Skip to main content
Gut logoLink to Gut
. 1993 Oct;34(10):1433–1437. doi: 10.1136/gut.34.10.1433

Human gastric alcohol dehydrogenase activity: effect of age, sex, and alcoholism.

H K Seitz 1, G Egerer 1, U A Simanowski 1, R Waldherr 1, R Eckey 1, D P Agarwal 1, H W Goedde 1, J P von Wartburg 1
PMCID: PMC1374557  PMID: 8244116

Abstract

As various isoenzymes of gastric alcohol dehydrogenase exist and as the effect of sex and age on these enzymes is unknown, this study measured the activity of gastric alcohol dehydrogenase at high and low ethanol concentrations in endoscopic biopsy specimens from a total of 290 patients of various ages and from 10 patients with chronic alcoholism. Gastric alcohol dehydrogenase was also detected by immunohistological tests in biopsy specimens from 40 patients by the use of a polyclonal rabbit antibody against class I alcohol dehydrogenase. A significant correlation was found between the immunohistological reaction assessed by the intensity of the colour reaction in the biopsy specimen and the activity of alcohol dehydrogenase measured at 580 mM ethanol. While alcohol dehydrogenase activity measured at 16 mM ethanol was not significantly affected by age and sex, both factors influenced alcohol dehydrogenase activity measured at 580 mM ethanol. Young women below 50 years of age had significantly lower alcohol dehydrogenase activities in the gastric corpus and antrum when compared with age matched controls (SEM) (6.4 (0.7) v 8.8 (0.6) nmol/min/mg protein; p < 0.001 and 6.0 (1.3) v 9.5 (1.3) nmol/min/mg protein; p < 0.001). Over 50 years of age this sex difference was no longer detectable, as high Km gastric alcohol dehydrogenase activity decreases with age only in men and not in women. In addition, extremely low alcohol dehydrogenase activities have been found in gastric biopsy specimens from young male alcoholics (2.2 (0.5) nmol/min/mg protein), which returned to normal after two to three weeks of abstinence. The activity of alcohol dehydrogenase in the human stomach measured at 580 mM ethanol is decreased in young women, in elderly men, and in the subject with alcoholism. This decrease in alcohol dehydrogenase activity may contribute to the reduced first pass metabolism of ethanol associated with raised ethanol blood concentrations seen in these people.

Full text

PDF
1433

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Buehler R., Hess M., Von Wartburg J. P. Immunohistochemical localization of human liver alcohol dehydrogenase in liver tissue, cultured fibroblasts, and HeLa cells. Am J Pathol. 1982 Jul;108(1):89–99. [PMC free article] [PubMed] [Google Scholar]
  2. 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]
  3. 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]
  4. 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]
  5. 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]
  6. 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]
  7. Gottfried E. B., Korsten M. A., Lieber C. S. Alcohol-induced gastric and duodenal lesions in man. Am J Gastroenterol. 1978 Dec;70(6):587–592. [PubMed] [Google Scholar]
  8. Halsted C. H., Robles E. A., Mezey E. Distribution of ethanol in the human gastrointestinal tract. Am J Clin Nutr. 1973 Aug;26(8):831–834. doi: 10.1093/ajcn/26.8.831. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. 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]
  11. Holmes R. S., Courtney Y. R., VandeBerg J. L. Alcohol dehydrogenase isozymes in baboons: tissue distribution, catalytic properties, and variant phenotypes in liver, kidney, stomach, and testis. Alcohol Clin Exp Res. 1986 Dec;10(6):623–630. doi: 10.1111/j.1530-0277.1986.tb05157.x. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. 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]
  14. 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]
  15. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  16. Maly I. P., Sasse D. Intraacinar profiles of alcohol dehydrogenase and aldehyde dehydrogenase activities in human liver. Gastroenterology. 1991 Dec;101(6):1716–1723. doi: 10.1016/0016-5085(91)90412-e. [DOI] [PubMed] [Google Scholar]
  17. Moreno A., Parés X. Purification and characterization of a new alcohol dehydrogenase from human stomach. J Biol Chem. 1991 Jan 15;266(2):1128–1133. [PubMed] [Google Scholar]
  18. Nakane P. K., Kawaoi A. Peroxidase-labeled antibody. A new method of conjugation. J Histochem Cytochem. 1974 Dec;22(12):1084–1091. doi: 10.1177/22.12.1084. [DOI] [PubMed] [Google Scholar]
  19. 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]
  20. Seitz H. K., Simanowski U. A., Egerer G., Waldherr R., Oertl U. Human gastric alcohol dehydrogenase: in vitro characteristics and effect of cimetidine. Digestion. 1992;51(2):80–85. doi: 10.1159/000200880. [DOI] [PubMed] [Google Scholar]
  21. Seitz H. K., Veith S., Czygan P., Bösche J., Simon B., Gugler R., Kommerell B. In vivo interactions between H2-receptor antagonists and ethanol metabolism in man and in rats. Hepatology. 1984 Nov-Dec;4(6):1231–1234. doi: 10.1002/hep.1840040623. [DOI] [PubMed] [Google Scholar]
  22. Vestal R. E., McGuire E. A., Tobin J. D., Andres R., Norris A. H., Mezey E. Aging and ethanol metabolism. Clin Pharmacol Ther. 1977 Mar;21(3):343–354. doi: 10.1002/cpt1977213343. [DOI] [PubMed] [Google Scholar]
  23. Wagner F. W., Parés X., Holmquist B., Vallee B. L. Physical and enzymatic properties of a class III isozyme of human liver alcohol dehydrogenase: chi-ADH. Biochemistry. 1984 May 8;23(10):2193–2199. doi: 10.1021/bi00305a014. [DOI] [PubMed] [Google Scholar]
  24. Zoller M., Matzku S. Antigen and antibody purification by immunoadsorption: elimination of non-biospecifically bound proteins. J Immunol Methods. 1976;11(3-4):287–295. doi: 10.1016/0022-1759(76)90122-8. [DOI] [PubMed] [Google Scholar]

Articles from Gut are provided here courtesy of BMJ Publishing Group

RESOURCES