Ammonia and Glutamine Metabolism During Liver Insufficiency: The Role of Kidney and Brain in Interorgan Nitrogen Exchange

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Abstract
Background: During liver failure, urea synthesis capacity is impaired. In this situation the most important alternative pathway for ammonia detoxification is the formation of glutamine from ammonia and glutamate. Information is lacking about the quantitative and qualitative role of kidney and brain in ammonia detoxification during liver failure. Methods: This review is based on own experiments considered against literature data. Results and conclusions: Brain detoxifies ammonia during liver failure by ammonia uptake from the blood, glutamine synthesis and subsequent glutamine release into the blood. Although quantitatively unimportant, this may be qualitatively important, because it may influence metabolic and/or neurotransmitter glutamate concentrations. The kidney plays an important role in adaptation to hyperammonaemia by reversing the ratio of ammonia excreted in the urine versus ammonia released into the blood from 0.5 to 2. Thus, the kidney changes into an organ that netto removes ammonia from the body as opposed to the normal situation in which it adds ammonia to the body pools.