Title:Methylenetetrahydrofolate Reductase: Biochemical Characterization and Medical Significance
Volume: 19
Issue: 14
Author(s): Elizabeth E. Trimmer
Affiliation:
Keywords:
Flavin, FAD, folate, MTHFR, methylenetetrahydrofolate, methyltetrahydrofolate, homocysteine, C677T polymorphism
Abstract: Methylenetetrahydrofolate reductase (MTHFR) catalyzes the reduction of 5,10-methylenetetrahydofolate (CH2-H4folate) to 5-
methyltetrahydrofolate (CH3-H4folate). The enzyme employs a noncovalently-bound flavin adenine dinucleotide (FAD), which accepts
reducing equivalents from NAD(P)H and transfers them to CH2-H4folate. The reaction provides the sole source of CH3-H4folate, which is
utilized by methionine synthase in the synthesis of methionine from homocysteine. MTHFR plays a key role in folate metabolism and in
the homeostasis of homocysteine; mutations in the enzyme lead to hyperhomocyst(e)inemia. A common C677T polymorphism in
MTHFR has been associated with an increased risk for the development of cardiovascular disease, Alzheimer’s disease, and depression in
adults, and of neural tube defects in the fetus. The mutation also confers protection for certain types of cancers. This review presents the
current knowledge of the enzyme, its biochemical characterization, and medical significance.