METHANOL METABOLISM IN THE RAT

¹ Department of Pharmacology and Toxicology, The University of Wisconsin, Madison, Wisconsin

Rats received labeled methanol and ethanol, and C¹⁴O₂ was collected as a measure of the rates of oxidation of these alcohols under a variety of conditions. It was concluded from these studies that the peroxidative system involving hepatic catalase plays a major role in the oxidation of methanol in the rat and that this system is not primarily responsible for the oxidation of ethanol. These conclusions were based on the following observations:

1. The upper limit of the "apparent in vivo Michaelis constant (K_m)" for C¹⁴-methanol oxidation was found to be 7.0 x 10^-4 mol/l of body water, a lower value than would have been expected if alcohol dehydrogenase were functioning as the major catalyst for methanol oxidation.

2. Ethanol and methanol are known to be equally reactive in the isolated peroxidative system. When equimolar amounts of ethanol and C¹⁴-methanol were given to the rat, the oxidation of methanol was reduced about 50%.

3. Hepatic alcohol dehydrogenase (ADH) is known to react readily with ethanol, but poorly with methanol. Methanol was found to have no effect on the rate of oxidation of 1-C¹⁴-ethanol in vivo, even when the methanol-ethanol molar dose ratio was as high as 8:1.

4. The reactivity of the isolated peroxidative system with 1-butanol is known to be relatively poor. 1-Butanol was found to be a very weak inhibitor of C¹⁴-methanol oxidation in vivo.

5. The affinity of butanol for the isolated ADH system is known to be greater than that of ethanol (K_m = 2 x 10^-3 M; 1-butanol; K_m = 2.2 x 10^-4 M). 1-Butanol was found to be a potent inhibitor of 1-C¹⁴-ethanol oxidation in vivo.

6. The rate of methanol metabolism was reduced about 50% in rats which had received the potent hepatic catalase inhibitor, 3-amino-1,2,4-triazole (AT). AT effected a shift in the "apparent in vivo K_m" for methanol oxidation from 7.0 x 10^-3 mol/l to 5.0 x 10^-2 mol/l, which may indicate a secondary metabolic pathway for methanol oxidation.

7. AT had no effect on 1-C¹⁴-ethanol oxidation.

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