Nitric Oxide Synthases: Properties and Catalytic Mechanism
Annual Review of PhysiologyPublished 1 October 1995
Owen W. Griffith, Dennis J. Stuehr
Citations1,289
SJR quartileQ1
SJR score7.82
SNIP4.62
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Abstract
Macrophage polarization refers to how macrophages have been activated at a given point in space and time. Polarization is not fixed, as macrophages are sufficiently plastic to integrate multiple signals, such as those from microbes, damaged tissues, and ...Read More
Keywords
MedicineBiochemistry, Genetics and Molecular Biology
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The pharmacology and toxicology of NO is described, and the major techniques for measuring NO in biological models are reviewed and several new amperometric microelectrode assays offer the potential to measure smaller amounts of NO, permitting NO measurement in intact issues and from single cells.
Journal of Biological ChemistryMolecular cloning and functional expression of an inducible nitric oxide synthase from a murine macrophage cell line.
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American Journal of Respiratory Cell and Molecular BiologyNitric Oxide Synthase in Human and Rat Lung: Immunocytochemical and Histochemical Localization
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Journal of Clinical InvestigationMolecular cloning and characterization of the constitutive bovine aortic endothelial cell nitric oxide synthase.
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European Journal of PharmacologySelective inhibition of the inducible nitric oxide synthase by aminoguanidine
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GC/MS experiments using L-[guanido-15N2]arginine established that the NO2-/NO3- and the nitrosyl group of N-nitrosomorpholine were derived exclusively from one or both of the terminal guanido nitrogens of arginine.
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The discovery of the release of NO by vascular endotheiial cells, the blosynthetk pathway leading to its generation, and its interaction with other vasoactive substances opens up new avenues for research into the physiology and pathophysioiogy of the vessd wall.
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The purification of inducible .NO synthase (EC 1.14.23) from activated murine macrophages using a two-column procedure is reported, indicating that the native enzyme exists as a dimer.
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The similarity (88%) between the human chondrocyte NO synthase cDNA sequence and that reported for the murine macrophage suggests that the inducible class of enzyme is conserved between different cell types and across species.
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Activated J774 cells form NO from omega-hydroxyl-L-arginine, confirming the proposal that this compound is an intermediate in the biosynthesis of NO, and determining the source of the oxygen in both NO and in citrulline.
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NA inhibition of inducible mouse macrophage NOS (iNOS) was weaker (Ki = 4.4 microM) and rapidly reversible and NA was a 300-fold more potent inhibitor of bovine brain cNOS than mousemacrophage iNOS.
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Results indicate that the ureido oxygen of the L-citrulline product of macrophage NO.synthase derives from dioxygen and not from water.
The Journal of ImmunologyInducible nitric oxide synthase from a rat alveolar macrophage cell line is inhibited by nitric oxide.
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Observations indicate that enzyme-bound heme plays a mechanistic role in the catalytic conversion of L-arginine to NO plus L-citrulline and NO may function as a negative feedback modulator of inducible NO synthase by interacting with enzyme- bound heme.
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The combined results exclude H4B as a stoichiometric reactant and suggest that H4 B enhances product formation by protecting enzyme activity against progressive loss, and preliminary studies indicate that the decreased activity in the absence of added H 4B does not depend on catalytic turnover of the enzyme.
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After prolonged incubation periods, NG-nitro-L-arginine induced a rapid inactivation of the enzyme, whereas the methyl derivative turned out to be a substrate of NO synthase, which was slowly converted into stoichiometric amounts of NO and L-citrulline.
PubMedIsoforms of nitric oxide synthase: functions in the cardiovascular system.
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Endothelium-derived NO is a physiologically significant vasodilator and inhibitor of platelet aggregation and adhesion, and vascular NO can prevent leukocyte adhesion to the endothelium by interfering with the adhesion molecule CD11/CD18, and NO has also been shown to inhibit the proliferation of vascular smooth muscle cells.
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Data indicate that the placental NOS is the constitutive NOS isozyme from endothelial tissue, and that the purified NOS was absolutely dependent on calcium and calmodulin.
Biochemical and Biophysical Research CommunicationsParticular Ability of Liver P450s3a to Catalyze the Oxidation of Nω-Hydroxyarginine to Citrulline and Nitrogen Oxides and Occurrence in NO Synthases of a Sequence Very Similar to the Heme-Binding Sequence in P450s
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The particular ability of P450s of the 3A subfamily to catalyze the second step of the oxidation of L-arginine by NO synthases (NOS) is shown, supported by a protein sequence comparison which shows that a 9-amino acid segment present in all NOSs exhibits a strong similarity with the sequence mainly responsible for heme binding in P 450s3A which is well conserved in all P450S.
