Role of extrahepatic alcohol dehydrogenase in rat ethanol metabolism

Abstract

Rat alcohol dehydrogenase exhibits three isoenzymes with very different capacities of ethanol oxidation and with characteristic distribution in tissues. ADH-1 (class II isoenzyme, K m = 5 M) is especially concentrated in the most external organs: auditive, bucal, and nasal mucoses, cornea, esophagus, stomach, rectum, penis, and vagina. ADH-2 (class III isoenzyme) is present in all organs but has a poor activity with ethanol. ADH-3 (class I isoenzyme, K m = 1.4 M) is the main liver isoenzyme, also present in lung, intestine, kidney, and sexual organs. At 33 m m ethanol and pH 7.5, total hepatic activity (3.5 ± 0.6 units) represents 90% of the whole activity in the male rat, while the remaining 10% is distributed in many organs. The skin is the extrahepatic organ with the highest total activity (88 ± 15 mU) followed by testis and small intestine. ADH-3 accounts for 96% of total activity (90% hepatic and 6% extrahepatic) and ADH-1 contributes with 4% (extrahepatic). However, in conditions that may be found in the digestive tract mucose after ethanol ingestion (pH 7.5,1 m ethanol), stomach and small intestine activities represent 10% of the liver activity at 33 m m ethanol. Therefore, oral administration of ethanol will result in a higher contribution of the extrahepatic activity than will intravenous or intraperitoneal administration, because of the great ADH-1 content of the digestive tract. On the other hand, pyrazole inhibition constants at pH 7.5 for ADH-1 (33 m m) and ADH-3 (4.2 μ m) are much higher than those at pH 10.0 (0.56 m m and 0.4 μ m) and indicate that at the usual concentration of inhibitor only ADH-3 activity will be effectively suppressed. ADH-1 will be, therefore, responsible in part for the residual ethanol oxidation activity in pyrazole-treated rats.