1. By Steven Knapp Chemistry 412 4-12-99

2.  Rose Engineering Firm welcomes you all  Nitric oxide NO now in natural and with stable  Our humble contribution

3. Discovered in 1772 by Joseph Priestly He referred to it “nitrous air”. A colourless and a toxic gas Since then, it has received the label of being a toxic gas and an air pollutant until over two hundred years As a pollutant it affects mainly Photosynthetic apparatus and chlorophyll levels in plants

4.  And care to Human Mankind Globally.  Know the wonder molecule NO, Nitric Oxide and how it helps to our human care.  Let us know about NO after it comes out from dark by eminent scientists and it was recognized as molecule of the year in 1992.  LET US KNOW THE GENIOUS CREW THOSE BRING OUT nitric oxide, NO and IN RETURN IT BRINGS GLORY TO THAT CREW AS “ NOBEL PRIZE”

6.  First described in 1979 as a potent relaxant of peripheral vascular smooth muscle.  Used by the body as a signaling molecule.  Serves different functions depending on body system. i.e. neurotransmitter, vasodilator, bactericide.  Environmental Pollutant  First gas known to act as a biological messenger

7.  Nitric oxide is a diatomic free radical consisting of one atom of nitrogen and one atom of oxygen  Lipid soluble and very small for easy passage between cell membranes  Short lived, usually degraded or reacted within a few seconds  The natural form is a gas NO

8.  Nitric oxide is a diatomic free radical consisting of one atom of nitrogen and one atom of oxygen  Lipid soluble and very small for easy passage between cell membranes  Short lived, usually degraded or reacted within a few seconds  The natural form is a gas NO

9.  NOS I  Central and peripheral neuronal cells  Ca+2 dependent, used for neuronal communication  NOS II  Most nucleated cells, particularly macrophages  Independent of intracellular Ca+2  Inducible in presence of inflammatory cytokines  NOS III  Vascular endothelial cells  Ca+2 dependent  Vascular regulation

10. NO was first characterized as a biological product of nitrite reduction by denitrifying bacteria. Its role was first identified as an agent responsible for promoting blood vessel relaxation and regulating vascular tone. This agent was named endothelium-derived relaxing factor (EDRF) and was later found to be nitric oxide.

11. Nitric Oxide in the human body has many uses which are best summarized under five categories. NO in the nervous system NO in the circulatory system NO in the muscular system NO in the immune system NO in the digestive system

12.  Nitric oxide as a neurotransmitter  NO is a signaling molecule, but not necessarily a neurotransmitter  NO signals inhibition of smooth muscle contraction, adaptive relaxation, and localized vasodilation  Nitric oxide believed to play a role in long term memory  Memory mechanism proposed is a retrograde messenger that facilitates long term potentiation of neurons (memory)  Synthesis mechanism involving Ca/Calmodulin activates NOS-I  NO travels from postsynaptic neuron back to presynaptic neuron which activates guanylyl cyclase, the enzyme that catalyzes cGMP production  This starts a cycle of nerve action potentials driven by NO

13.  NO serves as a vasodilator  Released in response to high blood flow rate and signaling molecules (Ach and bradykinin)  Highly localized and effects are brief  If NO synthesis is inhibited, blood pressure skyrockets  (Diagram of vasodilation mechanism after muscular system)  NO aids in gas exchange between hemoglobin and cells  Hemoglobin is a vasoconstrictor, Fe scavenges NO  NO is protected by cysteine group when O2 binds to hemoglobin  During O2 delivery, NO locally dilates blood vessels to aid in gas exchange  Excess NO is picked up by HGB with CO2

14.  NO was orginally called EDRF (endothelium derived relaxation factor)  NO signals inhibition of smooth muscle contraction  Ca+2 is released from the vascular lumen activating NOS  NO is synthesized from NOS III in vascular endothelial cells  This causes guanylyl cyclase to produce cGMP  A rise in cGMP causes Ca+2 pumps to be activated, thus reducing Ca+2 concentration in the cell  This causes muscle relaxation

15. Http://www.kumc.edu/research/medicine/biochemistry/bioc800/sig02-11.htm

16.  NOS II catalyzes synthesis of NO used in host defense reactions  Activation of NOS II is independent of Ca+2 in the cell  Synthesis of NO happens in most nucleated cells, particularly macrophages  NO is a potent inhibitor of viral replication  NO is a bactericidal agent  NO is created from the nitrates extracted from food near the gums  This kills bacteria in the mouth that may be harmful to the body

17.  NO is used in adaptive relaxation  NO promotes the stretching of the stomach in response to filling.  When the stomach gets full, stretch receptors trigger smooth muscle relaxation through NO releasing neurons

18. Ferid Murad John S. Dunn Distinguished Chair in Medicine and Physiology, Regental Professor and Chair of Department of Integrative Biology, Pharmacology, and Physiology and Director of the Institute of Molecular Medicine University of Texas-Houston Medical School, Houston, TX 77030 Nobel Prize Laureate, 1998

23.  Marieb, Elaine N. Human Anatomy and Physiology. (1998) 4 th ed. California, Benjamin/Cummings Science Publishing. 391, 826-27, 533, 859  Stryer Lubert. Biochemistry. (1996) 4 th ed. New York, W. H. Freeman and Company. 732  Keefer, Larry K. “Nitric oxide-releasing compounds: From basic research to promising drugs.” Modern Drug Discovery. November/December 1998. 20-29.

24. http://www.duj.com/Article/Lue.html http://www.duj.com/Article/Lue.html http://www.kumc.edu/research/medicine/biochemistry/bioc800/sig02-(01- 20).htm (01-20) stands for 20 distinct sites. http://www.kumc.edu/research/medicine/biochemistry/bioc800/sig02-(01- 20).htm http://www.med.nyu.edu/Research/S.Abramson-res.html http://biophysics.aecom.yu.edu/rousseau/nos/nos.htm http://keck.ucsf.edu.neuroscience.bredt.htm The following are all Omim sources written by McKusick, Victor A. NOS II http://www3.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?163729 NOS IIA http://www3.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?163730 NOS I http://www3.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?163731 NOS Chon http://www3.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?163728 NOS IIC http://www3.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?600719 NOS IIB http://www3.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?600720

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