- 作者: Jurandir F Comar; Fumie Suzuki-Kemmelmeir; Jorgete Constantin; Adelar Bracht
- 作者服務機構: Laboratory of Liver Metabolism, Biochemistry Department, University of Maringa, Maringa, Brazil
- 中文摘要: --
- 英文摘要:
Background : Glutaminase predominates in periportal hepatocytes and it has been proposed that it
determines the glutamine-derived nitrogen flow through the urea cycle. Glutaminederived
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.
Methods : Zonation 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).
Results : Ammonia 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.
Conclusions : In 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. - 中文關鍵字: --
- 英文關鍵字: --