A hierarchy of ATP-consuming processes in mammalian cells.
The rates of different ATP-consuming reactions were measured in concanavalin A-stimulated thymocytes, a model system in which more than 80% of the ATP consumption can be accounted for. There was a clear hierarchy of the responses of different energy-consuming reactions to changes in energy supply: pathways of macromolecule biosynthesis (protein synthesis and RNA/DNA synthesis) were most sensitive to energy supply, followed by sodium cycling and then calcium cycling across the plasma membrane. Mitochondrial proton leak was the least sensitive to energy supply. Control analysis was used to quantify the relative control over ATP production exerted by the individual groups of ATP-consuming reactions. Control was widely shared; no block of reactions had more than one-third of the control. A fuller control analysis showed that there appeared to be a hierarchy of control over the flux through ATP: protein synthesis > RNA/DNA synthesis and substrate oxidation > Na+ cycling and Ca2+ cycling > other ATP consumers and mitochondrial proton leak. Control analysis also indicated that there was significant control over the rates of individual ATP consumers by energy supply. Each ATP consumer had strong control over its own rate but very little control over the rates of the other ATP consumers.
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D019069:Cell Respiration / Q000187:drug effects; D002469:Cell Separation; D003208:Concanavalin A / Q000494:pharmacology; D003593:Cytoplasm / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D004734:Energy Metabolism; D005260:Female; D008213:Lymphocyte Activation; D008564:Membrane Potentials; D008565:Membrane Proteins / Q000378:metabolism; D008689:Methacrylates; D008928:Mitochondria / Q000378:metabolism; D010766:Phosphorylation; D014176:Protein Biosynthesis; D017494:Proton Pumps / Q000187:drug effects; D012313:RNA / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism*; D013844:Thiazoles / Q000494:pharmacology
D008565:Membrane Proteins; D008689:Methacrylates; D017494:Proton Pumps; D013844:Thiazoles; D003208:Concanavalin A; D012313:RNA; C030517:myxothiazol; D000255:Adenosine Triphosphate; D004247:DNA; D000252:Calcium-Transporting ATPases; D000254:Sodium-Potassium-Exchanging ATPase