Reduced Inactivation of Tyrosine Aminotransferase in the Perfused Rat Liver in the Presence of Ethanol

Livers from fasted male rats (250–300 g body weight) were isolated and perfused. The effect of ethanol in the perfusate (approximate concentration 0.2 (w/v)) on the activity of tyrosine aminotransferase was investigated in the presence and absence of dexamethasone (final concentration 20 (μ/ml) and/or cycloheximide (final concentration 25 μg/ml). The following observations were made: (1) Ethanol increased tyrosine aminotransferase activity both in the presence and absence of dexamethasone. (2) The addition of ethanol or its main metabolite acetaldehyde to the enzyme assay mixture did not increase enzyme activity. Neither did ethanol reduce the leakage of enzyme from liver to perfusate or bile. (3) Tyrosine aminotransferase activity declined more slowly in ethanol-treated livers than in control livers when protein synthesis was inhibited by cycloheximide. (4) Ethanol did not influence either the activity of another liver enzyme, tryptophan oxygenase, or the radioactivity remaining in labelled proteins 1 hr 30 min. after administration of cycloheximide. It is concluded that ethanol increased tyrosine aminotransferase activity in perfused livers by specific inhibition of enzyme inactivation.