Pivotal role of glutamine synthetase in ammonia detoxification.

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Hakvoort TB, He Y, Kulik W, Vermeulen JL, Duijst S, Ruijter JM, Runge JH, Deutz NE, Koehler SE, Lamers WH

Pivotal role of glutamine synthetase in ammonia detoxification.

Hepatology. 2017 Jan;65(1):281-293. doi: 10.1002/hep.28852. Epub 2016 Nov 12.

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27641632 [ View in PubMed
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Abstract

Glutamine synthetase (GS) catalyzes condensation of ammonia with glutamate to glutamine. Glutamine serves, with alanine, as a major nontoxic interorgan ammonia carrier. Elimination of hepatic GS expression in mice causes only mild hyperammonemia and hypoglutaminemia but a pronounced decrease in the whole-body muscle-to-fat ratio with increased myostatin expression in muscle. Using GS-knockout/liver and control mice and stepwise increments of enterally infused ammonia, we show that approximately 35% of this ammonia is detoxified by hepatic GS and approximately 35% by urea-cycle enzymes, while approximately 30% is not cleared by the liver, independent of portal ammonia concentrations

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