Methylmalonyl-coenzyme A mutase (MUT)

Methylmalonyl-coenzyme A mutase is a mitochondrial enzyme encoded by the MUT gene that catalyzes the isomerization of methylmalonyl-CoA to succinyl-CoA, an essential step in the catabolic pathway of certain amino acids (isoleucine, methionine, threonine, valine), odd-chain fatty acids, and cholesterol. The enzyme activity is dependent on the cofactor adenosylcobalamin (vitamin B12). Deficiency—usually through inherited mutations in the MUT gene—results in methylmalonic acidemia, a metabolic disorder leading to the toxic accumulation of methylmalonic acid and related compounds. Treatment strategies often involve vitamin B12 supplementation for responsive cases, while enzyme replacement, transplantation, and small-molecule chaperones are considered for non-responsive or more severe forms. The enzyme's structure includes conserved B12-binding and catalytic domains essential for its function. No pharmacological inhibitors or conventional antagonists are known, as the enzyme's loss is pathogenic rather than therapeutic.

Other names

Methylmalonyl-CoA mutaseMUTMCMMethylmalonyl-CoA isomerase

Enzyme activity is dependent on cofactor adenosylcobalamin (vitamin B12); drugs/supplements restore activity in B12-responsive patients by providing the necessary cofactor. Small molecule chaperones (experimental) may stabilize thermolabile or misfolded mutant proteins.