Kininogen precursor

Kininogens are precursors for kinin, and the two main types of them are highmolecular weight kininogen (HMWK) and lowmolecular weight kininogen (LMWK). HMWK also known as the Williams-Fitzgerald-Flaujeac factor is a protein from the blood coagulation system as well as the kinin-kallikrein system. It acts mainly as a cofactor on coagulation and inflammation, and has no intrinsic catalytic activity. LMWK is produced locally by numerous tissues, and secreted together with tissue kallikrein. Kininogens are synthesized in the liver and circulate in the plasma and other body fluids. The kinins are pharmacologically active polypeptides released in the tissues and body fluids as a result of the enzymatic action of kallikreins on kininogens. The kinin family includes bradykinin (BK) (Arg-Pro-Pro-gly-Phe- Ser-Pro-Phe-Arg), kallidin (Lys-Arg-Pro-Pro-Gly- Phe-Ser-Pro-Phe-Arg) and methionyl-lysyl-BK (Met-Lys-Arg-Pro-Pro-Gly-Phe-Arg). Kallidin and methionyl-lysyl-BK are converted into BK by aminopeptidases present in plasma and urine. Active tissue kallikrein acts on LMWK to release kallidin. The plasma kallikrein is found in circulation in an inactive form, which is known as prekallikrein or Fletcher factor. BK and kallidin act through activation of Gprotein- coupled constitutive B or inducible kinin B receptors linked to signaling pathways involving increased intracellular Ca concentrations and/or release of mediators including arachidonic acid metabolites, NO and EDHF (Endothelium-derived hyperpolarizing factor). In the cardiovascular system, the kallikrein-kinin system exerts a fine control of vascular smooth muscle tone and arterial blood pressure, and plays a significant cardioprotective effect.