FATTY ACIDS - aliphatic carboxylic acids, many of which are a part of animal and seed fats; in an organism of animals and in plants free. to. and. to., being a part of lipids, perform extremely important function — power and plastic. Unsaturated. to. participate in a human body and animals in biosynthesis of special group of biologically active agents — prostaglandins (see). Contents free and efirnosvyazanny. to. serves as additional diagnostic test at a number of diseases in blood serum. to. are widely used for preparation of various soaps, in production of rubber and rubber goods, varnishes, enamels and drying oils.
Depending on number of carboxyl groups in a molecule distinguish one - two - and polybasic. to., and on degree of a saturation of the hydrocarbon radical — saturated (limit) and unsaturated (nonlimiting). to. On number of carbon atoms in a chain. to. are divided into the lowest (C1 — C3), averages (C4 — C9) and the highest (C10 — C26) - Sated. to. have the general molecular formula of C n H 2 n O 2 . General formula of unsaturated. to. depends on number of the double or acetylene bonds which are contained in them.
For designation Zh. to. use the rational and systematic nomenclature; besides, many. to. have historically developed names. According to the rational nomenclature all. to. consider as derivatives acetic to - you, in a molecule a cut hydrogen atom of methyl group is replaced by the hydrocarbon radical. According to the systematic nomenclature the name Zh. to. comes from the name of hydrocarbon, the molecule to-rogo is constructed of the same number of carbon atoms, including carbon of a carboxyl group, as a molecule Zh. to. (e.g., propane — propane to - that, ethane — ethanoic to - that, hexane — hexane to - that etc.). In the name of unsaturated. to. the number of double bonds is specified (mono - di - three - etc.) also the termination «enovy» increases. Numbering of carbon atoms Zh. to. begins with carbon carboxyl (SOON —) groups and the Arab, is designated by figures. The next to the C-atom COOH group is designated as an alpha, next to it — a beta and trailer carbon atom in the hydrocarbon radical — an omega. A double bond in a molecule Zh. to. designate a symbol Δ or just provide number of carbon atom, at to-rogo the double bond with the instruction cis-or trans-configurations of a chain is located. Some most widespread. to. and their generic, rational and systematic names are provided in table 1.
the Lowest. to. represent volatile liquids with a pungent smell, averages — oils with an unpleasant rancid smell, the highest — the solid crystal matters which are almost deprived of a smell.
With water mix up in every respect only formic acid (see), acetic acid (see) and propionic to - that; at higher members of a row Zh. to. solubility quickly decreases and, at last, becomes equal to zero. In alcohol and ether Zh. to. rastvorima well.
Temperatures of melting in a homologous series. to. increase, but unevenly. to. with an even number of C-atoms melt at more high temperature, than following them. to., having one C-atom more (tab. 2). In both of these rows (with an even and odd number of C-atoms) temperature difference of melting of two following one after another of members gradually decreases.
Such peculiar distinction between. to. with an even and odd number of S-atoms in a molecule it is shown not only in temperatures of melting, but in a nek-swarm of degree in chemical and even in them biol, properties. So. to. with an even number of C-atoms break up, according to G. Embden, at hemorrhage in a liver to acetone, and. to. with an odd number of C-atoms — do not break up
. to. are strongly associated and even at temperatures exceeding their temperature of boiling show twice a bigger pier. weight, than it follows from their formula. This association is explained by emergence of hydrogen bindings between separate molecules Zh. to.
Chemical properties. to. are defined by properties of their COOH-group and the hydrocarbon radical. In COOH group communication O — H is weakened at the expense of the shift of electron density in double by C = O communications to oxygen and therefore the proton can be chipped easily off. It leads to emergence of stable anion to - you:
Affinity of the carbonyl rest to electrons can be partially satisfied at the expense of the next methylene group, hydrogen atoms a cut are most active in comparison with the others. Dissociation constant of COOH group Zh. to. it is equal to 10 - 4 — 10 - 5 The m, i.e. its size is much lower, than at inorganic to - t. The strongest of. to. is ant to - that. COOH group Zh. to. has ability to react in water solutions with alkaline earth metals. Salts of the highest. to. with these metals are called soaps (see). Soaps have properties of surfactants — detergents (see). Sodium soaps firm, potassium — liquid. Hydroxyl of COOH-group. to. it can be easily replaced on halogen with formation of acid halides which are widely used in organic sinteza. At substitution of halogen the rest another to - you forms anhydrides Zh. to., at substitution by the rest of alcohol — their esters, ammonia — amides, a hydrazine — hydrazides. Esters of the three-main alcohol of glycerin and the highest are most spread in the nature. to. — fats (see). Hydrogen of alpha and carbon atom Zh. to. it can be easily replaced with halogen with formation of galogensoderzhashchy. to. Nonlimiting. to. can exist in a look cis-and trans-isomers. Majority of natural unsaturated. to. have cis configuration (see. Isomerism ). Degree of unsaturation. to. determine by yodometrichesky titration of double bonds. Process of transformation of unsaturated. to. in saturated received the name of a hydrogenation, reverse — dehydrogenations (see. Hydrogenation ).
