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Mechanism and Regulation of Ethanol Elimination in Humans: Intermolecular Hydrogen Transfer and Oxidoreduction in Vivo
Author(s) -
Cronholm Tomas,
Jones A. Wayne,
Skagerberg Stefan
Publication year - 1988
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.1988.tb00265.x
Subject(s) - chemistry , acetaldehyde , ethanol , alcohol dehydrogenase , alcohol , ethanol metabolism , in vivo , hydride , dissociation (chemistry) , chromatography , hydrogen , stereochemistry , biochemistry , organic chemistry , microbiology and biotechnology , biology
Ethanol metabolism was studied in four healthy volunteers by intravenous infusion of a mixture of [1, 1‐ 2 H 2 ]ethanol (1.0 mmol/kg) and [2,2,2‐ 2 H 3 ]ethanol (1.0 mmol/kg) followed by blood sampling at 10‐min intervals. The concentrations of ethanols labeled with 1, 2, 3, and 4 deuterium atoms were determined by gas chromatography/mass spectrometry of the 3,5‐dinitrobenzoates. During the first 30 min mono‐ and tetradeuteriated molecules appeared rapidly, which indicates that a fraction of the ethanol was formed from acetaldehyde by exchange. This fraction was calculated to be 38–58% and the hydrogen incorporated during the reduction was mainly (63–82%) derived from C‐1 of ethanol, indicating slow exchange of enzyme‐bound NADH. After 30 min the elimination followed first‐order kinetics with t 1/2 of 18–31 min and with a small primary isotope effect (1.05–1.11). This indicates almost complete removal of ethanol from blood passing through the liver when the concentration is low (below 1 mM). The results indicate that as long as hepatic blood flow is not limiting, the rate of alcohol dehydrogenase‐catalyzed elimination of a small dose of ethanol in vivo is limited by the dissociation of NADH from the enzyme and by the rates of oxidation of acetaldehyde and reoxidation of NADH.