RADICALS FREE — the atoms or groups of chemically connected atoms having free valencies, i.e. not coupled (uncompensated) electrons on an external (valent) orbital. Existence of not coupled electrons defines high chemical reactivity and electronic spin magnetism of P.c. (see. Atom , Molecule ).
Numerous data confirm R.'s participation by the village in normal functioning of living cells and fabrics, and also in development of some patol. states. It is established that process of aging (see. Old age , aging) is followed by emergence and cumulation in fabrics of abnormal number of R. of page and peroxides (see). Rubles of page have the expressed mutagen effect (see. Mutagens ). Assume that free radical processes play an essential role in a carcinogenesis (see). Antibacterial action of some antibiotics explain them with ability to form R. the villages having cytolytic effect concerning bacterial cells.
There is a hypothesis based on theoretical representations and on experimental data that abiogenous predecessors of proteins (see), nucleic acids (see) and other biopolymers on Earth there were R. the pages formed of carbon dioxide gas, ammonia, water vapor, methane and other elementary connections of primary atmosphere of Earth.
Stable iminoksilny R. the pages allocated and in detail studied by E. G. Rozantsev, A. L. Buchachenko and M. B. Neumann, use as tags and probes during the studying of conformation of proteins and nucleinic to - t, and also during the studying of the mechanism of interaction of substrate with enzyme, enzyme with a coenzyme, antigen with an antibody and properties biol. membranes, including the mechanism of an immunolysis biol, membranes with the participation of complements.
Fundamental consistent patterns of reactions with R.'s participation by the village were determined by H. N. Semenov and his pupils also creations of the new section of physics — chemical physics formed a basis. In biol, processes 20 century began to study R.'s participation by the village in the 30th. The big contribution to the solution of this problem was made A. G. Gurvich, by H. M. Emanuel, B. N. Tarusov, L. A. Blyumenfeld, G. M. Frank, etc., abroad — R. Willstätter, Kommoner (V. Commoner), W. Gordy, Calvin (M. J. Calvin), J. S. Hyde, Chans (V. Chance), L. H. Piette, H. Beinert, Ingram (D. J. E. Ingram), A. Ehrenberg, A. Müller, J. McConnell, etc.
R. of page can be neutral or charged particles — a radical ion which depending on a sign of a charge call anionil a radical cation. Designate R. of page a R symbol, the point indicates existence of not coupled electron.
In live organisms of R. of page are formed as a result of reactions of one-electron oxidation or recovery of molecules by the corresponding donors or electron sinks, napr, by oxygen or metals of variable valency, and also directly under the influence of ionizing or Uv-radiations.
The simplest pages of living cell on R.'s structure are radical anion of superoxide (About - 2 ) and the neutral radical of a hydroxyl (IT) is a hydroxylic radical which are formed in reactions of consecutive one-electron recovery of molecular oxygen:
One-electron recovery of oxygen can happen in cells and fabrics with the participation of a number of enzymes, such as a xanthineoxidase (KF 1. 2. 3. 2), glucose oxydas (KF 1. 1. 3. 4), etc. The radical of superoxide has rather low reactivity whereas the hydroxylic radical enters interaction almost with all main chemical components of a cell: amino acids and proteins, nucleinic to-tami, many coenzymes and lipids that is the cornerstone of its cytotoxic action. In the englobing cells NADFN-oksidaza enzyme catalyzes education of superoxidic radicals who in turn form the hydrogen peroxide and hydroxylic radicals participating, apparently, in destruction of the bacterial cells taken by phagocytes. In other cells transformation of the superoxidic radical into a cytotoxic hydroxylic radical is prevented thanks to activity of protective enzymes — superoxide dismutases (peroxydismutases; KF 1. 15. 1. 1) and catalases (see):
Action of some antibiotics (e.g., Streptonigrinum) is based that they provide one-electron recovery of molecular oxygen, taking away a cathode rays from terminal oxidases (see) bacterial cell. The hydroxylic radicals causing eventually death of such cell are as a result formed superoxidic, so, and. However there are strains of the microorganisms having very high content super oxide of dismutase that does them steady against action of such antibiotics as Streptonigrinum.
At action ionizing and Uv-radiations on amino acids, proteins, nucleotides, nucleinic to - you, fat to - you and lipids as a result of photoionization, i.e. a separation of an electron or a rupture of chemical communication, are formed various R. by page, and also primary photolytes — solvated (i.e. taken by molecules of the environment, generally — waters) an electron, hydrogen atom and organic radicals.
On 100 ev energy of ionizing radiation 2 — 4 free radicals are formed, the photon yield of R. of page is low: at absorption of each 100 light quantums only several free radicals are formed.
