Kininase

Yang H, Erdos E Second kininase in human blood plasma. Nature 1967 215 1402-1403. 

Cat K inhibitor therapy may also result in protection against the development of atherosclerosis. Cat K-deficient mice show reduced atherosclerotic lesion number and size on an ApoE receptor-deficient background, compared to wild-type animals [38,39]. Cat K is also associated with increased adiposity in humans [27,28] and may also play a role as a kininase, suggesting a role in blood pressure regulation [40]. Cat K has also been postulated to play a role in the pathology of rheumatoid arthritis [41,42],... 

Figure 17.5 The dual vasodilatoiy effect of inhibitors of the angiotensin-converting enzyme (ACE). The ACE inhibitors not only inhibit ACE but also the kininase which degrades bradykinin. (See also Chapter 22).

ACE is a rather nonspecific peptidase that can cleave C-terminal dipeptides from various peptides (dipeptidyl carboxypeptidase). As kininase 11, it contributes to the inactivation of kinins, such as bradykinin. ACE is also present in blood plasma however, enzyme localized in the luminal side of vascular endothelium is primarily responsible for the formation of angiotensin 11. The lung is rich in ACE, but kidneys, heart, and other organs also contain the enzyme. 

This zinc-dependent enzyme [EC 3.4.15.1] (also known as dipeptidyl carboxypeptidase I, dipeptidyl-dipeptidase A, kininase II, peptidase P, and carboxycathepsin) catalyzes the release of a C-terminal dipeptide at a neutral pH. The enzyme will also act on bradykinin. The presence of prolyl residues in angiotensin I and in bradykinin results in only single dipeptides being released due to the activity of this enzyme, a protein which belongs to the peptidase M2 family. The enzyme is a glycoprotein, generally membrane-bound, that is chloride ion-dependent. 

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. 

AIIRAs do not inhibit ACE (kininase II, the enzyme that converts angiotensin I to angiotensin II and degrades bradykinin), nor do they bind to or block other hormone receptors or ion channels known to be important in cardiovascular regulation. Pharmacokinetics ... 

The kallikrein-kinin system. Kininase II is identical to converting enzyme peptidyl dipeptidase (ACE). 

Sheikh IA, Kaplan AP. Assessment of kininases in rheumatic diseases and the effect of therapeutic agents. Arthritis Rheum 1987 30(2) 138-45. 

Bhoola KD, Figueroa CD, Worthy K. Bioregulation of kinins Kallikreins, kininogens, and kininases. Pharmacol Rev 1992 44 1-80. 

Costerousse O, Jaspard E, Wei L, Corvol P. Alhenc-Gelas F. The angiotensin I-converting enzyme (kininase II) Molecular organization and regulation of its expression in humans. J Cardiovasc Pharmacol 1992 20(Suppl. 9) S10-S15. 

The angiotensin I-converting enzyme (ACE), designated peptidyl-dipeptidase A (E.C.3.4.15.1), is identical to the bradykinin-metabolizing enzyme kininase II (38). Its early history and initial characterizations have been reviewed (51-54). It was discovered by Skeggs and co-workers (55), and in their pioneering work they showed it to be inhibited by ethylene-diaminetetraacetic acid (EDTA) (37), to remove a dipeptide from the carboxyl terminus of angiotensin I (then called hypertensin I [56]) and to be activated by sodium chloride (55). The fact that ACE is a Zn2+-contain-ing peptidase was first reported by Das and Sofler in 1975 (57). 

Studies with BPF were continued by Ferreira in the laboratories of J. R. Vane, where it was also shown to increase the in vivo stability of bradykinin (76). Importantly, Ng and Vane established BPF as a potent inhibitor of angiotensin I conversion in the lung (77), and Bakhle in Vane s department demonstrated that BPF blocked the formation of angiotensin II from angiotensin I in vitro (78). Subsequently, Erdos and co-workers (35) established the identity of the bradykinin-metabolizing enzyme kininase II with the ACE. 

The kinin-kallikrein system (kinin system) is a poorly delineated system of blood proteins that plays a role in inflammation, blood-pressure control, coagulation and pain. Kinins are small peptides produced from kininogen by kallikrein, which are subsequently degraded by kininases. They act on phospholipase and increase arachidonic acid release and thus prostaglandin (PGE2) production. 

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