  methylenetetrahydrofolate reductase (mthfr) is the rate-limiting enzyme in the methyl cycle, and it is encoded by the mthfr gene. methylenetetrahydrofolate reductase catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a cosubstrate for homocysteine remethylation to methionine. genetic variation in this gene may influence susceptibility to occlusive vascular disease, neural tube defects, alzheimer's disease and other forms of dementia, colon cancer, and acute leukemia, because mutations in this gene are associated with methylenetetrahydrofolate reductase deficiency. == biochemistry == in the rate-limiting step of the methyl cycle, mthfr irreversibly reduces 5,10-methylenetetrahydrofolate (substrate) to 5-methyltetrahydrofolate (product). * 5,10-methylenetetrahydrofolate is used to convert dump to dtmp for de novo thymidine synthesis. * 5-methyltetrahydrofolate is used to convert homocysteine (a potentially toxic amino acid) to methionine by the enzyme methionine synthase. (note that homocysteine can also be converted to methionine by the folate-independent enzyme betaine-homocysteine methyltransferase (bhmt)) mthfr contains a bound flavin [[cofactor (bio
EC_1.5.1 Human_proteins