The solvated electron can join the connections containing SH groups, NH 2 - groups, etc. with formation of new P.c., or to molecular oxygen with education of the superoxidic radical. As a result of reaction to R.'s participation by the village in the irradiated proteins and nucleinic to-takh there is a chemical modification of macromolecules (ruptures of peptide or nucleotide bonds, formation of «stitchings», chemical changes of various amino-acid remains, nucleotides, etc.). Chemical modifications lead to structural change of a macromolecule, its form and biochemical, properties, to emergence of point mutations, to an inactivation of enzymes, destruction biol, membranes etc.
Believe that functionally the most important and universal group P. of page on distribution in living cells are the seven-quinones, radical anion which are constantly formed during a metabolism and energy (see) namely at oxidation-reduction transformations of carriers of electrons in mitochondrions, chlorolayers, membranes of bacterial cells and intracellular membranes of eukaryotes.
For the first time L. Michaelis pointed to participation of seven-quinones in redoxreactions (see) organic compounds in the 30th.
P.c are rather in detail studied. yellow enzymes (see), ubikhinon (a coenzyme of Q in zooblasts and a plastokhinona in plant cells), R. by page of naphthoquinone are found in a number of microorganisms (see. Quinones ). These R. of page take part in electron transfer in the power interfacing membranes and in systems of a hydroxylation at ksenobiont.
With transient formation of R. of page also oxidation ascorbic to - you (redoxon), tocopherol (vitamin E), many phenols (see) and other biologically active molecules which are a part of living cells is carried out.
Great value for normal cell activity, and also in development of a row patol, processes R. have the pages which are formed at oxidation of lipids molecular oxygen, first of all — at oxidation polyunsaturated fat to - t and fat to - t of the phospholipids which are a part of lipoproteids and biol, membranes.
As B. N. Tarusov (1954) showed, the mechanism of free radical oxidation of lipids in fabrics and membranes corresponds to the general laws of chain oxidation (see. Chain reactions ). Process of chain oxidation begins a stage of initiation, and as the initiator the OH radical capable to take away hydrogen atom from organic compounds (RH) with formation of water and the organic free radical can act:
Speed of free radical oxidation of lipids is proportional to concentration of double bonds in unsaturated fat to-takh, these lipids which are a part. The formed radicals unsaturated fat to - t (R) interact with oxygen, forming peroxide radicals (RO 2 ), and those, in turn, react with a new molecule unsaturated fat to - you with education To and accumulation of hydroperoxide of lipids (ROOH):
Alternation of two last reactions leads to chain peroxide oxidation fat to - t.
Direct detection of peroxide radicals of lipids of RO 2 it is possible only in model experiences.
In suspensions of organellas, the whole cells and in fabrics it is possible to find radicals of lipids of RO2 so far only an indirect way by means of registration of chemiluminescence (see. Biokhemilyuminestsention ) — the superweak luminescence accompanying process of interaction (recombination) of two RO 2 - radicals: RO 2 + RO 2 → intermediate product → alcohol + ketone + O 2 + light quantum. Thus reaction of interaction of peroxide radicals leads to break of chains of oxidation of lipids. In biol, systems value of this process for restriction of speed of peroxide oxidation of lipids, apparently, is small since the main number of RO2 radical disappears or in reactions with metals of variable valency (in particular, with ions of bivalent iron and copper), or at interaction with lipidic antioxidants: alpha tocopherol, estrogen, the thyroxine recovered by KOQ, phthiocol, glutathione (see), cysteine, etc.
Feature of free radical oxidation is that at action of elevated temperature, Uv-radiations or in the presence of metals of variable valency chain reaction becomes branched since the product of chain oxidation — hydroperoxide (ROOH) decays with R.'s education by the village beginning new chains of oxidation:
Regulation of peroxide oxidation in a cell can happen at a stage of a branching of chains. E.g., emergence of ions of bivalent iron leads to decomposition of hydroperoxides and emergence of new radicals, i.e. to acceleration of free radical oxidation of lipids. Process of recovery of trivalent iron to bivalent happens in a mitochondrial electron transport chain. However removal of hydroperoxides excludes a possibility of a branching of chains in actual practice of living cell since intensity of free radical oxidation decreases. Process of removal of hydroperoxides without R.'s education by the village is carried out in a cell due to recovery of ROOH by SH connections, in particular — the recovered glutathione, and catalyzed glutationperoksidazy (KF 1. 11. 1. 9), contained in all animals and vegetable fabrics.
Braking of free radical oxidation by SH connections can also result from interaction of SH-group of such connections with lipidic R. of page, at the same time tiolny radicals (RS) are formed.
