Vanadates inhibition

Sodium hexakis(formato)molybdate, 3, 1235 Sodium hypochlorite alkene epoxidation manganese catalysts, 6,378 Sodium ions biology, 6, 559 selective binding biology, 6, 551 Sodium molybdate, 3, 1230 Sodium peroxoborate, 3,101 Sodium/potassium ATPase, 6, 555 vanadate inhibition, 3, 567 Sodium pump, 6, 555 mechanism, 6, 556 Sodium pyroantimonate, 3, 265 Sodium salts... 

Abbreviations. a-M, a-mannosidase AP, acid phosphatase as-ni-ATPase, anion-stimulated, nitrate-inhibitable ATPase CCR, NAD(P)H-dependent cytochrome oreduc-tase cs-vi-ATPase, cation-stimulated, vanadate-inhibitable ATPase, CAT, catalase GS 1/11, glucan synthase 1 or 11 IDPase, inosine diphosphatase cs-PPase, cation-stimulated pyrophosphatase RNA polymerase, DNA-dependent RNA polymerase TP-25, 25 kDa tonoplast integral protein. 

Cuncic, C., N. Detich, D. Ethier, A.S. Tracey, M.J. Gresser, and C. Ramachandran. 1999. Vanadate inhibition of protein tyrosine phosphatases in Jurkat cells Modulation by redox state. J. Biol. Inorg. Chem. 4 354—359. 

Carreras, J., R. Bartrons, and S. Grisolia. 1980. Vanadate inhibits 2,3-bisphospho-glycerate dependent phosphoglycerate mutases but does not affect the 2,3-bisphos-phoglycerate independent phosphoglycerate mutases. Biochem. Biophys. Res. Commun. 96 1267-1273. 

Like insulin, vanadate inhibits protein degradation in hepatocytes105. Proteolysis in liver homogenates at pH 5 is inhibited, suggesting that the lysosomal proteinases are affected. 

The natriuresis and diuresis effect of vanadate, which concentrates in the proximal tubules of the kidney, is believed to be due to inhibition of the Na+, K+-ATPase of these tissues19,124,125. In contrast, the oubain insensitive vanadate inhibition of HCOJ, Cl, Na+, and H+ transport in bladder occurs by another, yet unknown, mechanism126-128. Vanadate effects on salt and water effluxes in gills have also been studied129. ... 

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. 

Hajjar JJ, Rowe WA, Tomicic TK. 1988. The nonspecific nature of the vanadate inhibition of rat ileal (NA, K)-ATPase. Life Sciences 43 1741-1746. 

The pseudohalide azide inhibits VCIPO. The first stmcturally characterised VHPO had in fact been crystallised in its azide-inhibited form. Inhibition has also been noted with hydroxylamine and hydrazine. Further, structural analogues of vanadate, such as [ALF4] and phosphate, are potent inhibitors. In turn, vanadate inhibits many phosphatases (and other phosphate-metabolising enzymes). On the other hand, apo-VHPOs can exhibit some phosphatase activity, and vanadate-inhibited phosphatases show some haloperoxidase activity. These phenomena will be discussed in Section 5.2.1. 

Vanadate-inhibited forms of RNases have been structurally characterised, and in Figure 5.18 two examples, bovine pancreatic RNase-A (I) ] and RNase-Ti (II) from the fungus Aspergillus oryzae, are shown, which exemplify two possible modes... 

Four examples of structurally characterised, vanadate-inhibited phosphorylation enzymes working on the hydrolysis of phospho-ester bonds in nucleotides I, the vanadate-uridine complex of bovine pancreatic ribonuclease-A II, the vanadate complex of ribonuclease-Tj from the fungus Aspergillus oryzae-. III, the vanadate-uridine complex of cyclic nucleotide phosphodiesterase from the cruciferous plant Arabidopsis thaliana-, IV, human tyrosyl-DNA phosphodiesterase (Ur = uridine). 

