LIPOMETABOLISM — set of processes of transformations of neutral fats (triglycerides) in an organism of animals and the person. Treat these processes: 1) digestion and absorption of fats and products of their disintegration in went. - kish. path; 2) an intermediate metabolism of fats and fat to - t in an organism; 3) release of fats and products of their exchange from an organism. Disturbances. lakes of various etiology serve as the reason of development of many patol. states.
Neutral enter into composition of tissues of animals and plants fats (see) and zhiropodobny connections (lipoida) combined by the general name lipids (see) therefore the concepts «lipometabolism» and «lipidic exchange» often are understood as synonyms.
Beginning of studying. the island treats 1823 when Shevrel (M. of Chevreul) opened the chemical nature triglycerides (see) which were esters fatty acids (see) and glycerin (see). This opening served as an incentive to carrying out researches on studying of chemical composition of various fats, including fats of animal origin. In the middle of 19 century existence of the splitting (lipazny) effect of gastric and pancreatic juice on fats was established. Later A. N. Lebedev proved a possibility of adjournment in fatty tissue of animals of not changed alien fat. In 1904 F. Knoop created the original theory of oxidation of fatty acids.
Considerable progress in studying of exchange of fats and intermediate products of their metabolism, first of all fat to - t, was reached in the second half of 20 century in connection with wide use of marked atoms and the general progress in development of biochemistry.
- 1 Digestion and absorption of fats
- 2 The intermediate metabolism of fats
- 3 Release of fats and products of their exchange from an organism
- 4 Disturbances of a lipometabolism
- 5 The lipometabolism at children
- 6 Changes of a lipometabolism in the course of aging
Digestion and absorption of fats
Splitting of fats in digestive tract
with food every day comes To an organism of the adult on average 70 g of fats of an animal and plant origin. In an oral cavity fats are not exposed to any changes since saliva does not contain lipolytic enzymes. Partial splitting of fats on glycerin (or mono - and diglycerides) and fat to - you begin in a stomach. However splitting of fats in a stomach proceeds with a small speed that is explained by the following reasons. First, in a gastric juice of the adult and mammals activity lipases (see) it is extremely low. Secondly, the size pH of a gastric juice is far from optimum for effect of this enzyme (the optimum pH value for a gastric lipase is in limits 5,5 — 7,5). Thirdly, in a stomach there are no conditions for emulsification of fats, and the lipase can hydrolyze actively only the fat which is in a form of a fatty emulsion. Therefore adults have not emulsified fats making the ground mass of food fat pass through a stomach without special changes.
At the same time hydrolytic decomposition of fats in a gastric cavity plays an important role in the course of digestion at children, especially at children of chest age. Moderate gastric acidity at children of chest age (pH apprx. 5,0) promotes digestion of the emulsified fat of milk a gastric lipase. Besides, at the long use of milk as a key product of food perhaps adaptive strengthening of synthesis of a gastric lipase at children of chest age.
In the 70th 20 century of R. Scow were established that the mucous membrane of an upper part of a gullet of the baby cosecretes an own lipase in response to the sucking movements of the child during the feeding by a breast. It is possible that this lipase and shows the action in a stomach of children of chest age.
In spite of the fact that splitting of fats in a stomach of the adult is small, it to some extent facilitates the subsequent digestion of fats in intestines. First, in a stomach there is a partial destruction of lipoproteidny complexes of membranes of cells of food that makes fats more available for the subsequent impact of a lipase of pancreatic juice on them. Secondly, even splitting of fats, insignificant on volume, in a stomach leads to emergence free fat to - t which, without being exposed to absorption in a stomach, come to intestines and there promote emulsification of fats.
The main part of food fats is exposed to splitting in upper parts of a small intestine at action of a lipase of pancreatic juice. Steapsin (KF 188.8.131.52) shows an optimum of action at pH apprx. 8,0 and splits the substrates which are in the emulsified state (action on the dissolved substrates is much weaker than it). Enzyme catalyzes hydrolysis of radio bonds in a molecule of triglyceride, in alpha provisions therefore two molecules fat to - t and a beta monoglyceride are formed. As intermediate products of a lipolysis beta diglycerides (scheme 1) are formed alpha:
Intestinal juice contains the lipase which is catalyzing hydrolytic decomposition of monoglycerides and not operating on di - and triglycerides. Its activity, however, is low therefore almost key products which are formed in intestines during the splitting of food fats are fat to - you and beta monoglycerides. As for glycerin, during the splitting of triglycerides in intestines it is formed in small amounts.
Emulsification of fats depends on a number of factors. Possess the strongest emulsifying action bile acids (see), getting into a duodenum with bile (see) in the form of sodium salts of the corresponding conjugates, hl. obr. glikokholeata and taurokholeata. In a duodenum together with food weight the quantity of the gastric juice containing salt to - that is brought a nek-swarm, edges in a duodenum it is neutralized generally by the bicarbonates which are contained in pancreatic and intestinal juice and bile. The vials of carbon dioxide gas which are formed at decomposition of bicarbonates loosen food gruel and promote its fuller hashing with digestive juices. At the same time emulsification of fat begins. Salts bilious to - t are adsorbed in the presence of small amounts free fat to - t and monoglycerides on a surface of droplets of fat in the form of the thin film interfering merge of these droplets. Besides, salts bilious to - t, reducing surface intention by interfaces of two phases — water and fat, promote a partition of big droplets of fat on smaller. Conditions for formation of a thin and steady fatty emulsion with a particle size of 0,5 microns and are created less. As a result of emulsification the surface of fats sharply increases that facilitates interaction them with a lipase, i.e. accelerates enzymic hydrolysis, and also absorption (see).
