Renin and Precursors: Purification, Characterization, and Studies on Active Site

  • Tadashi Inagami
  • Kazuo Murakami
  • Kunio Misono
  • Robert J. Workman
  • Stanley Cohen
  • Yasunobu Suketa
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 92)

Abstract

Renin is an enzyme elaborated in juxta glomerular cells of the kidney and released into the blood stream by various stimuli. Although it is an endopeptidase, its function is strictly limited to the formation of angiotensin I from angiotensinogen by the cleavage of a unique leucyl-leucine peptide bond in this substrate molecule (Fig.l). Angiotensin I is converted into the octapeptide angiotensin II by a carboxydipeptidase, known as converting enzyme, and thenceforth to the heptapeptide angiotensin III by an aminopeptidase. Not only is angiotensin II the most potent pressor substance known, but both angiotensin II and III also stimulate the adrenal cortex to release the mineral corticoid aldosterone. Thus, renin triggers a chain of events aimed at elevating the blood pressure. Because of its strategically important position in the renin-angiosin-aldosterone system, the activity of renin in the circulation is tightly regulated by intricate multiple feedback control mechanisms. Excellent reviews on the control of renin release have been published recently (1–4).

Keywords

Acidic Protease Porcine Kidney Human Renin Cupric Acetate Renin Substrate 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Oparil, S., and Haber, E. (1974) N. Eng. J. Med. 291, 389–401Google Scholar
  2. 2.
    Davis, J. O. (1973) Am. J. Med. 55, 339–350CrossRefGoogle Scholar
  3. 3.
    Zanchetti, A., Stella, A., Leonetti, G., Morganti, A., and Terzoli, L. (1976) Am. J. Cardiol. 37, 675–691PubMedCrossRefGoogle Scholar
  4. 4.
    Laragh, J., and Sealey, J. E. (1973) in Handbook of Physiology (Orloff, J., and Berliner, R. W., eds) Section 8 Renal Physiol., pp. 831–908, American Physiological Society, Washington, D.C.Google Scholar
  5. 5.
    Werle, E., Vogel, R., and Goldell, L. F. (1957) Arch. Exp. Pathol. 230, 236–244Google Scholar
  6. 6.
    Koch, C., and Unger, H. J. (1969) Naunyn-Schmiedeberg Arch. Pharmakol. 264, 257–258Google Scholar
  7. 7.
    Cohen, S., Taylor, J. M., Murakami, K., Michelakis, A. M., and Inagami, T. (1972) Biochemistry 11, 4286–4292PubMedCrossRefGoogle Scholar
  8. 8.
    Haas, E., Lumfrom, H., and Goldblatt, H. (1953) Arch. Biochem. Biophys. 42, 368–386PubMedCrossRefGoogle Scholar
  9. 9.
    Passanti, G. T. (1959) Biochim. Biophys. Acta 34, 246–248Google Scholar
  10. 10.
    Nairn, R. C., Chadwick, C. S., and Fraser, K. B. (1960) Brit. J. Exp. Path. 41, 214–221PubMedGoogle Scholar
  11. 11.
    Maier, G. D., and Morgan, W. S. (1966) Biochim. Biophys. Acta 128, 193–195PubMedCrossRefGoogle Scholar
  12. 12.
    Peart, W. S., Lloyd, A. M., Thatcher, G. N., Lever, A. F., Payne, N., and Stone, N. (1966) Biochem. J. 99, 708–716PubMedGoogle Scholar
  13. 13.
    Skeggs, L. T., Lentz, K. E., Kahn, J. R., and Hochstrasser, H. (1967) Cir. Res. 21, Suppl. II, 91–107Google Scholar
  14. 14.
