A numerical model for predicting hepatocytes ureagenesis and its related inborn enzyme deficiencies: case studies

Abstract

One of the important functionality of liver cells is ammonia detoxification and urea production. In this study, a numerical model of urea cycle in hepatocytes have been developed. Navier Stokes along with convection equations have been employed to study the process of ammonia elimination and urea production using a microfluidic channel.The concentration of urea and ammonia throughout the channel were obtained. Furthermore, the urea cycle was modeled regarding its four main enzymes. This resulted in twelve rate equations which were solved to determine the concentration of each metabolites participating in the urea cycle. Application of results were implied to common disorders such as Hyperammonemia type I and II and argininosuccinicaciduria type I and II. Result of this study indicated that there is 80% of reduction in concentration of Citrulline, Argininosuccinate, Arginin, Carbamoyl phosphate, Phosphate and Fumarate in hyperammonemia type II. A 10 fold increase of Argininosuccinate concentration was observed in both argininosuccinicaciduria I and II. The predicted result may be useful in better understanding and control of metabolite deficiencies in patient abnormalities.