View source for Basic reactive forms of oxygen and nitrogen

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'''Reactive forms''' are part of many pathological as well as physiological and biochemical processes. The most common reactive forms are the so-called free radicals. By free radical we mean any chemical entity (ie [[atom]], molecule or ion) that has at least one '''unpaired electron''' in the outer sphere of its electron shell. This causes its relatively '''high reactivity''', but is also capable of '''independent existence'''.

Reactive forms can react with [[fatty acids | fatty acids]], [[lipids]], [[amino acids | amino acids]], proteins, mono and polynucleotides (NK), with a number of low molecular weight metabolites, with [[coenzymes]], etc. These reactions '''disrupt the structures''' of the compounds, causing pathologies.

== Reactive Oxygen Species (ROS, '' Reactive Oxygen Species '') ==
Prolonged inhalation of pure [[oxygen]] is toxic to humans (oxygen alone is not toxic). Its derivatives - reactive forms - are toxic to the organism. These derivatives are formed even with a normal oxygen supply.

For some processes in the body, reactive forms are necessary - '''energy transfer, immune protection factors, signaling molecules of cell regulation'''.

{| class="wikitable"
 |+ 
 ! free oxygen radical !! Substances that are not free radicals
 |- 
 | Superoxide (•O<sub>2</sub><sup>−</sup>) || Hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>)
 |-
 | hydroxyl radical (HO•) || hypochlorous acid (HClO)
 |-
 | peroxyl (ROO•) || Ozone (O<sub>3</sub>)
 |-
 | Hydroperoxyl (•HO<sub>2</sub>) || singlet oxygen (<sup>1</sup>O<sub>2</sub>)
|}

[[File: Major cellular sources of Reactive Oxygen Species in living cells.jpg | preview | 350px | right | Origin of ROS]]

=== Superoxid • O <sub> 2 </sub> <sup> - </sup> ===
Medium reactive oxygen radical. It acts as an '' '''oxidizing and reducing agent''' ''. Due to the negative charge, it has a limited passage through [[Cell Membrane | Cell Membranes]] - it passes through anionic channels. It is able to release iron from the Fe-S cluster at the active site [[enzymes | enzyme]].

==== Origin in the organism ====
; Origin in the respiratory chain
In the body, it can arise in the [[respiratory chain | respiratory chain]] on the inner membrane [[mitochondria | mitochondria]]. During the formation of an electrochemical proton gradient, electrons can escape from the ''' complex I and III '''. Electrons react with free oxygen to form superoxide. About 1-2% of the total oxygen consumption is converted in this way.

All the basic ROS are gradually formed in the respiratory chain.

acceptance 1. e<sup>−</sup>: O<sub>2</sub> → '''•O<sub>2</sub><sup>−</sup>''';

acceptance 2. e<sup>−</sup>: •O<sub>2</sub><sup>−</sup> → '''H<sub>2</sub>O<sub>2</sub>''';

acceptance 3. e<sup>−</sup>: H<sub>2</sub>O<sub>2</sub> → H<sub>2</sub>O + '''HO•''';

acceptance 4. e<sup>−</sup>: HO• → H<sub>2</sub>O.

;Formation by NADPH oxidase
Cells '''capable of [[ phagocytosis]]''' form superoxide as a weapon against microorganisms ( '''respiratory inflammation''' )'''.''' A phagocyte (e.g., [[neutrophil]])  consumes [[ glucose]] through [[pentose cycle]] to form [[NADH, NADPH | NADPH]]'''.''' It is further converted to NADPH-oxidase, which converts oxygen to superoxide'''.''' 

O<sub>2</sub> + NADPH → •O<sub>2</sub><sup>−</sup> + NADP<sup>+</sup>

Dismutation of superoxide produces hydrogen peroxide. It then oxidizes chloride anions to '''hypochlorous acid''' (HClO), which contributes to the killing of bacteria.

H<sub>2</sub>O<sub>2</sub> + Cl<sup>−</sup> → HClO + OH<sup>−</sup>

;Formed by the action of enzymes
Some enzymes form superoxide as an intermediate. Examples include '''[[ xanthine oxidase | xanthine oxidase]], ''' '''cyclooxygenase''', and ''' lipoxygenase.

