Hepatic zonation of carbon and nitrogen fluxes derived from glutamine and ammonia transformationsReport as inadecuate

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Journal of Biomedical Science

, 17:1

First Online: 07 January 2010Received: 15 May 2009Accepted: 07 January 2010DOI: 10.1186-1423-0127-17-1

Cite this article as: Comar, J.F., Suzuki-Kemmelmeier, F., Constantin, J. et al. J Biomed Sci 2010 17: 1. doi:10.1186-1423-0127-17-1


BackgroundGlutaminase predominates in periportal hepatocytes and it has been proposed that it determines the glutamine-derived nitrogen flow through the urea cycle. Glutamine-derived urea production should, thus, be considerably faster in periportal hepatocytes. This postulate, based on indirect observations, has not yet been unequivocally demonstrated, making a direct investigation of ureogenesis from glutamine highly desirable.

MethodsZonation of glutamine metabolism was investigated in the bivascularly perfused rat liver with U-Cglutamine infusion 0.6 mM into the portal vein antegrade perfusion or into the hepatic vein retrograde perfusion.

ResultsAmmonia infusion into the hepatic artery in retrograde and antegrade perfusion allowed to promote glutamine metabolism in the periportal region and in the whole liver parenchyma, respectively. The results revealed that the space-normalized glutamine uptake, indicated by CO2 production, gluconeogenesis, lactate production and the associated oxygen uptake, predominates in the periportal region. Periportal predominance was especially pronounced for gluconeogenesis. Ureogenesis, however, tended to be uniformly distributed over the whole liver parenchyma at low ammonia concentrations up to 1.0 mM; periportal predominance was found only at ammonia concentrations above 1 mM. The proportions between the carbon and nitrogen fluxes in periportal cells are not the same along the liver acinus.

ConclusionsIn conclusion, the results of the present work indicate that the glutaminase activity in periportal hepatocytes is not the rate-controlling step of the glutamine-derived nitrogen flow through the urea cycle. The findings corroborate recent work indicating that ureogenesis is also an important ammonia-detoxifying mechanism in cells situated downstream to the periportal region.

Electronic supplementary materialThe online version of this article doi:10.1186-1423-0127-17-1 contains supplementary material, which is available to authorized users.

Jurandir F Comar, Fumie Suzuki-Kemmelmeier, Jorgete Constantin contributed equally to this work.

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Author: Jurandir F Comar - Fumie Suzuki-Kemmelmeier - Jorgete Constantin - Adelar Bracht

Source: https://link.springer.com/

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