    Newsome, H. H. (1969) Biochim. Biophys. Acta 185, 247–250PubMedCrossRefGoogle Scholar
  15. 15.
    Waldhäusl, W. K., Lucas, C. P., Conn, J. W., Lutz, J. H., and Cohen, E. L. (1970) Biochim. Biophys. Acta 221, 536–548Google Scholar
  16. 16.
    Lucas, C. P., Fukuchi, S., Conn, J. W., Berlinger, F. G., Waldhäusl, W. K., Cohen, E. L., and Rovner, D. R. (1970) J. Lab. Clin. Med. 76, 689–700PubMedGoogle Scholar
  17. 17.
    Poulsen, K., Burton, J., and Haber, E. (1975) Biochim. Biophys. Acta 400, 258–262PubMedCrossRefGoogle Scholar
  18. 18.
    Lauritzen, M., Damsgaard, J. J., Rubin, I., and Lauritzen, E. (1976) Biochem. J. 155, 317–323PubMedGoogle Scholar
  19. 19.
    Devaux, C., Menard, J., Sicard, P., and Corvol, P. (1976) Eur. J. Biochem. 64, 621–627PubMedCrossRefGoogle Scholar
  20. 20.
    Majestravich, Jr., J., Ontjes, D. A., and Roberts, J. C. (1974) Proc. Soc. Exp. Biol. Med. 146, 674–679CrossRefGoogle Scholar
  21. 21.
    Burton, J., Poulsen, K., and Haber, E. (1975) Biochemistry 14, 3892–3898PubMedCrossRefGoogle Scholar
  22. 22.
    Umezawa, H., Aoyagi, T., Morishima, H., Matsuzaki, M., Hamada, H., and Takeuchi, T. (1970) J. Antibiot. 23, 259–262PubMedCrossRefGoogle Scholar
  23. 23.
    Aoyagi, T., Morishima, H., Nishizawa, R., Kunimoto, S., Takuchi, T., and Umezawa, H. (1972) J. Antibiot. 25, 689–694PubMedCrossRefGoogle Scholar
  24. 24.
    Gross, F., Lazar, J., and Orth, H. (1972) Science 175, 656PubMedCrossRefGoogle Scholar
  25. 25.
    Miller, R. P., Pope, C. J., Wilson, C. W., and Devito, E. (1972) Biochem. Pharmacol. 21, 2941–2944PubMedCrossRefGoogle Scholar
  26. 26.
    McKown, M. M., Workman, R. J., and Gregerman, R. I. (1974) J. Biol. Chem. 249, 7770–7774PubMedGoogle Scholar
  27. 27.
    Corvol, P., Devaux, C., and Menard, J. (1973) FEBS Lett. 34, 189–192PubMedCrossRefGoogle Scholar
  28. 28.
    Murakami, K., Inagami, T., Michelakis, A. M., Cohen, S. (1973) Biochem. Biophys. Res. Commun. 54, 482–487Google Scholar
  29. 29.
    Murakami, K., and Inagami, T. (1975) Biochem. Biophys. Res. Commun. 62, 757–763Google Scholar
  30. 30.
    Rubin, I. (1972) Scand. J. Clin. Lab. Invest. 29, 51–58PubMedCrossRefGoogle Scholar
  31. 31.
    Matoba, T., Murakami, K., and Inagami, T. to be published Murakami, K., Inagami, T., and Haas, E., Cir. Res. in pressGoogle Scholar
  32. 32.
    Murakami, K., Inagami, T., and Haas, E., Cir. Res. in pressGoogle Scholar
  33. 33.
    Pickens, P. T., Bumpus, F. M., Lloyd, A. M., Smeby, R. R., and Page, I. H. (1965) Cir. Res. 17, 438–448CrossRefGoogle Scholar
  34. 34.
    Reniharz, A., Roth, M., Haefeli, L., and Schaechtelin, G. (1971) Enzyme 12, 212–218Google Scholar
  35. 35.
    Delpierre, G. R., and Fruton, J. S. (1965) Proc. Natl. Acad. Sci. U.S.A. 54, 1161–1167PubMedCrossRefGoogle Scholar
  36. 36.
    Rajagopalan, T. G., Stein, W. H., and Moore, S. (1966) J. Biol. Chem. 241, 4295–4297PubMedGoogle Scholar
  37. 37.
    Tang, J. (1971) J. Biol. Chem. 246, 4510–4517Google Scholar
  38. 38.
    Inagami, T., Misono, K., and Michelakis, A. M.,(1974) Biochem. Biophys. Res. Commun. 56, 503–509CrossRefGoogle Scholar
