Basic reactive forms of oxygen and nitrogen

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, lipids,  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.



Superoxid • O 2 -
Medium reactive oxygen radical. It acts as an  oxidizing and reducing agent . Due to the negative charge, it has a limited passage through Cell Membranes - it passes through anionic channels. It is able to release iron from the Fe-S cluster at the active site enzyme.

Origin in the organism
In the body, it can arise in the respiratory chain on the inner membrane  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.
 * Origin in the respiratory chain

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

acceptance 1. e−: O2 → •O2−;

acceptance 2. e−: •O2− → H2O2;

acceptance 3. e−: H2O2 → H2O + HO•;

acceptance 4. e−: HO• → H2O.

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  NADPH. It is further converted to NADPH-oxidase, which converts oxygen to superoxide.
 * Formation by NADPH oxidase

O2 + NADPH → •O2− + NADP+

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

H2O2 + Cl− → HClO + OH−

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

Formation of reactions with hemoglobin

It most often occurs in erythrocytes. Oxygen is removed by one Fe 2+ electron in the heme. This produces superoxide and methemoglobin. Erythrocytes regulate these reactions by antioxidant protection enzymes (eg superoxide dismutase).

Reaction
•O2− + •O2− + 2H+ → O2 + H2O2
 * Dismutation

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• + •O2− → OONO− (peroxinitrite see below)

Hydrogen peroxide H 2 O 2
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

H2O2 + Fe2+ → OH− + OH• + Fe3+

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  '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).

H2O → 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.

Nitric oxide NO
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 + O2 + NADPH → L-citrullin + NADP+ + 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 2 -,  peroxynitrite  is formed, which is the most important toxic product of nitric oxide.

NO • + • O 2 - → OONO - (peroxynitrite)

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

OONO - + H + → HOONO (peroxynitric acid) → OH • + • NO 2

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. 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 ( Ca 2+ entry into the cytosol) and  changes in enzyme activity.
 * Proteins

Damage to DNA can cause deoxyribose ring cleavage, base modification and damage, chain breaks. This can then manifest itself as  mutation, translation errors and inhibition of proteosynthesis.
 * DNA

Overall, reactive forms are a direct cause of the disease state in  carcinogenesis  due to ionizing radiation, premature retinopathy and hemochromatosis. Significantly involved in the pathogenesis of chronic inflammation,  ARDS,  atherosclerosis, brain trauma,  diabetes, ischemia and  aging.

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Související články

 * Oxidačný stres
 * Peroxidace lipidů jako příklad oxidačního poškození biomolekul
 * Antioxidační ochrana lidského těla
 * Fyziologická úloha reaktívnych foriem kyslíka v metabolizme
 * Vyšetření parametrů antioxidační kapacity
 * Oxygenoterapie • Hyperbarická oxygenoterapie • Toxicita kyslíku • Kyslíkové parametry

Source

 * ws:Základní reaktivní formy kyslíku a dusíku