Gene expression of urea cycle enzymes following two-thirds partial hepatectomy in the rat.

The effect of reduction of functional liver mass on the expression of enzyme systems for hepatic urea synthesis was assessed in rats following two-thirds partial hepatectomy. Results were related to normal, fed rats and to sham-operated rats, with identical timing for surgery and feeding. Among the five urea cycle enzymes the mRNA steady-state level was higher in hepatectomized than in sham-operated rats for carbamoyl phosphate synthetase and arginino-succinate lyase. The level for albumin mRNA remained close to that of the controls. Relative transcription rates were found to be increased for carbamoyl phosphate synthetase, arginino-succinate synthase and arginase. For albumin the transcription rate was drastically reduced initially, but recovered gradually during the experimental period. The data indicate that the expression of urea cycle enzymes, in particular that of carbamoyl phosphate synthetase which is the rate-limiting step, is up-regulated by partial hepatectomy. This helps to maintain urea synthesis rate at a normal or near normal level during the period of reduced liver mass, confirming metabolic studies. In contrast, the transcription for albumin was reduced. The immediate increase in urea cycle enzyme expression during the period of acute hepatocyte loss is consistent with the view that it is vitally important that urea synthesis, in contrast to e.g. albumin synthesis, remains intact when the metabolic capacity of the liver is reduced.