ATPase inhibition

Vanadate, dioxybis(oxamato)-bond-length ratios, 1,57 Vanadate, heptacyano-potassium salt structure, I, 72 Vanadate, hexafluoro-dipotassium salt history, I, 21 potassium salt history, 1,21 tripotassium salt history, 1,21 Vanadate, pentachloro-stereochemistry, 1,40 Vanadate, pentafluorooxy-stereochemistry, I, 50 Vanadates biochemistry, 3,456 calcium/magnesium ATPase inhibition, 6, 567 competition with phosphates physiology, 6,665 protonation, 3,1026 sodium pump, 6, 557 in uranium purification from ore, 6, 899 Vanadates, hexafluoro-, 3. 482,531 Vanadates, oxoperoxo-, 3,501 Vanadates, pentacarbonyl-, 3, 457 Vanadium biology, 6,665 determination, 1. 548 extraction... 

Figure 4.10 Effect of reduced glutathione (GSH) (0-1.0 mM) on Na/K ATPase inhibition associated with the addition of oxidized glutathione (GSSG) (1 me). Experiments were performed using an isolated bovine ventricular Na/K ATPase preparation. Na/K ATPase activity was quantified by the ouabain-sensitive hydrolysis of ATP to yield inorganic phosphate. The data are presented as means standard errors of the means (n = 6).

Bansal SK, Desaiah D. 1985. Chlordecone toxicity Effect of withdrawal of treatment on ATPase inhibition. Neurotoxicology 6(3) 103-107. 

Inhibits H K -ATPase Inhibits tumor cell division... 

Yoshimori T, Yamamoto A, Moriyama Y, Futai M, Tashiro Y. Bafilomycin Al, a specific inhibitor of vacuolar-type H(+)-ATPase, inhibits acidification and protein degradation in lysosomes of cultured cells. J Biol Chem 1991 266(26) 17707-17712. 

Mechanism of action Na"", K -ATPase inhibition Na /H " exchange mechanism inhibition (proximal tubule) Aldosterone antagonism Membrane effect... 

Mitochondrial ATPase inhibition. Smoke extract, in the mouse brain mitochondria culture in the presence or absence of vitamin C for 60 minutes, inhibited mitochondrial ATPase and cytochrome C oxidase activities in a dose-dependent manner. The effect of extract on mitochondria swelling response to calcium stimulation was dependent on calcium concentrations. The extract treatment induced mitochondrial inner membrane damage and vacuolization of the matrix, whereas the outer mitochondrial membrane was preserved. Nicotine produced no significant damage . Mitogenic activity. Water extract of the dried leaf, administered to mice at a concentration of 0.05%, was active on lymphocytes from mesenteric lymph node and lymphocytes B and T. Intracellular Ca level was unchanged. The extract was active on... 

Cardiac glycosides increase contraction of the cardiac sarcomere by increasing the free calcium concentration in the vicinity of the contractile proteins during systole. The increase in calcium concentration is the result of a two-step process first, an increase of intracellular sodium concentration because of Na+,K+ ATPase inhibition and second, a relative reduction of calcium expulsion from the cell by the sodium-calcium exchanger (NCX in Figure 13-1) caused by the increase in intracellular sodium. The increased cytoplasmic calcium is sequestered by SERCA in the SR for later release. Other mechanisms have been proposed but are not well supported. 

Digoxin Na +, K+ ATPase inhibition results in reduced Ca2+ expulsion and increased Ca2+ stored in sarcoplasmic reticulum Increases cardiac contractility cardiac parasympathomimetic effect (slowed sinus heart rate, slowed atrioventricular conduction) Chronic symptomatic heart failure rapid ventricular rate in atrial fibrillation Oral, parenteral duration 36-40 h Toxicity Nausea, vomiting, diarrhea cardiac arrhythmias... 

Ames and Kovacic [45] studied the electrochemistry of omeprazole, active metabolites and a bound enzyme model, with possible involvement of electron transfer in the antiulcer action of the drug. The active metabolites cyclic sulfenamide and sulfur radical entities, exhibited reduction potentials of 0.3 and 0.2 V, respectively. The value for the bound enzyme model was 0.7 V and that for omeprazole was >1.4 V. The results lend credence to the hypothesis that electron transfer comprises part of the mode of action in addition to H+/K+-ATPase inhibition. 

Puscas et al. [170] suggested that omeprazole has a dual mechanism of action H+/K+-ATPase inhibition and gastric mucosa carbonic anhy-drase enzyme inhibition and that these enzymes may be functionally coupled. 

T6. Tsakiris, S., Angelogianni, P, Schulpis, K. H., and Behrakis, P., Protective effect of L-cysteine and glutathione on rat brain Na+,K+-ATPase inhibition induced by free radicals. Z. Naturforsch. 55c, 271-277 (2000). 

As the H+, K+-ATPase inhibition is associated with the modification of mer-capto groups in the enzyme, the disulfide adduct (ESSR) can be considered as a model of the enzyme-inhibitor complex, and the sulfenamide, or possibly the sulfenic acid (C), formed from omeprazole can be considered to be the active inhibitor, which binds covalently to cysteine residues of the H+, K+-ATPase. 

Figala V, Klemm K, Kohl B, Kruger U, Rainer G, Schaefer H, et al. Acid activation of (H+-K+)-ATPase inhibiting... 

Kohl B, Sturm E, Senn-Bilfmger J, Simon WA, Kruger U, Schaefer H et al. (H+-K+)-ATPase inhibiting 2-[(2-pyridyl-methyl)sulfinyl]benzimidazoles. 

C.C. O Neal, P.D. Boyer, Assessment of the rate of bound substrate interconversion and of ATP acceleration of product release during catalysis by mitochondrial adenosine triphosphatase. J. Biol. Chem. 259, 5761-5767 (1984) R. Kagawa, M.G. Montgomery, K. Braig, A.G.W. Leshe, J.E. Walker, The structure of bovine Fi-ATPase inhibited by ADP and beryllium fluoride. EMBO J. 23, 2734-2744 (2004)... 

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