Role of hepatic tetrahydrofolate in the species difference in methanol toxicity. Proc Natl Acad Sci U S A 1985 Jun;82(11):3854-8
Date
06/01/1985Pubmed ID
3923481Pubmed Central ID
PMC397886DOI
10.1073/pnas.82.11.3854Scopus ID
2-s2.0-0013570453 (requires institutional sign-in at Scopus site) 64 CitationsAbstract
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.
Author List
Black KA, Eells JT, Noker PE, Hawtrey CA, Tephly TRAuthor
Janis Eells PhD Professor in the Biomedical Sciences department at University of Wisconsin - MilwaukeeMESH terms used to index this publication - Major topics in bold
AnimalsCarbon Dioxide
Chromatography, High Pressure Liquid
Liver
Macaca fascicularis
Methanol
Rats
Rats, Inbred Strains
Species Specificity
Tetrahydrofolates
