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Monday, June 11, 2012

Expression Pattern, Ethanol-Metabolizing Activities, and Cellular Localization of Alcohol and Aldehyde Dehydrogenases in Human Small Intestine

Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are principal enzymes responsible for metabolism of ethanol (EtOH). Functional polymorphisms of ADH1B, ADH1C, and ALDH2 genes occur among racial populations. This study aimed to systematically determine the functional expressions and cellular localization of ADH and ALDH family members in human small bowel.

One hundred and seventeen surgical specimens of duodenal mucosae, 34 jejunal mucosal specimens, and 14 paired specimens of stomach, duodenum, and jejunum from same individuals were investigated. The isozyme/allozyme expression patterns of ADH and ALDH were identified by isoelectric focusing, and the ADH/ALDH activities were assayed spectrophotometrically. The protein contents of ADH/ALDH isozymes were determined by immunoblotting using the corresponding purified class-specific antibodies, and the cellular localizations were detected by immunohistochemistry and histochemistry.

The activities of ADH1C*1/*1 allelotype were significantly higher than those of the ADH1C*1/*2 allelotype in duodenum (p < 0.001) and in jejunum (p < 0.05); and the activity of ADH2-expressing phenotype was significantly higher than that of the ADH2-missing phenotype in duodenum (p < 0.05). The activities of ALDH2-inactive phenotype were not significantly different from those of the ALDH2-active phenotype in duodenum and jejunum. Stomach exhibited significantly lower ADH activity (p < 0.05), and duodenum displayed significantly lower ALDH activity (p < 0.001) comparing the paired gastric, duodenal, and jejunal mucosae of same individuals. Gender and age did not significantly influence the ADH and ALDH activities in duodenum. The isozyme protein contents in duodenum and jejunum were in the following decreasing order: ALDH1A1, ADH1/ALDH2, ADH3, ADH2, and ALDH3A1. Villous epithelial cells, cryptic Paneth cells, and Brunner's gland ductal cells revealed a greater immunostaining intensity with ADH1, ALDH1A1, and ALDH2

ADH and ALDH isozymes are differentially expressed in the various cell types of duodenum and jejunum. The results suggest that proximal small intestine can substantively contribute to first-pass metabolism of EtOH under certain conditions and that cytotoxic acetaldehyde and EtOH perturbation of retinol metabolism might play an etiological role in the pathogenesis of small bowel.

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