[The physical chemical and biological features of triglycerides. The cell absorption of functionally different palmitic+oleic lipoproteins of very low and density and linoleic+linolenic lipoproteins of low density.]

The earlier insulin-independent low-density lipoproteins and more late insulin-dependent very low-density lipoproteins implement different functions at the stages of phylogenesis. The disorder of biological function of trophology, alteration of fatty acids in triglycerides, prevalence of palmitic very low-density lipoproteins over oleic very low-density lipoproteins supply mitochondria of cells with non-optimal substrate - palmitic saturated fatty acid for gaining energy, ATP synthesis. Physiologically, cells implement oleic alternative of fatty acids metabolism, oxidizing mainly ω-9 endogenous oleic mono-unsaturated fatty acid. The pathology of low density lipoproteins is primary deficiency of poly-unsaturated fatty acids in cells, atherosclerosis and atheromotosis of intima of arteries of elastic type with development of dense plaques from poly-unsaturated fatty acids in the form of polyethers of cholesterol. The pathology of very low-density lipoproteins includes: a) syndrome of resistance to insulin; b) pathology of phylogenetically earlier insulin-independent visceral fatty tissue - metabolic syndrome; c) pathology of phylogenetically later insulin-dependent subcutaneous adipocytes - obesity; d) secondary atherosclerosis, under cumulation of palmitic low-density lipoproteins in blood with development of atherothrombosis of intima of arteries, soft plaques rich with triglycerides. As for the prevention of disorders of transfer of fatty acids to very low-density lipoproteins and low-density lipoproteins is common in many ways - minimization of aphysiological effect of surplus amount of food, biological function of diet. The prevention at the level of population includes: a) maximal limitation of content of palmitic saturated fatty acid in food; b) moderate increasing of polysaturated fatty acids, ω-3 poly-saturated fatty acids predominantly; c) increasing of physical activity. The pharmaceuticals are not provided by biology in primary prevention of metabolic pandemics under aphysiological impact of environment factors.

[THE LIPOLYSIS IN PHYLOGENETICALLY EARLY LIPOPROTEINS OF LOW DENSITY AND MORE LATER LIPOPROTEINS OF VERY LOW DENSITY: FUNCTION AND DIAGNOSTIC VALUE OF APOE AND APOC-III].

According to phylogenetic theory of general pathology, the function of low density lipoproteins (LDL) and hydrolysis of triglycerides (TG) in them under the effect of hepatic glycerol hydrolase apoC-III (HGH) developed at much earlier stages of phylogenesis than functioning of insulin-dependent phylogenetically late very low density lipoproteins (VLDL). For millions ofyears, lipolysis and HGH+apoC-III have activated transfer of polyenic fatty acids (FA) in the form of cholesteryl polyesters (CLE) from high density lipoproteins (HDL) to linoleic and linolenic LDL under the effect of cholesteryl ester transfer protein. It is reasonable to suggest that hepatocytes physiologically secrete oleic and palmitic VLDL and linoleic and linolenic LDL. Cells uptake ligand oleic and palmitic VLVL by apoE/B-100 receptor-mediated endocytosis. Physiologically, VLDL are not converted to LDL. If hepatocytes secrete palmitic VLDL in greater amounts than oleic VLDL upon slow hydrolysis ofpalmitic TG and under the effect of postheparinic lipoprotein lipase+apoC-II, only some proportion of palmitic TG is uptaken by cells as VLDL, and the rest is converted in ligand-free palmitic LDL These LDL increase plasma contents of TG and LDL-cholesterol and form small dense palmitic LDL. Expression of HGH+apoC-III synthesis compensates TG hydrolysis in nonphysiological palmitic LDL. In vivo, apoC-III is neither physiological no pathological inhibitor of lipolysis. Increase in plasma apoC-III content is an indicator of accumulation of non-physiological palmitic LDL and atherosclerosis-atheromatosis risk factor ApoE content ofpalmitic LDL increases together with apoC-III, i.e., apoE in ligand VLDL is not internalized via apoE/B-100 endocytosis. An increase in apoC-III and apoE contents are reliable in vivo tests for the rise inpalmitic FA, palmitic TG and excessive secretion of palmitic VLDL by hepatocytes. ApoC-III and apoE contents in LDL are additional tests to evaluate the efficiency of atherosclerosis prevention when physiological function of trophology and biological reaction of exotrophy are normalized.

