Podcast
Questions and Answers
During glycolysis, what is the net yield of ATP and NADH per molecule of glucose that is fully processed?
During glycolysis, what is the net yield of ATP and NADH per molecule of glucose that is fully processed?
- 2 ATP, 4 NADH
- 4 ATP, 4 NADH
- 4 ATP, 2 NADH
- 2 ATP, 2 NADH (correct)
Which statement accurately describes the location of glycolysis and the citric acid cycle within a eukaryotic cell?
Which statement accurately describes the location of glycolysis and the citric acid cycle within a eukaryotic cell?
- Both glycolysis and the citric acid cycle occur in the cytoplasm.
- Both glycolysis and the citric acid cycle occur in the mitochondrial matrix.
- Glycolysis occurs in the cytoplasm, while the citric acid cycle takes place in the mitochondrial matrix. (correct)
- Glycolysis occurs in the mitochondrial matrix, while the citric acid cycle takes place in the cytoplasm.
Why is the reaction catalyzed by the pyruvate dehydrogenase complex considered an important control point in metabolism?
Why is the reaction catalyzed by the pyruvate dehydrogenase complex considered an important control point in metabolism?
- It irreversibly links glycolysis to the citric acid cycle and regulates the entry of pyruvate into the mitochondria. (correct)
- It determines the rate of oxidative phosphorylation by directly affecting ATP synthase activity.
- It controls the rate of fatty acid synthesis by regulating acetyl-CoA transport.
- It directly regulates the rate of glycolysis under anaerobic conditions.
Coenzyme A (CoA) is crucial to the citric acid cycle because it functions to:
Coenzyme A (CoA) is crucial to the citric acid cycle because it functions to:
How do lipoyllysine, thiamine pyrophosphate (TPP), and FAD contribute to the activity of the pyruvate dehydrogenase complex?
How do lipoyllysine, thiamine pyrophosphate (TPP), and FAD contribute to the activity of the pyruvate dehydrogenase complex?
What is the primary role of thiamine pyrophosphate (TPP) in the pyruvate dehydrogenase complex?
What is the primary role of thiamine pyrophosphate (TPP) in the pyruvate dehydrogenase complex?
A researcher mutates a bacterial strain such that lipoic acid can no longer be attached to the bacterial pyruvate dehydrogenase complex. What outcome do you expect?
A researcher mutates a bacterial strain such that lipoic acid can no longer be attached to the bacterial pyruvate dehydrogenase complex. What outcome do you expect?
Which of the following best describes the mobile arm of E2 (dihydrolipoyl transacetylase) in the pyruvate dehydrogenase complex?
Which of the following best describes the mobile arm of E2 (dihydrolipoyl transacetylase) in the pyruvate dehydrogenase complex?
What direct molecular change occurs during the reaction catalyzed by citrate synthase in the citric acid cycle?
What direct molecular change occurs during the reaction catalyzed by citrate synthase in the citric acid cycle?
To initiate catalysis within citrate synthase, which substrate binds first and what conformational change does this induce?
To initiate catalysis within citrate synthase, which substrate binds first and what conformational change does this induce?
What is the role of the iron-sulfur center in the aconitase enzyme during the citric acid cycle?
What is the role of the iron-sulfur center in the aconitase enzyme during the citric acid cycle?
How does the isocitrate dehydrogenase enzyme contribute to the regulation of the citric acid cycle?
How does the isocitrate dehydrogenase enzyme contribute to the regulation of the citric acid cycle?
Which enzymatic reaction in the citric acid cycle is most similar to the reaction catalyzed by the pyruvate dehydrogenase complex?
Which enzymatic reaction in the citric acid cycle is most similar to the reaction catalyzed by the pyruvate dehydrogenase complex?
During the conversion of succinyl-CoA to succinate, what type of reaction occurs, and what molecule is generated?
During the conversion of succinyl-CoA to succinate, what type of reaction occurs, and what molecule is generated?
What is the significance of succinate dehydrogenase being bound to the inner mitochondrial membrane, unlike other citric acid cycle enzymes?
