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Cobalamin‐dependent methionine synthase
Author(s) -
Banerjee Ruma V.,
Matthews Rowena G.
Publication year - 1990
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.4.5.2407589
Subject(s) - methionine synthase , cobalamin , homocysteine , methionine , biochemistry , atp synthase , enzyme , cystathionine beta synthase , chemistry , biosynthesis , megaloblastic anemia , nitric oxide synthase , biology , amino acid , vitamin b12
Cobalamin‐dependent methionine synthase catalyzes the transfer of a methyl group from N 5 ‐methyltetrahydrofolate to homocysteine, producing tetrahydrofolate and methionine. Insufficient availability of cobalamin, or inhibition of methionine synthase by exposure to nitrous oxide, leads to diminished activity of this enzyme. In humans, severe inhibition of methionine synthase results in the development of megaloblastic anemia, and eventually in subacute combined degeneration of the spinal cord. It also results in diminished intracellular folate levels and a redistribution of folate derivatives. In this review, we summarize recent progress in understanding the catalysis and regulation of this important enzyme from both bacterial and mammalian sources. Because inhibition of mammalian methionine synthase can restrict the incorporation of methyltetrahydrofolate from the blood into cellular folate pools that can be used for nucleotide biosynthesis, it is a potential chemotherapeutic target. The review emphasizes the mechanistic information that will be needed in order to design rational inhibitors of the enzyme.—B anerjee , R. V.; M atthews , R. G. Cobalamin‐dependent methionine synthase. FASEB J. 4: 1450‐1459; 1990.