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

In this study the network of ATP-consuming and -producing reactions, intera cting via the cytosolic ATP/ADP + P-i system, was studied for the first tim e in an intact organ, the isolated perfused rat liver, using top-down metab olic-control analysis. Flux control in the metabolically resting state (onl y oxidative phosphorylation and ion pumps active) was only in the ATP-consu mers, whereas in the metabolically active state (biosyntheses and ion-pumpi ng ATPases active) most control over oxidative phosphorylation was in itsel f and some control was in ion-pumping ATPases. All ATP-consumers had high c ontrol over themselves, and ion-pumping ATPases had high negative control o ver the other ATP-consuming branches. Oxidative phosphorylation had high po sitive control over ATP-consuming reactions exept for ion-pumping ATPases. It is concluded that in the active state ATP-consumers compete for cytosoli c ATP, but as the ion-pumping ATPases and oxidative phosphorylation are les s sensitive towards the cytosolic ATP, other ATP-consumers have low control over these pathways.