[HTML][HTML] Effects of the mitogen concanavalin A on pathways of thymocyte energy metabolism

S Krauss, F Buttgereit, MD Brand - Biochimica et Biophysica Acta (BBA) …, 1999 - Elsevier
S Krauss, F Buttgereit, MD Brand
Biochimica et Biophysica Acta (BBA)-Bioenergetics, 1999Elsevier
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 μg 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 (Δψm): the substrate …
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 μg 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 (Δψm): the substrate oxidation reactions, which produce the linking intermediate, and the proton conductance (or leak) and ATP turnover pathways which consume Δψm. 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 Δψm increase as Con A concentration is raised, but at higher concentrations the increase in respiration is less and Δψm falls; (2) Con A independently changes the kinetics of the reactions that produce and consume Δψm: the Δψm-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.
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