Pathway

The tricarboxylic acid cycle may be considered as starting with any of its components, but for ease of description the formation of citrate is a good starting point:

• citrate synthase converts acetyl-CoA and oxaloacetate into citrate
• aconitate hydratase converts citrate into isocitrate
• isocitrate dehydrogenase converts isocitrate into 2-oxoglutarate
• oxoglutarate dehydrogenase converts 2-oxoglutarate into succinyl-CoA
• succinyl-CoA synthetase converts succinyl-CoA into succinate
• succinate dehydrogenase converts succinate into fumarate
• fumarate hydratase converts fumarate into malate
• malate dehydrogenase converts malate into oxaloacetate

Essentially per turn of the cycle, one 2 carbon acetyl moiety combines with oxaloacetate to produce 6 carbon citrate; this is sequentially oxidized to yield 2 carbon dioxide molecules, 4 hydrogen molecules and 12 molecules of ATP. Oxaloacetate is regenerated.

Per turn of the cycle, the generation of energy occurs directly in the form of GTP and indirectly via the formation of 3 NADH and 1 FADH2 molecule. The latter two compounds generate ATP by feeding into the electron transport chain.

Pyruvate dehydrogenase is not strictly part of the cycle, but it is worth considering simultaneously as it supplies citrate synthase with acetyl-CoA. Any pathway that produces acetyl-CoA can feed into the TCA cycle. Further, the metabolism of certain amino acids produces intermediates such as succinyl-CoA. These are oxidized not by direct entry into the cycle, but rather by interconversion to acetyl-CoA.