Hepatic glutaminase--a special role in urea synthesis?
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.


CONCLUSIONS
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.
Brosnan
John T
JT
Department of Biochemistry, Memorial University of Newfoundland, St. John's, Newfoundland A1B 3X9, Canada.
Brosnan
Margaret E
ME
D000641:Ammonia / Q000378:metabolism; D000818:Animals; D019731:Carbon-Nitrogen Ligases / Q000378:metabolism*; D004790:Enzyme Induction; D008401:Gas Chromatography-Mass Spectrometry; D005934:Glucagon / Q000378:metabolism; D005972:Glutaminase / Q000378:metabolism*; D066298:In Vitro Techniques; D008099:Liver / Q000201:enzymology* / Q000378:metabolism; D008930:Mitochondria, Liver / Q000201:enzymology / Q000378:metabolism; D009587:Nitrogen Isotopes; D010477:Perfusion; D051381:Rats; D014508:Urea / Q000378:metabolism*
D009587:Nitrogen Isotopes; D000641:Ammonia; D014508:Urea; D005934:Glucagon; D005972:Glutaminase; D019731:Carbon-Nitrogen Ligases; C024233:carbamoyl-phosphate synthetase (N-acetylglutamate)