Everything about Nitric Oxide totally explained
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Nitric oxide or
Nitrogen monoxide is a
chemical compound with
chemical formula NO. This
gas is an important
signaling molecule in the body of
mammals, including
humans, and is an extremely important intermediate in the
chemical industry. It is also a
toxic air pollutant produced by
automobile engines and
power plants.
NO is an important messenger molecule involved in many physiological and pathological processes within the mammalian body both beneficial and detrimental. . Appropriate levels of NO production are important in protecting an organ such as the liver from ischemic damage. However sustained levels of NO production result in direct tissue toxicity and contribute to the vascular collapse associated with septic shock, whereas chronic expression of NO is associated with various carcinomas and inflammatory conditions including juvenile diabetes, multiple sclerosis, arthritis and ulcerative colitis.
Nitric oxide shouldn't be confused with
nitrous oxide (N
2O), a
general anaesthetic, and with
nitrogen dioxide (NO
2) which is another poisonous air pollutant. The nitric oxide molecule is a
free radical, which is relevant to understanding its high reactivity. It reacts with the
ozone in air to form
nitrogen dioxide, signalled by the appearance of the reddish-brown color.
Despite being a startlingly simple molecule, NO is a fundamental player in the fields of
neuroscience,
physiology, and
immunology, and was proclaimed “
Molecule of the Year” in 1992
Production environmental effects
From a thermodynamic perspective, NO is unstable with respect to O
2 and N
2, although this conversion is very slow at ambient temperatures in the absence of a
catalyst. Because the heat of formation of NO is
endothermic, its synthesis from molecular nitrogen and oxygen requires elevated temperatures, >1000°C. A major natural source is
lightning. The use of
internal combustion engines has drastically increased the presence of nitric oxide in the environment. One purpose of
catalytic converters in cars is to minimize NO emission by catalytic reversion to O
2 and N
2.
Nitric oxide in the air may convert to
nitric acid, which has been implicated in
acid rain. Furthermore, both NO and NO
2 participate in
ozone layer depletion. Nitric oxide is a small highly diffusible gas and a ubiquitous bioactive molecule.
Mechanism of action
There are several mechanisms by which NO has been demonstrated to affect the biology of living cells. These include oxidation of iron containing proteins such as ribonucleotide reductase and aconitase, activation of the soluble guanylate cyclase, ADP ribosylation of proteins, protein sulphhydryl group nitrosylation, and iron regulatory factor activation. NO has been demonstrated to activate NFkB in peripheral blood mononuclear cells, an important transcription factor in iNOS gene expression in response to inflammation. . It was found that NO acts through the stimulation of the soluble guanylate cyclase which is a heterodimeric enzyme with subsequent formation of cyclic GMP. Cyclic GMP activates protein kinases and leads ultimately to the dephosphorylation of the myosine light chain.
Technical applications
Although NO has relatively few direct uses, it's produced on a massive scale as an intermediate in the
Ostwald process for the synthesis of
nitric acid from
ammonia. In 2005, the US alone produced 6M metric tons of nitric acid. It finds use in the
semiconductor industry for various processes. In one of its applications it's used along with
nitrous oxide to form oxynitride gates in
CMOS devices.
Miscellaneous applications
Nitric oxide can be used for detecting surface radicals on polymers. Quenching of surface
radicals with nitric oxide results in incorporation of nitrogen, which can be quantified by means of
X-ray photoelectron spectroscopy.
Biological functions
NO is one of the few gaseous signaling molecules known. It is a key
vertebrate biological messenger, playing a role in a variety of biological processes. Nitric oxide, known as the '
endothelium-derived relaxing factor', or 'EDRF', is biosynthesised endogenously from
arginine and
oxygen by various
nitric oxide synthase (NOS)
enzymes and by reduction of inorganic nitrate. The
endothelium (inner lining) of
blood vessels use nitric oxide to signal the surrounding
smooth muscle to relax, thus resulting in
vasodilation and increasing blood flow. Nitric oxide is highly reactive (having a lifetime of a few seconds), yet diffuses freely across membranes. These attributes make nitric oxide ideal for a transient signal molecule between adjacent cells and within cells.
The production of nitric oxide is elevated in populations living at high-altitudes, which helps these people avoid
hypoxia. Effects include blood vessel dilatation,
neurotransmission (see
Gasotransmitters), modulation of the
hair cycle, and
penile erections.
Nitroglycerin and
amyl nitrite serve as vasodilators because they're converted to nitric oxide in the body. Sildenafil, popularly known by the trade name
Viagra, stimulates erections primarily by enhancing signaling through the nitric oxide pathway in the penis.
Nitric oxide (NO) contributes to vessel homeostasis by inhibiting vascular smooth muscle contraction and growth, platelet aggregation, and leukocyte adhesion to
the endothelium. In humans, a high-salt intake was demonstrated to attenuate NO production.
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Nitric oxide is also generated by
macrophages and
neutrophils as part of the human
immune response. Nitric oxide is toxic to
bacteria and other human
pathogens. In response, however, many bacterial pathogens have evolved mechanisms for nitric oxide resistance.
Nitric oxide can contribute to
reperfusion injury when an excessive amount produced during reperfusion (following a period of
ischemia) reacts with
superoxide to produce the damaging
free radical peroxynitrite. In contrast, inhaled nitric oxide has been shown to help survival and recovery from
paraquat poisoning, which produces lung tissue damaging superoxide and hinders NOS metabolism.
