UNCOUPLING OF OXIDATIVE PHOSPHORYLATION BY VANADATE

The addition of ammonium metavanadate to the diet of chicks at a level to supply 25 parts per million vanadium uncoupled oxidative phosphorylation in mitochondria isolated from the livers. In vitro studies revealed that 1 mM vanadate uncoupled oxidative phosphorylation in liver mitochondria. This uncoupling was manifest whether succinate or β-hydroxybutyrate was used as the substrate, suggesting that all three phosphorylating sites associated with electron transport were uncoupled.At a concentration of 0.1 mM, vanadate increased the destruction of adenosine triphosphate by mitochondria. As the concentration of vanadate was increased the destruction of adenosine triphosphate became progressively less. The exchange reactions of adenosine triphosphate with orthophosphate and with adenosine diphosphate, catalyzed by liver mitochondria, were inhibited by 0.1 mM vanadate. These results suggest the possibility that the known toxic effects of vanadium in vivo are related to the uncoupling of oxidative phosphorylation.