A liver metalloendopeptidase which degrades the circulating hypotensive peptide hormones bradykinin and atrial natriuretic peptide.
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 microM phosphoramidon and captopril, specific inhibitors of neutral endopeptidase (EC 3.4.24.11) and angiotensin-converting enzyme (EC 3.4.15.1), respectively. With M(r) 85 kDa the enzyme exhibits optimal activity at pH 7.5. The high affinity of this endopeptidase for bradykinin (Km = 10 microM) and for atrial natriuretic peptide (Km = 5 microM) suggests that it may play a physiological role in the inactivation of these circulating hypotensive peptide hormones.
Carvalho
K M
KM
Departamento de Fisiologia e Farmacologia, Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, CE, Brasil.
Nava
R A
RA
França
M S
MS
Medeiros
M A
MA
Camarão
G C
GC
Juliano
L
L
D000328:Adult; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D001920:Bradykinin / Q000378:metabolism*; D004789:Enzyme Activation; D006801:Humans; D008099:Liver / Q000201:enzymology*; D008666:Metalloendopeptidases / Q000302:isolation & purification* / Q000378:metabolism*
D009320:Atrial Natriuretic Factor; D008666:Metalloendopeptidases; D001920:Bradykinin