Vitamin B12 regulates folate metabolism by the supply of formate

Nitrous oxide (N2O) inactivates the B12 coenzyme involved in methionine synthesis and interrupts formation of the folate coenzyme (folate polyglutamate). Normal synthesis of folate polyglutamate is restored in the N2O-treated rat when folate carrying a single carbon unit is supplied at the formate level of oxidation. The activity of the enzyme, formyl synthetase, which links formate to tetrahydrofolate, is increased after exposure to nitrous oxide. Formate is normally derived from the oxidation of methyl groups, methionine being an important source. It is suggested that failure of methionine synthesis leads to a paucity of formate and in turn to inadequate formylation of tetrahydrofolate. Formyltetrahydrofolate is the required substrate for the synthesis of folate polyglutamate, and impairment of this step in turn compromises general folate metabolism.