[The fatty acids in blood plasma and erythrocytes in test of glucose tolerance].

The sample of 26 patients with ischemic heart disease and syndrome of insulin resistance was subjected to standard test of glucose tolerance. The content of individual fatty acids was detected using technique of gas chromatography and mass spectrometry. In blood plasma, after 2 hours of post-prandial hyperglycemia, reliably decreased content of C 16:1 of palmitoleic mono fatty acid, C 18:1 oleic mono fatty acid and in a lesser degree C 18:2 linoleic unsaturated fatty acid (p < 0.05). The level C 14:0 of myristic unsaturated fatty acid, C 16:0 of palmitic unsaturated fatty acid and with 18:0 of stearic unsaturated fatty acid, ratio C 16:0/C 16:1 and C 18:0/C 18:1 had no changes: content of both (omega-6 C 20:3 digomo-gamma-linoleic unsaturated fatty acid and essential polyenoic fatty acids remained the same. The significant differences between initial content in blood plasma of palmitic saturated fatty acid and oleic monoenic fatty acid was noted. The alteration in content of fatty acids in membranes of erythrocytes is the most expressed. In erythrocytes reliable (p < or = 0.05) decrease of content of C 16:0 palmitic fatty acid, C 18:0 stearic fatty acid and C 18:1 oleic fatty acid is established. The reliable decrease is noted in content of linoleic unsaturated fatty acid. In erythrocytes, moderate decrease is detected in levels of C 20:4 arachidonic polyenoic fatty acid, C 20:5 eicosapentaenoic polyenoic fatty acid. It is assumed that under post-prandial hyperglycemia insulin regulates metabolism of fatty acids, blocks lipolysis, decreases in cytosol of cells content of oleic and palmitic fatty acids inform of acetyl-KoA and forces mitochondrions intensively oxidate acetyl-KoA formed from pyruvate, from GLU. On surface of membrane, insulin increases number of glucose carriers GLUT4. Hypoglycemic effect of insulin is mediated by regulation first of all of metabolism of fatty acids. Hyperglycemia and insulin are two phylogenetically different humoral regulators. Insulin initiates blockade of lipolysis in adipocytes and positioning on membrane GLUT4. Hyperglycemia passively (activated) increases absorption by cells GLU on gradient of concentration inter-cellular medium--cytosol and synthesis of glycogen.

[Low and very low density lipoproteins: pathogenetic and clinical significance].

LDLP and VLDLP have different biological functions: phylogenetically older LDLP transfer FA that serve as substrates for intracellular production of energy and ATP while VLDLP transfer FA--precursors of cell membranes and eicosanoids. The cells absorb LDLP via apoB-100 endocytosis and VLDLP through apoE/B-100 receptors. VLDLP consist of palmitic and oleic VLDLP and LDLP of linoleic and linolenic LDLP. The contribution of LDLP to the development of HLP atherosclerosis and atheromatosis is negligible. LDLP form palmitic and oleic VLDLP with hydrated LDLP density. Blockade of LDLP absorption by apoB endocytosis and deficit of poly-FA constitute the etiological basis of atherosclerosis. Its pathogenetic basis is the excess of palmitic VLDLP with LDPL density in the intercellular space that block absorption of linoleic LDLP with all transferred SC poly-FA. Atheromatosis is clinically and prognostically most significant symptom of atherosclerosis associated with accumulation of ligand-free VLDLP and LDLP in arterial intima of the elastic type as the local pool of interstitial tissue for intravascular pool of intercellular medium. Type 2 diabetes mellitus in aged patients is a symptom of atherosclerosis resulting from SC poly-FA deficit and GLUT4 incompetence. Insulin-dependent cells differ in the degree of insulin resistance. Non-alcoholic fatty liver disease, synthesis of a physiological palmitic TG by hepatocytes and excessive formation of palmitic VLDLP in liver integrate pathogenesis of atherosclerosis and hepatic steatosis. The main pathogenetic factor is the excess of palmitic s-FA and palmitic TG.

