Urea production capacity in the wood frog (Rana sylvatica) varies with season and experimentally induced hyperuremia.

Wood frogs (Rana sylvatica) can accumulate substantial amounts of urea during fall and winter. In this study, maximal urea production capacity was examined in R. sylvatica collected at various times of the year and in response to experimental hyperuremia and dehydration. Activity and expression of carbamoyl phosphate synthetase I (CPS I), the hepatic regulatory enzyme of the urea cycle, were used as indicators of urea production capacity. The high levels of CPS I activity in summer frogs were maintained through much of winter, a time when many metabolic processes are downregulated, suggesting that urea production is important during hibernation. In laboratory experiments, hyperuremia in fully hydrated frogs caused CPS I activity to decrease by approximately 41%, suggesting that urea functions as a feedback inhibitor. In contrast, CPS I activity was maintained in hyperuremic, dehydrated frogs. The significance of this response is unclear, although perhaps urea functions to counteract inhibitory effects of concentrated salts. Generally, changes in CPS I activity were not reflected by corresponding changes in CPS I quantity, indicating that this enzyme is not primarily regulated through transcription and translation; rather, control may be achieved by posttranslational modifications and/or feedback inhibition. Our findings suggest that maintenance of urea production capacity in hibernating R. sylvatica facilitates accumulation of this osmolyte, which has important roles in the winter biology of this species.