Chronic ethanol intake reduces the flux through liver branched-chain keto-acid dehydrogenase

Abstract

Chronic ethanol intake selectively increases concentrations of branched-chain amino acids (BCAA) in the liver. To determine whether a reduced oxidation plays a role in this effect, we measured substrate flux through 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]) fluxes in the liver of ethanol-fed and control rats were 225 ± 18 and 319 ± 27 μmol/h per whole liver ( P < .05), respectively. We then studied whether this effect was due to either ethanol or the products of its metabolism, or to an alteration in the activity of BCKA dehydrogenase. Addition of ethanol (25 to 200 mmol/L) to the perfusion medium had no significant effect on the flux through BCKA dehydrogenase in the liver of control rats. Ethanol-fed rats had lower ( P < .01) basal activity (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 similar activity state (90% ± 4% v 99% ± 4%) of BCKA dehydrogenase. In conclusion, chronic ethanol intake reduces the flux through liver BCKA dehydrogenase by decreasing the basal and total activity of BCKA dehydrogenase and not increasing the conversion of the enzyme to its inactive form.