Stimulation of hepatic fatty acid synthetase activity in chick embryo by cycloheximide

Liver fatty acid synthetase activity is increased up to 25-fold at 10–24 h after administration of cycloheximide in 16-, 18-, and 20-day-old chick embryos. The extent of stimulation of the synthetase activity depended on the dose of the protein synthesis inhibitor, larger doses elevating the enzyme activity to a greater degree than smaller doses. Quantitative precipitin reactions using goat antibodies against chicken liver synthetase and partially purified liver extracts from normal and cycloheximide-treated embryos gave identical equivalence points, suggesting that the increase in the synthetase activity following cycloheximide injection resulted from an increase in the content of the enzyme and not from its activation. Although there was a strong inhibition of protein and fatty acid synthetase syntheses after cycloheximide injection, a twofold increase in the rate of enzyme synthesis, compared to saline-treated embryos, was observed at 12 h after injection of the antibiotic. During the period of active inhibition of synthetase synthesis in cycloheximide-treated embryos, the synthetase activity did not diminish. The results support the conclusion that a decrease in degradation and a subsequent increase in the synthesis of the enzyme are responsible for an increase in the content of the synthetase after cycloheximide treatment. Absence of a stimulatory effect of cycloheximide on synthetase activity of cultured avian liver expiants indicate that cycloheximide stimulates synthetase activity, in ovo, by an indirect action mediated by extrahepatic events. These results emphasize the ambiguity involved in interpretation of data derived from in vivo experiments with inhibitors of protein synthesis.