Catalase-dependent ethanol metabolism in vivo in deermice lacking alcohol dehydrogenase.
Pathways of ethanol elimination in alcohol dehydrogenase (ADH)-positive and -negative deermice were studied using the catalase inhibitor, 3-amino-1,2,4-triazole. To verify that aminotriazole inhibited catalase effectively, the characteristic decrease in catalase-H2O2 which occurs in saline-treated controls when ethanol is peroxidized was monitored at 660-640 nm in perfused deermouse livers. Following 1.5 hr of pretreatment with aminotriazole (1.5 g/kg), the peroxidatic activity of catalase measured in vitro was inhibited by greater than 99%. Under these conditions, ethanol did not decrease catalase-H2O2 in perfused livers, indicating that catalase was inhibited. Ethanol and aniline oxidation by microsomes were also inhibited by about 67-90% after 1.5 hr of pretreatment with aminotriazole. In ADH-positive deermice, pretreatment with aminotriazole for 1.5 hr prior to injection of ethanol (2.0 g/kg) decreased rates of ethanol elimination in vivo from 13.2 +/- 0.8 to 10.2 +/- 0.4 mmoles/kg/hr. In ADH-negative deermice, similar treatment decreased rates of ethanol elimination in vivo from 4.5 +/- 0.4 to 1.1 +/- 0.6 mmoles/kg/hr. Following pretreatment with aminotriazole (1.0 g/kg) for 6 hr, rates of ethanol elimination in ADH-negative deermice returned to near basal values. Under these conditions, the peroxidatic activity of catalase measured in vitro and the ethanol-dependent decrease in catalase-H2O2 in perfused livers also returned to near basal levels; however, the oxidation of ethanol by cytochrome P-450 was inhibited completely. It is concluded, therefore, that time of pretreatment with aminotriazole is an important variable which must be controlled carefully to inhibit catalase completely. Since catalase was active while cytochrome P-450 was not following 6 hr of pretreatment with aminotriazole, it is concluded that ethanol elimination occurs predominantly via catalase-H2O2 in ADH-negative deermice under these conditions.
D000426:Alcohol Dehydrogenase / Q000172:deficiency* / Q000378:metabolism; D000640:Amitrole / Q000494:pharmacology; D000814:Aniline Compounds / Q000378:metabolism; D000818:Animals; D002374:Catalase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000431:Ethanol / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000378:metabolism; D008099:Liver / Q000201:enzymology*; D008862:Microsomes, Liver / Q000201:enzymology; D010084:Oxidation-Reduction; D010542:Peromyscus
D000814:Aniline Compounds; D000431:Ethanol; D006861:Hydrogen Peroxide; D000426:Alcohol Dehydrogenase; D002374:Catalase; C023650:aniline; D000640:Amitrole