Inactivation of macrophage nitric oxide synthase activity by NG-methyl-L-arginine.
Biochem Biophys Res Commun
; 177(2): 828-33, 1991 Jun 14.
Article
em En
| MEDLINE
| ID: mdl-2049105
ABSTRACT
.N = O synthase catalyzes the oxidation of one of the two chemically equivalent guanido nitrogens of L-arginine to nitric oxide (.N = O). NG-Methyl-L-arginine has been previously characterized as a potent competitive inhibitor of both major types of .N = O synthases. Initial rate kinetics were performed with a spectrophotometric assay based on the oxidation of oxy- to methemoglobin by .N = O. NG-Methyl-L-arginine was a competitive inhibitor of .N = O synthase activity derived from activated murine macrophages with a Ki of 6.2 microM. When the enzyme was pre-incubated in the presence of the required cofactors NADPH and tetrahydrobiopterin, time- and concentration-dependent irreversible inactivation of the activity was observed. At 37 degrees C the kinact was 0.050 min-1. This inactivation process exhibited substrate protection, saturation kinetics and required the cofactors necessary for enzymatic turnover. These data indicate that NG-methyl-L-arginine acts as a mechanism-based enzyme inactivator of murine macrophage .N = O synthase.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Arginina
/
Ureia
/
Macrófagos
/
Óxido Nítrico
Limite:
Animals
Idioma:
En
Revista:
Biochem Biophys Res Commun
Ano de publicação:
1991
Tipo de documento:
Article