Human stomach alcohol and aldehyde dehydrogenases: comparison of expression pattern and activities in alimentary tract.

Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are the major enzymes responsible for ethanol metabolism in humans. The human stomach has been documented to be involved in the metabolism of first-passed alcohol. The aim of this study was to determine ethanol-metabolizing activities in the stomach with regard to sex, age, enzyme pattern, and polymorphism. A total of 209 surgical gastric mucosal specimens were investigated. The expression patterns of ADH and ALDH were identified by isoelectric focusing, and the activities were assayed spectrophotometrically. At 33 or 500 mmol/L ethanol, pH 7.5, the activities in the ADH3 1-1 phenotypic and mu-ADH-expressing mucosal specimens were significantly greater than that in the ADH3 1-2 phenotypic and mu-ADH absent mucosal specimens, respectively. The activities of the ALDH2-inactive phenotypes were significantly lower than that of the ALDH2-active phenotypes at 200 micromol/L acetaldehyde. The gastric ADH and ALDH activities were not significantly different between men and women with respect to age and genetic polymorphism. The stomach may contribute only a small portion of the alcohol metabolism observed in humans, and the liver may be the major site for first-pass metabolism. Differential expression patterns of ADH and ALDH in the alimentary tract suggest that different vulnerabilities to ethanol-induced mucosal injury may exist.