Human kallikrein enzyme

Fifth, certain kallikreins, such as human kallikrein 6, are highly expressed in the central nervous system. It has previously been shown that hK6, and possibly some other kallikreins, are implicated in inflammatory reactions within the central nervous system that lead to demyelination. The association of hK6 and some other kallikreins with AD and multiple sclerosis points to the possibility that some of these enzymes may play important roles within the central nervous system. In addition, many of these enzymes have been found in endocrine tissues such as the islets of Langerhans, thyroid, pituitary, and others, pointing to the possibility that they may participate in prohormone or hormone processing. 

Kinins. These hormones are small peptides that induce contraction of smooth muscles, lower blood pressure (Box 22-D), and increase vascular permeability.176 They also have a function in contact-activated blood coagulation. The most important human kinins are the nonapeptide bradykinin177178 and the related decapeptide lysine-bradykinin (Table 30-4). Other forms such as Met-Lys-bradykinin and Ile-Ser-bradykinin (T-kinin) are also known. The precursors to the kinins, the kininogens,176 are cleaved by the protease kallikrein (Fig. 12-17) or by kallikreinlike enzymes to form the kinins. Kinins are suspected of being important producers of pain in inflammatory conditions such as arthritis.1763... 

Antithrombin is a member of the SERPIN superfamily of proteins, which includes the inhibitors a2 an1 Pbsniin, ar antichymotrypsin, and a -proteinase inhibitor (79). Antithrombin is considered to be the primary inhibitor of coagulation (80) and targets most coagulation proteases as well as the enzymes trypsin, plasmin, and kallikrein (81). Inhibition takes place when a stoichiometric complex between the active site serine of the protease and the ARG393-SER394 bond of antithrombin forms (82,83), The tertiary structure of antithrombin resembles a,-antitrypsin in that it is folded into N-terminal domain helices and (3-sheets. This tertiary structure is maintained by the formation of three disulfide bonds (71). Four glycosylation sites exist on human... 

Kallikrein is a proteinase enzyme, which converts kininogen to vasodilative kinin peptides. The human tissue kallikrein gene, in the form of naked pDNA (CMV-cHK), was directly delivered by intracerebroventricular injection into hypertensive rats. The expression of human tissue kallikrein protein was identified in the cortex, cerebellum, brain stem, hippocampus, and hypothalamus of the treated rats. The expression level and its effect could lead to understanding the role of vasodilative KKS on the pathogenesis of hypertension. 

The acyl derivatives of kallikrein were prepared from porcine pancreatic kallikrein. In our experiments we used benzoyl-kallikrein. By deacylation the enzymatically active kallikrein was generated in plasma from benzoyl-kallikrein demonstrated by means of its amidolytic activity. From the time course of reactivation of benzoyl-kallikrein, a half-time of reactivation of 54 minutes was calculated. Benzoyl- kallikrein was protected from being inactivated by plasma inhibitors. Therefore, the kallikrein activity in plasma was higher after incubation with benzoyl-kallikrein than after incubation with the free enzyme. A comparatively high kinin activity was found in rabbit plasma. In human plasma, this effect was prevented by rapid degradation of kinin [42]. 

The five inhibitors were also tested against mouse plasma kallikrein (79% sequence identity) or the homologous human serine proteases factor XIa (63% sequaice identity) and thrombin (36% sequence identity). None inhibited these enzymes at the highest concentration tested (10 pM). 

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