METHANOL METABOLISM IN THE ISOLATED PERFUSED RAT LIVER

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

Studies employing isolated, perfused rat livers agree with previous findings using the intact rat that a catalase-peroxide system plays an important role in the oxidation of methanol in the rat and that this system is not primarily responsible for the oxidation of ethanol in this species. These conclusions were based on experiments that 1) took advantage of the known differential rates of oxidation of methanol, ethanol and 1-butanol by the peroxidative and the alcohol dehydrogenase systems, 2) employed 3-amino-1,2,4-triazole to depress hepatic catalase activity, and 3) used the rates of oxidation of methanol at different concentrations in the perfusion fluid to obtain an " apparent Michaelis constant."

The rate at which 1-C¹⁴-ethanol is metabolized to C¹⁴O₂ by the isolated perfused liver was found to be limited by the rate at which acetate is oxidized. This finding supports the view that the liver is incapable of oxidizing all of the acetate resulting from a high intake of alcohol and that extrahepatic tissues assume much of this function.

In general, values obtained for the metabolism of methanol in the isolated perfused liver agreed well with extrapolated values for the liver in situ