Ca. Bernal et al., CHRONIC ETHANOL INTAKE REDUCES THE FLUX THROUGH LIVER BRANCHED-CHAIN KETO-ACID DEHYDROGENASE, Metabolism, clinical and experimental, 44(10), 1995, pp. 1243-1246
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