Molecular Pharmacology, Vol 11, 841-849, Copyright © 1975 by the American Society for Pharmacology and Experimental Therapeutics

Hepatic Microsomal Alcohol-Oxidizing System in Normal and Acatalasemic Mice: Its Dissociation from the Peroxidatic Activity of Catalase-H₂O₂

¹ Section of Liver Disease and Nutrition, Veterans Administration Hospital, Bronx, New York 10468, and Department of Medicine, Mount Sinai School of Medicine of the City University of New York, New York, New York 10029

To assess whether catalase-H₂O₂ is an obligatory component in the microsomal alcoholoxidizing system, various primary alcohols were incubated with hepatic microsomes of both normal and acatalasemic mice in the presence of an NADPH-genenating system. Methanol, ethanol, propanol, butanol, and pentanol were metabolized at striking rates by microsomes of both strains. By contrast, when the NADPH-generating system was replaced by a H₂O₂-producing one, propanol, butanol, and pentanol were not metabolized, indicating that these higher aliphatic alcohols are not substrates for catalase-H₂O₂. Furthermore, mild heat treatment of microsomes of acatalasemic mice resulted in inactivation of contaminating catalase and virtually abolished alcohol peroxidation of methanol and ethanol by catalase-H₂O₂, whereas the rates of the NADPH-mediated alcohol oxidation by the microsomal fraction persisted with methanol, ethanol, propanol, butanol, and pentanol as substrates. In addition, the microsomal alcohol-oxidizing system of both normal and acatalasemic mice was solubilized and isolated from catalase by DEAE-cellulose column chromatography. These findings therefore dissociate the NADPH-dependent microsomal alcohol-oxidizing system from alcohol peroxidation via catalase-H₂O₂ by difference in substrate specificity and rule out an obligatory involvement of catalase-H₂O₂ in the microsomal system.

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ACKNOWLEDGMENTS The authors thank Miss L. M. DeCarli and Miss N. Lowe for their excellent technical assistance and valuable discussions throughout this study.