an acetyl group.
    • Lipoamide: A coenzyme bound to a protein of the pyruvate dehydrogenase complex, it can be oxidized or reduced.
    • Acetyl group transfer: The acetyl group is transferred from lipoamide to coenzyme A, producing acetylCoA.
    • Acetyl CoA: A thioester derivative with a high-energy bond, considered "active acetate".
    • Reoxidation of dihydrolipoamide: Dihydrolipoamide is reoxidized by dihydrolipoyl dehydrogenase, using FAD as an electron acceptor.
    • FAD: A coenzyme containing riboflavin, it accepts two electrons and two protons to form FADH2.

    Citric Acid Cycle (CAC)

    • Citric acid cycle: Also known as the tricarboxylic acid cycle or Krebs cycle.
    • Citrate: The first product of the CAC, a symmetrical compound.
    • Isocitrate: The asymmetrical product formed from citrate's conversion to isocitrate.
    • Isocitrate dehydrogenase: Catalyzes the oxidative decarboxylation of isocitrate to α-ketoglutarate.
    • Oxalosuccinate: An unstable intermediate with a carboxyl group located β to a carbonyl group.
    • α-ketoglutarate dehydrogenase: Catalyzes the oxidative decarboxylation of α-ketoglutarate to succinyl-CoA.
    • Succinyl CoA: A thioester with a high energy of hydrolysis.
    • Succinyl CoA synthase: Catalyzes the conversion of succinyl-CoA to succinate with the simultaneous production of GTP.
    • Net carbon input and output: Two carbons enter as acetylCoA and four as oxaloacetate; two carbons are released as CO2 and four are regenerated as oxaloacetate.
    • Energy balance: One cycle produces 3 NADH, 1 FADH2, and 1 GTP, storing most of the energy from acetylCoA in reduced cofactors.
    • CAC and oxidative phosphorylation: The electrons from the CAC (NADH and FADH2) are channeled into oxidative phosphorylation.

    Other Points

    • Key enzymes: Eight enzymes are involved in the CAC, students should memorize their names.
    • Biosynthetic pathways: The CAC provides intermediates for amino acid, purine, and pyrimidine biosynthesis.
    • Radioisotopes: Not yet available at the time Krebs discovered the TCA cycle and the urea cycle.

    Mitochondria

    • Contains a porous outer membrane and a convoluted inner membrane.
    • The inner membrane is impermeable to most polar and ionic materials.
    • Electron transport and oxidative phosphorylation occur within the inner membrane.

    Pyruvate Dehydrogenase Complex

    • Composed of three enzymes that transform pyruvate into acetyl-CoA.
    • Acetyl-CoA is used in the citric acid cycle for cellular respiration.
    • Found in the mitochondrial matrix of eukaryotes.
    • Consists of 96 subunits, containing three types of proteins.

    Pyruvate Dehydrogenase Reaction Mechanism

    • Pyruvate is attached to thiamine pyrophosphate and converted to a two-carbon hydroxyethyl intermediate with the release of carbon dioxide.
    • The two-carbon intermediate is then passed to lipoate and oxidized to an acetyl derivative.
    • Acetyl group is transferred to coenzyme A.
    • Lipoate is reduced during oxidation.
    • Reduced lipoate is reoxidized by FAD, forming FADH2.
    • FADH2 passes its electrons to NAD+ forming NADH.

    Thiamine Pyrophosphate (TPP)

    • First cofactor involved in the pyruvate dehydrogenase reaction.
    • The organic part of this cofactor is thiamine, which must be obtained from the diet.
    • Humans can add a pyrophosphate group to thiamine to produce TPP.

    Lipoamide

    • Covalently bound to a protein component of the pyruvate dehydrogenase complex.
    • Exists in oxidized and reduced forms.
    • Oxidized form contains a disulfide ring structure, while the reduced form is an open chain structure with two reduced sulfur groups.
    • Conversion to the reduced form involves the addition of two electrons and two protons.
    • The reduced form is dihydrolipoamide.

