The use of in situ haemoglobin-free perfused liver in metabolic-control analysis

Biochem Soc Trans. 2000 Feb;28(2):109-13. doi: 10.1042/bst0280109.

Abstract

In this study the network of ATP-consuming and -producing reactions, interacting via the cytosolic ATP/ADP+P(i) system, was studied for the first time in an intact organ, the isolated perfused rat liver, using top-down metabolic-control analysis. Flux control in the metabolically resting state (only oxidative phosphorylation and ion pumps active) was only in the ATP-consumers, whereas in the metabolically active state (biosyntheses and ion-pumping ATPases active) most control over oxidative phosphorylation was in itself and some control was in ion-pumping ATPases. All ATP-consumers had high control over themselves, and ion-pumping ATPases had high negative control over the other ATP-consuming branches. Oxidative phosphorylation had high positive control over ATP-consuming reactions except for ion-pumping ATPases. It is concluded that in the active state ATP-consumers compete for cytosolic ATP, but as the ion-pumping ATPases and oxidative phosphorylation are less sensitive towards the cytosolic ATP, other ATP-consumers have low control over these pathways.

MeSH terms

  • Adenosine Diphosphate / metabolism*
  • Adenosine Triphosphate / metabolism*
  • Animals
  • Cells, Cultured
  • Fasting
  • Liver / metabolism*
  • Models, Chemical
  • Models, Theoretical
  • Perfusion
  • Rats

Substances

  • Adenosine Diphosphate
  • Adenosine Triphosphate