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

Abstract

One important functionality of liver cells is ammonia detoxification and urea production. In this study, a numerical model of the urea cycle in hepatocytes was developed. Navier Stokes and convection equations were employed to study the process of ammonia elimination and urea production using a microfluidic channel. The concentration of urea and ammonia throughout the channel was obtained. Furthermore, the urea cycle was modelled with respect to its four main enzymes. This resulted in twelve rate equations that were solved to determine the concentration of each metabolite participating in the urea cycle. Application of results implied common disorders such as hyperammonemia types I and II and argininosuccinicaciduria types I and II. Result of this study indicated that there is 80% chance of a 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 types I and II. The predicted result may be useful in better understanding and controlling of metabolite deficiencies in patient abnormalities.