LIPOPROTEIDS (Greek lipos fat + proteids; synonym lipoproteins) — complexes of lipids with proteins; are a part of all live organisms, perform the most important function of transport and storage of lipids, are a necessary component of various morphological structures of a cell; the maintenance of lipoproteids in blood is important diagnostic test at a number of diseases. L., as well as other group-specific substances, are used in court. - medical practice for identification of material evidences, and also at establishment of a doubtful paternity or motherhood.
L. conditionally divide on free, or soluble in an aqueous medium (L. blood plasma, milk, yolk of eggs, etc.), and structural (L. membranes of cells, myelin cover of nerves, chlorolayers of plants, etc.).
Classification of L. it is based by hl. obr. on their behavior at ultracentrifuging (see) and electrophoresis (see). L., unlike other proteins, have rather low density therefore during the ultracentrifuging in salt solutions they float (emerge). Speed of flotation is characterized by coefficient of flotation of sf and expressed in svedberga (S). The sf symbol is usually used when density of solvent is equal to 1,063 g/ml; if density of solvent is equal to 1,21 g/ml, for designation of coefficient of flotation isiolzut a symbol F 1,21 . At an electrophoresis of L. move in a zone α-and β-globulins, from here and designations: alpha lipoproteids, pre - beta lipoproteids, beta lipoproteids. Proteinaceous components L. (apolipoproteida) according to one nomenclature designate as apo-A, apo-V, apo-S etc., on another — on their S-trailer amino-acid remains: it apolipoproteid-is scarlet, to an apolipoproteid-gl, etc. In each class L. there are usually several apolipoproteid.
L are the most studied. blood plasma of the person. They are divided into four classes: chylomicrons, L. Very Low Density (L.VLD), L. low density (LINDENS) and L. High Density (L.HD). On electrophoretic mobility of L. subdivide on pre - beta lipoproteids (LONP), beta lipoproteids (LNP), alpha lipoproteids (LVP).
In addition to these classes L., in a blood plasma sometimes find unusual L. Primer the so-called floating (emerging) beta lipoproteids can serve. Such L. float like lipoproteids of very low density at the density of solution of 1,006 g/ml, but have the electrophoretic mobility close to electrophoretic mobility (beta lipoproteids.
L. considerably differ on chemical structure, napr, the attitude of amount of protein towards quantity of lipids in chylomicrons makes about 1: 99, and at L. high density — 50: 50. It is normal of L. blood sera contain — 350 mg of % of alpha lipoproteids and — 450 mg of % of lipoproteids.
Big differences are observed also in physical. - chemical properties L. (tab. 1).
L. have a micellar structure. It is possible that micelles consist of the kernel formed by hydrophobic components of lipids, and the periblast consisting of protein and polar groups of phospholipids. Details of a structure of L. are not known yet.
Formation of chylomicrons and small part L. low and very low density occurs in epithelial cells of a small bowel; L. very low density and L. high density hl are synthesized. obr. in a liver; L. low density are formed in blood as a result of action on L. very low density of enzyme lipoproteidlipaza (see). Half-life of chylomicrons is less than an hour, L. very low density — 2 — 4 hours, L. low density — 2 — 4 days, L. high density — 5 days.
Functions L. in an organism are very various. Chylomicrons beggars, L carry out transport of fats. very low density transfer to the place of utilization triglycerides of an endogenous origin, and L. low density transfer cholesterol to cells; functions L. high density so far completely pe are found out, however some authors note their anti-atherogenous properties.
For definition of concentration of L. in a blood plasma it is necessary to prepost their fractionation. E.g., L. very low density and L. low density can besiege heparin (see. Burshteyna method ), at this L. high density remain in nadosadochny liquid. In the best way of division of L. preparative ultracentrifuging is.
