Previous studies in man and experimental animals suggest that urea production is decreased in cirrhosis. In the present study, NH4Cl solutions of increasing concentrations were infused into isolated, perfused livers of normal rats and the rates of ammonia uptake and urea production were calculated for each pre-hepatic ammonia concentration. A pattern of saturation kinetics was generated and characterized through computer analysis. The Vmax was 7.4 μmoles/min and Km was 86.3 μmoles/100 ml. The livers of rats with experimental cirrhosis induced by carbon tetrachloride produced less urea than controls (controls : 0.40 ± 0.03 ; cirrhotic 0.25 ± 0.02 μmole/min/g of wet liver weight ; P < 0.005) at infusion rates of NH4Cl, which resulted in ammonia levels approximately twice the Km value. Simultaneously performed taurocholate transport studies also revealed significant functional differences between cirrhotic and control livers. In summary, this study delineates a model to evaluate the kinetics of urea synthesis from NH4Cl in the isolated perfused rat liver. It was found that the livers of rats with CCl4-induced cirrhosis exhibited impaired ammonia utilization and urea production together with abnormalities of taurocholate transport.
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