Tephly T R
Department of Pharmacology, University of Iowa, Iowa City 52242.
Life Sci. 1991;48(11):1031-41. doi: 10.1016/0024-3205(91)90504-5.
Methanol toxicity in humans and monkeys is characterized by a latent period of many hours followed by a metabolic acidosis and ocular toxicity. This is not observed in most lower animals. The metabolic acidosis and blindness is apparently due to formic acid accumulation in humans and monkeys, a feature not seen in lower animals. The accumulation of formate is due to a deficiency in formate metabolism which is, in turn, related, in part, to low hepatic tetrahydrofolate (H4 folate). An excellent correlation between hepatic H4 folate and formate oxidation rates has been shown within and across species. Thus, humans and monkeys possess low hepatic H4 folate levels, low rates of formate oxidation and accumulation of formate after methanol. Formate, itself, produces blindness in monkeys in the absence of metabolic acidosis. In addition to low hepatic H4 folate concentrations, monkeys and humans also have low hepatic 10-formyl H4 folate dehydrogenase levels, the enzyme which is the ultimate catalyst for conversion of formate to carbon dioxide. This review presents the basis for the role of folic acid-dependent reactions in the regulation of methanol toxicity.
人类和猴子的甲醇中毒表现为长达数小时的潜伏期，随后出现代谢性酸中毒和眼部毒性。大多数低等动物并未观察到这种情况。代谢性酸中毒和失明显然是由于人类和猴子体内甲酸积累所致，而这一特征在低等动物中未见。甲酸积累是由于甲酸代谢缺陷，而这又部分与肝脏中低水平的四氢叶酸（H4叶酸）有关。已表明在物种内部和不同物种之间，肝脏H4叶酸与甲酸氧化速率之间存在良好的相关性。因此，人类和猴子肝脏中的H4叶酸水平较低，甲酸氧化速率较低，摄入甲醇后会出现甲酸积累。在没有代谢性酸中毒的情况下，甲酸本身会导致猴子失明。除了肝脏中H4叶酸浓度较低外，猴子和人类肝脏中的10-甲酰基H4叶酸脱氢酶水平也较低，该酶是将甲酸转化为二氧化碳的最终催化剂。本综述阐述了叶酸依赖性反应在甲醇毒性调节中作用的基础。
