The First Cleavage Site in Pepsinogen Activation

  • John Kay
  • Colin W. Dykes
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 92)


The carboxyl proteases which are responsible for initiating gastric digestion of proteins in most mammals are synthesized in precursor form. The pepsinogens from pig, cow and calf prochymosin, in particular, are well-characterized proteins (see Foltmann and Pedersen, Chapter 1 in this volume). These zymogens convert themselves into the more active forms of their respective enzymes by undergoing limited proteolysis in which an NH2-terminal ‘activation’ segment is cleaved off (Fig.l). In porcine pepsinogen, the activation follows an intramolecular mechanism at pH 3 and below, whereas above this pH value the reaction involves the intermolecular action of newly formed pepsin interacting with pepsinogen to form even more pepsin (1–3).


Activation Segment Formate Buffer Dansyl Chloride Active Pepsin Intermediate Protein 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Al-Janabi, J., Hartsuck, J. A., and Tang, J. (1972) J. Biol. Chem. 247, 4628–4632PubMedGoogle Scholar
  2. 2.
    McPhie, P. (1972) J. Biol. Chem. 247, 4277–4281PubMedGoogle Scholar
  3. 3.
    Sanny, C. G., Hartsuck, J. A., and Tang, J. (1975) J. Biol. Chem. 250, 2635–2639PubMedGoogle Scholar
  4. 4.
    Sepulveda, P., Marciniszyn, J. P., Liu, D., and Tang, J. (1975) J. Biol. Chem. 250, 5082–5088PubMedGoogle Scholar
  5. 5.
    Harboe, M., Andersen, P. M., Foltmann, B., Kay, J., and Kassell, B. (1974) J. Biol. Chem. 249, 4487–4494PubMedGoogle Scholar
  6. 6.
    Pedersen, V. B., and Foltmann, B. (1975) Eur. J. Biochem. 55, 95–103PubMedCrossRefGoogle Scholar
  7. 7.
    Tang, J. (1976) Trends in Biochem. Sci. 1, 205–208Google Scholar
  8. 8.
    Aoyagi, T., Kunimoto, S., Morishima, H., Takeuchi, T., and Umezawa, H. (1971) J. Antibiot. 24, 687–694PubMedCrossRefGoogle Scholar
  9. 9.
    Neumann, H., Zehavi, U., and Tanksley, T. D. (1969) Biochem. Biophys. Res. Commun. 36, 151–155PubMedCrossRefGoogle Scholar
  10. 10.
    Ryle, A. P. (1970) Methods Enzymol. 19, 316–336CrossRefGoogle Scholar
  11. 11.
    Kay, J. (1972) Abstr. Fed. Eur. Biochem. Soc. Meet. 8th, Amsterdam, Abstr. No. 458Google Scholar
  12. 12.
    Nevaldine, B., and Kassell, B. (1971) Biochim. Biophys. Acta 250, 207–209PubMedCrossRefGoogle Scholar
  13. 13.
    Kunimoto, S., Aoyagi, T., Nishizawa, R., Komai, T., Takeuchi, T, and Umezawa, H. (1974) J. Antibiot. 27, 413–418PubMedCrossRefGoogle Scholar
  14. 14.
    Kay, J., and Dykes, C. W. (1976) Biochem. J. 157, 499–502PubMedGoogle Scholar
  15. 15.
    Feinstein, G., and Feeney, R. E. (1966) J. Biol. Chem. 241, 5183–5189PubMedGoogle Scholar
  16. 16.
    Anson, M. L. (1948) in Crystalline Enzymes (Northrop, J. H., Kunitz, M., and Herriott, R. M. eds) pp. 305, Columbia Univ Press, New York.Google Scholar
  17. 17.
    Kay, J. (1975) Anal. Biochem. 67, 585–589PubMedCrossRefGoogle Scholar
  18. 18.
    Dykes, C. W., and Kay, J. (1976) Biochem. J. 153, 141–144PubMedGoogle Scholar
  19. 19.
    Clamp, J. R., Dawson, G., and Hough, L. (1967) Biochim. Biophys. Acta 148, 342–349PubMedCrossRefGoogle Scholar
  20. 20.
    Bhatti, T., Chambers, R. E., and Clamp, J. R. (1970) Biochim. Biophys. Acta 222, 339–347PubMedCrossRefGoogle Scholar
  21. 21.
    Knight, C. G., and Barrett, A. J. (1976) Biochem. J. 155, 117–125PubMedGoogle Scholar
  22. 22.
    Funatsu, M., Harada, Y., Hayashi, K., and Jirgensons, B. (1971) Agr. Biol. Chem. 35, 566–572CrossRefGoogle Scholar
  23. 23.
    Wang, J. L., and Edelman, G. M. (1971) J. Biol. Chem. 246, 1185–1191PubMedGoogle Scholar
  24. 24.
    Herriott, R. M. (1941) J. Gen. Physiol. 24, 325–338PubMedCrossRefGoogle Scholar
  25. 25.
    Anderson, W., and Harthill, J. E. (1973) Nature, 243, 417–419PubMedCrossRefGoogle Scholar
  26. 26.
    Marciniszyn, J. P., and Kassell, B. (1971) J. Biol. Chem. 246, 6560–6565PubMedGoogle Scholar
  27. 27.
    Bohak, Z. (1969) J. Biol. Chem. 244, 4638–4648Google Scholar
  28. 28.
    Green, M. L., and Llewellin, J. (1973) Biochem. J. 133, 105–115PubMedGoogle Scholar
  29. 29.
    Pedersen, V. B. (1976) Abstr. Xth Int. Union Biochem. Meet. Hamburg, Abstr. No. 04–3–319Google Scholar
  30. 30.
    Kay, J. and Dykes, C. W. (1975) Abstr. Fed. Eur. Biochem. Soc. Meet. X{h, Paris, Abstr. No. 758Google Scholar
  31. 31.
    Marciniszyn, J. P., Huang, J. S., Hartsuck, J. A., and Tang, J. (1976) J. Biol. Chem. 251, 7095–7102PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1977

Authors and Affiliations

  • John Kay
    • 1
  • Colin W. Dykes
    • 1
  1. 1.Department of BiochemistryUniversity CollegeCardiffWales, UK

Personalised recommendations