Eells J T, Makar A B, Noker P E, Tephly T R
J Pharmacol Exp Ther. 1981 Apr;217(1):57-61.
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. Nitrous oxide treatment was used to inhibit 5-methyltetrahydrofolate homocysteine methyltransferase (methionine synthetase, EC 4.2.99.10) in order to delineate the role of this enzyme in regulating the metabolism of formate in rats and in determining the sensitivity of this species to methanol intoxication. Nitrous oxide treatment resulted in a decrease in hepatic levels of nonmethylated tetrahydrofolate forms and an increase in 5-methyltetrahydrofolate. Rats treated with nitrous oxide exhibited a marked decrease in the rate of oxidation of formate to carbon dioxide. The rate of disappearance of formate from the blood in these animals was decreased to half the control rate. Rats treated with nitrous oxide 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 carbon dioxide as well as the importance of this pathway in determining the sensitivity of a species to methanol poisoning.
与甲醇中毒的人类和猴子不同，大鼠在摄入甲醇后不会蓄积甲酸。此外，大鼠不会表现出灵长类动物甲醇中毒特有的代谢性酸中毒和眼毒性。使用一氧化二氮处理来抑制5-甲基四氢叶酸同型半胱氨酸甲基转移酶（甲硫氨酸合成酶，EC 4.2.99.10），以阐明该酶在调节大鼠甲酸代谢以及确定该物种对甲醇中毒敏感性方面的作用。一氧化二氮处理导致肝脏中未甲基化的四氢叶酸形式水平降低，5-甲基四氢叶酸水平升高。用一氧化二氮处理的大鼠甲酸氧化为二氧化碳的速率显著降低。这些动物血液中甲酸的消失速率降至对照速率的一半。用一氧化二氮处理并给予甲醇的大鼠血液中蓄积了甲酸并出现了代谢性酸中毒。这些研究支持了甲硫氨酸合成酶在提供将甲酸叶酸依赖性氧化为二氧化碳所需的四氢叶酸方面起关键作用的概念，以及该途径在确定一个物种对甲醇中毒敏感性方面的重要性。