Histochemical methods of definition of lipoproteids in fabrics
L. kernels, microsomes, a lamellar complex (Golgi's device) are a part of cellular membranes, membranes of mitochondrions. Gistokhim, methods of determination of L. in fabrics are based on extraction of lipids from a lipidic and proteinaceous complex L., therefore methods of determination of L. are identical to methods of definition of lipids in fabrics (cm. Lipids). However in connection with gems that lipids in L. are strongly connected with protein, fabrics need pretreatment. So, exactly during the coloring of blood smears on lipids it was revealed that during the processing of smears organic to-tami (acetic, lemon, oxalic, ant) with the subsequent coloring by the ripening solution of Sudan black In in 70% alcohol coloring of mitochondrions in lymphocytes amplifies, thrombocytes begin to be painted. Many structures containing L., begin to be painted also after long washing of cuts or after their drying in a hot air, and also after heating to boiling in spirit solution of Sudan of black V.
Chislo of methods of determination of L. in fabrics (the connected lipids) it is very small. Berenbaum's method using Sudan black In, dissolved in acetone is most widespread, during the coloring the Crimea the connected lipids of chromatin, kernels, granules of neutrophilic leukocytes gain black color. For research during the determination of L. in frozen sections recommend benz (and) pyrene — a caffeine method of Berg. Among methods of an electronic histochemistry there is also very small number of methods for determination of L. At the same time often it is necessary to resort to a parallel research by means of light microscopy. During the fixing of fabrics for electronic microscopic examination in solution osmium tetroxide - zinc iodide such components of a cell as a lamellar complex, lysosomes, a granular cytoplasmic reticulum, mitochondrions are intensively contrasted. Consider that L give this reaction., being a part of membranes of cellular organellas.
Disturbances of lipoproteidny exchange
Disturbances of exchange of L. are various. They can be connected with disturbance of speed of formation of L. in a liver and a catabolism of L. in an organism or speed of transformation of one class L. a blood plasma in another, and also with education in a liver abnormal or patol. L. and, at last, with formation of autoimmune complexes a lipoproteid — an antibody. In general concentration in blood of this or that class L. the hl depends. obr. from balance of two processes: speeds of their education and receipt in blood and speed of their elimination from blood.
About disturbances of exchange of L. usually judge by qualitative and quantitative changes of their content in plasma (serum) of blood. Such changes combine the general term «dislipoproteinemiya». Here such concepts as hyper - and a gipolipoproteinemiya — the increased or lowered contents in a blood plasma of one, is more rare than two classes L enter.; an alipoproteinemiya — lack of some class L. in blood.
Fredrikson (D. S. Fredrickson) and coauthors offered Giperlipoproteinemiya the classification of giperlipoproteinemiya including the most often found disturbances of exchange of L. at the person. In 1970 it was approved by WHO experts with small additions. According to this classification distinguish the following five types of a giperlipoproteinemiya.
I type — a hyper chylomicronemia («the Lipemia induced by fats»). Main change in L. blood consists in the constant and high content of chylomicrons. Concentration of triglycerides in blood is sharply increased, concentration of cholesterol or within norm, or is slightly increased, the size of the relation cholesterol: triglycerides always less than 0,15. The insufficiency of enzyme of a lipoproteidlipaza carrying obviously, hereditary character is the cornerstone of this type of a giperlipoproteinemiya.
Clinically this type of disturbance of exchange of L. it is shown at early children's age first of all by adjournment of lipids in skin in the form of eruptive xanthomas (see), in a liver and a spleen (gepatosplenomegaliya). Attacks of intestinal colic are often observed. This type of a giperlipoproteinemiya meets extremely seldom, usually has family character and development of atherosclerosis is not characteristic of it.
II type — giperbetalipoproteinemiya. This type of a giperlipoproteinemiya is divided into two subtypes: The Pa who is characterized by high content in blood L. the low density of beta lipoproteids), and IIB which is characterized by high content at the same time of two classes L. — L. low density (beta lipoproteids) and L. very low density (pre - beta lipoproteids). At the II type of a giperlipoproteinemiya very high content of cholesterol in blood is noted high, and in certain cases. Sometimes at high hypercholesterolemia (see) adjournment of cholesterol in skin in the form of tubercular and flat xanthomas, and also in sinews and a cornea of an eye (a lipoid arch of a cornea) can be observed. Content of triglycerides in blood can be or normal (IIA type), or raised (IIB type).
