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5,10-methylenetetrahydrofolate reductase (MTHFR)

Function: - catalyzes formation of N5-methyltetrahydrofolate from 5,10-methylenetetrahydrofolate - in connection with methionine synthase, 5,10 methylenetetrahydrofolate reductase regulates methionine synthesis & tetrahydrofolate generation (see trans-sulfuration pathway) - tetrahydrofolate serves as a reservoir of methyl groups for thymine synthesis (see folate metabolism) - allosterically regulated by S-adenosylmethionine - one-carbon metabolism; tetrahydrofolate pathway 5-methyltetrahydrofolate + NAD+/NADP+ 5,10- methylenetetrahydrofolate + NADH/NADPH Cofactor: FAD Structure: - homodimer - belongs to the methylenetetrahydrofolate reductase family Polymorphism: - genetic variation in MTHFR influences susceptibility to a) peripheral vascular disease b) neural tube defects c) colon cancer d) acute leukemia Pathology: - defects in MTHFR are the cause of a) methylenetetrahydrofolate reductase deficiency b) susceptibility to ischemic stroke c) susceptibility to folate-sensitive neural tube defects Laboratory: - MTHFR gene mutation

Interactions

molecular events

Related

hyperhomocysteinemia methionine synthase; 5-methyltetrahydrofolate:homocysteine methyltransferase; vitamin-B12 dependent methionine synthase; tetrahydropteroyl-glutamate methyltransferase; MS (MTR) MTHFR gene mutation

General

oxidoreductase

Properties

SIZE: entity length = 656 aa MW = 75 kD MOTIF: active site

Database Correlations

OMIM correlations MORBIDMAP 607093 UniProt P42898 Pfam PF02219 Entrez Gene 4524 Kegg hsa:4524 ENZYME 1.5.1.20

References

  1. UniProt :accession P42898
  2. Atlas of genetics & cytogenetics in oncology & haematology http://atlasgeneticsoncology.org/genes/MTHFRID41448ch1p36.html
  3. GeneReviews https://www.genecards.org/cgi-bin/carddisp.pl?gene=MTHFR
  4. NIEHS-SNPs http://egp.gs.washington.edu/data/mthfr/
  5. SHMPD;The Singapore human mutation and polymorphism database http://shmpd.bii.a-star.edu.sg/gene.php?genestart=A&genename=MTHFR
  6. Wikipedia; methylenetetrahydrofolate reductase entry http://en.wikipedia.org/wiki/methylenetetrahydrofolate_reductase
  7. Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 2200