Localisation of the sites of action of cadmium on oxidative phosphorylation in potato tuber mitochondria using top-down elasticity analysis.
The aim of this study was to identify the significant sites of action of cadmium on oxidative phosphorylation in potato tuber mitocondria. We simplified the system to three convenient subsystems linked via the production or consumption of a common intermediate, namely protonmotive force. The three subsystems were substrate oxidation, which produces protonmotive force, and the proton leak reactions and the phosphorylation reactions, which consume protonmotive force. By measuring the effect of cadmium on the kinetic response of each subsystem to protonmotive force (top-down elasticity analysis), we found that cadmium stimulated proton leak reactions and strongly inhibited substrate oxidation, but had no measurable effect on the phosphorylation reactions. Cadmium therefore decreases the amount of ATP produced/oxygen consumed (the effective P/O ratio) not by inhibiting the phosphorylation reactions directly, but by inhibiting the production of protonmotive force and by diverting proton flux from phosphorylation reactions to the proton leak reactions.
Department of Biochemistry, University of Cambridge, England.
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D000255:Adenosine Triphosphate / Q000096:biosynthesis; D001665:Binding Sites; D002104:Cadmium / Q000633:toxicity*; D004734:Energy Metabolism / Q000187:drug effects; D004785:Environmental Pollutants / Q000633:toxicity; D007700:Kinetics; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D008954:Models, Biological; D009861:Onium Compounds / Q000378:metabolism; D010085:Oxidative Phosphorylation / Q000187:drug effects*; D010101:Oxygen Consumption / Q000187:drug effects; D011522:Protons; D011198:Solanum tuberosum / Q000187:drug effects* / Q000378:metabolism; D014320:Triphenylmethyl Compounds / Q000378:metabolism
D004785:Environmental Pollutants; D009861:Onium Compounds; D011522:Protons; D014320:Triphenylmethyl Compounds; D002104:Cadmium; C011561:triphenylmethylphosphonium; D000255:Adenosine Triphosphate