Effects of the mitogen concanavalin A on pathways of thymocyte energy metabolism.
The lectin concanavalin A (Con A) acts as a mitogen that preferentially activates T-cells. It stimulates the energy metabolism of thymocytes within seconds of exposure. We studied short-term effects (<30 min) of Con A on a conceptually simplified model system of rat thymocyte energy metabolism in the concentration range of 0-2 microg Con A per 107 cells, using metabolic control analysis. The model system consisted of three blocks of reactions, linked by the common intermediate mitochondrial membrane potential (Delta[psi]m): the substrate oxidation reactions, which produce the linking intermediate, and the proton conductance (or leak) and ATP turnover pathways which consume Delta[psi]m. Firstly, we used top-down elasticity analysis to establish which subsystems are targeted by Con A. Secondly, we quantitatively analysed the steady-state regulation of the system variables by Con A: how do the subsystem fluxes respond to Con A individually and as a whole? Our results indicate that: (1) steady-state respiration and Delta[psi]m increase as Con A concentration is raised, but at higher concentrations the increase in respiration is less and Delta[psi]m falls; (2) Con A independently changes the kinetics of the reactions that produce and consume Delta[psi]m: the Delta[psi]m-producing reactions are inhibited, and the reactions involved in ATP turnover are stimulated; and (3) the overall effects of Con A are mostly mediated by effects on ATP turnover.
Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1QW, UK. sk@mole.bio.cam.ac.uk
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Krauss
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Buttgereit
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D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology*; D004734:Energy Metabolism / Q000187:drug effects; D005260:Female; D007425:Intracellular Membranes / Q000187:drug effects; D008564:Membrane Potentials; D008934:Mitogens / Q000494:pharmacology*; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D008934:Mitogens; D003208:Concanavalin A; D000255:Adenosine Triphosphate