Natural. to. receive by hydrolysis of fats (their saponification) with the subsequent fractional distillation or hromatografichesky division of released. to. Not natural. to. receive by oxidation of hydrocarbons; reaction proceeds through a mode of formation of hydroperoxides and ketones.
Oxidation of fatty acids
As power material Zh. to. are used in the course of beta oxidation. In 1904 F. Knoop made the hypothesis explaining the mechanism of oxidation. to. in an animal organism.
This hypothesis was constructed on the basis of establishment of the nature of the end products of exchange allocated with urine after introduction by an animal co-phenyl of replaced. to. In F. Knoop's experiences introduction by an animal of phenylic replaced. to., the S-atoms containing an even number, was always followed by allocation with urine phenyl acetic to - you, and the S-atoms containing an odd number — allocation of the benzoic to - you. On the basis of these data F. Knoop assumed that oxidation of a molecule Zh. to. comes by consecutive cutting off from it two-carbon fragments from a carboxyl group (scheme 1):
F. Knoop's hypothesis which received the name of the theory of beta oxidation is a basis of modern ideas of the mechanism of oxidation. to. In development of these representations the important role was played by the following methods and opening: 1) introduction of a radioactive label ( 14 C) in a molecule Zh. to. for studying of their exchange; 2) establishment by Munoz and L. F. Leloir of the fact that for oxidation. to. cellular homogenates the same cofactors, as for oxidation of pyruvate are required (inorganic phosphate, ions of Mg 2+ , cytochrome with, ATP and any substrate of a cycle Tricarboxylic to - t — succinate, fumarates, etc.); 3) establishment of the fact that oxidation. to., as well as substrates of a cycle Tricarboxylic to - t (see. Tricarboxylic acids cycle ), proceeds only in mitochondrions of a cell [A. L. Lehninger and Kennedy (E. P. Kennedy)]; 4) establishment of a role of a carnitine in transport. to. from cytoplasm in a mitochondrion; 5) opening by F. Lipmann and F. Linen of a coenzyme And; 6) allocation from animal fabrics in the cleared look multienzyme-nogo of a complex responsible for oxidation. to.
Process of oxidation. to. in general it consists of the following stages.
Activation. Free. to. irrespective of length of a hydrocarbon chain is metabolic inert and cannot be exposed to these or those transformations, including oxidation until it is activated.
Activation. to. proceeds in cytoplasm of a cell, with the participation of ATP, the recovered KoA-SH and ions of Mg 2+ .
Reaction is catalyzed by enzyme a thiokinase:
As a result of this reaction it is formed atsil-KOA, being an active form Zh. to. Several thiokinases are allocated and studied. One of them catalyzes activation. to. with a hydrocarbon chain length from C2 to C3, another — from C4 to C12, the third — from C10 to C22.
Transport in mitochondrions. Koenzimny form Zh. to., as well as free. to., has no ability to get in mitochondrions where actually and their oxidation proceeds.
It is established that transfer of an active form Zh. to. in a mitochondrion it is carried out with the participation of nitrogen base of a carnitine. Connecting with. to. by means of enzyme of atsilkarnitinovy transferase, the carnitine forms the acylcarnitine having ability to get in a mitochondrial membrane.
In case of palmitic to - you, e.g., formation of a palmityl-carnitine is represented as follows:
In a mitochondrial membrane with the participation of KOA and mitochondrial palmitil-karnitinovy transferase there is reverse reaction — splitting of a palmityl-carnitine; at the same time the carnitine is returned to cytoplasm of a cell, and the active form palmitic to - you passes a palmitil-Co in mitochondrions.
