title: The toxicity of methanol.
abstract: 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.
authors.affiliation: Department of Pharmacology, University of Iowa, Iowa City 52242.
authors.forename: T R
authors.initials: TR
authors.lastname: Tephly
mesh_terms: D000818:Animals; D005557:Formaldehyde / Q000378:metabolism; D005561:Formates / Q000378:metabolism / Q000633:toxicity; D006801:Humans; D000432:Methanol / Q000378:metabolism / Q000633:toxicity*; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000378:metabolism; D011323:Primates / Q000502:physiology; D014018:Tissue Distribution; D014785:Vision, Ocular / Q000187:drug effects; D000099295:Formyltetrahydrofolate Dehydrogenase
chemical_list: D005557:Formaldehyde; D005561:Formates; D000432:Methanol; D000587:Oxidoreductases Acting on CH-NH Group Donors; D000099295:Formyltetrahydrofolate Dehydrogenase; C030544:formic acid