The Mechanism of Degradation of Bradykinin (Lysyl-Bradykinin) in Human Serum

Abstract

Bradykinin is rapidly degraded once it has been generated; this occurs most rapidly upon passage thru tissues such as the lung and it is also degraded in plasma or serum. Degradation of bradykinin in human plasma or serum appears to be mediated by two kininases. Carboxypepti-dase N or kininase I is known to remove the C-terminal peptide from bradykinin to yield des-arg bradykinin and free arginine. The angiotensin converting enzyme (ACE) or kininase II is a dipeptidase which removes the C-terminal phe-arg from bradykinin to yield a heptapeptide (Arg pro pro gly phe ser pro) and then cleave the C-terminal ser-pro from the heptapeptide leaving the pentapeptide Arg pro pro gly phe. Using purified ACE and bradykinin, there are no further cleavages seen upon incubation of the reactants for over 24 hours. Inokuchi and Nagamatsu first reported that des-arg -bradykinin could also be a substrate of ACE and that the products are Arg pro pro gly phe and ser-pro-phe indicating that the enzyme, in this instance has tripeptidase activity. We have confirmed this observation and the tripeptidase activity has been observed by others using alternative ACE substrates.