Nitric Oxide: Physiological Roles, Biosynthesis and Medical Uses
The discovery that nitric oxide (NO) has an important role in animal physiology is one of the most exciting and interesting of recent years. The story began when it was discovered that NO is a messenger molecule in the cardiovascular system but, since the
- PDF / 20,134,753 Bytes
- 186 Pages / 439.364 x 666.137 pts Page_size
- 51 Downloads / 182 Views
ADAMS I,
M.
2 BROCHWICZ-LEWINSKI ,
and A. R.
3 BUTLER ,*
IDepartment of Chemistry, Heriot Watt University, Edinburgh, Scotland 2Department of Radiology, The Royal Infirmary, Edinburgh, Scotland 3School of Chemistry, University of St. Andrews, Fife, Scotland
Contents List of Abbreviations and Acronyms
3
I. Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..
4
2. Discovery in the Vasculature . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5
3. Platelet Aggregation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
9
4. NO and the Immune System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..
10
5. NO and the Nervous System. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..
14
6. S-Nitrosothiols . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 6.1. NO-Release........................................... 6.2. Endogenous S-Nitrosothiols . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 6.3. S-Nitrosothiols as NO-Donor Drugs. . . . . . . . . . . . . . . . . . . . . . . . ..
16 16 18 19
7. NO Activity in the Mammalian Eye . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..
22
8. The 8.1. 8.2. 8.3.
23 23 28 33
NO Biosynthetic Pathway. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. Introduction........................................... Relation of Nitric Oxide Synthase to Cytochrome P450 . . . . . . . . . . .. NO Synthase Isoforms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..
9. Mechanism of the Nitric Oxide Synthase-Catalysed Reaction. 9.1. Mechanisms of Cytochrome P450-Mediated Oxidations 9.1.1. P450-Mediated Hydroxylation. . . . . . . . . . . . . 9.1.2. P450-Mediated N-Oxidation and N-Dealkylation 9.1.3. P450-Mediated Epoxidation . . . . . . . . . . . . . . 9.1.4. Aromatase Chemistry. . . . . . . . . . . . . . . . . . . 9.2. Mechanism of NOS Monooxygenation I . . . . . . . . . . . 9.3. Mechanism of NOS Monooxygenation II . . . . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
. . . . . . . .
W. Herz et al. (eds.), Fortschritte der Chemie organischer Naturstoffe / Progress in the Chemistry of Organic Natural Products © Springer-Verlag/Wien 1999
.. .. .. .. .. .. .. ..
36 36 36 39 43 43 44 50
2
D. R. ADAMS, M. BROCHWICZ-LEWINSKI, and A. R. BUTLER 9.4. 9.5.
Mechanism-Based Inhibitors of NOS . . . . . . . . . . . . . . . . . . . . . . . .. Summary.............................................
10. Nitric Oxide Synthase Structure. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.1. Primary Structure and Domain Organisation of NOS . . . . . . . . . . . . 10.1.1. Primary Structure .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.1.2. Domain Organisation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10.2.
Data Loading...