DEHYDROGENASE-DEPENDENT METABOLISM OF ALCOHOLS IN GASTRIC-MUCOSA OF DEER MICE LACKING HEPATIC ALCOHOL-DEHYDROGENASE

Deer mice (Peromyscus maniculatus) lacking hepatic alcohol dehydrogena se (ADH) have been used as a model for studies of ethanol elimination catalysed by non-ADH systems like catalase and cytochrome P450. Howeve r, in an in vivo study on these animals (ADH deer mice), we detected r eversibility in the oxidation of [H-2]ethanol, indicating that a major part of the ethanol elimination was due to a dehydrogenase (Norsten e t al., J Biol Chem 264: 5593-5597, 1989). In the present investigation , we found significant ethanol oxidizing activity in the gastric mucos a of the deer mice. Reversibility was demonstrated by the use of [H-2] acetaldehyde and gas chromatography-mass spectrometry of the products. The kinetic H-2 isotope effect of the gastric system was about 3.0 an d the system was comparatively insensitive to inhibition by 4-methylpy razole. The behavior of the deer mice gastric ADH in isoelectric focus ing and its higher activity with longer alcohols as substrates indicat ed similarity with the previously described human class IV enzymes. Ou r data are in agreement with results obtained in vivo and Indicate tha t ethanol is oxidized extrahepatically in ADH- deer mice. This has to be taken into account when deer mice are used to study non-ADH-depende nt ethanol oxidation in vivo.