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-ceIls. 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 mu g Con A per 10(7) 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 1 (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. (C) 1999 Elsevier Science B.V. All rights reserved.