Pulmonary ethanol metabolism
Abstract
The liver is the organ primarily responsible for ethanol oxidation, and alcohol dehydrogenase (ADH) is the major enzyme involved. There is limited evidence suggesting that the lung plays a role in ethanol metabolism. These studies were conducted to determine the involvement of the lungs in the metabolism of ethanol by examining some of the enzymatic pathways associated with the metabolism of ethanol, namely, alcohol dehydrogenase, fatty acid ethyl ester synthase (FAEES), UPD-glucuronyltransferase (UDPGT) and sulfotransferase (ST) in rats and rabbits. Comparisons were made with the liver and other organs which have been much better characterized. The catalytic properties of pulmonary ADH were examined kinetically, and the influence of pH and buffer constituents was determined. Even though pulmonary ADH activity is significant at high ethanol concentrations and high pH, this enzyme would make only a minor contribution to total ethanol metabolism at low ethanol concentrations under normal physiological conditions. The isolated perfused rabbit lung (IPRL) system was also utilized to investigate the capacity of the rabbit lung for oxidative metabolism of ethanol. There was a limited capacity for oxidative metabolism of ethanol as evidenced by lack of acetaldehyde production. Non-oxidative pathways for ethanol metabolism were demonstrated in the lungs. Fatty acid ethyl ester formation was determined in vitro in rat and rabbit lungs and in vivo in rat lungs. The lung is similar to other tissues in being capable of non-oxidative metabolism of ethanol in esterifying fatty acids in vivo and in vitro. Pulmonary UDPGT and ST activities were determined in subcellular fractions comparing ethanol with known substrates. Although pulmonary glucuronidation of ethanol was not detected, ethyl sulfate was detected, identified and quantified in incubations of pulmonary cytosolic fractions.
Degree
Ph.D.
Advisors
Carlson, Purdue University.
Subject Area
Pharmacology|Pharmaceuticals|Health
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