    Coenzyme A

    • Contains adenosine diphosphate connected to pantothenic acid.
    • Pantothenic acid is a vitamin that must be obtained from the diet.

    Acetyl-CoA

    • The intermediate that enters the TCA cycle.
    • An acetyl group is a two-carbon member of the more general class of acyl groups.

    TCA Cycle Preview

    • Converts the two carbons of acetyl-CoA into two molecules of carbon dioxide.
    • Produces 2 carbon dioxide, 8 electrons (6 as NADH and 2 as FADH2), and 1 GTP.

    TCA Cycle Reaction Logic

    • Acetyl-CoA condenses with oxaloacetate to form citrate, a six-carbon compound.
    • Citrate is rearranged to allow for β-cleavage reaction.

    TCA Cycle Products Formation

    • NADH and carbon dioxide are removed in the conversion of a C6 compound to a C5 compound.
    • NADH and carbon dioxide are removed in the conversion of a C5 compound to a C4 compound.
    • Oxidation reactions involving C4 intermediates produce one NADH, one FADH2, and one GTP.

    Carbon Loss in TCA Cycle

    • The two carbons lost as carbon dioxide initially come from oxaloacetate, not the acetyl-CoA.
    • In later cycles, the acetyl-CoA carbons will be lost.

    Citrate Synthase

    • Catalyzes the first reaction of the TCA cycle.
    • The methyl carbon of acetyl-CoA condenses with the carbonyl carbon of oxaloacetate, releasing the CoA group.
    • Energy released from the cleavage helps drive the reaction.
    • Produces citrate.

    Aconitase

    • Catalyzes the second reaction of the TCA cycle.
    • A two-step process that moves the hydroxyl group from citrate to isocitrate.
    • A dehydration reaction removes water to create a double bond, followed by a hydration reaction that adds water back and establishes a hydroxyl group.

    Energy Balance of the TCA Cycle

    • One round of the TCA cycle uses 3 NAD+, 1 FAD, and 1 GDP.
    • Produces 3 NADH, 1 FADH2, and 1 GTP.
    • Most of the energy from acetyl-CoA is tied up in the reduced cofactors.

    TCA Cycle Enzymes

    • Eight enzymes are involved in the TCA cycle.
    • Memorize their names.

    Electrons from the TCA Cycle

    • NADH and FADH2 produced in the TCA cycle are used in oxidative phosphorylation.
    • Electrons pass through the electron transport chain, driving proton flow out of the mitochondrial matrix.
    • Proton gradient drives the synthesis of ATP from ADP and Pi.

    TCA Cycle and Biosynthetic Pathways

    • Provides starting materials for various biosynthetic pathways, including amino acid, purine, and pyrimidine synthesis.

    Pyruvate Dehydrogenase Complex

    • The pyruvate dehydrogenase complex consists of three enzymes that convert pyruvate to acetyl-CoA.
    • This complex is located in the mitochondrial matrix of eukaryotic cells.
    • The complex consists of 96 subunits, with three types of proteins.
    • The reaction produces acetyl-CoA and NADH as products.
    • The NADH produced can be used as an electron donor in oxidative phosphorylation.

    Pyruvate Dehydrogenase Mechanism

    • The first step involves the attachment of pyruvate to thiamine pyrophosphate (TPP).
    • This results in the production of a two-carbon hydroxyethyl intermediate with the release of carbon dioxide.
    • The two-carbon intermediate is then transferred to lipoate and oxidized to an acetyl derivative.
    • The acetyl group is then transferred to coenzyme A.
    • Lipoate is reduced during the substrate oxidation and is reoxidized by FAD, which is converted to FADH2.
    • FADH2 then passes its electrons onto NAD+ forming NADH.

