3-Methylcrotonyl-CoA carboxylase (MCC)

3-Methylcrotonyl-CoA carboxylase (MCC) is a mitochondrial, biotin-dependent enzyme composed of two subunits (alpha and beta, encoded by MCCC1 and MCCC2 respectively) that catalyzes the carboxylation of 3-methylcrotonyl-CoA to 3-methylglutaconyl-CoA, a key step in the catabolic pathway of the essential amino acid leucine[1][3][4][5][7]. This reaction ultimately supports energy production by contributing to acetyl-CoA and acetoacetate pools. MCC deficiency is a well-characterized inborn error of metabolism leading to methylcrotonylglycinuria, and its diagnosis relies on detection of characteristic metabolites or reduced enzyme activity; the condition is often treatable with biotin supplementation due to the enzyme's strict requirement for biotin as a cofactor[4][6]. MCC belongs to the acyl-CoA carboxylase family, shares structural homology with propionyl-CoA carboxylase, and is widely conserved across mammals, plants, and bacteria[1][3][5][6][7].

Other names

3-methylcrotonoyl-CoA carboxylaseMethylcrotonyl-CoA carboxylaseMethylcrotonoyl-CoA carboxylaseMCC

Biotin supplementation: provides essential cofactor to restore or improve MCC activity in deficiency states No specific small-molecule inhibitors/activators of MCC in clinical use