Circadian rhythms of urea formation and argininosuccinate synthetase activity in rat liver.

The circadian rhythms of the urea concentrations in urine, serum, and liver and their generation mechanism were investigated. When rats were allowed to eat freely, the urea concentration and the total urea content of the urine were higher during the night than during the day-time. Consistent with these findings, the urea concentrations in the liver and serum had circadian rhythms with the highest values at 0200 hours and the lowest values at 1400 hours. The amplitude of the rhythm increased with increase in the dietary protein (casein) content. Of the five urea cycle enzymes in the liver, only argininosuccinate synthetase showed fluctuation in activity, and this had the same pattern as the circadian rhythms of urea concentrations. These findings suggest that the circadian rhythm of argininosuccinate synthetase in the liver might be directly responsible for the rhythms of change in urea concentrations in the liver, blood and urine. The circadian increase in enzyme activity was inhibited by cycloheximide, but not by actinomycin D.