title: A liver metalloendopeptidase which degrades the circulating hypotensive peptide hormones bradykinin and atrial natriuretic peptide.
abstract: 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.
authors.affiliation: Departamento de Fisiologia e Farmacologia, Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, CE, Brasil.
authors.forename: K M
authors.initials: KM
authors.lastname: Carvalho
authors.forename: R A
authors.initials: RA
authors.lastname: Nava
authors.forename: M S
authors.initials: MS
authors.lastname: França
authors.forename: M A
authors.initials: MA
authors.lastname: Medeiros
authors.forename: G C
authors.initials: GC
authors.lastname: Camarão
authors.forename: L
authors.initials: L
authors.lastname: Juliano
mesh_terms: 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*
chemical_list: D009320:Atrial Natriuretic Factor; D008666:Metalloendopeptidases; D001920:Bradykinin