Inhibition of ethanol metabolism by fructose in alcohol dehydrogenase-deficient deer mice in vivo.
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 H2O2 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 catalase-dependent ethanol metabolism in vivo by inhibiting hepatic H2O2 generation.
Bradford
B U
BU
Department of Pharmacology, University of North Carolina, Chapel Hill 27599-7365.
Handler
J A
JA
Seed
C B
CB
Forman
D T
DT
Thurman
R G
RG
D000227:Adenine Nucleotides / Q000378:metabolism; D000426:Alcohol Dehydrogenase / Q000172:deficiency*; D000818:Animals; D002374:Catalase / Q000378:metabolism; D000431:Ethanol / Q000378:metabolism*; D005632:Fructose / Q000494:pharmacology*; D006016:Glycolates / Q000494:pharmacology; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D000432:Methanol / Q000378:metabolism; D008862:Microsomes, Liver / Q000378:metabolism*; D008954:Models, Biological; D010542:Peromyscus
D000227:Adenine Nucleotides; D006016:Glycolates; D005632:Fructose; D000431:Ethanol; D000426:Alcohol Dehydrogenase; D002374:Catalase; D000432:Methanol