At the II type of a giperlipoproteinemiya develops coronary heart disease (see). Sudden death from a myocardial infarction at children's and youthful age is observed, as a rule, at persons with the II type of a giperlipoproteinemiya with homozygous heredity. At heterozygotes with the II type of a giperlipoproteinemiya coronary heart disease develops at later age and proceeds pe so sharply.
III type — the «floating» giperlipoproteinemiya, or a disbetalipoproteinemiya. Main change in qualitative structure of L. blood consists in emergence of H.p. unusually high content of cholesterol and high electrophoretic mobility (pathological, or floating, beta lipoproteids or L. very low density). These patol. L. collect in blood owing to disturbance of transformation pre - beta lipoproteids in beta lipoproteids.
At this type of a giperlipoproteinemiya in blood the content of cholesterol and triglycerides is increased, and the size of the attitude of concentration of cholesterol towards concentration of triglycerides is often close to 1 though it can vary from 0,3 to 2.
Quite often at patients with the III type of a giperlipoproteinemiya tolerance to carbohydrates is observed patol. The carbohydrate diet at such patients leads to the permanent and most expressed in comparison with other types of a giperlipoproteinemiya increase of content of triglycerides in blood. The III type of a giperlipoproteinemiya is often combined with various manifestations atherosclerosis (see), including with coronary heart disease and defeat of vessels of legs. At a part of patients at especially high content of cholesterol and triglycerides in blood adjournment of lipids in skin in the form of flat, tubercular and eruptive xanthomas is observed.
The III type of a giperlipoproteinemiya occurs seldom and preferential at adults.
IV type — a giperprebetalipoproteinemiya («the Lipemia induced by carbohydrates»). Main change in L. blood consists in strengthening of L. very low density (pre - beta lipoproteids). This type of a giperlipoproteinemiya is characterized by high content in blood of triglycerides at the normal or rather low level of cholesterol.
The V parts of patients with the IV type of a giperlipoproteinemiya decrease in tolerance to carbohydrates is noted; in response to a carbohydrate diet at such patients concentration of triglycerides in blood, however to a lesser extent increases, than patients with the III type have giperlipoproteinemiya. Clinically the IV type of a giperlipoproteinemiya is characterized by development of the atherosclerosis of coronary vessels which is shown coronary heart disease. At a number of patients the giperprebetalipoproteinemiya is combined with obesity (see) and a diabetes mellitus (see. diabetes mellitus ).
At very high concentration of triglycerides in blood lipids can be postponed in skin in the form of eruptive xanthomas. Giperlipoproteinemiya IV of type develops preferential at adults and represents very widespread type of a giperlipoproteinemiya.
V type — a hyper chylomicronemia and a giperprebetalipoproteinemiya («the mixed hyperlipemia»). Main changes in L. blood consist in strengthening of chylomicrons and L. very low density (pre - beta lipoproteids), to-rogo hypoactivity of a lipoproteidlipaza is the reason. Content of triglycerides in blood of such patients is increased, in certain cases to very high figures, concentration of cholesterol is normal or is a little increased. Size of the relation cholesterol: triglycerides from 0,15 to 0,6 fluctuates. Clinically the V type of a giperlipoproteinemiya is shown by the same symptoms, as the I type. Sometimes the V type of a giperlipoproteinemiya is combined with the hidden or moderately expressed diabetes mellitus. Usually at this type of disturbance of exchange of L. coronary heart disease is less often observed, than at II, III and IV types. Unlike the I type of a giperlipoproteinemiya, at Krom sharply expressed insufficiency of a lipoproteidlipaza is observed, at the V type activity of this enzyme is only slightly lowered. Primary giperlipoproteinemiya of the V type occurs at adults and has no wide spread occurance.
The listed types of a giperlipoproteinemiya can be genetically caused, and in this case they treat primary diseases of family character. However, despite the hereditary nature, a current and expressiveness of family giperlipoproteinemiya in many respects depend on alimentary, hormonal, emotional and other factors. Increase in maintenance of L. in blood, caused by any diseases, belongs to the category of secondary giperlipoproteinemiya and their current in many respects is defined by these diseases.
