Lysine-bradykinin

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... 

Bradykinin not only dilates arterioles but is thought to be linked with another accompaniment of the early inflammatory response, namely increased vascular permeability . The effect of several bradykinin analogs on vascular permeability was studied in guinea pigslS. Lysine bradykinin (kallidin) was more effective in increasing vascular permeability than was bradykinin itself. Glycyl bradykinin had about the same degree of activity as the parent compound, while all others were less active. 

This enzyme [EC 3.4.17.3] (also referred to as lysine carboxypeptidase, arginine carboxypeptidase, kininase I, or anaphylatoxin inactivator) is a zinc-dependent member of peptidase family M14. The enzyme hydrolyzes the peptide bond at the C-terminus provided that the C-terminal amino acid is either arginine or lysine. The enzyme inactivates bradykinin and anaphylatoxins in blood plasma. 

Bradykinin contains no lysines and two arginines. Cleavage will occur after the first arginine (carboxyl side) but not in front of the second arginine (amino side). The cleavage products will be... 

Bradykinin and kallidin ate potent vasodilators and hypotensive agents that have different peptide structures bradykinin is a nonapeptide, whereas kallidin is a decapepttde. Kdlidin is ly.syl-bradykinin that is. it has an additional lysine at the NH2 terminus of the chain. Tliese two compounds arc made available from kininogen. a hlood globulin, on hydrolysis. Trypsin, plasmin, or the proteases of certain snake venoms can catalyze the hydrolysis of kininogen. 

The human plasma metallo-protease carboxypeptidase N (CPN, arginine carboxypeptidase, anaphylatoxin inactivator, kininase I, EC 3.4.17.3) catalyzes the release of the basic amino acids lysine and arginine from the C-termini of peptides and proteins such as bradykinin and kallidin [95], the anaphylatoxins C3a, C4a, and C5a [96,97], fibrinopeptides 6A and 6D [98], hexapeptide enkephalins [99], protamine [100], and the creatine kinase MM-isoenzyme [101,102]. Its most likely physiological function is to protect the organism from the actions of potent peptides, which may escape from tissues or be released in the circulation. 

It acts in similar marmer to bradykinin, and it is easily converted to bradykinin by proteolytic cleavage of the N-terminal lysine catalyzed by aminopeptidases. 

Kallidin, the lysine-homologue of bradykinin, was as effective as bradykinin in increasing digital volume in man O both peptides may act by closure of arterial venous anastomosis which results in shunting of blood into capillary beds. 

Analysis of synthetic substrates hydrolyzed by the supernatant one sees in these cells, a good deal of dipeptidase and perhaps even tripeptidase activity, indicating a varied group of peptidases in these cells. In contrast to the blood enzyme (carboxypeptidase-N), enzymes in the white cells do not hydrolyze hippuryl-L-arginine or hippuryl-L-lysine. Therefore, from this evidence and other evidence we have, we have concluded that the type of attack by the kininase in the white cell is not the same as that of the plasma carboxypeptidase. The latter attacks at the carboxyl-terminal arginine of bradykinin. The attack by leucocyte kininases is probably somewhere in the middle of the molecule. 

Lysyl-bradykinin (kallidin), which has an additional lysine residue at the V-terminal atoms can also be released. This kinin-releasing activity is present in all venoms of Crotalidae and Viperidae. 

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