Journal article
Studies on the role of folic acid and folate-dependent enzymes in human methanol poisoning
Molecular pharmacology, Vol.31(5), pp.557-561
1987
DOI: 10.1016/S0026-895X(25)10468-9
PMID: 3574297
Abstract
Methanol toxicity is observed in monkeys and humans but is not seen in rats or mice. The expression of methanol poisoning is related to the ability of an animal to metabolize formate to carbon dioxide. Since the rate of formate oxidation is related to hepatic tetrahydrofolate (H4folate) content and the activities of folate-dependent enzymes, studies were designed to determine hepatic concentrations of H4folate and activities of folate-dependent enzymes of human liver and livers of species considered insensitive to methanol poisoning. An excellent correlation between hepatic H4folate and maximal rates of formate oxidation has been observed. In human liver, H4folate levels were only 50% of those observed for rat liver and similar to those found in monkey liver. Total folate was also lower (60% decreased) in human liver than that found in rat or monkey liver. Interestingly, mouse liver contains much higher hepatic H4folate and total folate than rat or monkey liver. This is consistent with higher formate oxidation rates in this species. A second important observation has been made. 10-Formyltetrahydrofolate dehydrogenase activity, the enzyme catalyzing the final step of formate oxidation to carbon dioxide, was markedly reduced in both monkey and human liver. Thus, two mechanisms may be operative in explaining low formate oxidation in species susceptible to methanol toxicity, low hepatic H4folate levels and reduced hepatic 10-formyltetrahydrofolate dehydrogenase activity.
Details
- Title: Subtitle
- Studies on the role of folic acid and folate-dependent enzymes in human methanol poisoning
- Creators
- Frederick C Johlin - Univ. Iowa, dep. internal medicine, Iowa City IA 52242, United StatesCarrie S Fortman - Univ. Iowa, dep. internal medicine, Iowa City IA 52242, United StatesDai D Nigheim - Univ. Iowa, dep. internal medicine, Iowa City IA 52242, United StatesThomas R Tephly - Univ. Iowa, dep. internal medicine, Iowa City IA 52242, United States
- Resource Type
- Journal article
- Publication Details
- Molecular pharmacology, Vol.31(5), pp.557-561
- Publisher
- American Society for Pharmacology and Experimental Therapeutics
- DOI
- 10.1016/S0026-895X(25)10468-9
- PMID
- 3574297
- ISSN
- 0026-895X
- eISSN
- 1521-0111
- Language
- English
- Date published
- 1987
- Academic Unit
- Gastroenterology and Hepatology; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9984094706502771
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