Role of hepatic tetrahydrofolate in the species difference in methanol toxicity.
- 1 June 1985
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 82 (11), 3854-3858
- https://doi.org/10.1073/pnas.82.11.3854
Abstract
The susceptibility of various species to methanol toxicity is inversely related to the rate of tetrahydrofolate (H4folate)-dependent formate oxidation to carbon dioxide. Thus, the levels of various folate derivatives and folate-dependent enzyme activities present in the livers of monkeys, which are sensitive to methanol, and rats, which are not, were compared in order to investigate the biochemical basis of this species difference. Hepatic H4folate levels in monkeys were 60% of those in rats, and formylated-H4folate derivatives were 2-fold higher in monkeys than in rats. No significant difference between monkeys and rats in the levels of total hepatic folate or 5-methyl-H4folate was observed. The activities of formyl-H4folate synthetase (EC 6.3.4.3) and formyl-H4folate dehydrogenase (EC 1.5.1.6) were 4- and 2-fold higher, respectively, in monkeys than in rats. There was no significant difference between monkeys and rats in methionine synthetase activity (EC 2.1.1.13). Dihydrofolate reductase activity (EC 1.5.1.3) in monkeys was 20% of that in rats. 5,10-Methylene-H4folate reductase (NADPH) activity (EC 1.1.1.171) in monkeys was 40% and 25% of that in rats when the rates of the forward and reverse reactions, respectively, were compared. Serine hydroxymethyltransferase activity (EC 2.1.2.1) was 2-fold higher in monkeys than in rats. The differences in the activities of methylene-H4folate reductase and serine hydroxymethyl-transferase between monkeys and rats may have contributed to the difference in hepatic H4folate levels. The 40% lower level of hepatic H4folate in monkeys, as compared to rats, relates well to the 50% lower maximal rate of formate oxidation in monkeys. Thus, the species difference in susceptibility to methanol may be explained by the difference in the level of hepatic H4folate.Keywords
This publication has 33 references indexed in Scilit:
- Species Differences in Methanol PoisoningCRC Critical Reviews in Toxicology, 1982
- Folate Distribution in Cultured Human CellsJCI Insight, 1979
- Lack of a role for formaldehyde in methanol poisoning in the monkeyBiochemical Pharmacology, 1979
- Methanol poisoning: Ocular toxicity produced by formateToxicology and Applied Pharmacology, 1978
- Experimental methanol toxicity in the primate: Analysis of metabolic acidosisToxicology and Applied Pharmacology, 1975
- Metabolism of formate in the ratJournal of Toxicology and Environmental Health, 1975
- Methanol poisoning I. The role of formic acid in the development of metabolic acidosis in the monkey and the reversal by 4-methylpyrazoleBiochemical Medicine, 1975
- Mammalian methylenetetrahydrofolate reductase Partial purification, properties, and inhibition by S-adenosylmethionineBiochimica et Biophysica Acta (BBA) - Enzymology, 1971
- Studies on serine hydroxymethylase isoenzymes from rat liverBiochimica et Biophysica Acta (BBA) - Enzymology, 1968
- Partial purification of a 10-formyl-tetrahydrofolate: NADP oxidoreductase from mammalian liverBiochemical and Biophysical Research Communications, 1968