EFFECTS OF 5-AZACYTIDINE ON POLYRIBOSOMES AND ON CONTROL OF TYROSINE TRANSAMINASE ACTIVITY IN RAT LIVER

1. 1. The effects of the nucleoside analog 5-azacytidine on general protein biosynthesis in rat liver, and on the induction and inactivation of hepatic tyrosine transaminase and tryptophan pyrrolase were investigated. 2. 2. 5-Azacytidine caused a breakdown of hepatic polyribosomes to inactive monomers and dimers, and inhibited the incorporation of amino acids into soluble liver proteins; these effects are attributed in part to incorporation of the analog into RNA. 3. 3. The hormonal induction of tryptophan pyrrolase, but not that of tyrosine transaminase, was inhibited by 5-azacytidine. 4. 4. 5-Azacytidine prevented the inactivation of tyrosine transaminase, but not that of tryptophan pyrrolase, which normally occurs following hormonal induction. 5. 5. The data support the hypothesis that the synthesis of tyrosine transaminase is controlled, at least in part, at the translational level of protein biosynthesis. The results also support the theory that the inactivation of tyrosine transaminase following its hormonal induction is dependent on the synthesis of a degradative enzyme. © 1969.