Abstract
Ethanol metabolism by gastric alcohol dehydrogenase (ADH) is thought to be an important determinant of peripheral ethanol time-concentration curves (AUCs) in rats and humans. We quantitated this metabolism in rats by measuring the gastric absorption of oral ethanol (0.25 g/kg) and the gastric venous-arterial (V-A) difference of ethanol versus ethanol metabolites (acetate, acetaldehyde, and bicarbonate). Over 1 h, approximately 20% of the ethanol was absorbed from the stomach and 70% was emptied into the duodenum. The gastric V-A difference of ethanol metabolites was less than 4% of that of ethanol. Thus, gastric metabolism accounted for less than 1% (less than 4% of 20% absorbed) of the dose. This negligible metabolism was predictable from the low affinity of gastric ADH for ethanol. In contrast, gastric ADH has a high affinity for octanol, and 66% of this compound was metabolized during gastric absorption. Evidence supporting gastric metabolism of ethanol largely derives from the lower AUCs observed after oral than after intravenous administration; however, we observed increasingly higher AUCs with increasingly rapid portal vein infusions of identical ethanol doses. We conclude that gastric metabolism of ethanol is negligible in the rat, and differences in AUCs ascribed to gastric metabolism may reflect differences in ethanol absorption.
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Selected References
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- Caballeria J., Baraona E., Lieber C. S. The contribution of the stomach to ethanol oxidation in the rat. Life Sci. 1987 Aug 24;41(8):1021–1027. doi: 10.1016/0024-3205(87)90691-6. [DOI] [PubMed] [Google Scholar]
- Caballeria J., Baraona E., Rodamilans M., Lieber C. S. Effects of cimetidine on gastric alcohol dehydrogenase activity and blood ethanol levels. Gastroenterology. 1989 Feb;96(2 Pt 1):388–392. doi: 10.1016/0016-5085(89)91562-x. [DOI] [PubMed] [Google Scholar]
- Caballeria J., Frezza M., Hernández-Muñoz R., DiPadova C., Korsten M. A., Baraona E., Lieber C. S. Gastric origin of the first-pass metabolism of ethanol in humans: effect of gastrectomy. Gastroenterology. 1989 Nov;97(5):1205–1209. doi: 10.1016/0016-5085(89)91691-0. [DOI] [PubMed] [Google Scholar]
- Carter E. A., Isselbacher K. J. The metabolism of ethanol to carbon dioxide by stomach and small intestinal slices. Proc Soc Exp Biol Med. 1971 Dec;138(3):817–819. doi: 10.3181/00379727-138-35997. [DOI] [PubMed] [Google Scholar]
- Cederbaum A. I., Pietrusko R., Hempel J., Becker F. F., Rubin E. Characterization of a nonhepatic alcohol dehydrogenase from rat hepatocellular carcinoma and stomach. Arch Biochem Biophys. 1975 Nov;171(1):348–360. doi: 10.1016/0003-9861(75)90042-9. [DOI] [PubMed] [Google Scholar]
- Coldwell B. B., Solomonraj G., Trenholm H. L., Wiberg G. S. The gas chromatographic estimation of ethanol, acetaldehyde, and acetone in ethanol metabolism studies. Clin Toxicol. 1971 Mar;4(1):99–113. doi: 10.3109/15563657108990152. [DOI] [PubMed] [Google Scholar]
- Cooke A. R., Birchall A. Absorption of ethanol from the stomach. Gastroenterology. 1969 Sep;57(3):269–272. [PubMed] [Google Scholar]
- DeMaster E. G., Shirota F. N., Nagasawa H. T. Role of propiolaldehyde and other metabolites in the pargyline inhibition of rat liver aldehyde dehydrogenase. Biochem Pharmacol. 1986 May 1;35(9):1481–1489. doi: 10.1016/0006-2952(86)90113-9. [DOI] [PubMed] [Google Scholar]
- DiPadova C., Worner T. M., Julkunen R. J., Lieber C. S. Effects of fasting and chronic alcohol consumption on the first-pass metabolism of ethanol. Gastroenterology. 1987 May;92(5 Pt 1):1169–1173. doi: 10.1016/s0016-5085(87)91073-0. [DOI] [PubMed] [Google Scholar]