Giperalfalipoproteinemiya. Cases of a family giperalfalipoproteinemiya, and also increase in abundance of L are described. this class in blood at athletes — runners on long ranges. Usually as criterion of a giperalfalipoproteinemiya serves the content of cholesterol and fraction of alpha lipoproteids which is easily determined in a blood plasma after preliminary sedimentation beta and pre - beta lipoproteids heparin in the presence of ions of manganese or calcium (see. Burshteyna method ). So, if concentration alpha lipoproteidnogo cholesterol in blood of men of middle age exceeds 80 mg of %, there are bases to regard it as a sign of a giperalfalipoproteinemiya. Giperalfalipoproteinemiya should be considered as «pathology», favorable for an organism, as alpha lipoproteids possess anti-atherogenous action. Some authors carry a giperalfalipoproteinemiya to factors of longevity.
Less than increase in maintenance of L. some classes in blood, other disturbance of exchange which is shown decrease or even total absence in blood L meets. this or that class.
The hereditary disease — the Tangier disease, or the aalfalipoproteinemiya for the first time found in residents of Tangier and which is characterized by absence in blood of normal L is known. high density (a-lipoproteids) and emergence of abnormal L., designated as L. high density of T. Concentration of the general cholesterol in blood at patients with the Tangier disease is lower than norm, however abundance of esterified cholesterol is increased. In this regard note the accumulation of ethers of cholesterol in reticuloendothelial system which is followed by a gepatosplenomegaliya. Changes from palatine tonsils are characteristic of the Tangier disease — tonsillitis with an orange and yellow-gray plaque. Despite low concentration of the general cholesterol in blood, at patients with the Tangier disease observe a prematurity of atherosclerosis and coronary heart disease that, obviously, it is connected with absence in blood of normal L. high density.
Other hereditary pathology of this kind — abetalipoproteinemiya (see) it is characterized by absence in blood not only beta lipoproteids as considered earlier, but also pre - beta lipoproteids and chylomicrons. The main metabolic defect in this case is connected with oppression in a liver of synthesis of protein apo-V, L, necessary for formation. the listed above classes. At the persons suffering from an abetalipoproteinemiya disturbance of absorption of food fats is noted. The atactic neuropathy, a pigmental retinitis and an acanthosis is often observed.
it is Less expressed about a wedge, the points of view proceed hypoalpha and a gipobetalipoproteinemiya. Gipoalfalipoproteinemiya quite often occurs at persons with the increased contents r-or pre-R ~ lipoproteids in blood (corresponds to II, IV and V types of a giperlipoproteinemiya). Long time the gipoalfalipoproteinemiya did not draw close attention to itself, especially if it was found against the background of hyper-beta and giperpre - beta lipoproteinemii which generally and caused concern of the doctor. At the same time the combination of a gipoalfalipoproteinemiya to the listed above types of a giperlipoproteinemiya substantially strengthens risk of development of atherosclerosis and the related complications. Apparently, in most cases the gipoalfalipoproteinemiya has the secondary nature.
Family gipobetalipoproteinemiya extremely rare disease. It is characterized by the low maintenance of p-lipoproteids in blood. The wedge, signs of a gipobetalipoproteinemiya either are absent or are shown by disturbance of absorption of fats in intestines. At adults with a gipobetalipoproteinemiya coronary heart disease is not revealed.
The hereditary disease called LHAT-insufficiency is known. Inborn suppression of synthesis of enzyme of lecithin-cholesterol-acyltransferase (LHAT) which catalyzes etherification of cholesterol in a blood plasma is the cornerstone of it. Owing to disturbance of etherification of cholesterol the chemical structure and morphology of L changes. all classes. The most characteristic change in L. high density is an emergence of fraction of the disk-shaped particles representing the bilayer membranes containing not esterified cholesterol, phospholipids and proteins — apoproteida. In fraction L. low density so-called lipoproteids - X, consisting generally of not esterified cholesterol, phospholipids, apoproteid With and albumine appear. Adjournment and accumulation of not esterified cholesterol in kidneys, a spleen, a cornea of an eye, a membrane of erythrocytes is characteristic of this disease. Clinically these changes are shown by hypochromia anemia (see), renal failure (see), splenomegaly (cm.), opacification corneas (see), etc. Emergence lipoproteidov-H is observed also at an obturatsionny disease of a liver.
