Methylmalonyl-CoA mutase (MUT) and Methionine synthase (MTR) (MUT/MTR)

Methylmalonyl-CoA mutase (MUT) and methionine synthase (MTR) are the two primary cobalamin-dependent enzymes in humans [1,2]. MUT is a mitochondrial enzyme that catalyzes the isomerization of methylmalonyl-CoA to succinyl-CoA, a critical step in the catabolism of odd-chain fatty acids and certain amino acids [1,4]. MTR is a cytosolic enzyme that converts homocysteine to methionine, linking the methylation cycle with the folate cycle and supporting DNA synthesis [2,3]. Deficiencies in these enzymes or their cobalamin cofactors lead to severe metabolic disorders such as methylmalonic acidemia and homocystinuria [4]. Therapeutic strategies primarily involve the administration of various forms of vitamin B12 (cobalamin) to restore enzyme activity [3]. Recent advancements include gene therapies and mRNA-based treatments, such as mRNA-3928, designed to provide functional copies of the MUT enzyme in patients with genetic mutations [5]. Monitoring efficacy involves measuring biomarkers such as methylmalonic acid and homocysteine levels in the blood and urine [4]. Sources: [1] UniProt P22033; [2] UniProt Q99707; [3] StatPearls: Vitamin B12 Deficiency; [4] NORD: Methylmalonic Acidemia; [5] Moderna Pipeline.

Other names

Cobalamin-dependent enzymesVitamin B12-dependent enzymesMethylmalonyl-CoA isomerase5-methyltetrahydrofolate-homocysteine methyltransferase

Cofactor supplementation to restore enzymatic activity or mRNA-mediated enzyme replacement therapy.