Methylcrotonoyl-CoA carboxylase subunit alpha (MCCCα (also referred to as MCCA))

Methylcrotonoyl-CoA carboxylase subunit alpha is one half of the heterododecameric mitochondrial enzyme methylcrotonoyl-CoA carboxylase (MCC), which catalyzes the ATP-dependent biotin-mediated conversion of 3-methylcrotonoyl-CoA into 3-methylglutaconyl-CoA—the fourth step in leucine catabolism. The human alpha subunit is encoded by the MCCC1 gene on chromosome 3q27 and contains a covalently bound biotin required for its catalytic activity. Together with six beta subunits encoded by MCCC2, it forms an active holoenzyme critical for energy production from branched-chain amino acids. Mutations affecting this protein cause MCC deficiency, an autosomal recessive disorder detected via newborn screening using specific acylcarnitines as biomarkers; clinical manifestations range from asymptomatic biochemical abnormalities to severe neonatal illness with risk for neurological damage if untreated[1][3][4].

Other names

3-methylcrotonyl-CoA carboxylase subunit alphaMCC alpha subunitMCCC1 gene productMCCA protein

For therapeutic intervention: - Dietary restriction of leucine reduces substrate load. For the enzyme itself: "MCC uses bicarbonate as a carboxyl group source to catalyze the ATP-dependent carboxylation of 3-methylcrotonoyl-CoA". Biotin supplementation may be used if there is evidence or suspicion of biotin-responsive forms.