The relationships between vitamin B12 and folic acid and the effect of methionine on folate metabolism

Mol Cell Biochem. 1975 Nov 14;9(2):97-108. doi: 10.1007/BF01732201.


The relationship between vitamin B12 and folate and the effect of methionine on folate metabolism during B12 deficiency in rats is best explained by the prevention of the accumulation of 5-methyl-H4PteGlu by vitamin B12 and/or methionine. Although several points remain to be clarified, the 'methyl trap' hypothesis provides the most satisfactory explanation for the relation between vitamin B12, methionine and folic acid. This concept is extended by the hypothesis that H4PteGlu is the most active substrate for pteroylpolyglutamate synthetase, and thus accounts for the effect of methionine or vitamin B12 increasing liver folate levels.

MeSH terms

  • Animals
  • Biological Transport
  • Diet
  • Folic Acid / blood
  • Folic Acid / metabolism*
  • Folic Acid / pharmacology
  • Formiminoglutamic Acid / metabolism
  • Histidine / metabolism
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Methionine / pharmacology*
  • Perfusion
  • Rats
  • S-Adenosylmethionine / metabolism
  • Vitamin B 12 / pharmacology*
  • Vitamin B 12 Deficiency / metabolism


  • Histidine
  • S-Adenosylmethionine
  • Formiminoglutamic Acid
  • Folic Acid
  • Methionine
  • Vitamin B 12