Vanadates sodium pump

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Much of current interest in vanadium stems from the discovery that vanadate (HV042 at pH 7) is a powerful inhibitor of ATPases such as the sodium pump protein (Na+ + K+)ATPase (Chapter 8), of phosphatases,623 and of kinases.624 This can be readily understood from comparison of the structure of phosphate and vanadate ions. 

A full consideration of the mechanism of the sodium pump requires an account of the role of the lipid, the binding sites for Na+, K+, Mg2+ and ATP, the mechanism of hydrolysis of ATP and the way in which this is coupled to the transport of the cation. In addition it should be noted that the enzyme also functions as a K+-dependent phosphatase, a reaction usually studied with p-nitrophenyl phosphate as substrate. Studies with inhibitors have been informative, notably with ouabain and with vanadate. Ouabain binds at one site per pump and so has been of value in quantitatively defining the enzyme in various preparations. 

Aiton JF, Cramb G. 1985. The effects of vanadate on rabbit ventricular muscle adenylate cyclase and sodium pump activities. Biochem Pharmacol 34 1543-1548. 

Beauge LA, Cavieres JJ, Glynn IM, et al. 1980. The effects of vanadate on the fluxes of sodium and potassium ions through the sodium pump. J Physiol 301 7-23. 

Cantley al. (50) found that vanadate was transported to the red blood cell where it inhibited the sodium pump by binding to (Na, K)-ATPase from the cytoplasmic side (the site of ATP hydrolysis). They suggested that the vanadium in mammalian tissue acts as a regulatory mechanism for the sodium pump that maintains a high intracellular id" to Na" ratio by coupling with ATP hydrolysis. 

Extrapolating from well-characterized enzymatic inhibition in test tubes, numerous mechanistic ideas concerning the in vivo effects of vanadium compounds have been advanced. The effects of vanadium compounds as transition-state analogs of certain enzymes with a phosphoprotein intermediate in their reaction scheme is proposed to account for the action of vanadium [11] in many biological systems. Unfortunately, it is often difficult to determine if the inhibition observed in the test tube occurs in vivo. For example, although vanadate is a potent inhibitor of plasma membrane ion pumps (such as the sodium potassium ATPase) in the test tube, it is difficult to determine if these pumps are actually inhibited in animals exposed to vanadium compounds. Currently, the role of vanadium compounds as protein phosphatase (PTP) inhibitors is believed to be related to the metabolic effects of this... 

In vitro experiments have shown that vanadium as vanadate inhibits sodium-potassium ATPase activity and thus inhibits the sodium potassium pump (Nechay and Saunders 1978). This pump is necessary for proper transport of materials across cell membranes. The kidney (Higashino et al. 

Among the other possible cellular receptors tested, it was found that palytoxin caused K " efflux in yeast expressing a hybrid between the Na KVATPase and the H, K -ATPase, converting this enzyme into and open channel. Interestingly, subsequent studies have described palytoxin-stimu-lated cation fluxes that were blocked by vanadate but resistant to ouabain in rat colon, suggesting that the toxin was able to convert a vanadate-sensitive H K ATPase into an electrogenic cation transporter and consequently, that the pore-forming action of palytoxin was not restricted to Na, K -ATPase since it was also observed with the coloific H, KVATPase, which is related to the sodium pmnp. The toxin was also found to interfere with the sarcolemmal calcium pump in cardiac myocytes as a secondary effect. Further smdies are required to determine how palytoxin interferes with each of the P-type ATPase pmnps or if the effects of the toxin on these pumps are consequences of structural similarities between the enzymes. ... 

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