Under certain conditions L. a blood plasma can function as autoantigens (see), causing antibody formation and eventually — autoimmune complexes antigen — an antibody. Emergence of such complexes is established at a multiple myeloma, a rhematoid syndrome, a macroglobulinemia, and also at atherosclerosis. There are, apparently, several kinds of autoimmune complexes a lipoproteid — an antibody, differing both on antigen, and on an antibody. Antigen contains significant amounts of lipids in such complexes and formation of complexes often is followed by a lipidemia. According to the autoimmune theory of a pathogeny of atherosclerosis offered by A. N. Klimov with sotr., autoimmune complexes possess a bigger aterogennost, than L., are also capable to initiate atherosclerotic process.
Treatment of disturbances of lipoproteidny exchange. If disturbances of exchange of L. have the secondary nature, i.e. are caused by some disease or action of such factors as an overeating, a slow-moving way of life, hron, alcohol intake, etc., the main attention shall be directed to treatment of a basic disease or elimination of harmful factors. Already one it often leads to normalization of maintenance of L. in blood. At the V type of a giperlipoproteinemiya successfully apply intravenous administration of heparin which activates a lipoproteidlipaza therefore the blood plasma is clarified (at the I type of a giperlipoiroteinemiya, at a cut synthesis of a lipoproteidlipaza is broken, administration of heparin does not give effect).
At treatment of primary giperlipoproteinemiya on the first place it is necessary to put a dietotherapy, napr, replacement of natural fats synthetic, containing korotkotsepochechny fat to - you, at a giperlipoproteinemiya of the I type. When the diet korrigirut disturbances of exchange of L insufficiently., use of the means reducing concentration of cholesterol and triglycerides in blood (tab. 2)
Methods of treatment of alipoproteinemiya is recommended are not developed yet.
Table 1 the Indicators characterizing physicochemical properties of lipoproteids of a blood plasma of the person
Table 2. Medical approaches at various types of a giperlipoproteinemiya
Bibliography: Gayer G. An electronic histochemistry, the lane with it., page 49, M., 1974; Karmansky I. M., Levitova E. N V. O ishpikiter. Properties, a structure and a role of lipoproteids of blood serum, in book: Progress biol, chemical, under the editorship of B. N. Stepanenko, t. 16, page 89, M., 1975; Klimov A. N. Lipoproteids of a blood plasma, in book: Lipids, Structure, biosynthesis, transformations and functions, under the editorship of S.E. Severin, page 57, M., 1977; To l to them about in And. H. and H and to at l the p e in and H. G. Types of giperlipoproteinemiya, their communication with atherosclerosis and treatment, Cardiology, t. 12, No. 6, page 133, 1972, bibliogr.; To l and-mov A. N., Nikulcheva N. G. ikrivoruchenko I. V. Phenotyping of giperlipoproteinemiya, there she, t. 14, No. 12, page 103, 1974; Preventive cardiology, under the editorship of G. I. Kositsky, page 260, M., 1977; Tumanov A. To. both T about m and l and V. V N. Hereditary polymorphism of isoantigens and enzymes of blood is normal also of pathology of the person, M., 1969; Blood lipids and lipoproteins, quantitation, composition and metabolism, ed. by G. J. Nelson, N. Y. — L., 1972; Hyperli-pidemia, diagnosis and therapy, ed. by B. M. Rifkind a. R. I. Levy, N. Y. 1977; The metabolic basis of inherited disease, ed. by J. B. Stanbury a. o., N. Y., 1972; Structural and functional aspects of lipoproteins in living systems, ed. by E. Tria a. A. M. Scanu, L. — N. Y., 1969.
V. O. Shpikiter; T. H. Thrush (gist.), A. N. Klimov (disturbance of exchange).