Methylenetetrahydrofolate reductase: a common human polymorphism and its biochemical implications.
Methlenetetrahydrofolate (CH2-H4folate) is required for the conversion of homocysteine to methionine and of dUMP to dTMP in support of DNA synthesis, and also serves as a major source of one carbon unit for purine biosynthesis. This review presents biochemical studies of a human polymorphism in methylenetetrahydrofolate reductase, which catalyzes the reaction shown below. The mutation decreases the flux of CH2-H4folate into CH3-H4folate, and is associated with both beneficial and deleterious effects that can be traced to the molecular effect of the substitution of alanine 222 by valine.
Matthews
Rowena G
RG
Biophysics Research Division, The University of Michigan, 930 N. University Avenue, Ann Arbor, Michigan 48109-1055, USA. rmatthew@umich.edu
D019943:Amino Acid Substitution; D000818:Animals; D002384:Catalysis; D005492:Folic Acid / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008745:Methylation; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D009154:Mutation; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology; D011110:Polymorphism, Genetic
D005492:Folic Acid; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)