The Gastric H,K-ATPase

  • Olga Vagin
  • Keith Munson
  • Jai Moo Shin
  • Nils Lambrecht
  • Steve Karlish
  • George Sachs

Abstract

This brief review addresses the mechanism of acid secretion and the structure-function relationship of the gastric acid pump, the H,K-ATPase. The growth in knowledge of this enzyme in the last few years, as a result of delineation of the cDNA sequence, determination of the effect of mutations on function, documentation of the site of action of various inhibitors, and recognition of the similarity in 3D structure to the SERCA Ca ATPase has been remarkable.

Keywords

Permeability Cysteine Adenosine Lysine Luminal 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Skou, J. C. (1973) The relationship of the (Na + + K+)-activated enzyme system to transport of sodium and potassium across the cell membrane. J. Bioenerg., 4,1–30.PubMedCrossRefGoogle Scholar
  2. 2.
    Bader, H., Sen, A.K., and Post, R. L. (1966) Isolation and characterization of a phosphorylated intermediate in the (Na+ + K+) system-dependent ATPase. Biochim Biophys Acta, 118, 106–115.PubMedCrossRefGoogle Scholar
  3. 3.
    Davies R.E. (1951) The mechanism of hydrochloric acid production by the stomach. Biol. Rev., 26, 87–120CrossRefGoogle Scholar
  4. 4.
    Sachs, G., Rabon, E., Saccomani, G. and Sarau, H. M. (1975). Redox and ATP in acid secretion. Ann N Y Adad. Sci 264:456–475.CrossRefGoogle Scholar
  5. 5.
    Sachs, G., Pacifico, A. Collier R.H. and Zweig, R.A (1968). A possible mechanism for acid secretion by gastric mucosa. Symposium on Biophysical Aspects of Permeability IUPAB pp 26–27, 1968Google Scholar
  6. 6.
    Ganser, A.L. and Forte, J. G. (1973) K + -stimulated ATPase in purified microsomes of bullfrog oxyntic cells. Biochim Biophys Acta, 307, 169–180.PubMedCrossRefGoogle Scholar
  7. 7.
    Lee, J., Simpson, G., and Scholes, P. (1974) An ATPase from dog gastric mucosa: changes of outer pH in suspensions of membrane vesicles accompanying ATP hydrolysis. Biochem Biophys Res Commun., 60(2), 825–832.PubMedCrossRefGoogle Scholar
  8. 8.
    Sachs, G., H. H. Chang, E. Rabon, R. Schackman, M. Lewin, and G. Saccomani. (1976) A nonelectrogenic H+ pump in plasma membranes of hog stomach. J. Biol. Chem., 251, 7690–7698.PubMedGoogle Scholar
  9. 9.
    Koelz, H. R., G. Sachs, and Berglindh, T. (1981). Cation effects on acid secretion in rabbit gastric glands. Am. J. Physiol., 241(5), G431-442. Google Scholar
  10. 10.
    Reenstra, W. W. and Forte, J. G. (1981) H+/ATP stoichiometry for the gastric (K+ + H+)-ATPase, J. Membr. Biol., 61, 55–60.PubMedCrossRefGoogle Scholar
  11. 11.
    Rabon, E. C., McFall, T. L., and Sachs, G. (1982). The Gastric [H,K]ATPase:H+/ATP Stoichiometry. J. Biol. Chem., 257, 6296–6299.PubMedGoogle Scholar
  12. 12.
    Skrabanja, A. T., J. J. De Pont, et al. (1984). The H+/ATP transport ratio of the (K+ + H+)-ATPase of pig gastric membrane vesicles. Biochim. Biophys. Acta, 774, 91–95.PubMedCrossRefGoogle Scholar
  13. 13.
    Forte, T. M. and Forte, J. G. (1971) A freeze-fracture study of bullfrog gastric oxyntic cells. J. Ultrastruct. Res., 37, 322–334.PubMedCrossRefGoogle Scholar
  14. 14.