What is the significance of succinate dehydrogenase being bound to the inner mitochondrial membrane, unlike other citric acid cycle enzymes?
Why is the free energy change ($\Delta G'$) for the malate dehydrogenase reaction highly positive, yet the citric acid cycle proceeds efficiently under cellular conditions?
Why is the free energy change ($\Delta G'$) for the malate dehydrogenase reaction highly positive, yet the citric acid cycle proceeds efficiently under cellular conditions?
What is meant by the statement that 'the citric acid cycle functions overall as a catalyst'?
What is meant by the statement that 'the citric acid cycle functions overall as a catalyst'?
What is the net result of one turn of the citric acid cycle?
What is the net result of one turn of the citric acid cycle?
Which best describes how the energy captured by electron transfer leads to the production of NADH and FADH2 during the citric acid cycle?
Which best describes how the energy captured by electron transfer leads to the production of NADH and FADH2 during the citric acid cycle?
Which of the following is an accurate statement regarding the regulatory mechanisms of the citric acid cycle?
Which of the following is an accurate statement regarding the regulatory mechanisms of the citric acid cycle?
How does ATP impact the regulation of pyruvate dehydrogenase?
How does ATP impact the regulation of pyruvate dehydrogenase?
Under what cellular conditions would you expect the citric acid cycle to be down-regulated?
Under what cellular conditions would you expect the citric acid cycle to be down-regulated?
Which of the following enzymes is directly regulated by calcium ions ($Ca^{2+}$) in certain cell types?
Which of the following enzymes is directly regulated by calcium ions ($Ca^{2+}$) in certain cell types?
What is the purpose of anaplerotic reactions related to the citric acid cycle?
What is the purpose of anaplerotic reactions related to the citric acid cycle?
What is the role of biotin in the pyruvate carboxylase reaction, and how does this relate to the larger metabolic landscape?
What is the role of biotin in the pyruvate carboxylase reaction, and how does this relate to the larger metabolic landscape?
Pyruvate carboxylase is an important enyzme in both gluconeogenesis and the citric acid cycle. What is the most important allosteric regulator of this enzyme?
Pyruvate carboxylase is an important enyzme in both gluconeogenesis and the citric acid cycle. What is the most important allosteric regulator of this enzyme?
If a researcher discovers a new metabolic disease characterized by the build-up of succinate, and wants to treat this disease through dietary restriction, what would their recommendation be?
If a researcher discovers a new metabolic disease characterized by the build-up of succinate, and wants to treat this disease through dietary restriction, what would their recommendation be?
In the context of the citric acid cycle and cellular metabolism, what is meant by the term 'biological tethers'?
In the context of the citric acid cycle and cellular metabolism, what is meant by the term 'biological tethers'?
How many ATP molecules can be generated from one molecule of succinate through citric acid cycle oxidation?
How many ATP molecules can be generated from one molecule of succinate through citric acid cycle oxidation?
Assuming that one mole of NADH is energetically equivalent to 2.5 moles of ATP and one mole of FADH2 is equivalent to 1.5 moles of ATP, arrange the following compounds based on their energy generating potential, from highest to lowest:
Assuming that one mole of NADH is energetically equivalent to 2.5 moles of ATP and one mole of FADH2 is equivalent to 1.5 moles of ATP, arrange the following compounds based on their energy generating potential, from highest to lowest:
During gluconeogenesis, which enzyme is responsible for converting oxaloacetate to phosphenolpyruvate (PEP)?
During gluconeogenesis, which enzyme is responsible for converting oxaloacetate to phosphenolpyruvate (PEP)?
If a genetic defect prevents a cell from producing a functional malic enzyme, what direct consequence would you expect to observe regarding the interplay between cellular respiration and gluconeogenesis?
If a genetic defect prevents a cell from producing a functional malic enzyme, what direct consequence would you expect to observe regarding the interplay between cellular respiration and gluconeogenesis?
What structural feature of biotin makes it ideally suited for its role in carboxylation reactions within metabolic pathways?
What structural feature of biotin makes it ideally suited for its role in carboxylation reactions within metabolic pathways?
Biotin is necessary for several metabolic processes. Which statement accurately describes how Biotin aids in the activity of pyruvate carboxylase?
