Thetricarboxylic acid cycle: Oxidation in the round

Having considered localisation of respiratory functions in mitochondria and in prokaryotic cells, it's time to return to the eukaryotic context and follow a molecule of pyruvate across the inner membrane of the mitochondrion to see what fate awaits it inside.

- TAPAN KUMAR MAITRA

In the presence of oxygen, pyruvate is oxidized fully to carbon dioxide, and the energy released in the process is used to drive ATP synthesis. The first stage in this process is a cyclic pathway that is a central feature of energy metabolism in almost all aerobic chemotrophs. An important intermediate in this cyclic series of reactions is citrate, which has three carboxylic acid groups and is therefore a tricarboxylic acid. For this reason, this pathway is usually called the tricarboxylic acid (TCA) cycle. It is also commonly referred to as the Krebs cycle in honor of Hans Krebs, whose laboratory played a key role in elucidating this metabolic sequence in the 1930s.

The TCA cycle metabolizes acetyl coenzyme A (acetyl CoA), which consists of a two-carbon acetate group linked to a carrier called coenzyme A. (Coenzyme A was discovered by Fritz Lipmann, who shared a Nobel Prize with Krebs in 1953 for their work on aerobic respiration.) Acetyl CoA arises either by oxidative decarboxylation of pyruvate or by the stepwise oxidative breakdown of fatty acids. Regardless of its origin, acetyl CoA transfers its acetate group to a four-carbon acceptor called oxaloacetate, thereby generating citrate. Citrate is then subjected to two successive decarboxylations and several oxidations, leaving a four-carbon compound from which the starting oxaloacetate is regenerated.