Plasma carboxypeptidase Kininase

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. 

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. 

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. 

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. 

The half-life of kinins in the circulation is measured in seconds. By the action of plasma kininase they are rapidly converted to biologically inactive compounds. The main kininase in the plasma is the carboxypeptidase N (kininase I) that splits off the C-terminal residue of bradykinin— the Phe -Arg bond. In addition, another kininase was discovered in human plasma— kininase II. which splits the Pro -Phe bond of bradykinin. Moreover, kallidin and methionyl-kallidin can be converted to bradykinin by the action of plasma aminopeptidase. 

---