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Biology of Nitric Oxide Synthases

Ingrid Fleming

10.1002/cphy.cp020403

Source: Supplement 9: Handbook of Physiology, The Cardiovascular System, Microcirculation

Originally published: 2008

Published online: January 2011

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 Characteristics of NOS Enzymes
1.1 nNOS
1.2 iNOS
1.3 eNOS
2 Basic Reaction Mechanism for no Production
2.1 Tetrahydrobiopterin (H4B)
3 When is A NOS not A no Synthase? The Uncoupling Phenomenon and the Generation of Reactive Oxygen Species
4 Regulation of NOS Function by Localization
4.1 nNOS
4.2 iNOS
4.3 eNOS
5 Regulation of NOS Function by Associated Proteins
5.1 nNOS
5.2 iNOS
5.3 eNOS
5.4 Calmodulin
5.5 Caveolin
5.6 Hsp90
5.7 Soluble Guanylyl Cyclase
5.8 Dynamin
5.9 G‐Protein‐Coupled Receptors
6 Regulation of NOS Function by Phosphorylation
6.1 nNOS
6.2 iNOS
6.3 eNOS
7 NOS and the Regulation of Vascular Tone
7.1 The NO/Cyclic GMP Pathway
7.2 S‐Nitrosylation
7.3 Inhibition of 20‐HETE formation
7.4 Blood Pressure Regulation
7.5 NO in Platelets
8 NO and Gene Expression in Vascular Cells
9 Outlook
Figure 1. Figure 1.

The eNOS molecule, showing binding sites for NADPH, FAD, and FMN in the carboxy terminal (reductase) domain and binding sites for CaM. heme and L‐arginine at the amino terminal (reductase) domain, (for further explanation see text).
Figure 2. Figure 2.

Phosphorylation sites on eNOS and the kinases reported to elicit phosphorylation in response to specific stimuli, that is, VEGF, fluid shear stress and receptor‐dependent agonists. (+) indicates that phosphorylation is associated with enzyme activation and (−) indicates that phosphorylation is associated with eNOS inactivation. AMPK. AMP‐activated protein kinase: PGI2, prostacyclin; PI 3‐K. Phosphatidylinositol 3‐kinase; PKA, Protein kinase A; PKC, Protein kinase C; PKG, Protein kinase G.
Figure 3. Figure 3.

NO effector mechanisms in endothelial cells, platelets, and smooth muscle cells. The classical NO/guanylyl cyclase (sGC)/cyclic GMP (cGMP) pathway regulates vascular smooth muscle contraction by decreasing [Ca2+]i at the same time as NO inhibits the generation of the vasoconstrictor prostanoid 20‐hydroxyeicosatetraenoic acid (20‐HETE) by CYP4A enzymes. S‐nitrosylation also regulates cellular signaling and the S‐nitrosylation (S‐NO) of caspase‐3 and thioredoxin have been linked to the inhibition of apoptosis. In platelets an increase in NOS activity attenuates aggregation by decreasing [Ca2+]i and elicits the discrete exocytosis of the contents of dense granules (ATP/ADP and serotonin/5‐HT). In endothelial cells, NO contributes to the cells antiatherogenic properties largely by regulating the activity of transcription factors, such as nuclear factor KB (NF‐KB), and the subsequent expression of genes, such as E‐selectin, monocyte chemoattractant protein‐1 (MCP‐1) and vascular cell adhesion molecule‐1 (VCAM‐1).


Figure 1.

The eNOS molecule, showing binding sites for NADPH, FAD, and FMN in the carboxy terminal (reductase) domain and binding sites for CaM. heme and L‐arginine at the amino terminal (reductase) domain, (for further explanation see text).



Figure 2.

Phosphorylation sites on eNOS and the kinases reported to elicit phosphorylation in response to specific stimuli, that is, VEGF, fluid shear stress and receptor‐dependent agonists. (+) indicates that phosphorylation is associated with enzyme activation and (−) indicates that phosphorylation is associated with eNOS inactivation. AMPK. AMP‐activated protein kinase: PGI2, prostacyclin; PI 3‐K. Phosphatidylinositol 3‐kinase; PKA, Protein kinase A; PKC, Protein kinase C; PKG, Protein kinase G.



Figure 3.

NO effector mechanisms in endothelial cells, platelets, and smooth muscle cells. The classical NO/guanylyl cyclase (sGC)/cyclic GMP (cGMP) pathway regulates vascular smooth muscle contraction by decreasing [Ca2+]i at the same time as NO inhibits the generation of the vasoconstrictor prostanoid 20‐hydroxyeicosatetraenoic acid (20‐HETE) by CYP4A enzymes. S‐nitrosylation also regulates cellular signaling and the S‐nitrosylation (S‐NO) of caspase‐3 and thioredoxin have been linked to the inhibition of apoptosis. In platelets an increase in NOS activity attenuates aggregation by decreasing [Ca2+]i and elicits the discrete exocytosis of the contents of dense granules (ATP/ADP and serotonin/5‐HT). In endothelial cells, NO contributes to the cells antiatherogenic properties largely by regulating the activity of transcription factors, such as nuclear factor KB (NF‐KB), and the subsequent expression of genes, such as E‐selectin, monocyte chemoattractant protein‐1 (MCP‐1) and vascular cell adhesion molecule‐1 (VCAM‐1).

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Article Title: Biology of Nitric Oxide Synthases
 

How to Cite

Ingrid Fleming. Biology of Nitric Oxide Synthases. Compr Physiol 2011, Supplement 9: Handbook of Physiology, The Cardiovascular System, Microcirculation: 56-80. First published in print 2008. doi: 10.1002/cphy.cp020403