Biotin is necessary for several metabolic processes. Which statement accurately describes how Biotin aids in the activity of pyruvate carboxylase?
Which of the enzymes listed requires both ATP and Biotin?
Which of the enzymes listed requires both ATP and Biotin?
During the first step of the pyruvate carboxylase reaction, biotin becomes?
During the first step of the pyruvate carboxylase reaction, biotin becomes?
What metabolic derangement would most likely result from a vitamin B7 (biotin) deficiency?
What metabolic derangement would most likely result from a vitamin B7 (biotin) deficiency?
Malate, oxaloacetate, and citrate are considered intermediates of the citric acid cycle. In what way are they used during the anabolic process?
Malate, oxaloacetate, and citrate are considered intermediates of the citric acid cycle. In what way are they used during the anabolic process?
Which process does NOT act to form oxaloacetate?
Which process does NOT act to form oxaloacetate?
How does high ATP affect the regulation of citrate synthase?
How does high ATP affect the regulation of citrate synthase?
Isocitrate dehydrogenase is considered ATP for the Citric Acid cycle. How would high levels of ATP in the cell act on Isocitrate dehydrogenase?
Isocitrate dehydrogenase is considered ATP for the Citric Acid cycle. How would high levels of ATP in the cell act on Isocitrate dehydrogenase?
Considering the irreversible nature of the pyruvate dehydrogenase complex reaction, under what conditions would the cell most likely rely on alternative pathways to generate acetyl-CoA?
Considering the irreversible nature of the pyruvate dehydrogenase complex reaction, under what conditions would the cell most likely rely on alternative pathways to generate acetyl-CoA?
If a researcher introduced a non-hydrolyzable analog of acetyl-CoA into a cell undergoing the citric acid cycle, what immediate effect would you expect to observe?
If a researcher introduced a non-hydrolyzable analog of acetyl-CoA into a cell undergoing the citric acid cycle, what immediate effect would you expect to observe?
In a scenario where a cell's mitochondrial membrane is compromised, leading to a loss of the proton gradient, how would the activity of the citric acid cycle be affected, and why?
In a scenario where a cell's mitochondrial membrane is compromised, leading to a loss of the proton gradient, how would the activity of the citric acid cycle be affected, and why?
What would be the immediate impact on the citric acid cycle if a mutation caused aconitase to bind citrate more tightly but release isocitrate less efficiently?
What would be the immediate impact on the citric acid cycle if a mutation caused aconitase to bind citrate more tightly but release isocitrate less efficiently?
If a researcher discovers a novel compound that selectively inhibits the carboxybiotinyl-enzyme intermediate formation in pyruvate carboxylase, what impact would this have on gluconeogenesis and the citric acid cycle?
If a researcher discovers a novel compound that selectively inhibits the carboxybiotinyl-enzyme intermediate formation in pyruvate carboxylase, what impact would this have on gluconeogenesis and the citric acid cycle?
Considering that succinate dehydrogenase is directly involved in the electron transport chain, what would be the immediate consequence of a genetic mutation that impairs its ability to bind FAD?
Considering that succinate dehydrogenase is directly involved in the electron transport chain, what would be the immediate consequence of a genetic mutation that impairs its ability to bind FAD?
Under conditions of extreme starvation, the body begins to break down muscle protein to provide carbon skeletons for energy production. How would the influx of amino acids affect the citric acid cycle, and what compensatory mechanisms would be activated?
Under conditions of extreme starvation, the body begins to break down muscle protein to provide carbon skeletons for energy production. How would the influx of amino acids affect the citric acid cycle, and what compensatory mechanisms would be activated?
If a cell were engineered to express a mutated malate dehydrogenase with a significantly lower affinity for NAD+, how would this alteration impact both the citric acid cycle and gluconeogenesis?
If a cell were engineered to express a mutated malate dehydrogenase with a significantly lower affinity for NAD+, how would this alteration impact both the citric acid cycle and gluconeogenesis?
Suppose a researcher introduces a synthetic molecule that effectively inhibits the movement of the E2 subunit's lipoyllysine arm within the pyruvate dehydrogenase complex. What direct effect would this have on the complex's function?
