TCA cycle or Krebs cycle / The citric acid cycle Animation - Biochemistry Metabolisms
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The citric acid cycle (CAC) – also known as the TCA cycle or the Krebs cycle - USMLE Step 1
Citric Acid Cycle
Citric Acid Cycle: central catabolic pathway used to generate energy through the oxidization of acetate (derived from carbohydrates, fats, and proteins) into CO2 and H2O
For each turn, the cycle produces 1 GTP, 3 NADH, 1 FADH2, and 2 CO2
1 NADH → 3 ATP equivalents
1 FADH2 → 2 ATP equivalents
However, because of the energy expenditure required to shuttle NADH and FADH to the ETC, each turn through the citric acid cycle yields:
3 NADH x 2.5 → 7.5 ATP equivalent
1 FADH2 x 1.5 → 1.5 ATP equivalent
1 GTP → 1 ATP equivalent
For a total of 12 potential and 10 actual ATPs
The citric acid cycle (tricarboxylic acid cycle or Krebs cycle) takes place in the mitochondrial matrix
Citrate synthase catalyzes the transfer of a 2-carbon acetyl group from acetyl-CoA to oxaloacetate, forming the 6-carbon molecule citrate
Citrate synthase is inhibited by ATP, NADH and succinyl CoA and stimulated by insulin
Strongly exergonic step, regulatory point in the cycle
Aconitase catalyzes the isomerization of citrate into isocitrate
Fluoroacetate (a metabolic poison) inhibits the enzyme aconitase
Isocitrate dehydrogenase catalyzes the oxidative decarboxylation of isocitrate to α-ketoglutarate
NAD+ → NADH, 1st molecule of CO2 is released
Key regulatory step that is stimulated by ADP (low energy state) and inhibited by ATP and NADH (high energy state)
The α-ketoglutarate dehydrogenase complex converts α-ketoglutarate to succinyl-CoA
NAD+ → NADH, 2nd molecule of CO2 is released
Regulatory step, regenerates a 4-carbon chain (CoA excluded) and requires many coenzymes, including vitamins B1, B2, B3, CoA, and lipoic acid
Note: the same cofactors are required in the pyruvate dehydrogenase complex.
α-ketoglutarate dehydrogenase is inhibited by NADH, succinyl CoA, ATP and GTP
Succinyl-CoA synthetase converts succinyl-CoA to succinate and CoA
Substrate level phosphorylation: GDP + Pi → GTP
The succinate dehydrogenase complex catalyzes oxidation of succinate to fumarate
FAD → FADH2
Mitochondrial fumarase converts fumarate to malate
Malate dehydrogenase oxidizes malate to oxaloacetate, and the cycle can begin anew
NAD+ → NADH
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