Hepatocyte heterogeneity in ammonia metabolism: Impairment of glutamine synthesis in CCl 4 induced liver cell necrosis with no effect on urea synthesis

Abstract

After induction of a perivenous liver cell necrosis by CCl 4 pretreatment of the rat, ammonia uptake by perfused liver is decreased. This was due to an inhibition of glutamine synthesis from added ammonia, whereas urea synthesis was not affected by CCl 4 pretreatment. The data confirm recent findings on hepatocyte heterogeneity in ammonia metabolism and are explained by an impairment of perivenous glutamine synthetase, but not of periportal urea synthesis, by the perivenous liver cell necrosis induced by CCl 4. Regarding the pathogenesis of hyperammonemia in acute severe liver disease like CCl 4 poisoning, the data point to a role of an impaired glutamine synthesis, but not to an impairment of urea synthesis.