Types of free radicals

Types of free radicals

           Free radicals can be defined as atoms that possess unpaired electrons in their outer atomic shell. Because it lacks a fixed number in its last shell, it is in constant motion to search for another atom or another molecule to attach to and achieve stability. Reactive oxygen species, or ROS, are by-products of normal oxygen metabolism, and play important roles in cellular signaling and cell homeostasis. Reactive oxygen compounds are an essential component of cellular functioning and are present at low, constant levels in normal, living cells. ROSs are involved in food metabolism, but they can cause DNA damage, which suggests that ROSs may have a dual role in organisms (detrimental or protective agents) or signals the balance between ROC production and dispose of them at the appropriate time and place, as the toxicity of oxygen compounds can arise from uncontrolled production or from ineffective removal by the antioxidant system. ROS levels can increase dramatically during times of cell stress such as exposure to ultraviolet light or exposure to heat, leading to significant damage to cellular structures. This damage, when accumulated, is known as oxidative stress. The production of ROSs is strongly affected by the response to stressors. Factors that increase the production of ROSs include: dehydration, elevated concentration of electrolytes, decreased ability of cells to defend against pathogens, nutrient deficiencies, poisoning with metals, UV rays, smoking, and more. ROSs are also generated from external sources such as ionizing radiation, which has effects on tissue growth in both animals and plants.
The reactive oxygen and nitrogen species may be radical or non-radical compounds. The reduction of molecular oxygen with four electrons leads to the formation of water without generating ROS, while the reduction of one electron leads to the formation of an •−O2 superoxide radical, H2O2 hydrogen peroxide, and a HO• hydroxyl radical. (OH −) and (O − −) have unpaired electrons in the outermost orbitals and are therefore defined as free radicals, while H2O2 does not have unpaired electrons and is therefore not a radical. Non-radical oxygen compounds include hydrogen peroxide (H2O2), ozone (O3), and singlet oxygen 1O2. The types of nitrogen radicals are (NO , ONOO , NO2 ).

Types of free radicals
1. Superoxide Radical (O2 −)
Types of ROS constantly appear during the biological activities within the cell in the mitochondria or blastia and the endoplasmic reticulum and many other cellular organelles as an inevitable result of aerobic respiration. One of the most important results of oxidation and reduction processes is the production of this free radical as a result of the interaction of oxygen with the electron transport chain (ETC), so oxygen is reduced by only one electron, and this radical (O2 −) is produced, which is the first type of ROS generated. The formation of this radical may stimulate the formation of other radicals such as hydroxyl (OH) which can cause oxidation of lipid membranes and exhaustion of the cell and can form a negatively charged HO radical above the plasma membrane which will in turn attack polyunsaturated fatty acids (PUFAs). The half-life of this root is 1-1000 µ/sec. And one of its most important interactions is its interaction with the hydrogen proton H+ to produce a very active Hydroxyperoxyl radical that can penetrate through cell membranes, two of which can interact to give oxygen and hydrogen peroxide H2O2. This radical also has the ability to reduce ferric Fe+3, Cu+2 and Cu+1 and to react with hydrogen peroxide.
Because Superoxide Radical (O2 −) is a highly reactive free radical, it can damage molecules (DNA, proteins, and lipids). It may also be produced in the immune system to kill invading microorganisms; Phagocytes, such as neutrophils, monocytes, neutrophils monocytes, macrophages, mast cells and dendritic cells, are transported by chemotaxis to the site of bacterial infection and killed. Bacteria are killed by a process mediated by Superoxide Radical (O2•−).
 Hydroxyl Radical (OH)
Chemically, it is the most reactive free radical formed in the living body. It is a strong oxidant and is produced in a wide range of environmental conditions. It has the ability to break down organic compounds, including DNA, proteins, carbohydrates and fats, causing very great damage compared to other types of ROS.

It is produced through
1- Fenton reaction, as hydrogen peroxide H2O2 reacts with metal ions of iron or copper, which are associated with various proteins such as ferritin, which stores iron, and Ceruloplasmin, which is the protein that transports copper. It will participate in the Fenton reaction to form Hydroxyl Radical (HO•). As ferric Fe+3 is reduced to ferrous Fe+2 by means of an (O2 −) radical, after which ferrous is able to enter into Fenton reactions and produce a Hydroxyl Radical (OH −)


Fe+3) + O2 •− →(Fe+2) +( O2•)) )
Fe+2) + H2O2→ (Fe+3) +(OH−) + (OH•)

2- It is also formed through the reaction of the superoxide radical and hydrogen peroxide in a reaction called the Haber-Weiss reaction.

The hydroxyl radical is Electrophile, meaning that it can attract a pair of electrons and has a high and strong affinity for electron-rich sites, especially molecules containing sulfur. Most ROS are converted to this radical, so it is considered the final compound for most free radicals. Finally, this radical is the main cause of oxidative damage to proteins, lipids and nucleic acids, and it is directly involved in the signaling of programmed cell death. It is estimated that OH is responsible for 60-70% of tissue damage from ionizing radiation. Hydroxyl radicals are also involved in many disorders, such as cardiovascular disease and cancer.