- Duane W. C., Levitt M. D., Staley N. A., McHale A. P., Wiegand D. M., Fetzer C. A. Role of the unstirred layer in protecting the murine gastric mucosa from bile salt. Gastroenterology. 1986 Oct;91(4):913–918. doi: 10.1016/0016-5085(86)90694-3. [DOI] [PubMed] [Google Scholar]
- Frezza M., di Padova C., Pozzato G., Terpin M., Baraona E., Lieber C. S. High blood alcohol levels in women. The role of decreased gastric alcohol dehydrogenase activity and first-pass metabolism. N Engl J Med. 1990 Jan 11;322(2):95–99. doi: 10.1056/NEJM199001113220205. [DOI] [PubMed] [Google Scholar]
- Giles H. G., Meggiorini S., Vidins E. I. Semiautomated analysis of ethanol and acetate in human plasma by head space gas chromatography. Can J Physiol Pharmacol. 1986 Jun;64(6):717–719. doi: 10.1139/y86-120. [DOI] [PubMed] [Google Scholar]
- Hempel J. D., Pietruszko R. Human stomach alcohol dehydrogenase: isoenzyme composition and catalytic properties. Alcohol Clin Exp Res. 1979 Apr;3(2):95–98. doi: 10.1111/j.1530-0277.1979.tb05280.x. [DOI] [PubMed] [Google Scholar]
- Hernández-Muñoz R., Caballeria J., Baraona E., Uppal R., Greenstein R., Lieber C. S. Human gastric alcohol dehydrogenase: its inhibition by H2-receptor antagonists, and its effect on the bioavailability of ethanol. Alcohol Clin Exp Res. 1990 Dec;14(6):946–950. doi: 10.1111/j.1530-0277.1990.tb01843.x. [DOI] [PubMed] [Google Scholar]
- Julià P., Boleda M. D., Parés X. Kinetic properties and physiological significance of the ADH-1 isoenzyme of rat stomach alcohol dehydrogenase. Prog Clin Biol Res. 1987;232:189–201. [PubMed] [Google Scholar]
- Julià P., Farrés J., Parés X. Characterization of three isoenzymes of rat alcohol dehydrogenase. Tissue distribution and physical and enzymatic properties. Eur J Biochem. 1987 Jan 2;162(1):179–189. doi: 10.1111/j.1432-1033.1987.tb10559.x. [DOI] [PubMed] [Google Scholar]
- Julkunen R. J., Di Padova C., Lieber C. S. First pass metabolism of ethanol--a gastrointestinal barrier against the systemic toxicity of ethanol. Life Sci. 1985 Aug 12;37(6):567–573. doi: 10.1016/0024-3205(85)90470-9. [DOI] [PubMed] [Google Scholar]
- Julkunen R. J., Tannenbaum L., Baraona E., Lieber C. S. First pass metabolism of ethanol: an important determinant of blood levels after alcohol consumption. Alcohol. 1985 May-Jun;2(3):437–441. doi: 10.1016/0741-8329(85)90111-9. [DOI] [PubMed] [Google Scholar]
- Lamboeuf Y., de Saint Blanquat G., Derache R. Mucosal alcohol dehydrogenase- and aldehyde dehydrogenase-mediated ethanol oxidation in the digestive tract of the rat. Biochem Pharmacol. 1981 Mar 1;30(5):542–545. doi: 10.1016/0006-2952(81)90643-2. [DOI] [PubMed] [Google Scholar]
- Lamboeuf Y., la Droitte P., de Saint-Blanquat G. The gastro-intestinal metabolism of ethanol in the rat. Effect of chronic alcoholic intoxication. Arch Int Pharmacodyn Ther. 1983 Jan;261(1):157–169. [PubMed] [Google Scholar]
- Pestalozzi D. M., Bühler R., von Wartburg J. P., Hess M. Immunohistochemical localization of alcohol dehydrogenase in the human gastrointestinal tract. Gastroenterology. 1983 Nov;85(5):1011–1016. [PubMed] [Google Scholar]
- Roine R., Gentry R. T., Hernández-Munõz R., Baraona E., Lieber C. S. Aspirin increases blood alcohol concentrations in humans after ingestion of ethanol. JAMA. 1990 Nov 14;264(18):2406–2408. [PubMed] [Google Scholar]
- Suokas A., Forsander O., Lindros K. Distribution and utilization of alcohol-derived acetate in the rat. J Stud Alcohol. 1984 Sep;45(5):381–385. doi: 10.15288/jsa.1984.45.381. [DOI] [PubMed] [Google Scholar]