Suppose a researcher introduces a synthetic molecule that effectively inhibits the movement of the E2 subunit's lipoyllysine arm within the pyruvate dehydrogenase complex. What direct effect would this have on the complex's function?
How does the presence of 'biological tethers,' such as lipoyllysine in the pyruvate dehydrogenase complex, contribute to the overall efficiency of metabolic pathways, and what would be the most likely consequence of their absence?
How does the presence of 'biological tethers,' such as lipoyllysine in the pyruvate dehydrogenase complex, contribute to the overall efficiency of metabolic pathways, and what would be the most likely consequence of their absence?
Flashcards
What is glycolysis?
What is glycolysis?
A pathway made up of 10 enzyme-catalyzed steps where glucose is transformed into 2 molecules of pyruvate.
What is an anaerobic process?
What is an anaerobic process?
Does not require O2.
What is Phase I of glycolysis?
What is Phase I of glycolysis?
5 steps where glucose is phosphorylated and split into 2 triose phosphates, costing 2 ATP.
What is Phase II of glycolysis?
What is Phase II of glycolysis?
Signup and view all the flashcards
What is a Kinase?
What is a Kinase?
Signup and view all the flashcards
What is an Isomerase?
What is an Isomerase?
Signup and view all the flashcards
What is a Dehydrogenase?
What is a Dehydrogenase?
Signup and view all the flashcards
What is a Mutase?
What is a Mutase?
Signup and view all the flashcards
What is a Lyase/Aldolase?
What is a Lyase/Aldolase?
Signup and view all the flashcards
Where does glycolysis occur?
Where does glycolysis occur?
Signup and view all the flashcards
Where does the citric acid cycle occur?
Where does the citric acid cycle occur?
Signup and view all the flashcards
Where does oxidative phosphorylation occur?
Where does oxidative phosphorylation occur?
Signup and view all the flashcards
What is pyruvate dehydrogenase complex?
What is pyruvate dehydrogenase complex?
Signup and view all the flashcards
What are the prosthetic groups of pyruvate dehydrogenase complex?
What are the prosthetic groups of pyruvate dehydrogenase complex?
Signup and view all the flashcards
What are the co-substrates of pyruvate dehydrogenase complex?
What are the co-substrates of pyruvate dehydrogenase complex?
Signup and view all the flashcards
What is Co-enzyme A (CoA)?
What is Co-enzyme A (CoA)?
Signup and view all the flashcards
What is thiamine pyrophosphate (TPP)?
What is thiamine pyrophosphate (TPP)?
Signup and view all the flashcards
What is Lipoic Acid?
What is Lipoic Acid?
Signup and view all the flashcards
What is Claisen Condensation?
What is Claisen Condensation?
Signup and view all the flashcards
What is dehydration/rehydration?
What is dehydration/rehydration?
Signup and view all the flashcards
What inhibits pyruvate dehydrogenase complex?
What inhibits pyruvate dehydrogenase complex?
Signup and view all the flashcards
What activates pyruvate dehydrogenase complex?
What activates pyruvate dehydrogenase complex?
Signup and view all the flashcards
What inhibits citrate synthase?
What inhibits citrate synthase?
Signup and view all the flashcards
What activates citrate synthase?
What activates citrate synthase?
Signup and view all the flashcards
What inhibits isocitrate dehydrogenase?
What inhibits isocitrate dehydrogenase?
Signup and view all the flashcards
What stimulates isocitrate dehydrogenase?
What stimulates isocitrate dehydrogenase?
Signup and view all the flashcards
What inhibits a-ketoglutarate dehydrogenase complex?
What inhibits a-ketoglutarate dehydrogenase complex?
Signup and view all the flashcards
What stimulates a-ketoglutarate dehydrogenase complex?
What stimulates a-ketoglutarate dehydrogenase complex?
Signup and view all the flashcards
What is the first anaplerotic reaction and equation shown?
What is the first anaplerotic reaction and equation shown?
Signup and view all the flashcards
What are the three domain's of Pyruvate Carboxylase?