    Helander, H. F. and Hirschowitz, B. I. (1974) Quantitative ultrastructural studies on inhibited and on partly stimulated gastric parietal cells. Gastroenterology, 67,447–452.PubMedGoogle Scholar
  15. 15.
    Smolka, A., H. F. Helander, and Sachs, G. (1983). Monoclonal antibodies against gastric H+ + K+ ATPase. Am. J. Physiol., 245(4), G589–596.Google Scholar
  16. 16.
    Mangeat, P., T. Gusdinar, Sahuquet, A., Hanzel, D. K., Forte, J. G., and Magous, R. (1990). Acid secretion and membrane reorganization in single gastric parietal cell in primary culture. Biol. Cell, 69(3), 223–231.PubMedCrossRefGoogle Scholar
  17. 17.
    Hanzel, D., Reggio, H., Bretscher, A., Forte, J. G., and Mangeat, P (1991). The secretion-stimulated 80K phosphoprotein of parietal cells is ezrin, and has properties of a membrane cytoskeletal linker in the induced apical microvilli. Embo J., 10(9), 2363–2373.PubMedGoogle Scholar
  18. 18.
    Jons, T., Lehnardt, S., Bigalke, H., Heim, H. K., and Ahnert-Hilger, G. (1999). SNARE proteins and rab3A contribute to canalicular formation in parietal cells. Eur. J. Cell Biol., 78(11), 779–786.PubMedCrossRefGoogle Scholar
  19. 19.
    Peranzl, G., D. Bayle, Lewin, M. J., and Soumarmon, A. (1991). The intramembranous particles of resting and secreting gastric (H+,K+)- ATPase membranes. Biol. Cell, 73(2–3): 163–171.CrossRefGoogle Scholar
  20. 20.
    Wolosin, J. M., Okamoto, C., Forte, T. M., and Forte, J. G. (1983). Actin and associated proteins in gastric epithelial cells. Biochim. Biophys. Acta, 761(2): 171–182.PubMedCrossRefGoogle Scholar
  21. 21.
    Namikawa, T., K. Araki, et al. (1998). Localization of cytoskeletal filaments during membrane rearrangement in rat parietal cells stimulated with gastrin. Arch. Histol. Cytol., 61(1): 47–56.PubMedCrossRefGoogle Scholar
  22. 22.
    Ogata, T. and Y. Yamasaki (2000). Morphological studies on the translocation of tubulovesicular system toward the intracellular canaliculus during stimulation of the gastric parietal cell. Microsc. Res. Tech., 48(5): 282–292.PubMedCrossRefGoogle Scholar
  23. 23.
    Ogata, T. and Y. Yamasaki (2000). Scanning EM of resting gastric parietal cells reveals a network of cytoplasmic tubules and cisternae connected to the intracellular canaliculus. Anat. Rec., 258(1): 15–24.PubMedCrossRefGoogle Scholar
  24. 24.
    Crowson, M. S. and G. E. Shull (1992). Isolation and characterization of a cDNA encoding the putative distal colon H+, K+-ATPase. Similarity of deduced amino acid sequence to gastric H+, K+-ATPase and Na+, K+-ATPase and mRNA expression in distal colon, kidney, and uterus. J. Biol. Chem., 267(19): 13740–13748.PubMedGoogle Scholar
  25. 25.
    Modyanov, N. N., P. M. Mathews, et al. (1995). Human ATP1AL1 gene encodes a ouabain-sensitive H-K-ATPase. Am J Physiol 269(4 Pt 1): C992–7.Google Scholar
  26. 26.
    Post, R. L., C. Hegyvary, and Kume, S. (1972). Activation by adenosine triphosphate in the phosphorylation kinetics of sodium and potassium ion transport adenosine triphosphatase. J. Biol. Chem., 247(20): 6530–6540.PubMedGoogle Scholar
  27. 27.
    Polvani, C., Sachs, G., and Biostein, R. (1989) Sodium ions as substitutes for protons in the gastric H,K-ATPase. J. Biol. Chem., 264(30), 17854–17859.PubMedGoogle Scholar
  28. 28.
