Molecular Pharmacology, Vol 4, 471-483, Copyright © 1968 by the American Society for Pharmacology and Experimental Therapeutics

Methanol Metabolism in the Monkey

¹ Department of Pharmacology, University of Minnesota, Minneapolis, Minnesota 66455

The peroxidative system involving hepatic catalase plays a major role in the oxidation of methanol in the rat (1), but in the monkey the peroxidative mechanism does not appear to be important. This conclusion is based on the following observations: (a) ethanol and methanol were about equally reactive with the peroxidative system, but ethanol was much more reactive with the alcohol dehydrogenase system than methanol. Ethanol was a much more effective inhibitor of methanol oxidation in the intact monkey than it was in the rat, which is what would be expected if methanol is oxidized by the alcohol dehydrogenase system in the monkey, but by the peroxidative system in the rat. (b) By similar reasoning, 1-butanol was a stronger inhibitor of methanol oxidation in the monkey than it should have been if the peroxidative system was involved. (c) 3-Amino-1,2,4-triazole, a potent inhibitor of hepatic catalase, greatly reduced methanol oxidation in the rat, but had no measurable effect on methanol oxidation in the monkey. (d) Ethylene glycol stimulated the rate of methanol oxidation in the rat, probably as a result of an increased H₂O₂ production that occurs when glycolic acid, a metabolite of ethylene glycol, is oxidized to glyoxylic acid (6,7); no such stimulation was seen in the monkey. Studies in vitro which measured the methanol-oxidizing activity of hepatic alcohol dehydrogenase isolated from monkeys also support the view that this enzyme is largely responsible for methanol oxidation in this species.

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ACKNOWLEDGMENTS This research was supported by United States Public Health Service Grant GM-10930. Part of this material appeared in abstract form [Pharmacologist 5, 236 (1963)] and in a thesis by A. B. Makar in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Department of Pharmacology, University of Minnesota, 1966. The authors grate-fully acknowledge the able technical assistance of Mr. Roger Cleve.

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