In plants, nitric oxide can be produced by any of four routes: (i)L-arginine-dependent nitric oxide synthase,
,,(although the existence animal NOS homologs in plants is debated),(ii) by plasma membrane-bound
nitrate reductase, (iii) by mitochondrial electron transport chain, or (iv) by non-enzymatic reactions. It is a signaling molecule, acts mainly against oxidative stress and also plays a role in plant pathogen interactions. Treating cut flowers and other plants with nitric oxide has been shown to lengthen the time before wilting.
A biologically important reaction of nitric oxide is S-nitrosylation, the conversion of
thiol groups, including
cysteine residues in proteins, to form S-nitrosothiols (RSNOs). S-Nitrosylation is a mechanism for dynamic, post-translational regulation of most or all major classes of protein.
Use in Pediatric Intensive Care
Nitric Oxide/Oxygen blends are used in critical care to promote capillary and pulmonary dilation to treat Primary Pulmonary Hypertension in neonatal patients post meconium aspiration and related to birth defect. These are often a last-resort gas mixture before the use of
ECMO. NO therapy has the potential to significantly increase the quality of life and in some cases save the lives of infants at risk for pulmonary vascular disease.
Reactions
- When exposed to oxygen, NO is converted into nitrogen dioxide. » 2NO + O2 → 2NO2
This conversion has been speculated as occurring via the ONOONO intermediate. In water, NO react with oxygen and water to form HNO2 or nitrous acid. The reaction is thought to proceed via the following stoichiometry: » 4 NO + O2 + 2 H2O → 4 HNO2
NO will react with fluorine, chlorine, and bromine to from the XNO species, known as the nitrosyl halides, such as nitrosyl chloride. Nitrosyl iodide can form but is an extremely short lived species and tends to reform I2. » 2NO + Cl2 → 2NOCl
Nitroxyl (HNO) is the reduced form of nitric oxide.
Nitric oxide reacts with acetone and an alkoxide to a diazeniumdiolate or nitrosohydroxylamine and Methyl acetate : »
» This is a very old reaction (1898) but of interest today in NO prodrug research. Nitric oxide can also react directly with sodium methoxide, forming sodium formate and nitrous oxide .
Preparation
As stated above, nitric oxide is produced industrially by the direct reaction of O2 and N2 at high temperatures. In the laboratory, it's conveniently generated by reduction of nitric acid:
» 8HNO3 + 3Cu → 3Cu(NO3)2 + 4H2O + 2NO
or by the reduction of nitrous acid:
» 2 NaNO2 + 2 NaI + 2 H2SO4 → I2 + 4 NaHSO4 + 2 NO
2 NaNO2 + 2 FeSO4 + 3 H2SO4 → Fe2(SO4)3 + 2 NaHSO4 + 2 H2O + 2 NO » 3 KNO2(l) + KNO3 (l) + Cr2O3(s) → 2 K2CrO4(s) + 4 NO (g)
The iron(II) sulfate route is simple and has been used in undergraduate laboratory experiments.
Commercially, NO is produced by the oxidation of ammonia at 750°C to 900°C (normally at 850°C) in the presence of platinum as catalyst:
» 4NH3 + 5O2 → 4NO + 6H2O
» The uncatalyzed endothermic reaction of O2 and N2 which is performed at high temperature (>2000°C) with lightning hasn't been developed into a practical commercial synthesis:
» N2 + O2 → 2NO
Coordination Chemistry
NO forms complexes with all transition metals to give complexes called metal nitrosyls. The most common bonding mode of NO is the terminal linear type (M-NO). The angle of the M-N-O group can vary from 160-180° but are still termed as "linear". In this case the NO group is formally considered a 3-electron donor. In the case of a bent M-N-O conformation the NO group can be considered a one electron donor.. Alternatively, one can view such complexes as derived from NO+, which is isoelectronic with CO.
Nitric oxide can serve as a one-electron pseudohalide. In such complexes, the M-N-O group is characterized by an angle between 120-140°.
The NO group can also bridge between metal centers through the nitrogen atom in a variety of geometries.
Measurement of nitric oxide concentration
The concentration of nitric oxide can be determined using a simple chemiluminescent reaction involving ozone: A sample containing nitric oxide is mixed with a large quantity of ozone. The nitric oxide reacts with the ozone to produce oxygen and nitrogen dioxide. This reaction also produces light (chemiluminescence), which can be measured with a photodetector. The amount of light produced is proportional to the amount of nitric oxide in the sample.
» NO + O3 → NO2 + O2 + light
Other methods of testing include electroanalysis(amperometric approach), where NO reacts with an electrode to induce a current or voltage change. The detection of NO radicals in biological tissues is particularly difficult due to the short lifetime and concentration of these radicals in tissues. One of the few practical methods is spin trapping of nitric oxide with iron-dithiocarbamate complexes and subsequent detection of the mono-nitrosyl-iron complex with Electron Paramagnetic Resonance (EPR).
A group of fluorescent dye indicators exist that are also available in acetylated form for intracellular measurements. The most common compound is 4,5-diaminofluorescein (DAF-2).
Further Information
Get more info on 'Nitric Oxide'.
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