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Questions and Answers
What type of enzyme is isocitrate dehydrogenase classified as?
What type of enzyme is isocitrate dehydrogenase classified as?
Which molecule acts as an allosteric inhibitor for isocitrate dehydrogenase?
Which molecule acts as an allosteric inhibitor for isocitrate dehydrogenase?
What is one of the products formed when a-ketoglutarate is decarboxylated?
What is one of the products formed when a-ketoglutarate is decarboxylated?
How many CO2 molecules are produced by the time a-ketoglutarate is converted to succinyl-CoA?
How many CO2 molecules are produced by the time a-ketoglutarate is converted to succinyl-CoA?
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Which product negatively regulates the a-ketoglutarate dehydrogenase complex?
Which product negatively regulates the a-ketoglutarate dehydrogenase complex?
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What effect does calcium ions (Ca2+) have on both isocitrate and a-ketoglutarate dehydrogenase?
What effect does calcium ions (Ca2+) have on both isocitrate and a-ketoglutarate dehydrogenase?
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What happens to the two carbon atoms contributed by acetyl-CoA in the citric acid cycle?
What happens to the two carbon atoms contributed by acetyl-CoA in the citric acid cycle?
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What occurs during the reaction of a-ketoglutarate to succinyl-CoA?
What occurs during the reaction of a-ketoglutarate to succinyl-CoA?
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What are the products formed when succinyl-CoA is converted to succinate?
What are the products formed when succinyl-CoA is converted to succinate?
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Which enzyme catalyzes the conversion of succinyl-CoA to succinate?
Which enzyme catalyzes the conversion of succinyl-CoA to succinate?
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What happens to the hydrogen atoms during the conversion of succinate to fumarate?
What happens to the hydrogen atoms during the conversion of succinate to fumarate?
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What type of reaction is the conversion of succinyl-CoA to succinate classified as?
What type of reaction is the conversion of succinyl-CoA to succinate classified as?
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Which of the following statements is true regarding the energy equivalency of GTP and ATP?
Which of the following statements is true regarding the energy equivalency of GTP and ATP?
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In the citric acid cycle, which compound is formed from the oxidation of succinate?
In the citric acid cycle, which compound is formed from the oxidation of succinate?
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Which functional group is present in succinate that is involved in its oxidation to fumarate?
Which functional group is present in succinate that is involved in its oxidation to fumarate?
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What is the significance of the thioester bond in succinyl-CoA during its conversion to succinate?
What is the significance of the thioester bond in succinyl-CoA during its conversion to succinate?
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What is the primary purpose of the citric acid cycle?
What is the primary purpose of the citric acid cycle?
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Which enzyme facilitates the isomerization of citrate to isocitrate?
Which enzyme facilitates the isomerization of citrate to isocitrate?
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What intermediate is formed during the conversion of citrate to isocitrate?
What intermediate is formed during the conversion of citrate to isocitrate?
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What type of reaction is catalyzed by isocitrate dehydrogenase?
What type of reaction is catalyzed by isocitrate dehydrogenase?
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What is the net effect of the reaction catalyzed by aconitase?
What is the net effect of the reaction catalyzed by aconitase?
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Why is the reaction converting isocitrate to alpha-ketoglutarate classified as irreversible?
Why is the reaction converting isocitrate to alpha-ketoglutarate classified as irreversible?
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Which molecule is produced when isocitrate loses two electrons during its conversion to alpha-ketoglutarate?
Which molecule is produced when isocitrate loses two electrons during its conversion to alpha-ketoglutarate?
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Which characteristic defines aconitase, despite its name having 'isomerase' in it?
Which characteristic defines aconitase, despite its name having 'isomerase' in it?
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What is the end product of glycolysis?
What is the end product of glycolysis?
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Where does the citric acid cycle take place in eukaryotic cells?
Where does the citric acid cycle take place in eukaryotic cells?
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What is the role of NAD+ in glycolysis?
