Tetrahydrofolate, Vitamin B12, and S-Adenosylmethionine

• One-carbon groups at lower oxidation states than carbon dioxide (which is carried by biotin) are transferred by reactions involving tetrahydrofolate, vitamin B₁₂, and S-adenosyl methionine.
• Tetrahydrofolate is produced from the vitamin folate and obtains one-carbon units from serine, glycine, histidine, formaldehyde, and formic acid.
• The carbon attached to tetrahydrofolate can be oxidized or reduced, thus producing a number of different forms of tetrahydrofolate. However, once a carbon has been reduced to the methyl level, it cannot be reoxidized.
• The carbons attached to tetrahydrofolate are known collectively as the one-carbon pool.
• The carbons carried by folate are used in a limited number of biochemical reactions but are very important in forming deoxythymidine monophosphate and the purine rings.
• Vitamin B₁₂ participates in two reactions in the body: conversion of L-methylmalonyl coenzyme A to succinyl coenzyme A and the conversion of homocysteine to methionine.
• S-adenosyl methionine, formed from adenosine triphosphate and methionine, transfers the methyl group to precursors forming a variety of methylated compounds.
• Both vitamin B₁₂ and methyl tetrahydrofolate are required in methionine metabolism; a deficiency of vitamin B₁₂ leads to overproduction and trapping of folate in the methyl form, leading to a functional folate deficiency. Such deficiencies can lead to
  • Megaloblastic anemia
  • Neural tube defects in newborn