GENE-EXPRESSION OF UREA CYCLE ENZYMES FOLLOWING 2 3 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 followi ng 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 leve l was higher in hepatectomized than in sham-operated rats for carbamoy l phosphate synthetase and arginino-succinate lyase, The level for alb umin mRNA remained close to that of the controls. Relative transcripti on rates were found to be increased for carbamoyl phosphate synthetase , arginino-succinate synthase and arginase, For albumin the transcript ion rate was drastically reduced initially, but recovered gradually du ring the experimental period. The data indicate that the expression of urea cycle enzymes, in particular that of carbamoyl phosphate synthet ase which is the rate-limiting step, is up-regulated by partial hepate ctomy, This helps to maintain urea synthesis rate at a normal or near normal level during the period of reduced liver mass, confirming metab olic studies. In contrast, the transcription for albumin was reduced. The immediate increase in urea cycle enzyme expression during the peri od of acute hepatocyte loss is consistent with the view that it is vit ally important that urea synthesis, in contrast to e.g. albumin synthe sis, remains intact when the metabolic capacity of the liver is reduce d.