MMUT

The gene MMUT encodes methylmalonyl-CoA mutase, a mitochondrial enzyme critical for branched-chain amino acid and fatty acid metabolism. It catalyzes the isomerization of methylmalonyl-CoA to succinyl-CoA, relying on adenosylcobalamin as a cofactor. Deficiencies cause methylmalonic acidemia, an inborn error leading to metabolic acidosis and neurological damage.
MMUT functions in propionate catabolism, intersecting with the citric acid cycle. Pathogenic variants disrupt vitamin B12-dependent reactions, accumulating toxic metabolites. Current management involves dietary restriction and cobalamin supplementation; gene therapy approaches are under preclinical evaluation for enzyme replacement.