MMUT Gene: Methylmalonyl-CoA Mutase Function, Mutations, and Disease

The MMUT gene encodes the mitochondrial enzyme methylmalonyl-CoA mutase (MCM), which catalyzes the isomerization of methylmalonyl-CoA to succinyl-CoA. This reaction is a critical step in the catabolism of branched-chain amino acids, odd-chain fatty acids, and cholesterol. The enzyme requires adenosylcobalamin (vitamin B12) as a cofactor. Mutations in MMUT cause methylmalonic acidemia (MMA), an autosomal recessive disorder of organic acid metabolism.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Propanoate metabolism (KEGG: hsa00640)

• Valine

• leucine and isoleucine degradation (KEGG: hsa00280)

• Metabolic pathways (KEGG: hsa01100)

Methylmalonyl-CoA mutase (MCM) is a homodimeric mitochondrial enzyme encoded by MMUT. Each subunit (750 amino acids) binds one molecule of adenosylcobalamin. The enzyme catalyzes the reversible isomerization of L-methylmalonyl-CoA to succinyl-CoA via a radical mechanism. Deficiency leads to accumulation of methylmalonic acid and propionyl-CoA, causing metabolic acidosis, neurological damage, and multi-organ failure. The protein structure includes an N-terminal mitochondrial targeting sequence, a cobalamin-binding domain, and a catalytic (mutase) domain.