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NITRIC OXIDE CALLED AS “NO” By Steven Knapp Chemistry 412 4-12-99

By Steven Knapp Chemistry 412 4-12-99. Rose Engineering Firm welcomes you all Nitric oxide NO now in natural and with stable Our humble contribution

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NITRIC OXIDECALLED AS

“NO”

By Steven KnappChemistry 412

4-12-99

Rose Engineering Firm welcomes you all

Nitric oxide NO now in natural and with stable

Our humble contribution

Joseph Priestly

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

NO, Wonder Molecule Serves

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”

Press ReleaseNOBELFÖRSAMLINGEN KAROLINSKA INSTITUTETTHE NOBEL ASSEMBLY AT KAROLINSKA INSTITUTETOctober 12, 1998

The Nobel Assembly at Karolinska Institute has today decided to award the Nobel Prize in Physiology or Medicine for 1998 jointly to Robert F. Furchgott, Louis J. Ignore and Ferid Murad for their discoveries concerning “nitric oxide as a signalling molecule in the cardiovascular system".

Robert F Furchgott

Louis J Ignore

Ferid Murad

What is Nitric Oxide?

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

The structure and nature of Nitric Oxide

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

N O

The structure and nature of Nitric Oxide

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

N O

Types of NOS

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

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.

INTRODUCTION

What is the role of Nitric Oxide in the human body?

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

Nitric Oxide in the Nervous System

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

Nitric Oxide in the Circulatory System

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

Nitric Oxide in the Muscular System

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

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

Nitric Oxide in the Immune System

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

Nitric Oxide in the Digestive System

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

Biological Effects of Nitric Oxide and its Role in Cell Signaling

Ferid MuradJohn 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

References

Marieb, Elaine N. Human Anatomy and Physiology. (1998) 4th ed. California, Benjamin/Cummings Science Publishing. 391, 826-27, 533, 859

Stryer Lubert. Biochemistry. (1996) 4th 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.

Sources on the World Wide Web

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.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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