CHRONIC ETHANOL INTAKE REDUCES THE FLUX THROUGH LIVER BRANCHED-CHAIN KETO-ACID DEHYDROGENASE

Chronic ethanol intake selectively increases concentrations of branche d-chain amino acids (BCAA) in the liver. To determine whether a reduce d oxidation plays a role in this effect. we measured substrate flux th rough branched-chain keto-acid (BCKA) dehydrogenase in livers of rats pair-fed liquid diets containing either 0% or 36% of total calories as ethanol for 21 days. Substrate (1.0 mmol/L ketoisocaproate [KIC]) flu xes in the liver of ethanol-fed and control rats were 225 +/- 18 and 3 19 +/- 27 mu mol/h per whole liver (P < .05), respectively. We then st udied whether this effect was due to either ethanol or the products of its metabolism, or to an alteration in the activity of BCKA dehydroge nase. Addition of ethanol (25 to 200 mmol/L) to the perfusion medium h ad no significant effect on the flux through BCKA dehydrogenase in the liver of control rats. Ethanol-fed rats had lower (P < .01) basal act ivity (0.84 +/- 0.11 v 1.39 +/- 0.12 U/g liver) and total activity (0. 94 +/- 0.11 v 1.42 +/- 0.11 U/g liver) than control rats, but a simila r activity state (90% +/- 4% v 99% +/- 4%) of BCKA dehydrogenase. In c onclusion, chronic ethanol intake reduces the flux through liver BCKA dehydrogenase by decreasing the basal and total activity of BCKA dehyd rogenase and not increasing the conversion of the enzyme to its inacti ve form. Copyright (C) 1995 by W.B. Saunders Company