Absorption of fats in intestines
Absorption of fats, as well as others lipids (see), occurs in a proximal part of a small intestine. Thinly emulsified fats can partially be soaked up through a wall of intestines without preliminary hydrolysis. In this case the factor limiting this process, apparently, is the size of fatty droplets of an emulsion, edges shall not exceed 0,5 microns. However the main part of fat is soaked up only after splitting by its steapsin on fat to - you and monoglycerides. Absorption of these connections happens with the participation of bile. Bile contains salts bilious to - t, phosphatides (see) and cholesterol approximately in the ratio 12,5: 2,5: 1,0. Fat to - you and monoglycerides form with these components of bile of a micelle, consisting of salts bilious to - t, phosphatides, cholesterol, fat to - t and monoglycerides. These micelles can connect additional amounts of not esterified cholesterol, and also fat-soluble vitamins (A, D, E and K). Structure of micelles such is that their hydrophobic kernel consisting of lipids is surrounded outside with a hydrophilic cover from bilious to - t and phosphatides. The sizes of micelles are about 100 times less than the smallest emulsified fatty drops. Thanks to such small sizes and existence of an outside hydrophilic cover of a micelle in an aqueous medium are in a type of the solution called by micellar. Fatty micelles are considered as a peculiar complex of lipids and products of their disintegration in intestines with bilious to-tami and other components of bile, providing solubility of lipids and products of their disintegration in an aqueous medium (so-called micellar solubilization of lipids) and their absorption in an intestinal wall.
Concerning the mechanism of absorption of fatty micelles there is no uniform point of view. The possibility of direct penetration of micelles into epithelial cells of fibers of a mucous membrane of a small intestine by the whole particle by so-called micellar diffusion without energy consumption is acknowledged. In cells of fibers there is a disintegration of a micellar complex, at the same time bilious to - you at once come to blood and with a blood flow through system of a portal vein are delivered in a liver where again come to bile. From a different perspective, penetration of fatty micelles in epithelial cells is partially or completely carried out in the way pinocytic (see). Also the possibility of transition only of lipidic ingredients (molecular diffusion of lipids) from fatty micelles in epithelial cells at contact of micelles with a mucosal surface of a cover of fibers of intestines is allowed. Thus salt bilious to - t do not get in cells, and remain in a gleam of intestines and hl are exposed to the return absorption. obr. in an ileal gut. Some researchers consider that instead of micellar diffusion active transfer by micelles of lipids on acceptors of cellular membranes of fibers of a mucous membrane of intestines, and then transition of lipids in cells can take place.
Whichever there was a mechanism of absorption of lipids in an intestinal wall, at the same time the enterogepatichesky circulation of bile acids providing absorption of large numbers fat to - t and monoglycerides has extremely important value (50 — 70, and sometimes and more than 100 g) at rather low common pool bilious to - t (2,8 — 3,5 g).
As it was already mentioned, at digestion of fats small amounts of glycerin are formed. Being well water soluble, glycerin is easily soaked up in a small intestine. Partially it is exposed to turning into alpha glycerophosphate in epithelial cells of intestines, partially comes to a blood channel. Fat to - you with a short carbon chain (less than 10 S-atoms) are also easily soaked up in intestines and come to blood of a portal vein, passing any turning into to an intestinal wall.
Resynthesis of fats in a wall of intestines and transition of fats to lymphatic system and blood
Got into cytoplasm of epithelial cells of a mucous membrane of fibers of a small intestine free fat to - you and monoglycerides are late in an endoplasmic reticulum. Here from fat to - the t is formed their active form — atsil-KOA and there is an acylation of monoglycerides to formation at first of diglycerides, and then triglycerides. Thus, the cleavage products of food fats formed in intestines and which came to its wall are used for resynthesis of fats.
Biol, sense of this process comes down to the fact that in a wall of intestines the fats specific to this species of an animal and differing by the nature from food fat are synthesized. To a certain extent it is provided that in an intestinal wall take part in synthesis of triglycerides and phosphatides along with exogenous and endogenous fat to - you, synthesized again or «modified», napr, by lengthening of a carbon chain, and also delivered in cells of an intestinal wall from a blood channel or synthesized in a liver and got at first into intestines as a part of phosphatides of bile, and then got into epithelial cells of intestines as a part of lipidic micelles. Besides, in cells of intestines there is a peculiar redistribution of a common pool fat to - t; e.g., fat to - that exogenous triglyceride-nogo of an origin can be used for etherification of cholesterol of both an exogenous, and endogenous origin; fat to - that, earlier being a part of phosphatides, can be used for resynthesis of triglycerides and vice versa etc.
At last, epithelial cells of a small intestine contain enzymes — the monoglitseridlipaza splitting a monoglyceride on glycerin and fat to - that, and a glitserolkinaz (KF 184.108.40.206), catalyzing transformation of the glycerin formed during the previous reaction or which is soaked up from intestines into alpha glycerophosphate. alpha Glycerophosphate, interacting with a zhirnokislotny atsil-KOA, participates in education fosfatidny to - you, edges in a wall of intestines the hl is used. obr. for resynthesis of phosphatides, but it can be partially used also for resynthesis of triglycerides in which all three zhirnokislotny rests are in that case newly synthesized.
However ability of an organism to synthesis in cells of a wall of intestines of the fat specific to this species of an animal, nevertheless is limited. By A. N. Lebedev it is shown, e.g., that during the feeding to the starving dogs of large amounts of alien fat (e.g., vegetable oil) a part it is found in fatty tissues of an animal in not changed look. Fat depos, apparently, are the only fabric where alien fats can be laid (it use in livestock production during the fattening on fat of animals, napr, pigs; quality of the fat which is formed during the fattening depends on structure of the set forages). As for the fat which is laid or entering exchange in cells of other bodies and fabrics, the structure it differs in high specificity and depends on food fats a little.
The mechanism of resynthesis of triglycerides and phosphatides in cells of a wall of intestines is in general identical to their biosynthesis in other fabrics.