[Lipoprotein-associated phospholipase A2 in subjects at low and moderate risk estimated by the SCORE scale].

The aim of the work was to elucidate the relationship between PLA2 content and results of the tests of abnormal lipid transfer in lipoproteins (LP) in subjects at low and moderate risk estimated by the SCORE scale. Another aim was to estimate the diagnostic value of plasma PLA2 content that was determined in 378 subjects (285 women and 93 men) aged 30-64 yr at low and moderate risk (SCORE scale). The patients were divided into groups depending on the age, the number of atheroscleroic plaques (ACP) in carotid arteries (0ACP 1 ACP, more than 1 ACP), enhanced and normal PLA2 levels. PLA2 was measured using PLAC Test Elisa Kits (DiaDexus, USA), with the upper normal limit assumed to be 200 ng/ml. In women, PLA2 levels positively correlated with apoA-1 (main HDLP apoprotein) content (r = 0.51, p < 0.03); in men, PLA2 negatively correlated with TG (r = -0.38, p < 0.01); in subjects with homogeneous ACP PLA2 positively correlated with LP(a) (r = -.38, p < 0.03). Simultaneous rise in PLA2 and LP(a) levels may be a significant risk factor of atherosclerosis and atherothromhosis. Enhanced levels of TG, PLA2, and LP(a) may be the biochemical triad of "soft" plaque formation in the intima.

[Diagnostic significance of different apolipoprotein levels during hypertriglyceridemia].

Active receptor-mediated uptake of fatty acids (as lipids in VLDLP and LDLP) involves dynamic apolipoproteins apoE and apoC-III. Modern methods allow apoB-100 and apoA-1 to be determined both separately and together in HDLP and VLDLP+LDLP. We estimated diagnostic significance of simultaneous apoE and apoC-III determination in the serum and two LP classes in the patients having either physiological levels of triglycerides or moderate and pronounced hypertriglyceridemia. Serum apoE and apoC-III increased with increasing triglyceride levels and percent of prebeta-LP fractions in electrophoresis. There was significant correlation between apoE and apoC-II content in the sera and in apoB-100 LP. It precludes using measurements of apoproteins for differential assessment of VLDLP and LDLP uptake by the cells or differential diagnostics of primary phenotypes and secondary hyperlipoproteinemias. The apoE content in LDLP was increased only in 1/5 of the patients with marked hyertriglyceridemia. The ApoE an apoC-III content in lipoproteins is of no diagnostic value; it is enough to determine serum apoprotein levels. Significant correlation between HDLP cholesterol and apoA-1 and between LDLP and apoB-100 questions the necessity of measuring serum apoA-1 and apoB.

[The subcellular organelles of peroxisome, realization of biologic functions of trophology, homeostasis, endoecology and functional bond with mitochondrion: the lecture].

The biologic role of peroxisomes in cells is that the organelles in respect to fatty acids, lipids and substrates synthesized from acetate implement the same fimnctions as the lysosomes exercise to proteins and polypeptides. The biologic role of peroxisomes is to optimize in vivo the exogenous fatty acids in hepatocytes under the realization of biologic functions of trophology, homeostasis, endoecology. About 800 individual fatty acids can penetrate into organism with food. At that, no more than thirty of them undergo the metabolic transformation in vivo. The rest hundreds of fatty acids are aphysiologic and have to be oxidized into peroxisomes under isochronic activation of alpha-, beta- and omega-oxydases without ATP formation. If in peroxisomes are formed fatty acids that can oxidize mitochondrions by beta-oxidation then the proteins of cytosol transfer fatty acids from peroxisomes to mitochondrions. The mitochondrions oxidize fatty acids in the Krebs cycle to form ATP. The oxidation in peroxisomes concerns the fatty acids with odd numbers of carbon atoms, the transforms of unsaturated fatty acids, the very long chain fatty acids, the fatty acids with carbon atoms side-chains, the dicarboxylic fatty acids, the fatty acids with benzene or indole rings in carbon atoms chains. The peroxisomes oxidize the surplus amount of exogenous palmitic saturated fatty acid too. The peroxisomes implement the biologic.function of endoecology on autocrine level supporting the "purity" of cells cytosol and interact functionally with mitochondrions. In the intercellular medium of paracrine cells coens the fimctions of endoecology are realized by the Toll-similar receptors by the "our-not our" principle concerning phospholipids, positional aphysiologic triglycerides and proteolipids. In the peroxisomes, under the simultaneous oxidation of very long chain fatty acids, the synthesis by primate cells is possible of some amount of essential unsaturated and polyene fatty acids. The limited formation by animal cells of glucose from fatty acids is possible in the sequence "acetoneacetol spirit-metilglyoxal-D-glucose. The mutations in primary structure of peroxisomes oxidases are the main in-herent pathology.