3- Peroxyl Radical (ROO)
Alkoxyl (RO•) and peroxyl (ROO•) radicals are oxygen-centered organic radicals that have the ability to accept electrons and then be reduced. These radicals have a very high positive reduction potential (1000 to 1600 mV). Peroxyl and alkoxyl radicals can be generated by heat- or radiation-induced decomposition of alkyl peroxides (ROOH) or reaction with transition metal ions and other oxidants capable of releasing hydrogen. It can also be generated by the oxidation of proteins and DNA. These radicals interact directly with biological molecules, such as DNA and thiol groups attached to albumin -SH-groups. They can also extract hydrogen from other molecules that have a lower scalar reducing capacity as observed in the propagation phase of lipid peroxidation. ROO• may spread to distant parts of cells. Their half-lives are on the order of seconds. Some peroxyl radicals either cleavage and release the superoxide anion, or react with each other to generate singlet oxygen

4. Hydroperoxyl Radical (HO2•)
Commonly called a hydroperoxyl radical or perhydroxyl radical, it is the simplest form of a peroxyl radical, which is produced by the protonation of a superoxide anion radical or by the decomposition of hydroperoxide and that approximately 0.3% of the oxide is The superoxide present in the cytosol is in protonated form. The HO radical produces the compound H2O2 which can react with metals including iron and copper, to catalyze Fenton or Haber-Weiss reactions. The hydroperoxyl radical can also release hydrogen atoms from NADH. The hydroperoxyl radical plays an important role in the chemistry of lipid peroxidation. It is a much stronger oxidizing agent than superoxide due to its ability to release hydrogen atoms from fatty acids, suggesting its role in initiating lipid oxidation.

5. Hydrogen Peroxide (H2O2)
Hydrogen peroxide occurs naturally in a reaction catalyzed by the SOD enzyme. It is not a radical, but it can cause cell damage at low concentrations. This compound is easily penetrated by cell membranes and has no direct effect on DNA, but its effect may be indirect through the production of hydroxyl radicals that damage cells, and the antioxidant enzymes that can remove it are catalase and glutathione peroxidase enzymes (GPX, CAT).  Peroxide results from the reduction of two electrons from the oxygen molecule in cells under stress conditions such as extreme temperatures, ultraviolet radiation, wounds, or infection with pathogens. It is a molecule with a relatively long life, and being the only one able to diffuse through Aquaporin membrane channels and cross longer distances inside the cell, it is capable of causing damage in areas far beyond the place of its production inside the cell. It is also of exceptional importance because it acts as a signal involved in the regulation of specific vital activities against stress and environmental pressures.

6. Singlet Oxygen (1O2)
Despite the fact that monooxygen is semi-equilibrium and has a short life span in cells, part of it can spread over reasonable distances and attack nucleic acids, pigments, lipids and proteins, as it rapidly oxidizes molecules that possess the double bond -C-C, forming Hydroperoxidase and Endoperoxidase, as it attacks amino acids and SH groups of thiols. Unsaturated fatty acids and guanine bases in nucleic acids.
7. Ozone (O3)
It is less reactive than HO and a much stronger oxidizing agent than oxygen. It can produce free radicals by oxidizing biological molecules and cause oxidative damage to lipids, proteins and nucleic acids and may cause chromosomal abnormalities. Ozone also plays an important role in inflammatory processes.
8. Hypochlorous Acid (HOCl)
It is a highly reactive species that participates in oxidation reactions and chlorination of protein and fat components. Produced by activation of neutrophils cells at the site of inflammation from the reaction of hydrogen peroxide and chloride, a reaction catalysed by the enzyme myeloperoxidase.

9. Carbonate Radical Anion (CO3 −)
It can be produced by radioactive decomposition of aqueous solutions of bicarbonates/carbonates; It can also form when •OH reacts with carbonate or bicarbonate ions. And the high levels of bicarbonate (25 mM) in the blood plasma allow this reaction to occur. Although it is not a strong oxidizing agent like hydroxyl radicals, (CO3 −). It has a much longer half-life than (OH) and can therefore diffuse further and oxidize cellular molecules. A variety of biomolecules can be oxidized by it. As a major oxidizing agent of proteins and nucleic acids, it oxidizes guanine bases in DNA via a single electron transfer process that results in the formation of stable guanine oxidation products.. It is known to play an important role in the modification of amino acids in proteins Under conditions of oxidative stress, aging, infections, neurodegeneration, cardiovascular disorders, and diabetes mellitus.

10. Nitric Oxide (NO)
Nitric oxide (NO), nitrogen dioxide (NO2) and peroxynitrite (ONOO−) and non-radical HNO2 and N2O4 (dinitrogen tetroxide) are included under the heading of reactive nitrogen species (RNS). Nitric oxide or nitrogen monoxide is a free radical with one unpaired electron and its chemical reactivity is rather limited, therefore its direct toxicity is lower than that of ROS. However, it reacts with O− and produces peroxynitrite anion (ONOO−), which is A very harmful type for proteins, lipids and DNA. Nitric oxide also reacts with molecular oxygen and nitrogen to form nitrogen dioxide or dinitrogen trioxide, both of which are toxic oxidizing agents. Nitric oxide is produced in biological tissues by specific nitric oxide synthases, through the reaction of H2O2 with arginine or through the decomposition of S-nitroso thiols in the presence of metal ions.
Nitric oxide is soluble in water and lipids, and thus diffuses easily through the cytoplasm and plasma membrane. If human blood plasma is exposed to nitrogen oxide, ascorbic acid and uric acid concentrations are depleted and lipid peroxidation is activated. Nitric oxide-derived species in cell membranes and lipoproteins react rapidly with fatty acids and lipid peroxyl radicals during lipid oxidation, producing oxidized products of free fats and cholesterol. 

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