Formation of chylomicrons and transport of triglycerides
Resintezirovannye in cells of an intestinal wall triglycerides and phosphatides, and also the cholesterol which came to these cells from a cavity of intestines which partially there are etherified connect in tanks of a smooth endoplasmic reticulum to a small amount of protein and form rather stable complex particles — chylomicrons. Chylomicrons contain apprx. 2% of protein, 84 — 87% of triglycerides, 4 — 7% of phosphatides and from 2 to 5% of cholesterol. Particle size of chylomicrons fluctuates from 120 to 1100 nanometers. Thanks to big particle sizes chylomicrons are not capable to get from endothelial cells of intestines into circulatory capillaries and diffuse in limf, system of intestines, and from the last — in a chest limf, a channel. From a chest limf, a channel chylomicrons come to blood. Thus, thanks to chylomicrons transport of exogenous triglycerides, cholesterol and, partially, phosphatides from intestines through limf, system in blood is carried out.
In 2 hours after meal, containing fats, the so-called alimentary hyperlipemia develops (see. Lipemia ), characterized first of all by strengthening of triglycerides in blood and emergence of chylomicrons in it. After reception of too greasy food the blood plasma accepts lactescence that is explained by emergence in it a large amount of chylomicrons. The peak of an alimentary hyperlipemia falls on the period between 4 — 6 hours after reception of greasy food. In 10 — 12 hours the content of fat in blood serum is returned to norm. By the same time at healthy people from a blood plasma chylomicrons completely disappear. In this regard capture of blood for a research of maintenance of lipids in it shall be carried out on an empty stomach later 14 hours after meal.
The liver and fatty tissue play the most important role in the future of chylomicrons. Since the endothelial layer of sinusoid of a liver has big openings, chylomicrons freely diffuse from a blood plasma in intercellular spaces of a liver. According to one researchers, at contact of chylomicrons with a cover of parenchymatous cells the last take only triglycerides of chylomicrons; according to others, hydrolysates of triglycerides of chylomicrons — glycerin and fat to - you get to parenchymatous cells. Therefore assume that hydrolysis of triglycerides of chylomicrons takes place as in hepatic cells, and outside, on their surface.
In cells of a liver there are fermental systems catalyzing transformation of glycerin into alpha glycerophosphate, and not esterified fat to - t (NEZhK) — in the KOA corresponding acyls. The last or are oxidized in a liver with allocation of energy, or are used for synthesis of triglycerides and phosphatides. The synthesized triglycerides and partially phosphatides are used for formation of lipoproteids of very low density (pre - beta lipoproteids) which cosecrete liver and come to blood. Lipoproteids of very low density are the main transport form of endogenous triglycerides and transfer per day in a human body from 25 to 50 g of triglycerides. Chylomicrons because of the big sizes are not capable to get into cells of fatty tissue therefore a triglitseridny part of chylomicrons is exposed to hydrolysis on a surface of an endothelium of capillaries of fatty tissue at effect of enzyme of a lipoproteidlipaza. Localization of this enzyme is closely connected with a surface of an endothelium of capillaries. At action of a lipoproteidlipaza on triglycerides of chylomicrons (and also on triglycerides pre - beta liioproteidov) there is an education fat to - t and glycerin. A part fat to - t passes in lipoblasts, and a part contacts albumine of blood serum and is carried away with its current. With a blood flow leave a capillary network of fatty tissue glycerin, and also particles of chylomicrons and pre - beta lipoproteids, the splittings of their triglitseridny component which remained later and received the name of «remnant». Remnanta are late in a liver and are exposed to disintegration.
After penetration into lipoblasts fat to - you turn into metabolic active forms (atsil-KOA) and react with the alpha glycerophosphate which is formed in fatty tissue of glucose. As a result of this interaction triglycerides which fill up the general reserve of triglycerides of fatty tissue resintezirutsya.
Splitting of triglycerides of chylomicrons in circulatory capillaries of fatty tissue and a liver leads to the actual disappearance of chylomicrons and is followed by «enlightenment» of a blood plasma, i.e. it loses lactescence. The enlightenment accelerates heparin. It is supposed that heparin activates solubilization of a lipoproteidlipaza and its action. At some diseases hypoactivity of a lipoproteidlipaza therefore in blood large amounts of chylomicrons constantly are defined (chylomicronemia) is noted.
The intermediate metabolism of fats
the Intermediate metabolism of fats includes the following processes: mobilization fat to - t from fat depos and their oxidation (beta oxidation — see. Fatty acids ), biosynthesis fat to - t and triglycerides and transformation nonlimiting fat to - t.
Mobilization of fatty acids (a lipolysis of fat of fatty tissue)
contains In fatty tissue of the person a large amount of fat, is preferential in the form of triglycerides which perform in exchange of fats the same function as a glycogen of a liver in exchange of carbohydrates. These connections represent storage compounds which can be consumed at starvation, physical. the work and other conditions of an organism demanding energy consumption. These substances are resupplied after consumption of food, and they, thus, are a peculiar buffer in processes of accumulation and use of energy in an organism.
Value of triglycerides of fatty tissue as power reserve convincingly is confirmed by the following figures. Also only 0,35 kg of a glycogen (1410 kcal) contain an organism of the healthy person apprx. 15 kg of triglycerides (140 000 kcal). The glycogen, two thirds of stocks to-rogo is in muscles, is used by an organism at the short-term and suddenly arising loadings. As for triglycerides of fatty tissue, at average energy needs of the adult in 3500 kcal in days of 15 kg of fat it is theoretically enough to provide with energy 40-day requirement of an organism.
Triglycerides of fatty tissue are exposed to a lipolysis under the influence of lipases. Fatty tissue contains several lipases from which the so-called gormonochuvstvitelny lipase (triglitseridlipaza), diglyceride lipase and a monoglitseridlipaza have the greatest value. The Gormonochuvstvitelny lipase is in fatty tissue in an inactive form and is activated under the influence of cyclic 3', 5 '-AMF (adenosinemonophosphate). The last is formed of ATP with the participation of adenylatecyclase. Influence of hormone (or hormones) is directed to primary cellular receptor which, connecting hormone, modifies the structure and in such form activates starting enzyme of a lipolysis — adenylatecyclase. Formed as a result of these reactions tsiklich. 3', 5 '-AMF activates enzyme a protein kinase (KF 220.127.116.11) which in turn activates a lipase by phosphorylation, turning it thereby from an inactive form in active (scheme 2).
