Methionine synthase and L-methylmalonyl-CoA mutase (MTR and MUT)

Methionine synthase (MTR) and L-methylmalonyl-CoA mutase (MUT) are the two essential enzymes in human metabolism that utilize Vitamin B12 (cobalamin) as a cofactor [1,2]. MTR, located in the cytosol, catalyzes the transfer of a methyl group from 5-methyltetrahydrofolate to homocysteine, producing methionine and regenerating tetrahydrofolate, which is crucial for DNA synthesis and methylation reactions [1,3]. MUT, located in the mitochondria, converts L-methylmalonyl-CoA to succinyl-CoA, a key intermediate in the tricarboxylic acid (TCA) cycle used for energy production from odd-chain fatty acids and branched-chain amino acids [2,4]. Impairment of these enzymes, often due to B12 deficiency or genetic mutations, leads to elevated levels of homocysteine and methylmalonic acid, contributing to megaloblastic anemia and progressive neurological damage [3,4]. Pharmacological management involves cobalamin supplementation to provide the necessary precursors for the active cofactors methylcobalamin and adenosylcobalamin [3].

Other names

5-methyltetrahydrofolate-homocysteine methyltransferaseMethylmalonyl-CoA isomeraseMCMMSCobalamin-dependent enzymes

Vitamin B12 acts as an essential cofactor; supplementation provides precursors for methylcobalamin and adenosylcobalamin to restore enzyme activity [3,4].