A Vulnerable and Rate-Limiting Step in Urea Synthesis in Patients with Hyperammoniaemia.

Abstract

This study was designed to demonstrate whether or not a specific point of breakdown in urea synthesis occur in patients with liver disease and hyperammoniaemia. Peripheral venous blood was analyzed for citrulline, arginine and ammonia. The mean level of plasma citrulline in patients with liver disease and hyperammoniaemia, was twice the normal. Between blood ammonia and plasma citrulline levels the calculated correlation coefficient was 0.66. Arginine in similar patients was normal but was elevated in patients with surgically constructed portal-systemic shunts. The elevated citrulline levels may indicate a rate-limiting step in urea synthesis. Arginine levels do not necessarilly reflect vulnerability of urea synthesis because arginine is a constituent of normal diet and arginine absorbed from the diet by-passes the liver through portal-systemic shunts and contributes to maintaining the peripheral level of arginine even in the presence of deficient urea synthesis.