What are the three domain's of Pyruvate Carboxylase?
Signup and view all the flashcards
What is biotin?
What is biotin?
Signup and view all the flashcards
What are fates of glycolysis and TCA cycle intermediates?
What are fates of glycolysis and TCA cycle intermediates?
Signup and view all the flashcards
What is the purposes of Anaplerotic reactions?
What is the purposes of Anaplerotic reactions?
Signup and view all the flashcards
What happens during net oxidation?
What happens during net oxidation?
Signup and view all the flashcards
Where is energy captured at?
Where is energy captured at?
Signup and view all the flashcards
What cycle completes?
What cycle completes?
Signup and view all the flashcards
Left side or right side for oxaloacetate?
Left side or right side for oxaloacetate?
Signup and view all the flashcards
Study Notes
Review of Glucose Metabolism
- Glycolysis involves 10 enzyme-catalyzed steps
- Glycolysis transforms one molecule of glucose (C6H12O6) into two molecules of pyruvate (C3H3O3)
- Glycolysis is an ancient anaerobic process and does not require O2
- Glycolysis enzymes and reactions are nearly identical in all cells, primarily differing in regulation
- Glycolysis has two phases: preparatory and payoff
Phase I - Preparatory
- It consists of 5 steps
- Requires glucose phosphorylation and split into 2 triose phosphates
- Requires 2 ATP
Phase II – Payoff
- It consists of 5 steps
- Oxidation and phosphorylation steps yield 2 NADH + 4 ATP
- Glycolysis has a net yield of 2 ATP and 2 NADH
Enzyme Cheat Sheet
- Kinases use Mg2+ as a cofactor
- Phosphorylation by Kinases involves ATP converting to ADP + P-R
- "R" is a sugar or protein
- Isomerases make intramolecular rearrangements
- Isomerases involve cis converting to trans
- Isomerases can convert aldehyde to ketone molecules
- Metals are variable metals and none are cofactors
- Dehydrogenases transfer hydride
- NAD+, NADP+, and FAD are common cofactors
- Hydride is typically moved to NAD+
- Dehydrogenases involves the formation of HO-CH2-R converting to O-CH-R + H:- + H+
- Examples include the enzyme class Mutase, and the elimination without hydrolysis reaction via Lyase and Aldolase
- Mutases use variable metals Mg2+, and B12 as cofactors
- Aldolases use variable metals PLP(carbolyase) as a cofactor
Location of Cellular Respiration
- Glycolysis occurs in the cytoplasm
- The citric acid cycle occurs in the mitochondrial matrix
- Except succinate dehydrogenase, which is located in the inner membrane
- Oxidative phosphorylation occurs in the inner membrane
Pyruvate Dehydrogenase Complex
- Pyruvate converts to Acetyl-CoA + CO2 through the pyruvate dehydrogenase complex
- E1 is pyruvate dehydrogenase
- transacetylase/dehydrogenase is E2/E3
- The reaction is irreversible and an important control point linking glycolysis and the TCA cycle
- The reaction is catalyzed using the the pyruvate dehydrogenase complex
- TPP, lipoyllysine, and FAD are prosthetic groups
- NAD+ and CoA-SH are co-substrates
- 10AG'° = -33.4 kJ/mol
- Keq = 7x105 (Irreversible)
Co-Enzyme A (CoA)
- Transfers functional groups from one molecule to another
- Derives from vitamin pantothenate
Thiamin pyrophosphate (TPP)
- Contains a thiazolium ring with a stable carbanion
Lipoic Acid
- Exists in oxidized and reduced forms, as well as acetylated forms
- Prosthetic groups are strongly bound to protein molecules
- Lipoic acid is covalently linked to enzymes through a lysine residue, forming lipoyllysine
NADH and FADH2
- Nicotinamide adenine is a dinucleotide
- Flavin adenine is a dinucleotide
- FADH2 acts as Flavin
Oxidative Decarboxylation of Pyruvate Reactants
- Requires pyruvate, TPP, CO2, Hydroxyethyl, Oxidized lipoyllysine, Acetyl lipoyllysine, Lys, Succinyl
