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.