Citric acid cycle

The citric acid cycle — also called the Krebs cycle or tricarboxylic acid (TCA) cycle — is the central metabolic pathway of aerobic energy production. Operating in the mitochondrial matrix, it completes the oxidation of fuel molecules by breaking down acetyl-CoA, the two-carbon product of carbohydrate, fat, and protein catabolism, into carbon dioxide.

Each turn begins when acetyl-CoA combines with the four-carbon molecule oxaloacetate to form six-carbon citrate. Eight enzymatic steps then regenerate oxaloacetate, releasing two CO₂ molecules along the way. The energy captured per acetyl-CoA is the exam-favorite tally: 3 NADH, 1 FADH₂, and 1 GTP (equivalent to ATP). Because one glucose yields two acetyl-CoA, the cycle turns twice per glucose molecule. The NADH and FADH₂ then deliver their electrons to the electron transport chain, where oxidative phosphorylation generates the bulk of the cell's ATP.

The cycle is aerobic in effect even though no step uses oxygen directly: without oxygen to regenerate NAD⁺ and FAD at the electron transport chain, the cycle stalls. Regulation responds to energy status — ATP and NADH slow key enzymes (citrate synthase, isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase), while ADP and calcium speed them up. The cycle is also amphibolic, supplying intermediates for biosynthesis of amino acids, heme, and glucose.

The citric acid cycle is tested across science-heavy exams: the MCAT covers it within bioenergetics and fuel metabolism, USMLE Step 1 tests its enzymes, products, and regulation in biochemistry, and the CSCS exam includes it among the biological energy systems that fuel exercise of different intensities and durations.