First stage of oxidation. In mitochondrions with the participation of dehydrogenases. to. (FAD-soderzhashchikh enzymes) oxidation of an active form Zh begins. to. according to the theory of beta oxidation.
At the same time atsil-KOA loses two hydrogen atoms in alpha and beta situation, turning into an unsaturated atsil-KOA:
Hydration. Unsaturated atsil-KOA attaches a water molecule with the participation of enzyme of enoil-hydratase therefore it is formed beta-gidroksiatsil-KOA:
Second stage of oxidation. Second stage of oxidation. to., just as the first, proceeds by dehydrogenation, but in this case reaction is catalyzed OVER - the containing dehydrogenases. Oxidation happens in the place of beta and carbon atom to education in this position of ketogroup:
Tioliz. The final stage of one complete cycle of oxidation is splitting beta-ketoatsil-KOA by a tioliz (but not hydrolysis as F. Knoop assumed). Reaction proceeds with the participation of KOA and enzyme thiomanholes. It is formed shortened on two carbon atoms atsil-KOA and one molecule acetic to - you in a look atsetil-KOA is released:
Atsetil-KOA is exposed to oxidation in a cycle Tricarboxylic to - t to CO 2 and H 2 O, and atsil-KOA passes all way of beta oxidation again, and so proceeds until all shortened on two carbon atoms atsil-KOA does not lead disintegration to formation of the last particle atsetil-KOA (scheme 2).
At beta oxidation, napr, palmitic to - you, 7 cycles of oxidation are repeated. Therefore the general result of its oxidation can be presented by a formula:
With 15 H 31 COOH + ATP + 8KoA-SH + 7NAD + 7FAD + 7H 2 O -> 8CH 3 CO — SKoA + AMF + 7NAD-N 2 + 7FAD-N 2 + pyrophosphate
Subsequent oxidation of 7 molecules NAD-N 2 oxidation of 7 molecules FAD-N educates 21 molecule ATP, 2 — 14 molecules ATP and oxidation of 8 molecules atsetil-KOA in a cycle of Tricarboxylic acids — 96 molecules ATP. Taking into account one molecule ATP spent right at the beginning for activation palmitic to - you, the overall energy effeciency at full oxidation of one molecule palmitic to - you in the conditions of an animal organism will make 130 molecules ATP (at full oxidation of a molecule of glucose only 38 molecules ATP are formed). Since change of free energy at complete combustion of one molecule palmitic to - you make — 2338 kcal, and high-energy phosphatic communication of ATP is characterized of 8 kcal, it is easy to count that about 48% of all potential energy palmitic to - you at its oxidation in an organism are used for resynthesis of ATP, and the rest, apparently, is lost in the form of heat.
Small amount. to. the omega oxidation (to oxidation in the place of methyl group) and to alpha oxidation is exposed in an organism (in the place of the second C-atom). In the first case it is formed dicarbonic to - that, in the second — shortened on one carbon atom Zh. to. Both types of oxidation proceed in microsomes of a cell.
Synthesis of fatty acids
As any of oxidation reactions. to. is in itself reversible, the assumption was made that biosynthesis. to. represents process, the return to their oxidation. So was considered till 1958, it was not established yet that in extracts of a liver of a pigeon synthesis. to. from acetate could proceed only in the presence of ATP and bicarbonate. Bicarbonate was absolutely necessary component though it in a molecule Zh. to. did not join.
Thanks to S. F. Wakil, F. Linen and Vagelos's researches (R. V. of Vagelos) in 60 — the 70th 20 century were established that the actual unit of biosynthesis. to. is not atsetil-KOA, and malonil-KOA. The last is formed at a carboxylation atsetil-KOA:
For a carboxylation atsetil-KOA bicarbonate, ATP, and also ions of Mg2+ were also required. The enzyme catalyzing this reaction, atsetil-KOA — a carboxymanhole contains in quality of prosthetic group biotin (see). Avidin, inhibitor of biotin, oppresses this reaction, as well as synthesis. to. in general.
Totally synthesis. to., napr, palmitic, with participation malonil-KOA it can be presented by the following equation:
As appears from this equation, for formation of a molecule palmitic to - you are required 7 molecules malonil-KOA and only one molecule atsetil-KOA.
