5-methyltetrahydrofolate-homocysteine methyltransferase (Methionine synthase) (MTR)

Methionine synthase (MTR) is a critical enzyme that resides at the intersection of the folate and methionine cycles, facilitating the remethylation of homocysteine to methionine. In mammals, this process is strictly dependent on methylcobalamin (Vitamin B12) as a cofactor and 5-methyltetrahydrofolate as the methyl donor. By regenerating tetrahydrofolate, MTR supports the synthesis of purines and thymidylate, which are essential for DNA replication and cell division. Dysfunction or inhibition of MTR leads to the "methyl-folate trap," where folate is sequestered in an unusable form, resulting in megaloblastic anemia and elevated homocysteine levels. In oncology, MTR is a target of interest because many cancer cells exhibit methionine dependence and rely on this pathway for survival in physiological folate environments. Furthermore, the structural differences between human cobalamin-dependent MTR and fungal cobalamin-independent MTR make it a promising target for developing selective antifungal agents.

Other names

Methionine synthaseMSMetHMeSecblGHMAG5-methyltetrahydrofolate-homocysteine methyltransferase

Catalyzes the transfer of a methyl group from 5-methyltetrahydrofolate to homocysteine to form methionine and tetrahydrofolate, utilizing a methylcobalamin cofactor and requiring reductive activation by methionine synthase reductase.