Abstract
In the presence of extracellular K, intracellular orthovanadate is a potent inhibitor of (Na+ + K+)ATPase1–3, and because this effect may have a physiological role3–6, it is interesting to ask at which step in the enzyme cycle vanadate acts. In experiments with red cells and squid axons containing high concentrations of ATP, Beaugé and DiPolo7,8 found that added vanadate modified the effects of extracellular K, or congeners of K, in a similar way to lowered ATP concentration. They suggested that vanadate might act by retarding the relatively slow, ATP-sensitive, conformational change that is thought to follow the hydrolysis of phosphoenzyme, when that hydrolysis is catalysed by extracellular K (ref. 9). There are several reasons for thinking that the same conformational change (E2K → E1K) is the rate-limiting step in the conversion of E2K to E1Na that occurs when sufficient Na is added to (Na+ + K+)ATPase preparations suspended in low-K media in conditions which preclude phosphorylation10–14. The speed of the E2K → E1K change, in those circumstances, can be measured by the use of several different fluorescent techniques10–12,15, and we report here experiments with a fluorescein-labelled enzyme to investigate the effects of vanadate. It turns out that, in the same conditions in which vanadate inhibits (Na+ + K+)ATPase activity, it greatly slows the rate of the conformational change E2K → E1K.
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Karlish, S., Beaugé, L. & Glynn, I. Vanadate inhibits (Na+ + K+)ATPase by blocking a conformational change of the unphosphorylated form. Nature 282, 333–335 (1979). https://doi.org/10.1038/282333a0
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DOI: https://doi.org/10.1038/282333a0
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