Methods of definition The river of the page and processes proceeding with their education are various. Direct definition of R. of page in cells and fabrics, in solutions and suspensions of cellular organellas at fiziol, temperatures is difficult feasible because of high reactivity of R. of page and small time of life owing to what their stationary concentration in the studied objects is very low. During the freezing of objects the speed of free radical processes is slowed down, and at deep cooling (to 77 ° To) it is almost equal to zero. In such samples of R. of page can be registered by optical techniques: measurement of absorption spectrums (see. Spectral analysis ) or luminescences (see). However the most objective direct method of detection and R.'s definition by the village is the method of an electronic paramagnetic resonance (see) — EPR. The EPR method allows to establish a chemical structure of R. of page, their concentration in solution. Use of so-called spin adducts — the molecules forming with R. page rather steady connections allowed to expand possibilities of this method. The EPR method after the beginning of use in biol, experiments of the spin tags and probes which are stable R. page became even more informative.
A sensitive method of detection of R. of page of some types is the method of chemiluminescence. Chemical methods of registration of R. of page, napr, the method based on R.'s ability of page to initiate reaction of copolymerization (see), with use of radioactive monomers and biopolymers are developed. Upon termination of reaction the monomers which did not join in copolymer delete and by means of counters of radiation estimate extent of copolymerization.
Free radical oxidation polyunsaturated fat to - t study on the basis of diene conjugation. Delocalization of not coupled electron in R. polyunsaturated fat to - you leads page to emergence of the so-called conjugated dienes in reaction products (in peroxide of ohms the radical, and then in hydroperoxide fat to - you) that is registered by means of usual optical techniques of a research (see).
The important role of R. of page in normal cellular metabolism is proved by means of a large number of experiments. The river of page, formed in an electron transport chain, provide transfer on a chain of one electron while participation of molecules provides single-step transfer not less than two electrons. As in tsitokhroma (see) and in zhelezosulfoproteida the elementary act redox is process one-electron, inclusion of an organic molecule in such chain assumes redoxreaction. Ubikhinona and flavins participate in one-electron transfer through a mode of formation of R. of page. An opportunity and conditions of education of superoxidic and lipidic R. of page at the expense of R. of the pages which are formed in an electron transport chain are not found out yet.
By E. B. Burlakova, A. I. Zhuravlev, V. E. Kagan, S. A. Neyfakh, etc. it is established that normal in cells processes of free radical oxidation of lipids constantly proceed. There are series of observations about nesemikhinonny R.' participation by the village in functioning of mitochondrions. In 1968 3. Gorkin with sotr. found effect of transformation of activity of enzymes at action of products of free radical oxidation on them; e.g., monoamine oxidase (see) mitochondrions gained properties of diaminoxidase (KF 1. 4. 3. 6). Believe that oxidation of Shgroup of enzymes is the cornerstone of such transformation. Data on R.'s participation by the village in processes of oxidizing phosphorylation are obtained (see) in mitochondrions. Phagocytosis of microorganisms and viruses is followed by activation of free radical oxidation.
The question of R.'s role of page of lipids in normally functioning organism remains a subject of a discussion so far. Destruction of intracellular membranes in reticulocytes is connected with peroxide oxidation saturated fat to - to the t catalyzed by enzyme a lipoxygenase (KF 1. 13. 11. 12) and the page going through a mode of formation of R. Apparently, the enzymic free radical oxidation of lipids connected with oxidation of NADFN in an endoplasmic reticulum of a liver happens in the course of destruction of membranes endoplazmaticheskoko a reticulum. Bystry self-updating of lipidic structure of these membranes is probably partially provided with free radical oxidation of lipids and resynthesis of new lipidic components of a membrane.
Accumulation of intermediate products of free radical oxidation of lipids (hydroperoxides) leads to nek-rum to change of properties of a lipidic layer in biol, membranes: to decrease in its water repellency and probable increase in permeability for ions. Pages of SH group of enzymes biol, membranes which oxidation leads to increase in permeability of membranes for cations and anions are most sensitive concerning R. Final (usually water-soluble) products of free radical oxidation of lipids — aldehydes, ketones, aldo-and ketonic acids cause the increase in permeability of a lipidic layer for protons leading to dissociation of oxidizing phosphorylation and breath in mitochondrions. These end products of free radical oxidation increase a surface-bound (negative) charge biol, membranes, reduce electric stability lipidic bisloya. In the course of free radical oxidation are spent first of all less viscous polyunsaturated to - you. The general increase in viscosity of the environment leading usually to decrease of the activity of enzymes results. All these phenomena are the cornerstone of cytotoxic action of R. of page and products of free radical oxidation which in low concentrations cause disturbance of cellular division, and in higher — death and killing.