    Thiamine Pyrophosphate (TPP)

    • TPP is a coenzyme essential for pyruvate dehydrogenase activity.
    • It contains thiamine, which is a B vitamin that should be obtained from the diet.
    • The thiazole ring is the active region of catalysis.
    • The carbon atom at the top of the thiazole ring is essential for the reaction.

    Coenzyme A

    • Coenzyme A is synthesized from pantothenic acid.
    • The sulfhydryl group at the end of the molecule is bonded to and activates acyl groups by forming a thioester bond.

    Citric Acid Cycle (TCA Cycle)

    • The TCA cycle is also known as the tricarboxylic acid cycle and the Krebs cycle.
    • The TCA cycle converts acetyl-CoA into two molecules of carbon dioxide, GTP, NADH, and FADH2.
    • The cycle starts with the condensation of acetyl-CoA and oxaloacetate to produce citrate.
    • The six-carbon citrate molecule is then rearranged to allow for β-cleavage reactions.
    • The carbons lost as carbon dioxide in each round are not the ones initially entering the cycle but come from oxaloacetate.

    Key Facts

    • Acetyl-CoA is the primary substrate for the TCA cycle.
    • Approximately 20% of the free energy change during glucose metabolism occurs in glycolysis, with another 20% released during the conversion of pyruvate to acetyl-CoA.
    • The remaining 60% of the energy is released during the TCA cycle.

    ### Mitochondria

    • Mitochondria are organelles found in eukaryotic cells.
    • They have a permeable outer membrane and an impermeable inner membrane.
    • The inner membrane contains the electron transport and oxidative phosphorylation systems.

    Pyruvate Dehydrogenase Complex

    • The pyruvate dehydrogenase complex catalyzes the breakdown of pyruvate, the three-carbon product of glycolysis.
    • It produces the two-carbon intermediate acetylCoA plus carbon dioxide.

    Citric Acid Cycle

    • Also known as the tricarboxylic acid cycle or Krebs Cycle.
    • The citric acid cycle is localized in the mitochondria.
    • It is metabolically linked to glycolysis through pyruvate.
    • The TCA cycle converts the two carbons of acetylCoA into two molecules of carbon dioxide.
    • The net products of the TCA cycle are 2 carbon dioxide, 8 electrons (6 as NADH and 2 as FADH2) and 1 GTP.

    The Chemical Logic of the TCA Cycle

    • AcetylCoA is condensed with oxaloacetate to make the six-carbon compound citrate.
    • Citrate is then rearranged to perform a β-cleavage reaction.

    Key Reactions of the Citric Acid Cycle

    • Isocitrate dehydrogenase: Catalyzes an oxidative decarboxylation reaction.
      • The hydroxyl group of isocitrate is oxidized to a ketone, coupled to the reduction of NAD+ to NADH.
      • This produces oxalosuccinate, which is then decarboxylated to α-ketoglutarate.
      • This is the first reaction in the TCA cycle which produces NADH.
    • α-Ketoglutarate dehydrogenase: Catalyzes another oxidative decarboxylation, where the product is also condensed with Coenzyme A.
      • The mechanism and cofactors are very similar to the pyruvate dehydrogenase reaction.
      • Carbon dioxide is released, and the product succinyl-CoA, which has four carbons, is produced.
      • This is the second reaction in the TCA cycle that produces NADH.
    • Succinyl CoA Synthase: Uses the energy from hydrolysis of a thioester bond to produce a GTP molecule.
      • SuccinylCoA is a thioester with a very high standard state free energy of hydrolysis (ΔG0’).

    Coenzyme A

    • The working part of coenzyme A is the sulfhydryl group at the very end of the molecule.
    • The sulfur becomes connected to and activates various acyl groups by means of a thioester bond.

    FAD and NAD+

    • Flavin adenine dinucleotide (FAD) contains the elements of adenosine diphosphate connected to ribitol, which in turn is connected to an isoalloxazine ring system.
    • Riboflavin is a B vitamin.
    • NAD+ is reduced to NADH during the TCA cycle.
    • NADH donates two electrons to the electron transport system, which leads to the production of ATP.
    • FADH2 is used for the production of ATP.

