Methionine synthase: Difference between revisions

'''Methionine synthase''' (MS; EC: 2.1.1.13) is the enzyme in [[one-carbon metabolism]] linking the folate and the methionine cycle. MS catalyzes the transfer of a methyl group from methyltetrahydrofolate (MTHF) to homocysteine, resulting in the formation of methionine. Methionine is an essential amino acid required by our bodies for healthy cell and tissue growth. It is essential as it is not naturally derived in our bodies. As it is used as a methyl donor in the form of S-adenosylmethionine, the resulting homocysteine is recyled to form methionine again.

MS is a B12-dependent enzyme responsible for regenerating methionine from homocysteine and uses vitamin B12 Cobalamin as a cofactor. The change from homocysteine to methionine is an SN2 reaction, as seen above, where the methyl group on N-5 from methyltetrahydrofolate (MTHF), is donated. MTHF is a product of methylenetetrahydrofolate reductase [[MTHFR]] from the folate cycle. This is a complex reaction as tetrahydrofolate (THF), the product, is a poor leaving group and requires a "super nucleophile", vitamin B12 Cob(I)alamin, to carry out the reaction<ref>DOI:10.1146/annurev.biochem.72.121801.161828</ref><ref name="Kung et al">DOI: 10.1038/nature10916</ref>; the methyl carrier.  

Methionine synthase contains four domains, each with a unique function that bind to Cob(I)alamin as the methyl carrier, MTHF as the methyl donor in the catalytic cycle, homocysteine as the methyl acceptor, and S-adenosylmethionine or SAM, as the methyl donor in the reactivation cycle<ref name="Bandarian et al">DOI: 10.1038/nsb738</ref>. The orientation of the domains changes during the catalytic cycle.