Effect of triiodothyronine on alcohol dehydrogenase and aldehyde dehydrogenase activities in rat liver. Implications for the control of ethanol metabolism.
Treatment of rats with 20 micrograms of 3,3',5-triiodo-L-thyronine (T3) per 100 g body wt for a period of 6 days led to a 45% decrease in total liver alcohol dehydrogenase and a 36% decrease in total liver aldehyde dehydrogenase. Most of the latter decrease was directly attributable to a 57% fall in the level of the physiologically-important low Km mitochondrial isoenzyme. The high Km isoenzyme of the postmitochondrial and soluble fractions was much less affected by T3-treatment. T3, at concentrations up to 0.1 mM, did not inhibit the activity of aldehyde dehydrogenase in vitro. Despite these large losses of the two enzymes most intimately involved in ethanol metabolism, the rate of ethanol elimination in vivo was the same in T3-treated and control animals. Moreover, there was no difference between the two groups in the susceptibility of ethanol elimination to inhibition by 4-methylpyrazole, making it unlikely that an alternative route of ethanol metabolism had been significantly induced by treatment with T3. As it had been suggested that T3 might create a "hypermetabolic state" in which constraints normally imposed on alcohol dehydrogenase and aldehyde dehydrogenase are removed thereby compensating for any loss in total enzymic activity, 2,4-dinitrophenol (0.1 mmoles/kg body wt) was administered to rats in order to raise the general metabolic rate. However, the uncoupler proved to be lethal to T3-treated animals and did not stimulate ethanol elimination in controls. The results do not support the notion that ethanol elimination in vivo is normally governed either by the level of alcohol dehydrogenase or by that of hepatic aldehyde dehydrogenase. However, the mode of control remains unclear.
Smith
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Dawson
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D000426:Alcohol Dehydrogenase; D000429:Alcohol Oxidoreductases / Q000378:metabolism*; D000444:Aldehyde Dehydrogenase / Q000378:metabolism*; D000818:Animals; D000431:Ethanol / Q000378:metabolism*; D005260:Female; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D014284:Triiodothyronine / Q000494:pharmacology*
D014284:Triiodothyronine; D000431:Ethanol; D000429:Alcohol Oxidoreductases; D000426:Alcohol Dehydrogenase; D000444:Aldehyde Dehydrogenase