'''Formation of reactions with hemoglobin'''

It most often occurs '''in [[red blood cells | erythrocytes]]'''. Oxygen is removed by one Fe <sup> 2+ </sup> electron in the [[hem|heme]]. This produces '''superoxide and [[ methemoglobin]]'''. Erythrocytes regulate these reactions by  [[antioxidant protection]] enzymes (eg superoxide dismutase).

==== Reaction ====
; Dismutation
•O<sub>2</sub><sup>−</sup> + •O<sub>2</sub><sup>−</sup> + 2H<sup>+</sup> → O<sub>2</sub> + H<sub>2</sub>O<sub>2</sub>

This reaction takes place spontaneously in the body. In the presence of the enzyme '''superoxide dismutase''', the superoxide is directly converted to peroxide.

'''Reactions with nitric oxide'''

NO• + •O<sub>2</sub><sup>−</sup> → OONO<sup>−</sup> (peroxinitrite see below)

=== Hydrogen peroxide H <sub> 2 </sub> O <sub> 2 </sub> ===
They are reactive forms that are not radicals. Due to its small size, it can pass freely through cell membranes - it acts in a different place than where it originated. It is not very reactive in itself. Its reactivity increases as it interacts with the transition metal (iron and copper).

==== Origin in the organism ====
Hydrogen peroxide is formed by the already mentioned dismutation of superoxide, or by the action of some enzymes - '''xanthine oxidase, monoamine oxidase'''. '''Glutathione peroxidase''', '''peroxiredoxin''' or '''catalase''' ensure safe removal of hydrogen peroxide from the body.

==== Reaction ====
'''Fenton reaction'''

H<sub>2</sub>O<sub>2</sub> + Fe<sup>2+</sup> → OH<sup>−</sup> + OH• + Fe<sup>3+</sup>

This reaction occurs when the peroxide interacts with the iron cation. A '''hydroxyl radical''' is formed, which is the most dangerous oxidizing agent in the body. The Fenton reaction is one of the basic mechanisms of oxidative tissue damage.

=== Hydroxyl radical OH • ===
'''''Extremely reactive''''' molecule. Immediately after its formation, it reacts with the closest possible structure. It damages biomolecules in its environment (cell membranes, proteins, DNA). The most common cause is the formation of '' '[[Lipid peroxidation as an example of oxidative damage to biomolecules |lipoperoxides]]''.

==== Origin in the organism ====
It can be formed in the body by the already described Fenton reaction (hydrogen peroxide with a transition metal).

It is also formed by the action of '''ionizing radiation''' (eg gamma radiation, X-rays). Ionizing radiation most often decomposes water (there is a large amount in the body).

H<sub>2</sub>O → H• + OH•

When [[ ionizing radiation]] acts on oxygen, so-called '' '''singlet oxygen''''' is formed, which, like the hydroxyl radical, , reacts with MK to form lipoperoxides.

== Reactive Nitrogen Species (RNS) ==
{| class="wikitable"
 |+ 
 ! Free nitrogen radicals !! substances that are not free radicals
 |- 
 | nitric oxide (NO•) || Nitrosyl (NO<sup>+</sup>)
 |-
 | nitrogen dioxide (NO<sub>2</sub>•) || nitrous oxide (NO)
 |-
 |  || Peroxynitrite (ONOO<sup>−</sup>)
 |-
 |  || Alkylperoxynitrite (ROONO)
|}

=== Nitric oxide NO ===

<big>'''NO:'''</big> {{Video | url=https://youtu.be/pPAt6kXc90c?t=54}}

Gaseous radical with a short biological half-life. When inhaled, it is toxic (smog) to the body. Inside the body, it is created physiologically as a mediator (eg vasodilation). By binding to guanylate cyclase, it stimulates cGMP production leading to smooth muscle relaxation. It has a high '' affinity '''for heme iron''' ''. It is'' '''taken up by erythrocytes''', in which it reacts with hemoglobin to form methaemoglobin and nitrate (physiological inactivation of NO).''

