Different levels of gene realization in the diurnal control of rat liver enzymes.
Diurnal rhythms are demonstrated in five rat liver enzymes : argininosuccinate synthetase, ATP : citrate lyase, glutamate dehydrogenase, phosphoenolpyruvate carboxykinase, and succinate dehydrogenase. In a 12 : 12 h light-dark cycle, maxima of enzyme activities occur at the beginning of the dark phase in the case of phosphoenolpyruvate carboxykinase, at the end of the dark phase in ATP : citrate lyase, and in the middle of the dark phase in the other three enzymes. The diurnal increase of phosphoenolpyruvate carboxykinase is blocked by cycloheximide, cordycepin, alpha-amanitin, and 5-azacytidine. The maximum of ATP : citrate lyase is likewise suppressed at the levels of both translation and transcription, as shown by administration of cycloheximide and 5-azacytidine, respectively. Hence, these two enzymes appear to be regulated transcriptionally. The diurnal rise of argininosuccinate synthetase an glutamate dehydrogenase is also totally inhibited by cycloheximide, whereas cordycepin, alpha-amanitin, and 5-azacytidine are ineffective in the first phase of enzyme accumulation. In a later phase, however, alpha-amanitin and 5-azacytidine become inhibitory. The two enzymes therefore seem to be regulated sequentially by post-transcriptional and transcriptional mechanisms. The diurnal increase of succinate dehydrogenase is nearly insensitive to alpha-amanitin and 5-azacytidine; cycloheximide is only partially inhibitory and, in particular, almost ineffective during the late rise. Thus, the rhythm of this enzyme might be controlled mainly by an activation and, perhaps, by a transitory post-transcriptional mechanism.