The effect of nitrous oxide-induced inactivation of vitamin B 12 on serine transhydroxymethylase

Abstract

The cobalamin cofactor in methionine synthetase undergoes rapid oxidation in rats breathing N2O. The activity of methionine synthetase falls to very low levels and there is impaired synthesis of folate polyglutamate and impaired methylation of deoxyuridine. The last two effects are overcome by supplying tetrahydrofolate carrying a formate substituent but not by tetrahydrofolate itself. The serine-glycine reaction is a major source of single carbon units. The enzyme concerned, serine transhydroxymethylase was unimpaired in both marrow and liver of rats exposed to N2O and hence single carbon units at the formaldehyde level of oxidation are available to the N2O-treated rat. The failure of formaldehyde carbon (methylene) to substitute for formate in the N2O-treated rat is probably due to depressed cyclohydrolase activity preventing oxidation of methylene to formate.