    Stewart, B., Wallmark, B., and Sachs, G. (1981). The interaction of H+ and K+ with the partial reactions of gastric H,K-ATPase. J. Biol. Chem., 256, 2682–2690.PubMedGoogle Scholar
  29. 29.
    Wallmark, B., Stewart, H. B., Rabon, E., Saccomani, G. and Sachs, B. (1980). The catalytic cycle of gastric (H++K+)-ATPase. J. Biol. Chem., 255, 5313–5319.PubMedGoogle Scholar
  30. 30.
    Brzezinski, P., Malmstrom, B. G., Lorentzon, P., and Wallmark, B. (1988). The catalytic mechanism of gastric H/K-ATPase: simulations of pre-steady-state and steady-state kinetic results, Biochim. Biophys. Acta, 942, 215–219.PubMedCrossRefGoogle Scholar
  31. 31.
    Thomas, R. C. (1972) Electrogenic sodium pump in nerve and muscle cells. Physiol. Rev., 52, 563–594.PubMedGoogle Scholar
  32. 32.
    Sachs, G., Chang, H. H., Rabon, E., Schackman, R., Lewin, M., and Saccomani, G. (1976). A nonelectrogenic H+ pump in plasma membranes of hog stomach. J.Biol. Chem., 251, 7690–7698.PubMedGoogle Scholar
  33. 33.
    Burnay, M., and Horisberger J.-D. (2001). A single amino acid mutation in the 5th transmembrane segment of the Bufo Marinus Bladder H, K-ATPase makes its activity electrogenic. USGEB Young Investigator Meeting, Lausanne (Dorigny), March 10, 2001Google Scholar
  34. 34.
    Schackmann, R., Schwartz, A., Saccomani, G., and Sachs, G. (1977). Cation transport by gastric H+:K+ ATPase. J. Membr. Biol., 32(3–4): 361–381.PubMedCrossRefGoogle Scholar
  35. 35.
    Rabon, E. C., Smillie, K., Seru, V., and Rabon, R. (1993). Rubidium occlusion within tryptic peptides of the H,K-ATPase. J. Biol. Chem., 268, 8012–8018.PubMedGoogle Scholar
  36. 36.
    Soumarmon, A., P. K. Rangachari, and Lewin, M. J. (1984). Passive transport of Rb+ by hog gastric (H+, K+)-ATPase. J Biol Chem., 259(19): 11861–11867.PubMedGoogle Scholar
  37. 37.
    Bamberg, K., Mercier, F., Reuben, M. A., Kobayashi, Y., Munson, K. B. and Sachs, G. (1992). cDNA cloning and membrane topology of the rabbit gastric H/K-ATPase α- subunit. Biochim. Biophys. Acta, 1131, 69–77.PubMedCrossRefGoogle Scholar
  38. 38.
    Reuben, M. A., Lasater, L. S. and Sachs, G. (1990). Characterization of a ß subunit of the gastric H/K-ATPase. Proc. Natl. Acad. Sei. U.S.A., 87, 6767–6771.CrossRefGoogle Scholar
  39. 39.
    Besancon, M., Shin, J. M., Mercier, F., Munson, K., Miller, M., Hersey, S., and Sachs, G. (1993). Membrane topology and omeprazole labeling of the gastric H, K-adenosinetriphosphatase. Biochemistry, 32, 2345–2355.PubMedCrossRefGoogle Scholar
  40. 40.
    Shin, J. M., Kajimura, M., Arguello, J. M., Kaplan, J. H., and Sachs, G. (1994) Biochemical identification of transmembrane segments of the Ca-ATPase of sarcoplasmic reticulum. J. Biol. Chem., 269, 22533–22537.PubMedGoogle Scholar
  41. 41.
    Bamberg, K. and Sachs, G. (1994). Topological analysis of the H,K-ATPase using in vitro translation. J. Biol. Chem., 269, 16909–16919.PubMedGoogle Scholar
  42. 42.
    Shin, J.M., Besancon, M., Simon, A., and Sachs, G. (1993). The site of action of pantoprazole in the gastric H/K-ATPase. Biochim. Biophys. Acta, 1148(2) 223–233.PubMedCrossRefGoogle Scholar
  43. 43.