At action on triglycerides of the triglitseridlipaza activated in such difficult way, and then at action on intermediate products of a lipolysis of di - and a monoglyceride lipases end products — glycerin and NEZhK which of fatty tissue come to a blood channel (glycerin — in a free look are formed; NEZhK — in the form of a complex with albumine of a blood plasma). Actually the destiny of NEZhK in the most fatty tissue in many respects depends on contents in the last glucose or, more precisely, on intensity proceeding in it glycolysis (see). This results from the fact that formed during glycolysis dioksiatsetonfosfat partially it is recovered at action of a glitserofosfatdegidrogenaza in alpha glycerophosphate which in turn reacts with fat to-tami therefore triglycerides are again formed.
Resintezirovanny triglycerides remain in fatty tissue, promoting, thus, preservation of its general stocks. Such state takes place at full animals. At starvation when the content of glucose in fatty tissue is lowered and only insignificant amounts of alpha glycerophosphate released during a lipolysis of NEZhK are formed cannot be used by fatty tissue for resynthesis of triglycerides and therefore they quickly leave this fabric. Thus, activation of glycolysis in fatty tissue is the factor promoting accumulation in it of triglycerides, and oppression of glycolysis, on the contrary, promotes their removal.
In all cases strengthening of a lipolysis in fatty tissue is followed by increase of concentration free fat to - t in blood. A complex albumine — free fat to - you contain 99% of protein and only 1% fat to - t. Despite such rather low contents fat to - t in this complex, their transport is carried out in big sizes: in a human body from 50 to 150 g fat to - t are transferred per day. It is explained by high speed of updating of a complex (the period of its half-decay apprx. 5 min.).
Connected with albumine fat to - you get with a blood flow to bodies and fabrics where are exposed to beta oxidation (see. Fatty acids ), and then to oxidation in a cycle Tricarboxylic to - t (see. Tricarboxylic acids cycle ). Apprx. 30% fat to - the t is late in a liver already at single passing through it of blood where a part them is used for synthesis of triglycerides. Resintezirovanny triglycerides go for education pre - beta lipoproteids. Nek-roye quantity fat to - the t is oxidized in a liver to ketone bodies (see) — acetoacetic and beta and hydroxy-butyric to - t. Ketone bodies, without being exposed to further turning into of a liver, get with a blood flow to other bodies and fabrics (muscles, heart, etc.) where are oxidized to CO 2 and H 2 O. A small part mobilized fat to - t is used in various fabrics for etherification of cholesterol, synthesis of phosphatides, sphingolipids and other connections.
Biosynthesis of triglycerides
Triglycerides are synthesized in many bodies and fabrics, but the most important role is played in this respect by a liver, a wall of intestines and fatty tissue. The way of biosynthesis of triglycerides proceeds through formation of alpha glycerophosphate as intermediate compound.
In a wall of intestines and kidneys where activity of a glitserolkinaza (KF 18.104.22.168) is high, alpha glycerophosphate is formed directly by phosphorylation of glycerin with the participation of ATP. In fatty tissue and muscles owing to extremely low activity of this enzyme the way of formation of alpha glycerophosphate is connected with glycolysis (or a glycogenolysis). In a liver both ways of formation of alpha glycerophosphate take place. alpha Glycerophosphate reacts with two molecules activated fat to - t therefore it is formed fosfatidny to - that:
Fosfatidny to - that, at one time being considered as hypothetical intermediate compound in biosynthesis of triglycerides and phosphatides, is found in many fabrics. In a liver, e.g., falls to its share apprx. 1% of all phosphatides. Fosfatidny to - that at effect of phosphatase fosfatidny to - you (fosfatidatfosfataza; KF 22.214.171.124.) loses phosphoric to - that and turns in an alpha, beta diglyceride:
the alpha, beta Diglyceride is the main final substrate in synthesis of triglycerides, and also phosphatides in most bodies and fabrics, except for an intestinal wall. The completing reaction proceeds by interaction of diglyceride with activated fat to - that (atsil-KOA):
In a wall of intestines as it was noted above, for resynthesis of triglycerides the monoglycerides in large numbers arriving from intestines after splitting of food fats are used. At the same time the following reaction sequence is carried out: a monoglyceride + zhirnokislotny atsil-KOA -> diglyceride; diglyceride + zhirnokislotny atsil-KOA —> triglyceride.
Release of fats and products of their exchange from an organism
Is normal amount of neutral fats and fat to - the t which are allocated from a human body in not changed look does not exceed 5% of amount of the fat accepted with food. At the same time the main way of removal of fat and fat to - t is carried out through skin with secrets grease and sweat glands. The secret of sweat glands contains hl. obr. water-soluble fat to - you with a short carbon chain; in a secret of sebaceous glands neutral fats, ethers of cholesterol with the highest fat to-tami and free the highest fat to - you which rancidification causes off-flavor of these secrets prevail. A small amount of fat is allocated as a part of the tearing-away cells of epidermis.
At the diseases of skin which are followed by the strengthened secretion of sebaceous glands (seborrhea, psoriasis, eels, etc.) or the strengthened keratinization and exfoliating of epithelial cells, removal of fat and fat to - the t through skin considerably increases.
In the course of digestion of fats in went. - kish. a path is exposed to absorption apprx. 98% fat to - the t which are a part of food fats, and practically all formed glycerin. The remained small part fat to - t is allocated with excrements in not changed look or zhepodvergatsya to influence of microbic flora of intestines. At the same time there is a recovery nonlimiting fat to - t, formation of oxyacids, to - t to a branched side chain, etc. In general per day at the person with excrements it is allocated apprx. 5 g fat to - t, and not less than a half has them completely microbic origin. With urine a small amount korotkotsepochechny fat to - t (acetic, oil, valerian), and also beta and hydroxy-butyric and acetoacetic to - you is allocated. The number of the last in daily urine makes from 3 to 15 mg. Emergence of the highest fat to - t in urine is observed at a lipoid nephrosis, fractures of tubular bones, at diseases of the uric ways which are followed by the strengthened exfoliating of an epithelium and at the states connected with emergence in urine of albumine (albuminuria).
