Alcohol and Aldehyde Dehydrogenases in Human Esophagus: Comparison With the Stomach Enzyme Activities

Abstract

Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) isoenzymes from surgical esophageal and gastric mucosa were compared by agarose isoelectric focusing. Two prominent ADH forms, designated mu 1 (equivalent to the recently reported mu-form) and mu 2, were expressed in all the 15 esophagus specimens studied, whereas only four of seven examined gastric specimens exhibited a weak to moderately strong mu 1-ADH activity band on the isoelectric focusing gels. pI values of the esophageal mu 1-ADH and mu 2-ADH, and the liver pi-ADH were determined to be 8.61, 8.13, and 8.90, respectively. mu-ADHs exhibited high Km for ethanol (12 mM) and low sensitivity to 4-methylpyrazole inhibition. ALDH3 (BB form) and ALDH1 were the major high- and low-Km aldehyde dehydrogenase in the esophagus, respectively. The ADH and ALDH activities were determined at pH 7.5 to be 751 +/- 78 and 29.9 +/- 3.0 nmol/min/g tissue, respectively (measured at 500 mM ethanol or at 200 microM acetaldehyde; mean +/- SEM; N = 15). The esophageal ADH activity was approximately 4-fold and the ALDH activity 20% that of the stomach enzyme. Because the presence of high activity and high Km mu-ADHs as well as low-activity ALDH1 were found in human esophageal mucosa, it is suggested that there may exist an accumulation of intracellular acetaldehyde during alcohol ingestion. This reactive and toxic metabolite may be involved in the pathogenesis of alcohol-induced esophageal disorders.

Pharmacological recruitment of aldehyde dehydrogenase 3A1 (ALDH3A1) to assist ALDH2 in acetaldehyde and ethanol metabolism in vivo

“…Because relatively high levels of ALDH3A1 are present in the esophagus, upper aerodigestive track, and stomach (20)(21)(22), Alda-89 may contribute to a faster elimination of acetaldehyde in organs shown to be more vulnerable to acetaldehyde-induced cancers in humans with the ALDH2*2 mutation (3, 4).…”

“…We therefore set out to identify a pharmacologic tool to "recruit" another member of the ALDH family to enhance the elimination of acetaldehyde. We focused on ALDH3A1 because it is highly expressed in the epithelial cell layer of the UADT, stomach, liver, and kidney (20)(21)(22). ALDH3A1 metabolizes aromatic, aliphatic medium chain aldehydes and α,β-hydroxyalkenal aldehydes, but not acetaldehyde under basal condition (21,23).…”

Overview of the role of alcohol dehydrogenase and aldehyde dehydrogenase and their variants in the genesis of alcohol-related pathology

“…Low levels of ALDH1 and ALDH2 mRNA are found in the placenta, brain and pancreas, which may be relevant to the genesis of fetal alcohol syndrome, alcoholic neurotoxicity and chronic alcoholic pancreatitis. In man the oral mucosa expresses ALDH3, the oesophagus expresses ALDH1 and ALDH3, the stomach expresses ALDH1, 2 and 3, while the colon expresses predominantly ALDH1, and the lung expresses ALDH2 (Yin et al 1993(Yin et al , 1997. The breast is reported to express ALDH1 and ALDH3 (Sreerama & Sladek, 1997) and the placenta expresses low levels of ALDH5 mRNA (Stewart et al 1996b).…”

Interaction between a single nucleotide polymorphism in the alcohol dehydrogenase 3 gene, alcohol consumption and oral cancer risk

“…Oxidation of ethanol occurs primarily in the liver, but also in the gastrointestinal tract and oral cavity. [12][13][14][15][16] Seven human genes coding for ADH have been identified to date and 3 of these (ADH1, ADH2 and ADH3) are located in a cluster on chromosome 4. 17,18 Single nucleotide polymorphisms (SNPs) that exhibit different enzymatic properties have been reported for some of these ADH genes.…”