Methylmalonyl-CoA epimerase and cobalamin-dependent enzymes (MCEE/MMUT/MTR)

Methylmalonyl-CoA epimerase (MCEE) and cobalamin-dependent enzymes, primarily methylmalonyl-CoA mutase (MMUT) and methionine synthase (MTR), are essential catalysts in human metabolism. MCEE facilitates the conversion of D-methylmalonyl-CoA to L-methylmalonyl-CoA, which is subsequently processed by the adenosylcobalamin-dependent MMUT into succinyl-CoA for entry into the tricarboxylic acid (TCA) cycle [1, 2]. MTR utilizes methylcobalamin to convert homocysteine to methionine, linking the folate and methionine cycles [3]. Deficiencies in these enzymes or their cobalamin cofactors result in metabolic disorders such as methylmalonic acidemia (MMA) and homocystinuria, characterized by the toxic accumulation of organic acids and metabolic intermediates [4]. Therapeutic interventions include high-dose vitamin B12 (cobalamin) supplementation to maximize residual enzyme activity, dietary management, and novel mRNA-based therapies like mRNA-3927 that aim to restore functional MMUT protein levels [5].

Other names

DL-methylmalonyl-CoA epimeraseMethylmalonyl-CoA racemaseMCEEMethylmalonyl-CoA mutaseMMUTMethionine synthaseMTRMCM

Cofactor supplementation to enhance enzymatic activity; mRNA-mediated enzyme replacement therapy.