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  • Title: Hepatic glutaminase--a special role in urea synthesis?
    Author: Brosnan JT, Brosnan ME.
    Journal: Nutrition; 2002 Jun; 18(6):455-7. PubMed ID: 12044815.
    Abstract:
    OBJECTIVE: To investigate the relationship between hepatic glutaminase and the urea cycle with particular reference to the possibility of the existence of a metabolic channel between glutaminase and carbamylphosphate synthetase I (CPS-I). METHODS: Rat livers were perfused in the non-recirculating mode with 15-N labeled ammonia and glutamine. The incorporation of 15-N into nitrogenous products was determined by gas chromatography-mass spectrometry. RESULTS: We devised and validated a theoretical framework that described the incorporation of the 15-N into the various urea mass isotopomers as a function of the isotopic abundance of 15-N in the two precursor molecules, aspartate and citrulline. We then compared the incorporation of 15-N from amino-labeled and amide-labeled glutamine. Glucagon activated incorporation of these labels into products, consistent with an activation of glutaminase. However, the results indicated no metabolic channel between glutaminase and CPS-I. CONCLUSION: We suggest that glutaminase may play a role in promoting urea production by virtue of N-acetylglutamate synthesis rather than by a channeling mechanism. Glutaminase may provide glutamate, a substrate for the synthesis of N-acetylglutamate which is an obligatory activator of CPS-1.
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