Citric Acid Cycle
The central metabolic cycle that oxidizes acetyl-CoA into carbon dioxide, harvesting electrons and energy for aerobic organisms.
The citric acid cycle — also called the Krebs cycle or the tricarboxylic acid (TCA) cycle — is the metabolic pathway at the center of aerobic energy metabolism. It oxidizes the two-carbon fragment acetyl-CoA to carbon dioxide, harvesting the released energy as reduced electron carriers and GTP. In eukaryotic cells the cycle runs in the mitochondrial matrix; in bacteria it runs in the cytosol.
Acetyl-CoA enters the cycle from multiple sources: from pyruvate produced by glycolysis, from the breakdown of fatty acids, and from certain amino acids. Each turn of the cycle processes one acetyl-CoA and produces three molecules of NADH, one of FADH2, one GTP (equivalent to ATP), and two molecules of CO2. The NADH and FADH2 are not the final product — they feed electrons into the electron transport chain, where oxidative phosphorylation converts their energy into ATP with oxygen as the final electron acceptor. The complete oxidation of one glucose molecule yields roughly 30–32 ATP, with the majority generated from the cycle's reduced carriers.
The cycle is a circle of eight reactions. Acetyl-CoA condenses with oxaloacetate to form citrate; citrate is isomerized to isocitrate; isocitrate is oxidatively decarboxylated to α-ketoglutarate (the first CO2 and NADH); α-ketoglutarate is oxidatively decarboxylated to succinyl-CoA (the second CO2 and NADH); succinyl-CoA generates GTP and succinate; succinate is oxidized to fumarate (FADH2); fumarate is hydrated to malate; and malate is oxidized back to oxaloacetate (NADH), which is ready to accept another acetyl-CoA. Oxaloacetate is regenerated rather than consumed, which is what makes the pathway a cycle.
The cycle is regulated at its irreversible steps, chiefly by the availability of substrates and by product inhibition: high levels of NADH, ATP, and acetyl-CoA slow the cycle down, while high demand for energy speeds it up. It is also amphibolic — it serves biosynthesis as well as catabolism. Intermediates are drawn off to make amino acids (α-ketoglutarate → glutamate), heme (succinyl-CoA), and other molecules, and are replenished by anaplerotic reactions such as pyruvate carboxylation.
Because the cycle is the shared endpoint for carbohydrates, fats, and proteins, defects in its enzymes cause severe metabolic disease, and its dependence on oxygen means that anaerobic cells must rely on glycolysis and fermentation instead. In plants and algae, the cycle's counterpart — photosynthesis — builds the carbohydrates that the cycle later oxidizes.
Tags
biochemistry cellular respiration metabolism