  39. 39.
    McKown, M., and Gregerman, R. I. (1975) Lif Sci. 16, 71–79CrossRefGoogle Scholar
  40. 40.
    Workman, R. J., and Inagami, T. (1975) Endocrinology 95 Suppl., 138Google Scholar
  41. 41.
    Bayliss, R. S., Knowles, J. R., Wybrandt, G. B. (1969) Biochem. J. 113, 377–386PubMedGoogle Scholar
  42. 42.
    Keilova, H. (1970) FEBS Lett. 6, 312–314PubMedCrossRefGoogle Scholar
  43. 43.
    Sodek, J., and Hofmann, T. (1970) Can. J. Biochem. 48, 1014–1016PubMedCrossRefGoogle Scholar
  44. 44.
    Roth, M., and Reinharz, A. (1966) Hely. Chim. Acta 49, 1903–1907CrossRefGoogle Scholar
  45. 45.
    Skeggs, L. T., Lentz, K. E., Kahn, J. R., and Schumway, N. P. (1958) J. Exp. Med. 108, 283–297PubMedCrossRefGoogle Scholar
  46. 46.
    Skeggs, L. T., Lentz, K. E., Kahn, J. R., and Hochstrasser, H. (1968) J. Exp. Med. 128, 13–34PubMedCrossRefGoogle Scholar
  47. 47.
    Suketa, Y., and Inagami, T. (1975) Biochemistry 14, 3188–3194PubMedCrossRefGoogle Scholar
  48. 48.
    Morris, B. J., and Lumbers, E. R. (1972) Biochim. Biophys. Acta 289, 385–385PubMedCrossRefGoogle Scholar
  49. 49.
    Boyd, G. W. (1973) in Hypertension ‘72 (Genet, J., and Koiw, E., eds) pp. 161–169, Springer, Berlin and New YorkGoogle Scholar
  50. 50.
    Leckie, B. (1973) Clin. Sci. 44, 301–304PubMedGoogle Scholar
  51. 51.
    Boyd, G. W. (1974) Cir. Res. 35, 426–438CrossRefGoogle Scholar
  52. 52.
    Day, R. P., and Luetscher, J. A. (1975) J. Clin. Endocrinol. Metab. 38, 923–926CrossRefGoogle Scholar
  53. 53.
    Day, R. P., and Leutscher, J. A. (1975) J. Clin. Endocrinol. Metab. 40, 1085–1093PubMedCrossRefGoogle Scholar
  54. 54.
    Skinner, S. L., Cran, E. J., Gibson, R., Taylor, R., Walter, W. A. W., and Catt, K. J. (1975) Am. J. Obstet. Gynecol. 121, 623–630Google Scholar
  55. 55.
    Leckie, B. J., and McConnell, A. (1975) Cir. Res. 36, 513–519CrossRefGoogle Scholar
  56. 56.
    Inagami, T., and Murakami, K. (1975) Circulation 52 Suppl. II, 14Google Scholar
  57. 57.
    Levine, M., Lentz, K. E., Kahn, J. R., Dorer, F. E., Skeggs, L. T. (1976) Cir. Res. 38 Suppl. II 90–94CrossRefGoogle Scholar
  58. 58.
    Barrett, J. D., Eggena, P., Sambhi, M. P. (1977) Cir. Res. in pressGoogle Scholar
  59. 59.
    Aoi, W., Grim, C. E., and Weinberger, M. H. (1977) Cir. Res. in pressGoogle Scholar
  60. 60.
    Inagami, T., Murakami, K. (1977) Cir. Res. in pressGoogle Scholar
  61. 61.
    Day, R. P., Leutscher, J. A., and Gonzales, C. M. (1975) J. Clin. Endocrinol. Metab. 40, 1078–1084PubMedCrossRefGoogle Scholar
  62. 62.
    Slater, E. E., and Haber, E. (1976) Circulation 54, Suppl. II 143 AbsGoogle Scholar
  63. 63.
    Reniharz, A., and Roth, M. (1969) Eur. J. Biochem. 7, 334–339CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1977

Authors and Affiliations

  • Tadashi Inagami
    • 1
  • Kazuo Murakami
    • 1
  • Kunio Misono
    • 1
  • Robert J. Workman
    • 1
  • Stanley Cohen
    • 1
  • Yasunobu Suketa
    • 1
  1. 1.Departments of Biochemistry and MedicineVanderbilt University School of MedicineNashvilleUSA

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