What is the role of NAD+ in glycolysis?
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Which conditions lead to the fermentation of pyruvate?
Which conditions lead to the fermentation of pyruvate?
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What type of respiration occurs under aerobic conditions after glycolysis?
What type of respiration occurs under aerobic conditions after glycolysis?
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How is pyruvate transported into the mitochondria?
How is pyruvate transported into the mitochondria?
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What does the citric acid cycle produce that is essential for ATP synthesis?
What does the citric acid cycle produce that is essential for ATP synthesis?
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What is the primary function of the pyruvate dehydrogenase complex (PDC)?
What is the primary function of the pyruvate dehydrogenase complex (PDC)?
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What type of enzyme is fumarase classified as?
What type of enzyme is fumarase classified as?
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Which molecule is produced from the oxidation of L-malate?
Which molecule is produced from the oxidation of L-malate?
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What is the role of FAD in succinate dehydrogenase's function?
What is the role of FAD in succinate dehydrogenase's function?
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Which of the following is NOT a product of the citric acid cycle?
Which of the following is NOT a product of the citric acid cycle?
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What happens to the chiral center in the L-malate during its transformation to oxaloacetate?
What happens to the chiral center in the L-malate during its transformation to oxaloacetate?
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In the citric acid cycle, NAD+ is reduced to what in the final step involving malate dehydrogenase?
In the citric acid cycle, NAD+ is reduced to what in the final step involving malate dehydrogenase?
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What is the immediate effect of the reaction catalyzed by fumarase on fumarate?
What is the immediate effect of the reaction catalyzed by fumarase on fumarate?
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Which of the following statements about the citric acid cycle is false?
Which of the following statements about the citric acid cycle is false?
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What is produced when acetyl-CoA combines with oxaloacetate in the citric acid cycle?
What is produced when acetyl-CoA combines with oxaloacetate in the citric acid cycle?
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Which of the following statements about the reactions in the first half of the citric acid cycle is true?
Which of the following statements about the reactions in the first half of the citric acid cycle is true?
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What role does citrate synthase play in the citric acid cycle?
What role does citrate synthase play in the citric acid cycle?
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Which of the following molecules can downregulate citrate synthase activity?
Which of the following molecules can downregulate citrate synthase activity?
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What is the immediate product after the combination of acetyl-CoA and oxaloacetate?
What is the immediate product after the combination of acetyl-CoA and oxaloacetate?
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What happens to carbon atoms during the citric acid cycle?
What happens to carbon atoms during the citric acid cycle?
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Which of the following describes the citric acid cycle accurately?
Which of the following describes the citric acid cycle accurately?
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How many steps are involved in the citric acid cycle?
How many steps are involved in the citric acid cycle?
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Study Notes
Citric Acid Cycle Introduction
- Glucose catabolism is examined, including glycolysis, where glucose is converted into two pyruvate molecules.
- Glycolysis requires NAD+. Anaerobic conditions regenerate NAD+ through fermentation. Aerobic conditions regenerate NAD+ through aerobic respiration.
- Aerobic respiration (after glycolysis) continues with the citric acid cycle, producing NADH and FADH2.
- These molecules enter the electron transport chain, ultimately passing electrons to oxygen (O2).
- The energy from these reactions is used for ATP synthesis.
Pyruvate Entry into the Citric Acid Cycle
- The end product of glycolysis is pyruvate.
- Under anaerobic conditions, pyruvate is fermented into ethanol or lactate.
- Under aerobic conditions, pyruvate is typically sent to the citric acid cycle.
- In eukaryotes, the citric acid cycle happens inside the mitochondria.
- Glycolysis occurs in the cytosol.
- Pyruvate must be transported from the cytosol into the mitochondria to enter the citric acid cycle.
- Mitochondria have two membranes:
- Outer membrane is permeable to most ions and small molecules
- Inner membrane is much more selective, having crucial transport proteins for pyruvate import.
