Medicines associated with folate-homocysteine-methionine pathway disruption

Arch Toxicol. 2019 Feb;93(2):227-251. doi: 10.1007/s00204-018-2364-z. Epub 2018 Nov 29.

Abstract

Folate is vital for cell development and growth. It is involved in one-carbon transfer reactions essential for the synthesis of purines and pyrimidines. It also acts in conjunction with cobalamin (vitamin B12) as a fundamental cofactor in the remethylation cycle that converts homocysteine to methionine. A deficiency in folate or vitamin B12 can lead to elevated homocysteine level, which has been identified as an independent risk factor in several health-related conditions. Adequate folate levels are essential in women of childbearing age and in pregnant women, and folate deficiency is associated with several congenital malformations. Low folate levels can be caused by dietary deficiencies, a genetic predisposition or treatment with medicines that affect folate concentration. Women who are pregnant or of child-bearing age commonly use medicines, so it is important to identify the basic biochemical mechanisms by which medicines interfere with the folate-homocysteine-methionine pathway. This review focuses on prescription medicines associated with folate disruption. It also summarizes their undesirable/toxic effects. Recommendations regarding folate supplementation during medical therapy are also reviewed.

Keywords: Anti-folates; Folate antagonism; Folate supplementation; Folate–homocysteine–methionine pathway; Toxicity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Enzyme Inhibitors / adverse effects*
  • Enzyme Inhibitors / therapeutic use
  • Female
  • Folic Acid / metabolism*
  • Folic Acid / pharmacology
  • Folic Acid Antagonists / adverse effects*
  • Folic Acid Deficiency / complications
  • Folic Acid Deficiency / etiology*
  • Homocysteine / metabolism*
  • Humans
  • Methionine / metabolism*
  • Pregnancy
  • Tetrahydrofolate Dehydrogenase / metabolism
  • Thymidylate Synthase / antagonists & inhibitors
  • Vitamin B 12 Deficiency / etiology

Substances

  • Enzyme Inhibitors
  • Folic Acid Antagonists
  • Homocysteine
  • Folic Acid
  • Methionine
  • Tetrahydrofolate Dehydrogenase
  • Thymidylate Synthase