    Besancon, M., Simon, A., Sachs, G., and Shin, J. M. (1997) Sites of Reaction of the Gastric H,K-ATPase with Extracytoplasmic Thiol Reagents. J. Biol. Chem., 272, 22438–22446.PubMedCrossRefGoogle Scholar
  44. 44.
    Shull, G. E., Lane, L. K., and Lingrel, J. B. (1986) Amino-acid sequence of the alpha-subunit of the Na K ATPase deduced from a cDNA. Nature. 321(6068):429–431.PubMedCrossRefGoogle Scholar
  45. 45.
    Hall, K., Perez, G., Anderson, D., Gutierrez, C., Munson, K., Hersey, S. J., Kaplan, J. H., and Sachs, G. (1990). Location of the carbohydrates present in the H,K-ATPase vesicles isolated from hog gastric mucosa. Biochemistry ,29, 701–706.PubMedCrossRefGoogle Scholar
  46. 46.
    Munson, K. B., Gutierrez, C., Balaji, V. N., Ramnarayan, K., and Sachs, G. (1991). Identification of an extra-cytoplasmic region of H,K-ATPase labeled by a K+-competitive photoaffinity inhibitor. J. Biol. Chem. ,266, 18976–18988.PubMedGoogle Scholar
  47. 47.
    Melle-Milovanovic, D., Milovanovic, M., Nagpal, S., Sachs, G., and Shin, J. M. (1998) Regions of Association Between the Alpha and the Beta Subunit of the Gastric H,K-ATPase, J.Biol. Chem., 273 11075–11081.PubMedCrossRefGoogle Scholar
  48. 48.
    Shin, J. M. and Sachs, G. (1994) Identification of a region of the H,K-ATPase α- subunit associated with the ß-subunit J. Biol. Chem., 269, 8642–8646.PubMedGoogle Scholar
  49. 49.
    Chow, D. C., Browning, C. M., and Forte, J. G. (1992). Gastric H,K-ATPase activity is inhibited by reduction of disulfide bonds in ß-subunit. Amer. J. Physiol, 263, C39-C46.PubMedGoogle Scholar
  50. 50.
    Asano S, Kawada K, Kimura T, Grishin AV, Caplan MJ, Takeguchi N. (2000) The roles of carbohydrate chains of the beta-subunit on the functional expression of gastric H(+),K(+)-ATPase. J. Biol. Chem., 275(12), 8324–8330.PubMedCrossRefGoogle Scholar
  51. 51.
    Toyoshima, C., M. Nakasako, Nomura, H. and Ogawa, H. (2000). Crystal structure of the calcium pump of sarcoplasmic reticulum at 2.6 A resolution. Nature 405(6787): 647–655.PubMedCrossRefGoogle Scholar
  52. 52.
    Zhang, P., Toyoshima, C., Yonekura, K., Green, N. M., and Stokes, D. (1998) Structure of the calcium pump from sarcoplasmic reticulum at 8-A resolution. Nature, 392, 835–839.PubMedCrossRefGoogle Scholar
  53. 53.
    Auer, M., Scarborough, G. A., and Kuhlbrandt, W. (1998) Three-dimensional map of the plasma membrane H+-ATPase in the open conformation. Nature, 392, 840–843.PubMedCrossRefGoogle Scholar
  54. 54.
    Goldshleger, R. and S. J. Karlish (1999). The energy transduction mechanism of Na,K-ATPase studied with iron- catalyzed oxidative cleavage. J. Biol. Chem., 274(23): 16213–21.PubMedCrossRefGoogle Scholar
  55. 55.
    Goldshleger, R. and S. J. Karlish (1997). Fe-catalyzed cleavage of the alpha subunit of Na/K-ATPase: evidence for conformation-sensitive interactions between cytoplasmic domains. Proc. Natl. Acad. Sei., USA., 94(18): 9596–9601.CrossRefGoogle Scholar
  56. 56.
