Inhibition of ethanol metabolism by fructose in alcohol dehydrogenase-deficient deer mice in vivo

Abstract

The purpose of this work was to compare the roles of a newly described mitochondrial dehydrogenase and catalase in ethanol elimination in deer mice deficient in alcohol dehydrogenase (ADH −). Fructose was used because of its well-known ability to stimulate dehydrogenase-dependent ethanol metabolism. Rates of ethanol metabolism in vivo were decreased significantly by about 60% in a dose-dependent manner by fructose in deer mice fed an ethanol-containing or a corn oil control diet. In addition, rates of metabolism of methanol, a selective substrate for catalase in rodents, were similar to rates of ethanol elimination and were decreased from 6.9 ± 1.0 to 1.7 ± 0.5 mmol/kg/h by fructose, supporting the hypothesis that catalase and not a mitochondrial dehydrogenase predominates in ethanol oxidation in ADH − deer mice. Glycolate, a substrate for peroxisomal H 2O 2 generation, reversed the inhibition of alcohol metabolism by fructose completely, indicating that fructose did not inhibit catalase directly. As expected, the ATP ADP ratio was decreased by fructose significantly from 4.2 ± 0.4 to 2.4 ± 0.4 in deer mouse livers. These data are consistent with the hypothesis that fructose decreases catalasedependent ethanol metabolism in vivo by inhibiting hepatic H 2O 2 generation.