- Utilise pyruvate dehydrogenase (E1), dihydrolipoyl transacetylase (E2), and dihydrolipoyl dehydrogenase (E3) in the process
Proteins in Pyruvate Dehydrogenase Complex
- Pyruvate dehydrogenase is E1
- Dihydrolipoyl dehydrogenase is E3
- E2 has a small flexible 'carrier domain' – lysine-lipoic acid
The Citric Acid Cycle (TCA)
- It occurs in the mitochondrial matrix
- Acetyl-CoA input is one molecule
- Output includes 3 NADH molecules, 1 FADH2 molecule, 1 GTP molecule, and 2 CO2 molecules
Citrate Synthesis
- The reaction is exergonic because of the highly exergonic free energy change accompanying hydrolysis of acetyl-CoA
- Its ΔG'° is −32.2 kJ/mol
- It's an acetylation of oxaloacetate by acetyl-CoA
- The first regulatory step of the TCA cycle
Citrate Synthase Dynamics
- Oxaloacetate binds first, inducing an open form of the enzyme that can accommodate acetyl-CoA
- Acetyl-CoA then binds, causing the enzyme to close into a more compact form that is optimal for catalysis
- Requires the coenzyme A molecule
Mechanism of Citrate Synthase
- This mechanism should be known to be identified
- Also know that amino acids Histidine and Aspartate participate in this process
Isocitrate Synthesis
- The catalysis is mediated through the action of a basic residue on the enzyme (B) and the iron-sulfur center
- Reaction is unfavorable under standard conditions: driven to right because isocitrate rapidly consumed in the next step
- Its ΔG'° = 13.3 kJ/mol
α-ketoglutarate Synthesis
- Oxidation of isocitrate yields a-ketoglutarate and CO2
- Oxidative decarboxylation catalyzed by isocitrate dehydrogenase
- Mn2+ stabilizes intermediates in active site (metal catalysis)
- This is the 1st oxidative decarboxylation step of the cycle, using NAD+ or NADP+ as electron acceptors
- Also the second regulatory point of the TCA cycle
- Its ΔG'o = –20.9 kJ/mol
Succinyl-CoA
- The mechanism is identical to the pyruvate dehydrogenase reaction
- The α-ketoglutarate dehydrogenase complex has similar E1, E2 and E3 domains as pyruvate dehydrogenase and uses TPP and Lipoic acid as co-factors
- This is an oxidative decarboxylation process
- This step is the third regulatory step in the TCA cycle
Synthesis of Succinate
- The free energy released when the high energy thioester is hydrolyzed is conserved in the formation of GTP from GDP and Pi
- This is a substrate-level phosphorylation event
- GTP and ATP are energetically equivalent because both have same hydrolysis free energy - ΔG°' = -30.5 kJ/mol
- Its ΔG'° = −2.9 kJ/mol
Fumarate Synthesis
- Succinate is oxidized to fumarate, with free energy stored in reduced FAD, covalently attached to the enzyme
- Its ΔG'° = 0 kJ/mol
- The enzyme is attached to the mitochondrial inner membrane (membrane-bound)
- All other citric acid cycle enzymes are free to diffuse in the mitochondrial matrix
- Enzyme molecules and produced FADH2 molecules are shared with the electron transport chain
Malate Production
- Fumarase stereospecifically adds water across C=C bond.
- Its ΔG'° = -3.8 kJ/mol
- Maleate (cis double bond) and D-malate are not substrates for this enzyme
Oxaloacetate Regeneration
- Oxidation of malate produces oxaloacetate
- The equilibrium of this reaction lies far to the left under standard conditions
- But in intact cells, oxaloacetate is continually removed via the highly exergonic citrate synthase reaction
- Its ΔG'° = 29.7 kJ/mol
- Oxaloacetate concentration cell is extremely low (
Studying That Suits You
Use AI to generate personalized quizzes and flashcards to suit your learning preferences.
Related Documents
Description
Summary of metabolic process of glycolysis. It transforms one molecule of glucose into two molecules of pyruvate. Glycolysis is an ancient anaerobic process and does not require O2.