Samuel P. Bessman, Edward R.B. McCabe
Apr 15, 1972
Citations
1
Influential Citations
47
Citations
Journal
Biochemical pharmacology
Abstract
1,4-Butanediol (1,4-BD) is oxidized, with the concomitant reduction of NAD, by a rat liver 100,000 g supernatant and by horse liver alcohol dehydrogenase. The apparent Km for this reaction in the rat liver system is 0·61 mM as compared with an apparent Km for ethanol of 1·3 mM in the same system. Pyrazole, an inhibitor of alcohol dehydrogenase, competitively blocks the oxidation of 1,4-BD by the rat liver supernatant. Administration in vivo of pyrazole to the rat prevents the appearance of γ-hydroxybutyrate, a 1,4-BD metabolite, in the blood and also prevents the neuropharmacological effects of 1,4-BD. In contrast, pyrazole prolongs the neuropharmacological effects of the related compound, γ-butyrolactone. 1,4-BD, as a normal component of the “diol lipids” of rat liver, might represent a physiological substrate for alcohol dehydrogenase. It is speculated that ethanol might competitively block 1,4-BD metabolism with accumulation in the liver of unesterified 1,4-BD and 1,4-BD esterified in the diol lipids.