In living cell regulation of free radical oxidation of lipids is carried out at a stage initiation — activation of formation of the superoxidic radical in electronic and transport systems or, on the contrary, inhibition of toxic action radical superoxide and the hydroxylic radical with the participation of a superoxide scavenger and a catalase at a stage of chain oxidation unsaturated fat to - t by maintenance of a certain fat and acid structure of lipids of membranes at the level of a branching of chains of oxidation. Recovery of hydroperoxides due to SH connections with participation of a glutationreduktaza (KF 1. 6. 4. 2) reduces the speed of a branching of chains of oxidation and reduces the speed of free radical oxidation. This braking of speed can be carried out also due to binding of ions of metals of variable valency. E.g., activation of free radical oxidation in fabrics at Wilson's disease (see. Hepatocerebral dystrophy) is defined by surplus in fabrics of sick loosely coupled copper ions. Introduction of D-penitsilamina (an alpha, an alpha' - dimethylcysteine) which is actively connecting copper and bringing her out of an organism reduces weight a wedge, displays of a disease. Regulation of free radical oxidation by means of bioantioxidants is the cornerstone of their use as stabilizers of the pharmaceuticals containing unsaturated fat to - you.
The role of free radicals in pathological processes
can lead Strengthening of free radical oxidation of lipids to disturbance of normal life activity of an organism and create conditions for development of a number of diseases. Signs of participation of free radical oxidation of lipids in development of this or that disease, in addition to activation of free radical oxidation, are increase the wedge, symptoms, and also improvement of a condition of the patient or his full treatment as a result of braking of free radical oxidation of lipids as a result of therapy by antioxidants.
About activation of process of free radical oxidation judge usually by increase in content in fabrics and sick R.' blood of page, lipidic hydroperoxides, aldehydes, in particular low-new dial, and also by decrease in content of lipidic antioxidants. The method of registration of level of free radical oxidation in an organism of patients in a wedge, conditions on the maintenance of a pentane in expired air is developed. Strengthening of free radical oxidation of lipids was revealed in a liver at poisoning with perchloromethane, alcohol, salts of copper, ozone, oxygen, in skin after UF-radiation, in the centers of a hypoxia and an inflammation and at burns, in a retina of an eye at excessive lighting, in all bodies and fabrics at development of a radial illness (see) and at certain stages of a carcinogenesis, at some inf. diseases, Avitus Minozakh, inflammatory processes; in a brain of animals strengthening of free radical oxidation of lipids was revealed at experimental epilepsy etc. However the pathogenetic role of free radical oxidation of lipids in all these cases is not clear yet.
The state sick or animal (in experimental conditions) almost always considerably improves after therapy by antioxidants; e.g., the erythema caused by radiation of skin UF-light decreases, toxic action on an organism of perchloromethane decreases, epileptic seizures are stopped (in an experiment), terms of preservation of cells and bodies increase. Successful use of antioxidants at treatment of burns and the coronary heart disease connected with atherosclerosis is described.
Researchers pay much attention to R.'s role page in a carcinogenesis. Correlation between ability of a number of oncogenes to R.'s education by the village and their oncogenous activity is found. As a rule, in process of development of a tumor R.'s concentration of page in fabrics decreases by 2 — 6 times in comparison with control, and intensity of free radical oxidation in other body tissues usually increases, especially on end-stages of a disease that, perhaps, is connected with redistribution of antioxidants between fabric of a malignant tumor and other fabrics.
Bibliography: Azhipa Ya. I. Medicobiological aspects of use of a method of an electronic paramagnetic resonance, M., 1983, bibliogr.; Vladimirov Yu. A. and Archakov A. I. Peroxide oxidation of lipids in biological membranes, M., 1972; Zhuravlev A. I. and at r and in l e in and A. I. A superweak luminescence of blood serum and its value in complex diagnosis, M., 1975; KA of l-manson of A. E. Use of a method of an electronic paramagnetic resonance in biochemistry, in book: Progress biol, chemistry, under the editorship of B. N. Stepanenko, etc., t. 5, page 289, M., 1963; Kayushin L. P., Gribova 3. Item and Azizova O. A. Electronic paramagnetic resonance of photoprocesses of biological connections, M., 1973; Kozlov Yu. P. Free radicals and their role in normal and pathological processes, M., 1973; Free radicals in biology, under the editorship of U. Pryor, the lane with English, t. 1 — 2, M., 1979; Tarusov B. N. Primary processes of radiation injury, M., 1962; Emanuel N. M., Denisov E. T. and Mayzus 3. K. Chain reactions of oxidation of hydrocarbons in a liquid phase, M., 1965.
Yu. A. Vladimirov, A. I. Zhuravlev, A. E. Kalmanson.