    Thiamine Pyrophosphate (TPP) Catalysis

    • TPP is a crucial coenzyme in carbohydrate metabolism, especially in the pyruvate dehydrogenase complex
    • TPP's thiazole ring plays a central role in catalysis
    • The carbon atom at the top of the thiazole ring, positioned between a nitrogen and sulfur atom, serves as the functional site of catalysis
    • The delocalized aromatic nature of the thiazole ring makes the hydrogen atom on this carbon more acidic than usual

    Pyruvate Dehydrogenase Complex (PDC)

    • PDC consists of multiple enzymes and cofactors that act in concert to convert pyruvate to acetyl-CoA
    • The PDC reaction involves a series of steps, each catalyzed by a specific enzyme
    • TPP, lipoamide, and coenzyme A are crucial cofactors in the PDC reaction
    • PDC serves as a critical link between glycolysis and the citric acid cycle

    Pyruvate-TPP Interaction

    • Pyruvate approaches the thiazole carbon of TPP, initiating the catalytic process
    • Deprotonation of the thiazole carbon generates two unpaired electrons that attack the carbonyl carbon of pyruvate
    • This attack leads to the formation of a covalent bond between the thiazole carbon and pyruvate
    • The resulting intermediate is known as pyruvyl-TPP

    Decarboxylation of Pyruvyl-TPP

    • Release of carbon dioxide from pyruvyl-TPP generates a hydroxyethyl intermediate
    • Decarboxylation is facilitated by electron transfer from the carboxylate anion to the adjacent carbon, then to the thiazole carbon
    • Electron movement is accompanied by the release of CO2 and neutralization of the thiazole nitrogen's positive charge

    Transfer to Lipoamide

    • The hydroxyethyl intermediate is transferred from TPP to lipoamide
    • The transfer involves an oxidation of the hydroxyethyl group to an acetyl group
    • The oxidized acetyl group is attached to lipoamide through a thioester bond
    • Lipoamide exists in two forms: oxidized form with a disulfide ring and reduced form with an open chain and two reduced sulfurs

    Formation of Acetyl-CoA

    • Dihydrolipoyltransacetylase catalyzes the transfer of the acetyl group from lipoamide to coenzyme A
    • This reaction produces acetyl-CoA, the final product of the PDC reaction
    • Acetyl-CoA is a high-energy thioester that can be transferred to various carbon acceptors, making it a central metabolite in metabolism

    Regeneration of Lipoamide

    • The reduced dihydrolipoamide must be reoxidized to lipoamide to continue the PDC reaction
    • Dihydrolipoyl dehydrogenase catalyzes the reoxidation using FAD as an electron acceptor

    Citric Acid Cycle (TCA Cycle)

    • The TCA cycle is a central metabolic pathway that oxidizes acetyl-CoA to CO2, producing reducing equivalents (NADH and FADH2)
    • The TCA cycle is also known as the tricarboxylic acid cycle or the Krebs cycle
    • The cycle starts with the condensation of acetyl-CoA with oxaloacetate to form citrate

    Citrate Synthase

    • Citrate synthase catalyzes the condensation of acetyl-CoA and oxaloacetate to form citrate
    • The reaction involves a nucleophilic attack of the methyl group of acetyl-CoA on the carbonyl carbon of oxaloacetate
    • The cleavage of the thioester bond in acetyl-CoA releases energy, driving the reaction forward

    Aconitase

    • Aconitase catalyzes the isomerization of citrate to isocitrate
    • The reaction involves a two-step process: dehydration followed by hydration
    • The isomerization results in a shift of the hydroxyl group from the middle carbon to the lower carbon, creating isocitrate

