TY - JOUR T1 - THE ROLE OF HYDROGEN PEROXIDE AND CATALASE IN HEPATIC MICROSOMAL ETHANOL OXIDATION JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 441 LP - 448 VL - 1 IS - 1 AU - RONALD G. THURMAN AU - ROLAND SCHOLZ Y1 - 1973/01/01 UR - http://dmd.aspetjournals.org/content/1/1/441.abstract N2 - The basic evidence upon which a unique microsomal ethanol-oxidizing system was postulated was the following: a) requirements for NADPH and oxygen; b) partial inhibition by carbon monoxide; c) induction by chronic ethanol pretreatment; and d) different sensitivities of MEOS and catalase to inhibitors (table 5). On the other hand, the requirement for NADPH and oxygen and partial sensitivity to CO are also properties of microsomal hydrogen peroxide formation from NADPH, which is also induced by chronic ethanol pretreatment.5 Moreover, several investigators have failed to differentiate a unique MEOS from catalase based on inhibitor studies [fig. 3; table 2 (6, 216; table 5]. In addition, the inhibition of microsomal ethanol oxidation by formate, azide, and H2O2 utilizing systems and its stimulation by menadione are consistent with a peroxidatic process catalyzed by contaminating catalase which utilizes hydrogen peroxide formed from NADPH. Lastly, an active reconstituted mixed function oxidation system free of catalase activity failed to oxidize ethanol (table 3). Thus, it is our conclusion that the microsomal ethanol-oxidizing system is due to generation of hydrogen peroxide by microsomal components (e.g., NADPH oxidase, cytochrome P-450) and NADPH (fig. 8). Hydrogen peroxide in turn acts with contaminating catalase to convert ethanol into acetaldehyde. As can be seen from a careful examination of table 5, the postulation of a unique MEOS in addition to the peroxidatic reaction of catalase is superfluous. Copyright © 1973 by The American Society for Pharmacology and Experimental Therapeutics ER -