Inhibition of Induction of Rat Liver Tyrosine Aminotransferase by d-Galactosamine: ROLE OF URIDINE TRIPHOSPHATE

Abstract

Abstract 1. An injection of d-galactosamine at the same time as an injection of dexamethasone inhibits the increase of rat liver tyrosine aminotransferase activity normally observed following injection of dexamethasone alone. The galactosamine-mediated inhibition is dose dependent: a 50% inhibition of the increase of enzyme activity is observed at 10 mg of galactosamine·HCl per 100 g of body weight, and a total inhibition is observed at 15 mg per 100 g of body weight. Following a single injection of 37.5 mg of galactosamine·HCl per 100 g of body weight, the basal level of tyrosine aminotransferase activity does not change for at least 16 hours. 2. Induction of the enzyme by glucagon or dibutyryl cyclic AMP is only partially inhibited by a dose of 37.5 mg of galactosamine·HCl per 100 g of body weight. 3. The total inhibition of the dexamethasone-induced enzyme increase is specific for galactosamine. A high dose of d-glucose or d-galactose has no inhibitory effect, and a high dose of d-glucosamine or 2-deoxy-d-galactose has only a partially inhibitory effect. 4. The inhibition by galactosamine of the dexamethasone-induced enzyme increase can be prevented by simultaneous injection of uridine. Determination of the uridine phosphate levels following injection of different doses of galactosamine reveals a partial inhibition of the enzyme induction below 100 nmoles of UTP+UDP per g of liver and a total inhibition of enzyme induction below 40 to 50 nmoles of UTP+UDP per g of liver. 5. There is little or no relationship between levels of galactosamine metabolites in the liver and inhibition of enzyme induction. 6. Unlike actinomycin D, injection of galactosamine at various times after injection of dexamethasone does not result in a superinduction of tyrosine aminotransferase.