| ANAPLEROTIC ('FILLING UP') REACTIONS
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As noted above (Fig. 13.1), TCA cycle intermediates participate in biosynthetic processes, which all require anaplerosis. For example, removal of succinyl-CoA for heme biosynthesis could gradually deplete mitochondrial oxaloacetate. The TCA cycle would cease to function if the intermediates were not replenished, because acetyl-CoA cannot yield a net synthesis of TCA cycle intermediates. Anaplerotic reactions provide the TCA cycle with intermediates other than acetyl-CoA to maintain activity of the cycle. Pyruvate carboxylase is an example of an enzyme that catalyzes an anaplerotic reaction. It converts pyruvate to malate, a precursor of oxaloacetate, which is required for initiation of the cycle. Malic enzyme in the cytoplasm also converts pyruvate to malate, which can enter the mitochondrion as a substrate for the TCA cycle. α-Ketoglutarate can be produced through an aminotransferase reaction from glutamate, as well as by the glutamate dehydrogenase reaction. Several other 'glucogenic' amino acids (Chapter 18) may also serve as sources of pyruvate or TCA cycle intermediates, guaranteeing that the cycle is never stalled because of a lack of intermediates.
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