Figure 1.

Potential metabolic functions of MCCase. MCCase catalyzes the ATP-dependent carboxylation of MC-CoA to form MG-CoA. This reaction may be required in the catabolism of Leu to acetoacetate and acetyl-CoA (reactions 1–6). MCCase may also function to convert mevalonate (MVA) to acetoacetate and acetyl-CoA (via isopentenyl pyrophosphate [IPP] and 3-methylcrotonoic acid) by the “mevalonate shunt.” A third function of MCCase may be as part of an isoprenoid catabolic pathway (via geranoyl-CoA). Reactions 4 to 6 are common to all three processes. The products of these processes, acetoacetate and acetyl-CoA, can be further metabolized to isoprenoids, polyketide derivatives (e.g. flavonoids, stilbenoids), and fatty acids, to Glc in tissues engaging the glyoxylate cycle, or respired to CO₂ in the tricarboxylic acid cycle. The enzymes of Leu catabolism are: (a) branched-chain amino acid aminotransferase, (b) BCKDH complex, (c) branched-chain acyl-CoA dehydrogenase, (d) MCCase, (e) MG-CoA hydratase, and (f) HMG-CoA lyase. The asterisks denote the carbon atom expected to be radioactively labeled when NaH¹⁴CO₃ is supplied for the MCCase reaction.