ALCOHOL AND ALDEHYDE DEHYDROGENASES IN HUMAN ESOPHAGUS - COMPARISON WITH THE STOMACH ENZYME-ACTIVITIES

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 mu1 (equivalent to the recently reported mu-form) and mu2, were expressed in all the 15 esophagus specimens studied, whereas only four of seven examined gastric specimens exhibited a weak to moderately strong mu1-ADH activity band on the isoelectric focusing gels. pI values of the esophageal mu1-ADH and mu2-ADH, and the liver pi-ADH were determined to be 8.61, 8.13, and 8.90, respectively. Mu-ADHs exhibited high K(m) for ethanol (12 mm) and low sensitivity to 4-methylpyrazole inhibition. ALDH3 (BB form) and ALDH1 were the major high- and low-K(m) 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 mum 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 K(m) 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.