Dehydrogenase-dependent metabolism of alcohols in gastric mucosa of deer mice lacking hepatic alcohol dehydrogenase.
Deer mice (Peromyscus maniculatus) lacking hepatic alcohol dehydrogenase (ADH) have been used as a model for studies of ethanol elimination catalysed by non-ADH systems like catalase and cytochrome P450. However, in an in vivo study on these animals (ADH- deer mice), we detected reversibility in the oxidation of [2H]ethanol, indicating that a major part of the ethanol elimination was due to a dehydrogenase (Norsten et al., J Biol Chem 264: 5593-5597, 1989). In the present investigation, we found significant ethanol oxidizing activity in the gastric mucosa of the deer mice. Reversibility was demonstrated by the use of [2H]acetaldehyde and gas chromatography-mass spectrometry of the products. The kinetic 2H isotope effect of the gastric system was about 3.0 and the system was comparatively insensitive to inhibition by 4-methylpyrazole. The behavior of the deer mice gastric ADH in isoelectric focusing and its higher activity with longer alcohols as substrates indicated similarity with the previously described human class IV enzymes. Our data are in agreement with results obtained in vivo and indicate that ethanol is oxidized extrahepatically in ADH- deer mice. This has to be taken into account when deer mice are used to study non-ADH-dependent ethanol oxidation in vivo.
Department of Physiological Chemistry, Karolinska Institute, Stockholm, Sweden.
G
G
Ekström
T
T
Cronholm
C
C
Norsten-Höög
M
M
Ingelman-Sundberg
D000079:Acetaldehyde / Q000378:metabolism; D000426:Alcohol Dehydrogenase / Q000378:metabolism*; D000445:Aldehyde Oxidoreductases / Q000378:metabolism; D000818:Animals; D003600:Cytosol / Q000201:enzymology; D000431:Ethanol / Q000378:metabolism*; D005753:Gastric Mucosa / Q000201:enzymology*; D007525:Isoelectric Focusing; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D008297:Male; D051379:Mice; D010088:Oxidoreductases / Q000378:metabolism*; D010542:Peromyscus / Q000033:anatomy & histology*; D013270:Stomach / Q000201:enzymology
D000431:Ethanol; D010088:Oxidoreductases; D000426:Alcohol Dehydrogenase; D000445:Aldehyde Oxidoreductases; D000079:Acetaldehyde