Methylcrotonoyl-CoA carboxylase (MCC) (MCC)

Methylcrotonoyl-CoA carboxylase (MCC) is a mitochondrial, biotin-dependent enzyme that plays a vital role in the catabolism of the essential amino acid leucine. It catalyzes the fourth step of the leucine degradation pathway, specifically the carboxylation of 3-methylcrotonyl-CoA to 3-methylglutaconyl-CoA. The enzyme exists as a heterododecamer composed of six alpha subunits (MCCC1) and six beta subunits (MCCC2). Genetic deficiencies in these subunits lead to 3-methylcrotonyl-CoA carboxylase deficiency (MCCD), an autosomal recessive disorder characterized by the accumulation of toxic metabolites like 3-hydroxyisovaleric acid. While many individuals with MCCD remain asymptomatic, others may experience severe metabolic crises, including ketoacidosis and hyperammonemia, often triggered by infection or fasting. Therapeutic management involves biotin supplementation to enhance residual enzyme activity, along with carnitine and glycine to facilitate the detoxification of accumulated intermediates. Additionally, MCC has recently been investigated for its potential role in cancer progression, where its overexpression in certain tumors suggests it may serve as a metabolic target for oncological intervention.

Other names

3-methylcrotonyl-CoA carboxylaseMCCase3-methylcrotonyl-CoA:carbon dioxide ligaseMethylcrotonoyl-Coenzyme A carboxylase

Cofactor supplementation (Biotin) to restore enzyme activity; Substrate reduction (low-leucine diet); Detoxification and excretion of toxic metabolites (Carnitine and Glycine); Direct enzyme inhibition (Valproic acid/Valproyl-CoA).