Relief of the Crabtree Effect by Arsenate1

Arsenate, an uncoupler of oxidative phosphorylation, relieved the Crabtree effect in Ehrlich-Lett réhyperdiploid ascites tumor cells. Respiration was measured with an oxygen electrode. High arsenale concentrations (30 to 60 ITIM)were needed to produce a 2-fold increase in the depressed respiratory rate. Arsenate concentrations below 10 HTMhad little or no effect. The relief by arsenale was reversible with oligomycin, indicating lhal arsenale had noi caused a nonspecific uncoupling. A comparison of Ihe effecls of arsenale on oxidalive phosphorylalion in isolaled Ehrlich-Lellré hyperdiploid asciles lumor milochondria and on Ihe onsel of Ihe Crablree effecl in intact Ehrlich-Lellréhyperdiploid asciles lumor cells suggesled lhal Ihe high arsenale concenlralions were needed lo overcome a slrong anlagonism by inorganic phosphale for Ihe arsenale uncoupling. The resulls supporl Ihe con cepìlhal Ihe Crablree effecl is caused by a decrease in Ihe availabilily of ADP and/or inorganic phosphale lo oxidalive phosphorylalion.