== Regulation of a lipometabolism ==. the lake is under the regulating influence of c. the N of page, a cut is carried out by the direct direction of impulses to fatty tissues or to hemadens. Participation of the highest departments of c. N of page in regulation. the lake is visually illustrated by experiments in which damage of hypothalamic area of a brain caused development of obesity in animals.
Influence of c. the N of page as it was established still by researches of I. P. Pavlov and his employees, is shown already at a stage of splitting and absorption of fats in went. - kish. a path by impact on amount of the cosecreted digestive juices and on contents in them depending on structure of food of various enzymes, including and lipases. Denervation of the sites isolated in the operational way went. - kish. a path, and also the condition of an anesthesia is led to delay of splitting and absorption of fats.
Neurohormonal influence on. the lake first of all is connected with regulation of process of mobilization fat to - t from fat depos (tab). It is well known that at emotional stresses in blood the maintenance of NEZhK sharply increases. This phenomenon is explained by sharp increase in emission in blood of catecholamines and activation of adenylatecyclase by the last in fatty tissue. Finally there is an activation of a lipolysis and release of NEZhK. It is long the proceeding negative emotional stress can cause in such way noticeable weight loss. Fatty tissue, besides, is innervated by fibers of a sympathetic nervous system, and excitement of these fibers is followed by allocation of noradrenaline directly in fatty tissue and activation of a lipolysis in it. That is why denervation of fatty tissue leads to accumulation of fat in it. Through activation or oppression of a lipolysis action is carried out on. the lake and many other hormones — glucocorticoids (see. Glucocorticoid hormones ), glucagon (see), AKTG (see. Adrenocorticotropic hormone ), a lipomobilizuyushchy factor of a hypophysis (see. Lipotropic factors of a hypophysis ), thyroxine (see), and also influence various fiziol, conditions of an organism is implemented (starvation, cooling, etc.).
Table. Influence of some factors on mobilization of fatty acids from fatty tissue
As it was already noted, increase in concentration of glucose in fatty tissue and increase in speed of glycolysis oppress a lipolysis. It is necessary to add to it that strengthening of glucose stimulates secretion of the insulin which is inhibitor of adenylatecyclase that also leads to oppression of a lipolysis in blood. Thus, when enough carbohydrates comes to an organism and the speed of their splitting is high, mobilization of NEZhK and their oxidation go with the lowered speed. As soon as reserves of carbohydrates are exhausted and intensity of glycolysis decreases, there is strengthening of a lipolysis therefore fabrics receive the increased quantities fat to - t for oxidation. At the same time increase in contents long-chain fat to - the t causes decrease in intensity of utilization and oxidation of glucose, napr, in muscles. All this demonstrates that. lake and carbohydrate metabolism (see) — the main power forming processes in an animal organism — are so closely connected with each other that many factors influencing one exchange directly or indirectly affect a current of another.
Speaking about hormonal influence on. the lake, it should be noted the activating influence of hormone of a thyroid gland on oxidation fat to - t, and also a promoting effect of insulin on synthesis of fats from carbohydrates. Hyperfunction of a thyroid gland is followed by weight loss and reduction of reserve fat, hypofunction — is frequent obesity. Removal of gonads (castration) causes in animals and the excess adiposity is frequent at the person.
Important value in regulation. the lake has character of food. Long excess consumption of the food rich with fats and carbohydrates leads to a considerable adiposity, and in this case no regulatory mechanisms can prevent this process. At a lack of food lipotropic substances (see), in particular the phosphatides or substances which are their part (sincaline, an inositol) and also methionine (see) the excess adiposity in a liver («a fatty liver») is observed. Emergence of «a fatty liver» is explained most likely by the fact that for lack of phosphatides the liver cannot utilize triglycerides for formation of lipoproteids. In a pancreas substance is revealed lipocainum (see), introduction to-rogo prevents development of «a fatty liver».
Disturbances of a lipometabolism
Disturbance of absorption of fats
One of the reasons of the lowered absorption of fats in a small intestine can be their insufficiently full splitting or owing to hyposecretion of pancreatic juice (a lack of steapsin), or owing to the lowered biliation (a shortcoming bilious to - t for emulsification of fat and formation of fatty micelles). The dysfunction of an intestinal epithelium observed at enterita, hypovitaminoses, insufficiency of bark of adrenal glands and some other patol, states is the second, most frequent reason of the lowered absorption of fat. In this case beta monoglycerides and fat to - you, formed in a cavity of intestines, cannot normally be soaked up because of damage of an epithelial cover of intestines.
Disturbance of absorption of fats is observed at pancreatitis of various etiology, obstruction of biliary tract, a massive resection of a small intestine, and also at complications after surgical intervention, at resections of a stomach and gullet. In the latter case the cause of infringement of absorption of fats is connected with the section of fibers of a vagus nerve leading to decrease in a tone of a gall bladder and the slowed-down intake of bile in intestines. The lowered absorption of fat is noted at hypogammaglobulinemias, a disease to a spr (see), Whipple's diseases (see. Intestinal lipodystrophy ), at a radial illness, and sometimes and at radiation therapy.
Disturbance of absorption of fat in a small intestine leads to emergence of a large amount of fat and fat to - t in Calais — to a steatorrhea (see). At long disturbance of absorption of fat the lowered receipt in an organism of fat-soluble vitamins is observed.
