METHANOL POISONING AND FORMATE OXIDATION IN NITROUS OXIDE-TREATED RATS

  • 1 January 1981
    • journal article
    • research article
    • Vol. 217  (1) , 57-61
Abstract
Formic acid does not accumulate in the rat after the administration of methanol as it does in methanol-poisoned humans and monkeys. In addition, rats do not manifest the metabolic acidosis and ocular toxicity characteristic of methanol intoxication in primates. N2O treatment was used to inhibit 5-methyltetrahydrofolate homocysteine methyltransferase (methionine synthetase, EC 4.2.99.10) to delineate the role of this enzyme in regulating formate metabolism in rats and in determining the sensitivity of this species to methanol intoxication. N2O treatment resulted in a decrease in hepatic levels of nonmethylated tetrahydrofolate forms and an increase in 5-methyltetrahydrofolate. Rats treated with N2O exhibited a marked decrease in the rate of oxidation of formate to CO2. The rate of disappearance of formate from the blood in these animals was decreased to half the control rate. Rats treated with N2O and administered methanol accumulated formate in blood and developed metabolic acidosis. These studies support the concept of a key role of methionine synthetase in supplying the tetrahydrofolate required for the folate-dependent oxidation of formate to CO2, as well as the importance of this pathway in determining the sensitivity of a species to methanol poisoning.

This publication has 8 references indexed in Scilit: