The effect of vitamin B12 inhibition in vivo: impaired folate polyglutamate biosynthesis indicating that 5-methyltetrahydropteroylglutamate is not its usual substrate

Using 5-[14C] methyltetrahydropteroylglutamate and [3H] pteroylglutamate it was found that vitamin B12 dependent methyltransferase can be inhibited in vivo in mice by nitrous oxide. Examination of the liver [3H] folates showed as expected that both controls and nitrous oxide treated mice had synthesised the reduced 5-methyl form. However, the controls had converted [3H] almost exclusively into a polyglutamate with virtually no monoglutamate present, while nitrous oxide treated mice had failed to add glutamates to over half of the incorporated folate. Thus in vivo demethylation may be necessary prior to polyglutamate biosynthesis and act as a method of controlling folate accumulation, or be used to create a concentration gradient with the circulating folate.