Studies of the digestion of bradykinin, lysyl bradykinin, and kinin-degradation products by carboxypeptidases A, B, and N.
We have compared the digestion of bradykinin, lysyl bradykinin, and kinin degradation products by carboxypeptidases N, B and A (CPN, CPB and CPA). Carboxypeptidase N removed the C-terminal arginine from bradykinin or lysyl bradykinin to leave the des-Arg derivative of each, and no further degradation occurred regardless of enzyme concentration or time of incubation. However, both CPB and CPA degraded the des-Arg derivatives to remove the C-terminal phenylalanine. The inhibitory effect of phosphate ions upon this activity of CPB (but not CPA) suggests that CPA may be responsible for the formation of free phenylalanine seen upon degradation of kinins in plasma or serum. However, angiotensin converting enzyme degraded des-Arg9-bradykinin in plasma or serum prior to such Phe removal to yield the pentapeptide Arg-Pro-Pro-Gly-Phe and the tripeptide Ser-Pro-Phe. We demonstrated that CPB degraded Arg-Pro-Pro-Gly-Phe but not Ser-Pro-Phe; this reaction was also inhibited by phosphate ions. Carboxypeptidase A, on the other hand, liberated Phe from both peptides in phosphate-buffered saline and accounted, at least in part, for the free phenylalanine detected. Carboxypeptidase N did not digest the aforementioned pentapeptide or tripeptide. It is clear that carboxypeptidase B and carboxypeptidase A had overlapping activities, depending upon the substrate tested, and were distinguished by the effects of different ionic environments. We further suggest a role for carboxypeptidases other than CPN in the degradation of kinins in human plasma or serum.
D001120:Arginine / Q000378:metabolism; D001920:Bradykinin / Q000031:analogs & derivatives / Q000378:metabolism*; D043424:Carboxypeptidase B; D002268:Carboxypeptidases / Q000494:pharmacology*; D043422:Carboxypeptidases A; D007609:Kallidin / Q000378:metabolism*; D007705:Kinins / Q000378:metabolism*; D001121:Lysine Carboxypeptidase / Q000494:pharmacology*; D010649:Phenylalanine / Q000378:metabolism
D007705:Kinins; C024626:bradykinin, des-Arg(9)-; D007609:Kallidin; D010649:Phenylalanine; D001120:Arginine; D002268:Carboxypeptidases; D043422:Carboxypeptidases A; D043424:Carboxypeptidase B; D001121:Lysine Carboxypeptidase; D001920:Bradykinin