Brazilian Journal of Medical and Biological Research
On-line version ISSN 1414-431X
CARVALHO, K.M. et al. A liver metalloendopeptidase which degrades the circulating hypotensive peptide hormones bradykinin and atrial natriuretic peptide. Braz J Med Biol Res [online]. 1999, vol.32, n.1, pp. 51-54. ISSN 1414-431X. http://dx.doi.org/10.1590/S0100-879X1999000100007.
A new metalloendopeptidase was purified to apparent homogeneity from a homogenate of normal human liver using successive steps of chromatography on DEAE-cellulose, hydroxyapatite and Sephacryl S-200. The purified enzyme hydrolyzed the Pro7-Phe8 bond of bradykinin and the Ser25-Tyr26 bond of atrial natriuretic peptide. No cleavage was produced in other peptide hormones such as vasopressin, oxytocin or Met- and Leu-enkephalin. This enzyme activity was inhibited by 1 mM divalent cation chelators such as EDTA, EGTA and o-phenanthroline and was insensitive to 1 µM phosphoramidon and captopril, specific inhibitors of neutral endopeptidase (EC 184.108.40.206) and angiotensin-converting enzyme (EC 220.127.116.11), respectively. With Mr 85 kDa, the enzyme exhibits optimal activity at pH 7.5. The high affinity of this endopeptidase for bradykinin (Km = 10 µM) and for atrial natriuretic peptide (Km = 5 µM) suggests that it may play a physiological role in the inactivation of these circulating hypotensive peptide hormones.
Keywords : liver metalloendopeptidase; bradykinin; atrial natriuretic peptide.