    Isocitrate Dehydrogenase

    • Isocitrate dehydrogenase catalyzes an oxidative decarboxylation of isocitrate, producing α-ketoglutarate
    • The reaction involves two steps: oxidation of the hydroxyl group to a ketone, followed by decarboxylation of the β-keto acid
    • This reaction generates the first NADH in the TCA cycle, which will contribute to ATP production

    α-Ketoglutarate Dehydrogenase

    • α-ketoglutarate dehydrogenase catalyzes another oxidative decarboxylation, producing succinyl-CoA
    • The reaction mechanism and cofactors are similar to the pyruvate dehydrogenase reaction
    • This reaction generates the second NADH in the TCA cycle

    Succinyl-CoA Synthase

    • Succinyl-CoA synthase catalyzes the conversion of succinyl-CoA to succinate, coupled with the synthesis of GTP
    • The energy released from the hydrolysis of the thioester bond in succinyl-CoA drives the synthesis of GTP

    Pyruvate Dehydrogenase Complex & Citric Acid Cycle

    • Pyruvate Dehydrogenase Complex:
      • Converts pyruvate (3-carbon product of glycolysis) into acetyl-CoA (2-carbon intermediate) and carbon dioxide.
      • Located in the mitochondrial matrix of eukaryotic cells.
      • Composed of three enzymes:
        • E1: Pyruvate dehydrogenase
        • E2: Dihydrolipoyl transacetylase
        • E3: Dihydrolipoyl dehydrogenase
      • Cofactors:
        • Thiamine pyrophosphate (TPP)
        • Lipoic acid
        • Coenzyme A
        • FAD
        • NAD+
    • Citric Acid Cycle (TCA Cycle):
      • Series of reactions that oxidize acetyl-CoA into two molecules of carbon dioxide.
      • Occurs in the mitochondrial matrix.
      • Key Enzymes:
        • Citrate synthase
        • Aconitase
        • Isocitrate dehydrogenase
        • α-ketoglutarate dehydrogenase
        • Succinyl-CoA synthetase
        • Succinate dehydrogenase
        • Fumarase
        • Malate dehydrogenase
      • Products:
        • 3 NADH
        • 1 FADH2
        • 1 ATP (as GTP)
        • 2 CO2
      • Energy Yield:
        • The TCA cycle generates only 1 ATP directly, but the NADH and FADH2 produced are used in oxidative phosphorylation to produce a significant amount of ATP.
      • Inputs & Outputs:
        • 2 Carbons in (from Acetyl-CoA)
        • 4 Carbons in (from oxaloacetate)
        • 2 Carbons out (as CO2)
        • 4 Carbons out (as oxaloacetate)
        • The cycle regenerates oxaloacetate to continue the cycle.
    • Mitochondrial Structure:
      • Mitochondria are eukaryotic organelles with two membranes:
        • Outer membrane: Porous
        • Inner membrane: Folded into cristae, impermeable to most polar molecules.
      • Electron transport chain and oxidative phosphorylation systems are located in the inner membrane.
    • Energy Production:
      • The combined processes of glycolysis, pyruvate dehydrogenase complex, and the TCA cycle release a substantial amount of free energy for ATP synthesis, with the TCA cycle contributing the majority.
    • Biosynthetic Pathways:
      • The TCA cycle is not just about energy production. It provides intermediates for other pathways, including amino acid synthesis, purine and pyrimidine biosynthesis, and heme synthesis.
    • Metabolic Link Between Glycolysis & TCA Cycle:
      • Pyruvate, the end product of glycolysis, is transported into the mitochondria and converted to acetyl-CoA by the pyruvate dehydrogenase complex, linking glycolysis to the TCA cycle.

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    Description

    This quiz explores the fascinating roles of mitochondria and the pyruvate dehydrogenase complex in eukaryotic cells. Discover key components such as the function of thiamine pyrophosphate and the importance of acetyl-CoA in metabolism. Test your knowledge of these crucial cellular processes.

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