Disturbance of processes of transition of fat of blood to fabrics
At insufficient activity of a lipoproteidlipaza is observed disturbance of transition fat to - t from chylomicrons and lipoproteids of low density (pre - beta lipoproteids) a blood plasma in fat depos. Most sharply this disturbance is presented at the I type of a giperlipoproteinemiya [on D. S. Fredrickson's classification with sotr.]. This type of a giperlipoproteinemiya called also by «the lipemia induced by fats» or a hyper chylomicronemia is characterized by the fact that owing to total absence of activity of a lipoproteidlipaza of hereditary character triglycerides of a blood plasma cannot be exposed to splitting and collect in blood. The blood plasma in such cases has lactescence because of extremely high content of chylomicrons, and at its standing the slivkoobrazny layer of chylomicrons emerges. The most effective treatment of this disease consists in replacement of natural fats synthetic, containing korotkotsepochechny fat to - you with 8 — 10 carbon atoms which are soaking up from intestines directly in blood without preliminary formation of chylomicrons. At the V type of a giperlipoproteinemiya called also by «the mixed hyperlipemia» owing to hypoactivity of a lipoproteidlipaza in blood collect together with chylomicrons pre - beta lipoproteids. Intravenous administration of the heparin which is the activator of a lipoproteidlipaza by the patient with the V type of a giperlipoproteinemiya leads to an enlightenment of a blood plasma (at the I type administration of heparin does not give effect). At the V type of a giperlipoproteinemiya the diet with the low content of fats and limited content of carbohydrates is appointed.
At disturbance of process of transformation pre - beta lipoproteids in beta lipoproteids in blood the so-called pathological «floating» beta lipoproteids (the III type of a giperlipoproteinemiya) collect. The lowered tolerance to carbohydrates is characteristic of patients with the III type of a giperlipoproteinemiya: loading carbohydrates leads to permanent increase in content of triglycerides and pre - beta lipoproteids in blood. The frequent combination of this type of a giperlipoproteinemiya to diabetes is characteristic.
Excess accumulation of fat in fatty tissue
At almost healthy people, especially middle and advanced age, is quite often observed an excess adiposity in a hypodermic fatty tissue and other fatty tissues. Excessive consumption of food is the reason of such adiposity, the general caloric content a cut exceeds a metabolic cost of an organism. The excess adiposity is often observed upon transition from physically vigorous activity to a slow-moving way of life when the previous level of excitability of the food center and former appetite remains, and energy expenditure of an organism considerably decreases. Patol. obesity (see) it is observed when separately or in a complex the following factors work: 1) hypoactivity of fatty tissue concerning mobilization of fat and its superactivity concerning an adiposity, 2) the strengthened transition of carbohydrates to fats, 3) a hyperexcitability of the food center, 4) the muscular mobility lowered in comparison with norm. Decrease of the activity of fatty tissue concerning mobilization of fat is observed, e.g., at defeats of the hypothalamic centers when the impulses going to fatty tissue on sympathetic ways and accelerating a lipolysis of triglycerides are weakened. Braking of mobilization of fat from its depot takes also place during the weakening of function of a thyroid gland and hypophysis which hormones (thyroxine, thyritropic and somatotropic hormones, a lipomobilizuyushchy factor of a hypophysis) activate a lipolysis. The lowered function of gonads leads to an excess adiposity, especially if it is followed by disturbance of activity of a hypophysis, the hypothalamic centers and decrease in muscular activity (see. Adiposogenital dystrophy ; Itsenko — Cushing a disease ; Laurence — Muna — Bidlya a syndrome ). Strengthening of transition of carbohydrates to fats and adjournment them in fatty tissue takes place at hypersecretion of AKTG, glucocorticoids and insulin. Hypersecretion of insulin is the main factor in development of so-called hereditary and constitutional obesity.
The unusual adiposity can be observed in certain sites of fatty tissue, including located on zones of distribution of nerve fibrils of certain segments of c. N of page that indicates that the similar adiposity or, on the contrary, an atrophy of hypodermic fatty tissue are connected with change of trophic function of a nervous system as in its central departments, and peripheral (see. Derkuma disease , Lipomatoz , Lipodystrophy , Madelunga syndrome ).
The insufficient adiposity in fatty tissue (emaciation) develops owing to oppression of excitability of the food center (see. Anorexia ), decreases in absorption of fats and carbohydrates (e.g., at enterita), dominance of processes of mobilization of fat of fatty tissue over its adjournment and at long starvation.
Disturbance of formation of fat from carbohydrates can be observed at defeats of the vegetative (trophic) centers pituitary dientsefalicheskoy systems, and also bark of adrenal glands. Such disturbances are the cornerstone of the progressing exhaustion at Simmonds's disease (see. Pituitary cachexia ) and addisonovy disease (see).
Fatty infiltration of a liver
Accumulation of fat in hepatic parenchymatous cells often is reaction of a liver to various diseases, toxic influences and damages. With biochemical, the points of view accumulation of fat in a liver happens when the speed of formation of triglycerides in it exceeds the speed of their utilization (a lipolysis of triglycerides and the subsequent oxidation fat to - t, inclusion of triglycerides in pre - beta lipoproteids and their secretion in a blood channel).
Fatty infiltration of a liver is observed at diabetes, obesity, proteinaceous insufficiency, at poisoning with perchloromethane, phosphorus, alcohol and at insufficiency of lipotropic substances.
One of the most widespread disturbances. the lake at the person is a ketosis — the increased education in an organism, accumulation in fabrics and blood and allocation with urine of ketone bodies.
A lipometabolism at radiation injury
as a result of radiation exposure in various body tissues Zh. the lake undergoes the expressed changes which have both the qualitative and temporary features depending on a type of fabric. Defeat at radiation of a small intestine leads to reduction of maintenance of lipoproteids, phospholipids, fat to - t and cholesterol in a mucous membrane that is caused along with destruction of cells suppression of synthesis of lipids. Activity of hydrolases in a mucous membrane of a small bowel goes down therefore intensity of splitting of fats and absorption of triglycerides decreases; absorption fat to - t is oppressed to a lesser extent. Depending on conditions of food the maintenance of lipids in a liver increases or remains normal, but synthesis of the general lipids and their separate fractions — triglycerides, phospholipids, fat to - t and cholesterol anyway amplifies. At the same time there is an oppression of the synthesis of fats interfaced to glycolysis (or a glycogenolysis) and activation of synthesis of fats from acetic to - you.