==== Origin in the organism ====
'''NO synthase reaction'''

L-arginin + O<sub>2</sub> + NADPH → L-citrullin + NADP<sup>+</sup> + NO•

We distinguish three different synthases, which differ according to the site of action. '' '''NOS I''' ''(neuronal, constitutive) - memory and learning, '' '''NOS II''''' (phagocytes, inducible) - stimulated by cytokines and microbes, '' '''NOS III''' '' (endothelial, constitutive) - vasodilatory effect.

==== Reaction ====
'''Reactions with superoxide'''

During the reaction of NO • se • O <sub> 2 </sub> <sup> - </sup>, '' '''peroxynitrite''' '' is formed, which is the most important toxic product of nitric oxide.

NO • + • O <sub> 2 </sub> <sup> - </sup> → OONO <sup> - </sup> (peroxynitrite)

Peroxinitrite is the '''most powerful producer of free radicals''''' in cells.''

OONO <sup> - </sup> + H <sup> + </sup> → HOONO (peroxynitric acid) → OH • + • NO <sub> 2 </sub>

== Pathogenesis ==
Among the main target structures on which reactive forms act:

'''Unsaturated MK in lipids (cell membranes)'''

Damage to fatty acids can cause the loss of double bonds and condition the formation of reactive metabolites (peroxides, aldehydes). This causes a '''change in the fluidity and permeability''' of the membranes. Chemoreactive substances for microphages are formed.
;Proteins
Damage to proteins can cause their aggregation, cross-linking, fragmentation, cleavage, reaction with heme iron, modification of thiol groups and benzene nuclei of AMK. This causes '' '''changes in ion transport''''' ([[Calcium | Ca <sup> 2+ </sup>]] entry into the cytosol) and '' '''changes in enzyme activity'''''.

; DNA
Damage to [[DNA (nucleic acid) | DNA]] can cause deoxyribose ring cleavage, base modification and damage, chain breaks. This can then manifest itself as '' [[mutation|'''mutation''']]'', [[translation | translation]] errors and inhibition of proteosynthesis.

Overall, reactive forms are a direct cause of the disease state in '' [[carcinogenesis|'''carcinogenesis''']] '' due to ionizing radiation, [[premature retinopathy]] and [[hemochromatosis | hemochromatosis]]. Significantly involved in the pathogenesis of [[chronic inflammation | chronic inflammation]], [[Acute respiratory distress syndrome | ARDS]], [[Atherosclerosis | atherosclerosis]], brain trauma, [[Diabetes mellitus | diabetes]], [[ischemia]] and '' [[Aging |'''aging''']]''.

{{Netisknout|
<noinclude>
== Odkazy ==
=== Související články ===
* [[Oxidative stress]]
* [[lipid peroxidation as an example of oxidative damage to biomolecules]]
* [[antioxidant protection of the human body]]
* [[physiological role of reactive oxidative species in metabolism]]
* [[investigation of antioxidant capacity parameters]]
* [[Oxygen therapy]] • [[hyperbaric oxygen therapy]] • [[oxygen toxicity]] • [[oxygen parameters]]
===Zdroj===
* {{Citace|typ = web|příjmení1 = Pláteník|jméno1 = Jan|název = Reaktivní formy kyslíku v lidském těle. Antioxidační ochrana|rok = 2015
|citováno = 3.12.2018
|url = https://ulbld.lf1.cuni.cz/file/1971/ros-cze1516b.pdf}}
=== References ===
*{{Citace 
| typ = kniha
| příjmení1 = Ledvina
| jméno1 = Miroslav
| kolektiv = ano
| titul = Biochemie pro studující medicíny
| vydání = 1
| vydavatel = Karolinum
| místo = Praha
| rok = 2004
| isbn =  80-246-0851-0
}}
</noinclude>
}}

[[Category: Pathobiochemistry]]
[[Category: Biochemistry]]


=== Source ===
* [[ws:Základní reaktivní formy kyslíku a dusíku]]