Process of synthesis. to. it is studied at E in detail. coli and some other microorganisms. The fermental system called sintetazy fatty acids consists at E. coli from 7 individual enzymes connected with the so-called acyltransferring protein (APB). AP B is allocated in pure form, and its primary structure is studied. Pier. the weight of this protein is equal to 9750. In its structure there is a fosforilirovanny pantheteine with free SH group. AP B has no enzymatic activity. Its function is connected only with transfer of acylic radicals. Reaction sequence of synthesis. to. at E. coli can be presented in the following form:
Further the cycle of reactions is repeated, beta-ketokapronil-S-APB with the participation of NADF-N 2 it is recovered in beta-gidroksikapronil-S-APB, the last is exposed to dehydration with education unsaturated geksenil-S-APB which then is recovered in sated kapronil-S-APB, having a carbon chain is two atoms longer, than butiril-S-APB, etc.
Thus, the sequence and the nature of reactions in synthesis. to., since education beta-ketoatsil-S-APB and finishing end of one cycle of lengthening of a chain on two C-atoms, are back reactions of oxidation. to. However ways of synthesis and oxidation. to. are not crossed even partially.
In tissues of animals it was not succeeded to find APB. From a liver the multifermental complex containing all enzymes necessary for synthesis is allocated. to. Enzymes of this complex are so strongly connected with each other that all attempts to isolate them in an individual look were not crowned with success. In a complex there are two free SH groups, one of which, as well as in APB, belongs to fosforilirovanny pantheteine, another — to cysteine. All synthetic reactions. to. proceed on a surface or in this multifermental complex. Free SH groups of a complex (and it is possible, and hydroxylic group of the serine which is its part) take part in binding atsetil-KOA and malonil-KOA, and in all subsequent reactions the panteteinovy SH group of a complex carries out the same role, as well as the APB SH group, i.e. participates in binding and transfer of the acylic radical:
The further course of reactions in an animal organism just the same as it is given above for E. coli.
To the middle of 20 century was considered that the liver is the only body where there is a synthesis. to. Then it was established that synthesis. to. occurs also in a wall of intestines, in pulmonary fabric, in fatty tissue, in marrow, in l to the drawing-up mammary gland and even in a vascular wall. As for cellular localization of synthesis, that is the basis to consider that it proceeds in cytoplasm of a cell. It is characteristic that in cytoplasm of hepatic cells the hl is synthesized. obr. palmitic to - that. As for others. to., the main way of their education in a liver consists in lengthening of a chain on the basis of already synthesized palmitic acid or. to. an exogenous origin, arrived from intestines. Are formed by such way, e.g. to., the containing 18, 20 and 22 S-atoms. Education. to. by lengthening of a chain occurs in mitochondrions and microsomes of a cell.
Biosynthesis. to. in animal fabrics it is regulated. Long ago it is known that the liver of the starving animals and the animals sick with diabetes, slowly includes 14C-acetate in. to. The same was observed also at animals, the Crimea was entered by excess amounts of fat. It is characteristic that in homogenates of a liver of such animals it was slowly used for synthesis. to. atsetil-KOA, but not malonil-KOA. It formed the basis to assume that the reaction limiting the speed of process in general is connected with activity atsetil-KOA — carboxymanholes. Really, F. Linen showed that long-chain acylic derivative KOA in concentration 10 - 7 M inhibited activity of this carboxymanholes. Thus, accumulation. to. exerts the braking impact on their biosynthesis on a feedback mechanism.
Other control factor in synthesis. to., apparently, is lemon to - that (citrate). The mechanism of effect of citrate is also connected with its influence on atsetil-KOA — to a carboxymanhole. In lack of citrate atsetil-KOA — a carboxymanhole of a liver is in a type of inactive monomer about a pier. weighing 540 000. In the presence of citrate enzyme turns into the active trimmer having a pier. weight apprx. 1 800 000 and providing 15 — 16-fold increase in speed of synthesis. to. It is possible to assume, therefore, that the content of citrate in cytoplasm of hepatic cells exerts the regulating impact on the speed of synthesis. to. At last, importance for synthesis. to. concentration of NADF-N has 2 in a cell.
Exchange of unsaturated fatty acids
the convincing evidence Is obtained that in a liver of animals stearin to - that can turn in olein, and palmitic — in palmitoleic to - that. These transformations proceeding in microsomes of a cell demand availability of molecular oxygen, the recovered system of pyridinic nucleotides and b5 cytochrome. In microsomes transformation monounsaturated to - t in diunsaturated, napr, olein to - you in 6,9-octadecadienoic to - that can be also carried out. Along with desaturation. to. in microsomes also their elongation proceeds, and both of these processes can be combined and repeat. By such way, e.g., from olein to - you are formed nervonovy and 5, 8, 11-eykozatetrayenovy to - you.
