Hepatic zonation of carbon and nitrogen fluxes derived from glutamine and ammonia transformations

Journal of Biomedical Science

Research

Jorgete Constantin¹  Adelar Bracht¹  Jurandir F Comar¹  Fumie Suzuki-Kemmelmeier¹ 

[1] Laboratory of Liver Metabolism, Biochemistry Department, University of Maringá, Maringá, Brazil;

关键词: Hepatic Artery;    Hepatic Vein;    Metabolic Flux;    Urea Cycle;    Glutamine Metabolism;   

DOI  :  10.1186/1423-0127-17-1

 received in 2009-05-15, accepted in 2010-01-07,  发布年份 2010

来源: Springer

【 摘 要 】

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-14C]glutamine 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 14CO2 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.

【 授权许可】

Unknown   
© Comar et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.