Kininogens

Title: Kininogens
CAS Registry Number: 12244-26-7
Literature References: Precursor molecules of the vasoactive kinins. Also serve as endogenous cysteine proteinase inhibitors known as type 3 cystatins and are essential cofactors for the contact activation of blood clotting. Single chain glycoproteins synthesized by hepatocytes and secreted into plasma. Three forms have been identified in mammals: H-kininogen (HK) having a molecular mass of 88-115 kDa, L-kininogen (LK) with molecular mass of 50-68 kDa, and T-kininogen, mol wt 68 kDa, which has been found only in rats. Structures consist of an amino-terminal heavy chain portion linked to a carboxy terminal light chain by the kinin segment which is released by kallikrein, q.v. The heavy chain contains 3 tandemly repeated domains that are structurally homologous to the type-2 cystatins, q.v. The HK light chain contains 2 additional domains that are responsible for the procoagulant activity. Purification from bovine serum: E. Habermann et al., Z. Phys. Chem. 332, 121 (1963); eidem, Biochem. Z. 337, 440 (1963). Isoln of 2 forms from human plasma: F. M. Habal et al., Biochem. Pharmacol. 23, 2291 (1974). Review of purification methods and structure: H. Kato et al., Methods Enzymol. 80, Part C, 172-199 (1981). Identity with a-cysteine proteinase inhibitors: W. Müller-Esterl et al., FEBS Lett. 182, 310 (1985). Review of structure and function: R. A. DeLa Cadena, R. W. Colman, Trends Pharmacol. Sci. 12, 272-275 (1991); of biological role: K. D. Bhoola et al., Pharmacol. Rev. 44, 1-80 (1992); C. Blais, Jr. et al., Peptides 21, 1903-1940 (2000).
Derivative Type: H-Kininogen
CAS Registry Number: 308068-04-4
Additional Names: a1-CPI; a1-cysteine proteinase inhibitor; high molecular weight kininogen
Literature References: Preferred substrate for plasma kallikrein to release bradykinin, q.v.
Properties: a-globulin; isoelectric point 4.3. Plasma conc in humans: 90 mg/ml.
Derivative Type: L-Kininogen
Additional Names: a2-CPI; a2-cysteine proteinase inhibitor; low molecular weight kininogen
Literature References: Preferred substrate for tissue kallikrein to release kallidin, q.v.
Properties: b-globulin; isoelectric point 4.7. Plasma conc in humans: 170 mg/ml.
Kinoprene Kistrin Kitol Kodel? Kojic Acid

Kininogens are proteins that are defined by their role as precursors for kinin, but that also can have additional roles.

The two main types are:

  • High-molecular-weight kininogen, which is produced by the liver together with prekallikrein. It acts mainly as a cofactor on coagulation and inflammation, and has no intrinsic catalytic activity. These high molecular weight kininogens are cleaved into bradykinin and kallidin by tissue and plasma kallikreins.
  • Low-molecular-weight kininogen, which is produced locally by numerous tissues, and secreted together with tissue kallikrein.

They are both spliced from the same precursor.

A third type, T-kininogen, is found in rats but not humans.[1]