Mitochondrial Matrix and Pyruvate Dehydrogenase Complex
- The mitochondrial matrix contains various proteins, including the pyruvate dehydrogenase complex (PDC).
- PDC catalyzes the decarboxylation of pyruvate to form acetyl coenzyme A (acetyl-CoA) and CO2.
- This process involves three enzymes, each with specific coenzymes
- Pyruvate dehydrogenase (E1), using thiamine pyrophosphate
- Dihydrolipoyl transacetylase (E2), using lipoic acid as cofactor
- Dihydrolipoyl dehydrogenase (E3), using FAD as coenzyme
- The net reaction of PDC is: Pyruvate + NAD+ + CoA-SH → Acetyl-CoA + NADH + CO2
- Acetyl-CoA enters the citric acid cycle. NADH yields energy, and CO2 is released.
- Pyruvate dehydrogenase is inactivated by phosphorylation by pyruvate dehydrogenase kinase (PDK).
- Pyruvate dehydrogenase kinase (PDK) is activated by products of the PDC itself: Acetyl-CoA and NADH.
- PDK activation inhibits the PDC.
- PDK is downregulated by pyruvate, coenzyme A and NAD+, thereby indirectly activating the PDC.
- Pyruvate dehydrogenase phosphatase is activated by factors like insulin and calcium ions (muscle contractions), which promotes PDK deactivation, and reactivates the PDC
Citric Acid Cycle Reactions
- The citric acid cycle is an 8-step metabolic pathway.
- It starts when a 2-carbon acetyl group (from acetyl-CoA) combines with a 4-carbon oxaloacetate molecule, forming a 6-carbon citrate molecule.
- Two carbon atoms are sequentially released as CO2.
- The 6-carbon molecule goes through a series of transformations to regenerate the original 4-carbon oxaloacetate molecule, allowing the cycle to continue.
- Three steps are predominantly irreversible under physiological conditions and, consequently, key regulatory points
- One of the key steps (Step 1) condenses acetyl-CoA and oxaloacetate to form citrate, with citrate synthase as the enzyme.
- Step 2 converts citrate to isocitrate through two intermediate steps (cis-aconitate) using aconitase, an enzyme that acts as a lyase.
- Citrate is a non-chiral precursor for isocitrate. Step 3, facilitated by isocitrate dehydrogenase, results in an oxidative decarboxylation converting isocitrate to α-ketoglutarate. It is an oxidoreductase reaction, with two electrons transferring to NAD+ to make NADH.
- Step 4, utilizing α-ketoglutarate dehydrogenase complex, involves an oxidative decarboxylation resulting in the conversion of α-ketoglutarate to succinyl-CoA, which also creates a molecule of NADH.
- Succinyl-CoA synthetase in Step 5 catalyzes hydrolysis of the high-energy thioester in succinyl-CoA that generates GTP by reacting with GDP.
- Step 6 involves succinate dehydrogenase and converts succinate to fumarate, forming FADH2.
- Step 7, using fumarase, hydrates fumarate to L-malate
- Step 8, facilitated by malate dehydrogenase, oxidizes L-malate to oxaloacetate, yielding another NADH molecule
Citric Acid Cycle Products
- The net reaction results in the production of 2CO2, 3 NADH, 1 FADH2, and 1 GTP (or ATP).
- Oxaloacetate is not a net product. It is regenerated, but it is consumed each cycle
- These products (NADH, FADH2, and GTP) are crucial for ATP production in later stages
Alternative Entry Points
- Certain amino acids can directly convert into a-ketoglutarate, entering the cycle later, bypassing two NADH-forming steps.
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Description
Explore the key processes involved in glucose catabolism, including glycolysis, the transition of pyruvate, and the citric acid cycle. Learn how these steps contribute to energy production through ATP synthesis. Understand both anaerobic and aerobic conditions that affect pyruvate metabolism.