As a result of changes. the lake after radiation in a liver, as a rule, develops a hyperlipemia (after nonspecific reaction). In early terms after radiation the hyperlipemia is caused by increase in content of triglycerides, phospholipids, cholesterol and its ethers, and in later — and fat to - t. Mobilization of lipids from peripheral depots how many strengthening of their biosynthesis in a liver is the cornerstone of the mechanism of a post-radiation hyperlipemia not so much. The mechanism of transfer of lipids from blood in fabric after radiation does not change. Stimulation of biosynthesis of fats in a liver from acetic to - you is not result of direct impact of radiation on a liver, and is initially caused by post-radiation destruction of radio sensitive fabrics, catabolits a cut, hl. obr. a lactate and amino acids, coming much to a liver, induce a gluconeogenesis that is accompanied by oppression of glycolysis and according to synthesis of lipids from glucose and strengthening of synthesis of lipids from acetic to - you as a result of activation of the fermental system catalyzing biosynthesis fat to - t.
In the first days after radiation in fatty tissue synthesis of lipids from glucose and its metabolites amplifies that is also connected with activation of a gluconeogenesis both the subsequent hyperglycemia and increase in content of insulin in blood. In later terms after radiation synthesis of fats in fatty tissue goes down and replaced by mobilization of fats. The specified changes. lakes begin to develop in several hours after radiation, soon reach a maximum and remain at this level within several days. At the majority of experimental animals these disturbances. the lakes called by radiation are leveled within a week, except for mobilization of lipids from depot, edges time proceeds still a nek-swarm, and have quantitative and qualitative specific features. In an adenoid tissue (a thymus gland and a spleen) in several hours after radiation concentration of the general lipids and fat to - t increases, and also synthesis of cholesterol and the general lipids is stimulated. In the same terms in marrow increase in contents fat to - t is observed, the maintenance of lipids increases later; for a week after radiation in marrow there is a sinusoidal increase and reduction of concentration saturated and unsaturated fat to - t at normal general contents fat to - t in blood serum. Increase in maintenance of lipids in marrow is caused by strengthening of their biosynthesis preferential in hemopoietic, but not in lipoblasts. Along with increase in intensity of synthesis of lipids in marrow after initial strengthening sharp and long braking of oxidation fat to - t to CO2 and H2O is noted, a cut continues also after recovery of normal cellular structure of marrow. In radio resistant fabrics (a brain, kidneys, easy, skeletal muscles and muscles of heart) of essential changes in. the lake does not occur. Activation of synthesis of cholesterol in adrenal glands is connected with the stressful reaction developing after radiation and strengthening of biosynthesis of corticosteroids from cholesterol.
The lipometabolism at children
Composition of triglycerides in fatty tissue of the newborn is excellent from maternal since the human fruit synthesizes individualnospetsifichesky fats from NEZhK and glucose arriving transplatsentarno or with current of umbilical blood.
The share of fat in a body of the newborn depends on his weight at the birth: weighing 1500 g it makes about 3%, 2500 — 8%, and 3500 g — 16% (norm). Fatty tissue of the child contains amount of diglycerides, bigger in comparison with fatty tissue of the adult, water, a glycogen, DNA, phospholipids and smaller — neutral fats, unsaturated fat to - t with a long carbon chain, cholesterol; also decrease in size of coefficient cholesterol/phospholipids is characteristic. With age these features are gradually leveled.
Gistol, and anatomic feature of fatty tissue of newborns is existence of accumulations of brown fat (to 8% of body weight) around bodies, between shovels, behind a breast, around a neck, along a backbone. This fat plays a role of a peculiar temperature regulator owing to the high heat production provided with high content in mitochondrions of tsitokhrom. Hypoxemic and iron deficiency states at children (pneumonia, anemia, intoxication) are followed by exhaustion of brown fat, falloff of heat production that can promote easy emergence of overcooling of the newborn.
At the child of all age is higher, than at adults, ability to synthesize and accumulate fat, more intensively oxidation fat to - t, process of inclusion of 14C-glucose in fat to - you is more active and triglycerides of cells of fatty tissue, concentration of KOA is higher. In process of growth and development of the child these distinctions are erased.
Lipolytic activity of blood serum at children is stable, differs from activity of lipases in blood serum of adults a little, but extent of braking of a lipolysis glucose increases with age, and activation by adrenaline decreases.
During the first hours lives of the child are observed considerable changes of size of a ratio of NEZhK and glycerin of blood serum; at the baby it is lower, than at adults. At prematurity and a hypotrophy the size of this ratio sharply decreases; in blood also keeping of the highest unsaturated fat to - t of rather total quantity unsaturated fat to - t decreases that is explained by slowness of exchange processes.
In blood of newborns concentration of lipids and lipoproteids is rather low. So, the average content of the general cholesterol makes apprx. 70 mg of %, and triglycerides apprx. 40 mg of %. At the low maintenance of all classes of lipoproteids rather high abundance of alpha lipoproteids is characteristic. Concentration of NEZhK in blood of newborns can be lower or higher in comparison with concentration of NEZhK in blood of mother — it depends on the weight of the newborn, his donoshennost or prematurity, a condition of food (normo-, hypo - or a paratrofiya); it is subject to more considerable, than at adults, to fluctuations under the influence of quantity and quality of food (carbohydrate and greasy food increases concentration of NEZhK, proteinaceous — reduces) and various diseases. Physical. and mental loadings, starvation, adrenal hormones, a hypophysis, a thyroid gland promote easier strengthening of NEZhK, and administration of glucose, insulin and protein — to the same decrease in concentration of NEZhK in blood at children (in comparison with adults).
At newborn children dominance of NEZhK over esterified fat to-tami (EZhK), at babies and children of more advanced age this ratio the return, as well as at adults is noted; other indicators of lipidic exchange also approach similar indicators at adults.
