The anaplerotic metabolic flux through pyruvate carboxylase is a prerequisite for ammonia detoxification in acute and chronic liver failure
Leibfritz D, Zwingmann C, Butterworth R
University of Bremen
Liver failure results in acute or chronic Hepatic Encephalopthay (HE) - due to ammonia neurotoxicity. It is suggested that the osmotic effect of astrocytic glutamine is responsible for developmentof HE. We suggest that, rather than glutamine accumulation, limited glutamine synthesis account for HE development. In order to evaluate the association of anaplerosis with glutamine synthesis in HE, high resolution NMR was used to measure carbon flux in brain, liver and muscle of rats with different forms of liver failure. The data show that the muscle is the major organ for ammonia detoxification, and that glutamine formation is dependent on anaplerotic flux through pyruvate carboxylase.