At the same time tissues of the person and a number of animals lost ability to synthesize some polyunsaturated to - you. Treat them linoleic (9,12-octadecadienoic), linolenic (6,9,12-oktadekatriyenovy) and arachidonic (5, 8, 11, 14-eykozatetrayenovy) to - you. These to - you refer to category of irreplaceable. to. At their long absence in food at animals lag in growth is observed, characteristic defeats from skin and indumentum develop. Cases of insufficiency of irreplaceable are described. to. and at the person. Linoleic and linolenic to - you, the containing respectively two and three double bonds, and also related to them polyunsaturated. to. (arachidonic, etc.) are conditionally united in group under the name «vitamin F».
Biol, role of irreplaceable. to. cleared up in connection with opening of a new class of physiologically active connections — prostaglandins (see). It is established that arachidonic to - that and to a lesser extent linoleic are predecessors of these connections
Main plastic function Zh. to. comes down to their participation as a part of lipids in creation biol, the membranes making a skeleton of animal and plant cells. In biol, membranes hl are found. obr. ethers of the following. to.: stearin, palmitic, olein, linoleic, linolenic, arachidonic and dokozageksayenovy. Unsaturated. to. lipids biol, membranes can be oxidized with formation of lipidic peroxides and hydroperoxides — so-called peroxide oxidation unsaturated. to.
In an organism of animals and the person only unsaturated are easily formed. to. with one double bond (e.g., olein to - that). Polyunsaturated are much more slowly formed. to., most of which part is delivered in an organism with food (essential. to.). There are special fat depos from which after hydrolysis (lipolysis) of fats Zh. to. can be mobilized for satisfaction of needs of an organism.
It is experimentally shown that food the fats containing large numbers of sated. to., promotes development of a hypercholesterolemia; use with food of the vegetable oils containing large numbers of unsaturated. to., promotes decrease in content of cholesterol in blood (see. Lipometabolism ).
The medicine pays the greatest attention to unsaturated. to. It is established that excess oxidation them on the peroxide mechanism can play an essential role at development various patol, states, napr, at radiation damages, malignant new growths, avitaminosis E, a hyperoxia, poisoning with perchloromethane. One of products of peroxide oxidation of unsaturated. to. — lipofuscin — collects in fabrics during the aging. Mix of ethyl ethers unsaturated. to., consisting from olein to - you (apprx. 15%), linoleic to - you (apprx. 15%) and linolenic to - you (apprx. 57%), so-called. linaetholum (see), it is used in prevention and treatment atherosclerosis (see) and outwardly — at burns and radiation injuries of skin.
In clinic methods of quantitative definition free (not esterified) and efirnosvyazanny are most widely applied. to. Methods of quantitative definition of efirnosvyazanny. to. are based on their transformation in corresponding hydroxamic to - you which, interacting with ions of Fe 3+ , form color complex salts.
Normal the blood plasma contains from 200 to 450 mg of % esterified. to. and from 8 to 20 mg of % not esterified. to. Increase in contents of the last is noted at diabetes, nefroza, after administration of adrenaline, at starvation, and also at an emotional stress. Decrease in maintenance of not esterified. to. it is observed at hypothyroidisms, at treatment by glucocorticoids, and also after an injection of insulin.
Table 1. NAMES AND FORMULAS of SOME MOST WIDESPREAD FATTY ACIDS
Table 2. PHYSICAL PROPERTIES of MONOBASIC FATTY ACIDS [on Karrera (R. Karrer), 1959]
Bibliography: Vladimirov Yu. A. and Archakov A. I. Peroxide oxidation of lipids in biological membranes, M., 1972; Zinovyev A. A. Chemistry of fats, M., 1952; H yu with x about l of m E. and Start To. Regulation of metabolism, the lane with English, M., 1977; Perekalinv. Century and Zonne S.A. Organic chemistry, M., 1973; Biochemistry and methodology of lipids, ed. by A. R. Jonson a. J. B. Davenport, N. Y., 1971; Fatty acids, ed. by K. S. Markley, pt 1—3, N. Y. — L., 1960 — 1964, bibliogr.; Lipid metabolism, ed. by S. J. Wakil, N. Y. — L., 1970.
A. H. Klimov, A. I. Archakov.