Newborn children and children of early age have a splitting and absorption of fats has a number of features. They are caused by functional immaturity of hepatic cells and are shown by a relative shortcoming bilious to - to the t limited thereof by emulsification of fats in intestines and disturbance of their transfer through an epithelium of a mucous membrane. Therefore at children more often than at adults, the diarrheas connected with disorder of digestion and absorption of lipids meet.
Concentration of chylomicrons increases in proportion to degree of a maturity of the child: at premature their number in 1 mm2 of a cytometer makes 1400, at full-term — 7800. It is the reason of easier development of disturbances of lipidic exchange in premature children too.
Lability of a functional condition of systems of regulation. the lake, inherent to the child, conducts (especially at premature children and at children with hypotrophies or paratrofiya) to more resistant and expressed, than adults, to changes of structure of lipids have blood (dislipidemiya) at inflammatory and allergic diseases of skin, infections, intoxications, digestive disturbances, hypersensitivity to allergens, at growth disorder and development. At children the hyperlipemia caused by adaptation strengthening of mobilization of the deposited fats is more often observed, a cut with hypotrophies causes such bystry and deep exhaustion of energy resources in premature children and children that it can threaten life of the patient. These features shall be considered at appointment to such children of complex therapy (artificial saturation by the nutrients, mixes close on structure to breast milk, glucose and physiologically active drugs: The ATP, redoxon and vitamins of group B, enzymes accelerating digestion and absorption of fats and carbohydrates, anabolic hormones).
Not all disturbances of lipidic composition of blood at children have secondary character. For the purpose of early diagnosis of possible primary hereditary dislipidemiya at the child any hyperlipemia and other revealed changes. islands demand the careful analysis etiol, factors, the accounting of the family anamnesis, exact identification of nature of changes, their comparison to clinic and other exchange and hormonal indicators. See also Gargoilizm , Hypercholesterolemia , to Gosha disease , Lipemia , Lipidoses , Nimanna-Pika disease , Sphingolipidoses , Henda-Schuellera-Krischena disease .
Changes of a lipometabolism in the course of aging
Disturbances. lakes during the aging are shown first of all in increase in the general content of fat in an organism. In old age the absolute speed of accumulation of fat decreases, but its relative gain (as a percentage to dry weight) is higher, than at young age. The general content of fat increases also in fabrics (in fat depos, a liver, skeletal muscles, a spleen, etc.), and in blood (men have 60 — 74 years to 472,5 ± 27,6 mg of %, at women of the same age to 517,9 ± 26,6 mg of %). In old age, according to most of researchers, the content of the general cholesterol in blood increases (see. Hypercholesterolemia ), its maximum concentration in blood (260 mg of %) is observed at men in 40 — 50 years, and at women for about 10 years later. Strengthening of the general cholesterol happens both at the expense of its free, and at the expense of efirnosvyazanny fractions, contents it increases in walls of an aorta, in intercostal and intervertebral cartilages, in a brain, a liver, kidneys, a spleen, in cordial and skeletal muscles. In skin concentration of cholesterol decreases, and in lungs and adrenal glands remains at the previous level. Direct dependence between concentration of cholesterol in blood and contents it in fabrics is not established. With age cholesterol collects also in subcellular structures (kernels, mitochondrions, microsomes) that can lead to decrease in permeability of cellular membranes and by that — to disturbance of processes of a metabolism.
With age changes as well qualitative composition of phospholipids: in a brain concentration of a difosfoinozitid, kephalin and especially sphingomyelin increases. The amount of phospholipids in blood serum of elderly and old people reaches at men 216,4 ± 3,9 mg of %, at women 236,7 ± 7,9 mg of %. Reduction of size of the relation phospholipids/cholesterol demonstrates decrease in reliability of the systems regulating constant concentration of cholesterol in blood with age. In the course of aging in blood the content of triglycerides considerably increases: at old men it increases to 113,9 ± 5,8 mg of %, at women to 104,1 ± 6,0 mg of %. At loadings fat concentration of triglycerides in blood of old people increases more, than at young people, and is returned to initial sizes more slowly. Studying of speed of a lipogenesis on inclusion acetate-1-14C demonstrates decrease during the aging of speed of synthesis of triglycerides as de novo, and from preformirovanny fat to - t. Strengthening of triglycerides in blood in old age can be caused by reduction of speed of their disintegration, and also deterioration in transport of triglycerides from blood in fabric. During the aging in blood the maintenance of NEZhK increases that, perhaps, is connected with decline in the ability of the growing old organism to their utilization, in particular to their oxidation in fabrics. In old age the content in blood unsaturated fat to - t, and also fat to - t with a long carbon chain increases. It leads to decrease in permeability of cellular membranes and promotes education of the free radicals having the damaging effect on the genetic device of a cell and by that accelerating aging. With age in blood of people contents and - and, the main thing, pre - beta lipoproteids increases. Uneven change of amount of the general cholesterol and cholesterol connected with p-lipoproteids demonstrates its redistribution during human life between lipoproteidny fractions. With age the maintenance of atherogenous lipoproteids increases, the number of persons in whom the giperlipoproteinemiya of various degree is found grows. Accumulation of cholesterol in p-lipoproteids reduces stability of lipoproteidny complexes and promotes its adjournment in walls of arteries. With age also lipolytic activity in a wall of an aorta, in a spleen, lungs, valves of heart decreases. Changes in. lakes during the aging are result of shifts in various links of its neurohumoral regulation, weakening of influence of the highest vegetative centers on closed glands, decreases of the activity of the last, sensitizations of fabrics to effect of hormones. Disturbance. the lake in old age creates metabolic premises for development of a number of diseases — atherosclerosis (see), idiopathic hypertensia (see), coronary insufficiency, diabetes, etc.
See also Metabolism and energy .
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A. H. Klimov; L. H. Bogatskaya (geront.), A. V. Kartelishev (ped.), I. N. Kendysh (I am glad. bio.).