    Patchornik, G., Goldshleger, R., and Karlish, S. J. (2000) The complex ATP-Fe2+ serves as a specific affinity cleavage reagent in ATP-Mg2+ sites of Na,K-ATPase: altered ligation of Fe2+ (Mg2+) ions accompanies the E1P_E2P conformational change. Proc Natl Acad Sci USA. 97, 11954–9.PubMedCrossRefGoogle Scholar
  57. 57.
    Tal. D. M., Capasso, J. M., Munson, K., and Karlish, S. J. (2001) Proximity of Transmembrane Segments M3 and Ml of the alpha Subunit of Na+,K+-ATPase Revealed by Specific Oxidative Cleavage Mediated by a Complex of Cu(2+) Ions and 4,7-Diphenyl-l,10-phenanthroline. Biochemistry. 40, 12505–12514.PubMedCrossRefGoogle Scholar
  58. 58.
    Shin, J. M., R. Goldshleger, Munson, K. B., Sachs, G., and Karlish, S. J. (2001). Selective Fe2+-catalyzed oxidative cleavage of gastric H+,K+-ATPase. Implications for the energy transduction mechanism of P-type cation pumps. J. Biol. Chem., 276(51), 48440–48450.PubMedGoogle Scholar
  59. 59.
    Patchornik G, Munson, K., Sachs, G., and Karlish S.J. (2001) Interactions between N, P and A cytoplasmic domains of Na,K-ATPase studied with ATP-Fe2+-catalysed oxidative cleavage and molecular modeling. Evidence for one ATP site. (Manuscript to be submitted to J. Biol. Chem.)Google Scholar
  60. 60.
    Asano, S., Tega, Y., Konishi, K., Fujioka, M., and Takeguchi, N. (1996) Functional expression of gastric H+,K+-ATPase and site-directed mutagenesis of the putative cation binding site and catalytic center. J. Biol. Chem., 271(5), 2740–2745.PubMedCrossRefGoogle Scholar
  61. 61.
    Vagin, O., Munson, K., Lambrecht, N., Karlish, S. J., and Sachs, G. (2001) Mutational analysis of the K+-competitive inhibitor site of gastric H,K-ATPase. Biochemistry. 40(25), 7480–7490.PubMedCrossRefGoogle Scholar
  62. 62.
    Hermsen, H. P., Swarts, H. G., Wassink, L., Koenderink, J. B., Willems, P. H., and De Pont, J. J. (2001) Mimicking of K+ activation by double mutation of glutamate 795 and glutamate 820 of gastric H+,K+-ATPase. Biochemistry, 40(21), 6527–6533.PubMedCrossRefGoogle Scholar
  63. 63.
    Sweadner, K. J. and C. Donnet (2001). Structural similarities of Na,K-ATPase and SERCA, the Ca(2+)-ATPase of the sarcoplasmic reticulum. Biochem. J., 356(Pt 3): 685–704.PubMedCrossRefGoogle Scholar
  64. 64.
    Wallmark, B., Briving, C., Fryklund, J., Munson, K., Jackson, R., Mendlein, J., Rabon, E., and Sachs, G. (1987). Inhibition of gastric H,K-ATPase and acid secretion by SCH28080, a substituted pyridyl[l,2α]imidazole. J. Biol. Chem., 262, 2077–2084.PubMedGoogle Scholar
  65. 65.
    Lambrecht, N., K. Munson, et al. (2000). Comparison of covalent with reversible inhibitor binding sites of the gastric H,K-ATPase by site-directed mutagenesis. J Biol Chem 275(6): 4041–8.PubMedCrossRefGoogle Scholar
  66. 66.
    Munson, K. B., N. Lambrecht, et al. (2000). Effects of mutations in M4 of the gastric H+,K+-ATPase on inhibition kinetics of SCH28080. Biochemistry, 39, 2997–3004Google Scholar

Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • Olga Vagin
    • 2
  • Keith Munson
    • 2
  • Jai Moo Shin
    • 2
  • Nils Lambrecht
    • 2
  • Steve Karlish
    • 1
  • George Sachs
    • 2
  1. 1.Weizmann InstituteRehovotIsrael
  2. 2.UCLALos AngelesUSA

Personalised recommendations