What is the Citric Acid Cycle (CAC)?
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The Citric Acid Cycle (CAC), also called the Krebs cycle or TCA, is a series of reactions in the mitochondria that catabolize Acetyl‑CoA into hydrogen equivalents.
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What is the Citric Acid Cycle (CAC)?
The Citric Acid Cycle (CAC), also called the Krebs cycle or TCA, is a series of reactions in the mitochondria that catabolize Acetyl‑CoA into hydrogen equivalents.
Where in the cell does the CAC occur?
The CAC occurs in the mitochondria.
Which hydrogen carriers are produced by the CAC and how much ATP do they yield?
NADH+H+ → 3 ATP and FADH2 → 2 ATP when oxidized via the electron transport chain (ETC).
What is the fate of NADH and FADH2 produced in the CAC?
They feed into the Electron Transport Chain (ETC) to generate ATP.
Are CAC steps catalyzed by reversible or irreversible enzymes?
Many CAC steps are catalyzed by irreversible enzymes; biochemical pathways often include irreversible regulatory steps.
What is the primary purpose of the Citric Acid Cycle?
To produce hydrogen equivalents (NADH, FADH2) for ATP synthesis and to supply intermediates for biosynthetic pathways.
Which enzyme catalyzes the condensation of Acetyl‑CoA with oxaloacetate?
Citrate synthase (a condensing enzyme) catalyzes formation of citrate from Acetyl‑CoA and oxaloacetate.
Which enzyme converts citrate to isocitrate?
Aconitase converts citrate to isocitrate (via cis‑aconitate).
Which enzyme catalyzes oxidative decarboxylation of isocitrate?
Isocitrate dehydrogenase catalyzes oxidative decarboxylation of isocitrate, producing CO2 and NADH.
Which enzyme converts α‑ketoglutarate to succinyl‑CoA?
The α‑ketoglutarate dehydrogenase complex catalyzes oxidative decarboxylation of α‑ketoglutarate to succinyl‑CoA.
Which enzyme converts succinate to fumarate and what cofactor does it use?
Succinate dehydrogenase converts succinate to fumarate and uses FAD to generate FADH2.
Which enzyme converts malate to oxaloacetate?
Malate dehydrogenase converts malate to oxaloacetate, producing NADH.
How many ATP are produced from one Acetyl‑CoA in the CAC?
One Acetyl‑CoA yields 12 ATP in the CAC (3 NADH → 9 ATP, 1 FADH2 → 2 ATP, 1 GTP → 1 ATP).
How many NADH and FADH2 are produced per Acetyl‑CoA in the CAC?
Per Acetyl‑CoA the CAC produces 3 NADH+H+ and 1 FADH2.
What is the total ATP yield from complete aerobic oxidation of one glucose molecule?
Complete aerobic oxidation of one glucose yields 38 ATP (including glycolysis, link reaction, and CAC).
How much ATP is produced from glucose under anaerobic conditions?
Anaerobic glycolysis yields 2 ATP per glucose and produces 2 lactate molecules.
How many ATP are produced by 2 Acetyl‑CoA going through the CAC?
Two Acetyl‑CoA molecules generate 24 ATP in the CAC (2 × 12 ATP).
What is produced by substrate‑level phosphorylation in the CAC?
A GTP is produced (equivalent to 1 ATP) by substrate‑level phosphorylation.
What does it mean that the CAC is 'amphibolic'?
The CAC is amphibolic—it functions in both catabolism (energy production) and anabolism (providing biosynthetic precursors).
How is citrate used in fatty acid and cholesterol synthesis?
Citrate is transported to the cytosol and cleaved by ATP‑citrate lyase to yield Acetyl‑CoA for fatty acid and cholesterol synthesis.
How does malate contribute to NADPH production and pyruvate formation?
The malic enzyme converts malate → pyruvate + CO2 and generates NADPH, which is used in biosynthesis.
Which CAC intermediates are precursors for non‑essential amino acids?
α‑Ketoglutarate → glutamate and oxaloacetate → aspartate are precursors for non‑essential amino acids.
How does oxaloacetate feed gluconeogenesis?
Oxaloacetate in the cytosol is converted to PEP, which enters gluconeogenesis to form glucose.
What biosynthetic roles does succinyl‑CoA and CO2 play?
Succinyl‑CoA is used in heme synthesis, detoxification, and ketone body oxidation; CO2 is used in CO2 fixation, purine/pyrimidine synthesis, urea synthesis, and buffer system synthesis.
How does Acetyl‑CoA regulate the CAC?
Acetyl‑CoA activates citrate synthase and influences oxaloacetate/citrate equilibrium to regulate flux through the cycle.
What is the effect of Succinyl‑CoA on α‑ketoglutarate dehydrogenase?
Succinyl‑CoA inhibits the α‑ketoglutarate dehydrogenase complex (feedback inhibition).
How do high NADH/NAD+ and ATP/ADP ratios affect the CAC?
High NADH/NAD+ and high ATP/ADP ratios inhibit citrate synthase, isocitrate dehydrogenase, and α‑ketoglutarate dehydrogenase.
What effect does ADP have on CAC enzymes?
High ADP stimulates the CAC enzymes (increases activity of rate‑limiting dehydrogenases).
Is the α‑ketoglutarate dehydrogenase complex regulated by covalent modification?
No — the α‑ketoglutarate dehydrogenase complex is not regulated by covalent modification.
What toxin produces fluorocitrate and what does fluorocitrate inhibit?
Fluoroacetyl‑CoA combines with oxaloacetate to form fluorocitrate, which inhibits aconitase.
Which compound competitively inhibits succinate dehydrogenase?
Malonic acid (malonate) is a competitive inhibitor of succinate dehydrogenase.
How do arsenite and mercury inhibit CAC enzymes?
Arsenite and mercury react with –SH groups (e.g., on lipoic acid) to inhibit pyruvate dehydrogenase and α‑ketoglutarate dehydrogenase complexes.
What metabolites accumulate when PDH and α‑KGDH are inhibited, and what is the consequence?
α‑Ketoglutarate, pyruvate, and lactate accumulate, leading to acidosis due to impaired aerobic oxidation.
What type of inhibition does malonate exert on succinate dehydrogenase?
Malonate exerts competitive inhibition on succinate dehydrogenase.
