THE ROLE OF GASTROINTESTINAL FACTORS IN ALCOHOL METABOLISM

Although the lives is the major organ responsible for ethanol metaboli sm, such metabolism also occurs in the gastrointestinal (GI) tract. Ho wever, compared to the liver, GI metabolism of ethanol is quantitative ly much lower. Various enzyme systems have been characterized in GI mu cosal cells including various isozymes of alcohol dehydrogenase (ADH), cytochrome P450 2E1 (CYP 2E1) and catalase. Gastric ADH activity is o ne factor by which first pass metabolism (FPM) is influenced and its a ctivity is modulated by genetics, gender, age, drugs and gastric morph ology. Another important factor in FPM of ethanol is the speed of gast ric emptying. In addition to mucosal ethanol metabolism, ethanol can a lso be oxidized by many bacterial species in the upper GI tract includ ing oropharynx and stomach as well as in the large intestine. GI metab olism of ethanol may influence systemic bioavailability of ethanol and may lead to local toxicity most likely mediated by acetaldehyde. Such toxicity could be of importance in ethanol-associated carcinogenesis.