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Biological and Biochemical Foundations of Living Systems

Citric Acid Cycle

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Acetyl-CoA production

A key source of acetyl-CoA is from the pyruvate produced by glycolysis, which undergoes oxidative decarboxylation by pyruvate dehydrogenase (generating a 2-carbon group from a 3-carbon molecule, releasing CO2 and reducing NAD+ to NADH in the process). Other sources include transformation from amino acids and ketone bodies as well as beta-oxidation of fatty acids.

Reactions of the cycle, substrates and products

Acetyl-CoA interacts at the start of the citric acid cycle, transferring its 2-carbon acetyl group to the 4-carbon oxaloacetate to produce the 6-carbon citrate. One turn of the citric acid cycle takes this molecule through a series of oxidations, eventually recreating oxaloacetate to begin anew cycle, producing along the way: 3 NADH, 1 FADH2, 1 GTP, and the release of 2 CO2.

  • citrate undergoes isomerization to isocitrate
  • isocitrate undergoes oxidative decarboxylation to α-ketoglutarate (5-carbon), producing NADH and CO2
  • α-ketoglutarate undergoes oxidative decarboxylation to succinyl CoA (4-carbon), producing NADH and CO2
  • succinyl CoA converts to succinate, producing GTP
  • succinate converts to fumarate, producing FADH2
  • fumarate (with H2O) converts to malate
  • malate converts to oxaloacetate, producing NADH

Regulation of the cycle

The citric acid cycle is regulated significantly by the availability of electron carriers NAD and FAD, thus requiring the presence of O2 to act as the final electron acceptor of the electron transport chain. Buildup of NADH will slow the reactions of the citric acid cycle.

Net molecular and energetic results of respiration processes

Together glycolysis and the pyruvate dehydrogenase complex produce 2 net ATP and 4 NADH per glucose.

Each turn of the citric acid cycle produces 1 ATP (generated from GTP), 3 NADH, and 1 FADH2 (that is 2 ATP, 6 NADH, and 2 FADH2 per glucose, two turns of citric acid cycle).

Together, glycolysis, the conversion of pyruvate, and the citric acid cycle produce 4 ATP, 10 NADH, and 2 FADH2 per molecule of glucose. Oxidative phosphorylation via the electron transport chain then produces 4 + 30 + 4 = 38 ATP per glucose. Transport of NADH produced from glycolysis in the cytosol into the mitochondria in eukaryotes requires 1 ATP each, so the net ATP production becomes 36 ATP.

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