The inhibition of PTPs by vanadate is of particular interest since this mode of action is supposed to be the primary effect exerted by vanadium applied as an insulin-mimetic agent (see 5.1.1.5). The vanadate-inhibited PTP-IB VIII in Figure 5.19, the structure of which was revealed both by single-crystal X-ray diffraction and two-dimensional H- N NMR spectroscopy, was prepared by treating the phosphatase with either vanadyl sulfate or bis(maltolato)oxovanadium(lV) (BMOV) (7a in Figure 5.2). Irrespective of the nature of the intrinsically applied vanadium species, the same compound with incorporated vanadate(V) was obtained, nicely demonstrating that the active species is vanadate(V), formed by elimination of the ligands and oxidation of to V. In vivo studies further showed that intracellular PTP-IB from rat heart tissue was actively inhibited, and autophosphorylation of the insulin receptor concomitantly enhanced. 

VI-IX are structurally characterised, vanadate-inhibited phosphatases. VI, Rat prostat acid phosphatase VII, bovine phosphotyrosyl phosphatase VIII, mammalian protein tyrosine phosphatase PTP-IB (mutant Cys215Ser) IX, E. coli alkaline phosphatase. For comparison, the active centre of vanadate-dependent haloperoxidases (VHPO) (V), is also shown. The structures Xa and Xb have been proposed, based on EPR, for the vanadyl complexes formed with the PTP-IB active site peptide Val-His-Cys-Ser-Ala-Gly. 

Haloperoxidase Activity of Vanadate-inhibited Phosphatases Phosphatase Activity of Apo-haloperoxidases... 

Due to its electronic configuration of 3d 4 s, vanadium is mostly present in the + 5 oxidation state that forms the oxyanion vanadate (VO4 Due to its structural similarity to phosphate P04 , 4 is taken up by phosphate uptake systems and treated like phosphate by the cell (Mahanty etal. 1991). However, since vanadate does not form stable molecules as does phosphate (Ivancsits et al. 2002), this leads to vanadate toxicity. This ability is also used for in-vitro and in-vivo vanadate-inhibition experiments (Rensing et al. 1997). 

For instance, vanadate inhibited lipolysis and stimulated lipogenesis in adipocytes.Glucose uptake and transport were enhanced by vanadate in... 

Other tissue types mouse brain,rat skeletal muscle,and isolated villus cells. Conversely, vanadate inhibited glucose transport in rat intestine when added to the perfusate of an everted gut sac preparation, or when added as a supplement to the drinking water of diabetic and non-diabetic rats at concentrations up to 0.08 mM for 2-4 weeks. ... 

Sodiuim bexakis(formato)molybdate, 1235 Sodium complexes crown ethers, 37 Sodium molybdate, 1230 Sodium peroxoborate, 101 Sodium/potassium ATPase vanadate inhibition, 567 Sodium pyroantimonate, 265 Sodium tetrahydroborate, 101... 

Magnesium and potassium facilitate vanadate Inhibition of (Na, K)-ATPase activity and they both appear to bind synerglstically with vanadate (56). ATP depressed vanadate inhibition of enzyme activity (48). On the other hand. Gibbons... 

Fig. 2. Left The active centers of the bromoperoxidase (VBrPO) from A nodosum (6). Center The active center of the chloroperoxidase (VClPO) from C. inaequalis (8). Right Vanadate-inhibited rat prostate acid phosphatase. Some of the hydrogen-bonding interactions with amino acid side-chains are shown. For highlighted amino acids, see the text.

Vanadate and Phosphatases. The structural similarity between vanadate and phosphate is impressively demonstrated by the fact that apo-VHPOs can exhibit some phosphatase activity, whereas certain vanadate-inhibited phosphatases exert haloperoxidase activity, a fact which roots in homologies of the active site protein pockets of both classes of enzymes, and the structural analogy of the active centers (the histidine-coordinated vanadate) in the VHPOs and the phosphatases (17) cf Fig. 2. Vanadate-inhibited phosphatases for which peroxidase activity has been reported are of bacterial Shigella flexneri, Salmonella enterica (18)) and fungal origin (ph3rtases from Aspergillus (19)). 

Cantley Jr. LC, Resh MD, Guidotti G. 1978. Vanadate inhibits red cell (Na, K AT-Pase from cytoplasmic side. Nature 272 552-554. 

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