The use of in situ haemoglobin-free perfused liver in metabolic-control analysis.
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.
Soboll
S
S
Institut für Physiologische Chemie I, Heinrich-Heine-Universität Düsseldorf, Germany.
Brown
G C
GC
D000244:Adenosine Diphosphate / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D005215:Fasting; D008099:Liver / Q000378:metabolism*; D008956:Models, Chemical; D008962:Models, Theoretical; D010477:Perfusion; D051381:Rats
D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate