Substrate Modulation as a Control Mechanism of Plasma Multienzyme Systems

Conference paper
Part of the Colloquium der Gesellschaft für Biologische Chemie 26.–28. April 1979 in Mosbach/Baden book series (MOSBACH, volume 30)


Plasma contains several complex enzyme systems involved in homeostasis and defense reactions: the clotting, fibrinolytic, kallikrein-kinin, and complement systems. Other than cellular structures plasma lacks any compartmentalization, it is a homogeneous medium allowing deliberate contact and interaction of its constituents which are all dissolved. This special feature necessitates special mechanisms of activation and control. Hageman factor-dependent systems and complement depend on several preenzymes which are activated in sequence by more or less specific trigger events and are limited in activity by plasma enzyme inhibitors. Some of the complement enzymes are labile protein complexes, their activity decays by spontaneous dissociation. In addition, a third principle has turned out to work as a control mechanism: the necessity for a substrate (e.g., a complement component) to be modulated by interaction with a specific partner (e.g., another, activated complement component) in order to be accessible to hydrolytic activation by the relevant, specific enzyme. At least six reactions in which substrate modulation seems essential are now known.


Sialic Acid Alternative Complement Pathway Substrate Modulation High Molecular Weight Kininogen Cobra Venom Factor 
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  1. Chan JYC, Habal FM, Burrowes CE, Movat HZ (1976) Interaction between factor XII (Hageman factor), high molecular weight kininogen and prekallikrein. Thromb Res 9:423–432Google Scholar
  2. Fearon DT (1978) Regulation by membrane sialic acid of ßlH dependent decay-dissociation of the amplification C3 convertase of the alternative complement pathway. Proc Natl Acad Sci USA 75: 1971–1975PubMedCrossRefGoogle Scholar
  3. Fearon DT, Austen KF (1977) Activation of the alternative complement pathway with rabbit erythrocytes by circumvention of the regulatory action of endogenous control proteins. J Exp Med 146: 22–33PubMedCrossRefGoogle Scholar
  4. Fearon DT, Austen KF, Ruddy S (1974) Properdin factor D: Characterization of its active site and isolation of the precursor form. J Exp Med 139: 355–366Google Scholar
  5. Fujita T, Gigli I, Nussenzweig V (1978) Human C4-binding protein II. Role in proteolysis of C4b by C3b-inactivator. J Exp Med 148: 1044–1051PubMedCrossRefGoogle Scholar
  6. Gigli I, Austen KF (1969a) Fluid phase destruction of C2hu by Clhu I. Its enhancement and inhibition by homologous and heterologous C4. J Exp Med 129: 679–696PubMedCrossRefGoogle Scholar
  7. Gigli I, Austen KF (1969b) Fluid phase destruction of C2hu by Clhu II. Unmasking by C1hu of cihu specificity for C2hu. J Exp Med 130: 833–846PubMedCrossRefGoogle Scholar
  8. Götze O, Müller-Eberhard HJ (1971) The C3-activator system: an alternate pathway of complement activation. J Exp Med 134: 90s–l08sPubMedGoogle Scholar
  9. Griffin JH, Cochrane CG (1976) Mechanisms for the involvement of high molecular weight kininogen in surface-dependent reactions of Hageman factor. Proc Natl Acad Sci USA 73: 2554–2558PubMedCrossRefGoogle Scholar
  10. Kazatchkine MD, Fearon DT, Austen KF (1979) Human alternative pathway: membrane-associated sialic acid regulates the competition between B and ß1H for cell-bound C3b. J Immunol 122: 75–81PubMedGoogle Scholar
  11. Lesavre PH, Müller-Eberhard HJ (1978) Mechanism of action of factor D of the alternative complement pathway. J Exp Med 148: 1498–1509PubMedCrossRefGoogle Scholar
  12. Mandle RJ, Colman RW, Kaplan AP (1976) Identification of prekallikrein and high-molecular-weight kininogen as a complex in human plasma. Proc Natl Acad Sci USA 73: 4179–4183PubMedCrossRefGoogle Scholar
  13. Molenaar JL, Müller MAC, Engelfriet CP, Pondman KW (1974) Changes in antigenic properties of human C3 upon activation and conversion by trypsin. J Immunol 112: 1444–1451PubMedGoogle Scholar
  14. Müller-Eberhard HJ, Götze 0 (1972) C3 proactivator convertase and its mode of action. J Exp Med 135: 1003–1008Google Scholar
  15. sPangburn MK, Müller-Eberhard HJ (1978) Complement C3 convertase: cell surface restriction of ß1H control and generation of restriction on neuraminidase-treated cells. Proc Natl Acad Sci USA 75: 2416–2420CrossRefGoogle Scholar
  16. Pangburn MK, Schreiber RD, Müller-Eberhard HJ (1977) Human complement C3b inactivator: isolation, characterization, and demonstration of an absolute requirement for the serum protein ßlH for change of C3b and C4b in solution. J Exp Med 146: 257–270PubMedCrossRefGoogle Scholar
  17. Schiffman S, Lee P (1975) Partial purification and characterization of contact activation cofactor. J Clin Invest 56: 1082–1092PubMedCrossRefGoogle Scholar
  18. Vogt W, Dieminger L, Lynen R, Schmidt G (1974) Alternate pathway to complement activation in human serum: formation and composition of the comples with cobra venom factor which cleaves the third component of complement. Hoppe Seylers Z Physiol Chem 355: 171–183PubMedCrossRefGoogle Scholar
  19. Vogt W, Schmidt G, Dieminger L, Lynen R (1975) Formation and composition of the C3 activating enzyme complex of the properdin system. Sequential assembly of its components on solid-phase trypsin-agarose. Z Immunitätsforsch 149: 440–455Google Scholar
  20. Vogt W, Dames W, Schmidt G, Dieminger L (1977) Complement activation by properdin system: formation of a stoichiometric, C3 cleaving complex of properdin factor B with C3b. Immunochemistry 14: 201–205PubMedCrossRefGoogle Scholar
  21. Vogt W, Schmidt G, von Buttlar B, Dieminger L (1978) A new function of the activated third component of complement: binding to C5, an essential step for C5 activation. Immunology 34: 29–40PubMedGoogle Scholar
  22. Weiler JM, Daha MR, Austen KF, Fearon DT (1976) Control of the amplification convertase of complement by the plasma protein ßlH. Proc Natl Acad Sci USA 73: 3268–3272PubMedCrossRefGoogle Scholar
  23. Whaley K, Ruddy S (1976) Modulation of the alternative complement pathway by ß1H globulin. J Exp Med 144: 1147–1163PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1979

Authors and Affiliations

  • W. Vogt
    • 1
  1. 1.Department of Biochemical PharmacologyMax-Planck-Institut für Experimentelle MedizinGöttingenGermany

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