[The unity of pathogenesis of insulin resistance syndrome and non-alcoholic fatty disease of liver. The metabolic disorder of fatty acids and triglycerides].

The pathogenesis of non-alcoholic fatty disease of liver (steatosis) is still as unclear as a loss of hepatocytes similar to apoptosis, development of biological reaction of inflammation, its transformation into steatohepatitis with subsequent fibrosis and formation of atrophic cirrhosis. The article suggests that steatosis is developed due to higher concentration of palmitic saturated fatty acid (C 16:0) in food, intensification of its endogenic synthesis from food carbohydrates and glucose and development of insulin resistance. It is displayed in in hormone ability to activate both oxidation in cells of glucose and synthesis of oleic monoene fatty acid from palmitic saturated fatty acid (C 18:1). The insulin resistance initiates pathologic process on the level of paracrine associations of cells resulting in permanent increase of concentration of non-etherified fatty acids in intercellular medium and intensification of their passive absorption by cells. The phylogenetically ancient mitochondrions will not to oxidize glucose until non-etherified fatty acids are present in cytosol and hence there is an opportunity to oxidize them. To eliminate undesirable action of polar saturated palmitic fatty acid, the cells etherify it by spirit glyceride into triglycerides to deposit in cytosol or to secrete into blood in a form of lipoproteins of very low density. Under insulin resistance, saturated palmitic fatty acid synthesized by hepatocytes from glucose, does not further transform into oleic monoenic fatty acid. The cells are to etherify endogenic (exogenic) palmnitic saturated fatty acid into composition of aphysiologic palmitic triglycerides (saturated palmitic fatty acid in position sn-2 of spirit glyceride). At that, triglycerides of palmitat-palmitat-oleat and even tripalmitat type are formed. The melting temperature of tripalmitat is 48 degrees C and melting temperature of physiologic trioletat is 13 degrees C. The intracellular lipases factually can't hydrolyze palmitic triglycerides. So, hepatocytes, overloaded by them, are destroyed in a way similar to apoptosis. The formed corpuscles of apoptosis disorder the biologic function of endoecology and trigger biologic reaction of inflammation. At that, steatosis changes into steato-hepatitis. The prevention of steatosis consists in dramatic restriction of concentration of palmitic saturated fatty acid in food. The treatment effect is targeted to: decreasing the formation of palmitine triglycerides by force of concurrent etherification of palmitic saturated fatty acid not into triglycerides but into phosphatidylcholine (symmetric phospholipids of soya); intensification of oxidation of palmitic saturated fatty acid in peroxisomes (glytazones and fibrates); decrease of insulin resistance (binuanide metformine).

[The secretory phospholipase A2 and transport of lipids by lipoproteins in patients with the risk of cardio-vascular pathology (the system "score") of lower and average degree. The diagnostic significance of the test].

The clinical and pathomorphologic data demonstrate that the most frequent cause of cardiac infarction is the formation of "soft" atheromatosis plaques in the intima of arteries. Their rupture results in thrombosis of coronary arteries. The plaques are characterized by higher content of triglycerides. On the basis of the research data, it is possible to validly consider that the detection of secretary phospholipase content A2 conjugated with lipoproteins is the test of systemic inflammatory response. This response is formed under atherosclerosis in vivo as a feedback to the accumulation in the intercellular medium of the endogenic flogogens (initiators of biological reaction of inflammation)--lipoproteins of lower density subclass A. Their utilization in the intima, as a pool of local interstitial tissue, by the resident macrophagocytes transformed from monocytes result in the formation of doth soft and disposed to laceration atheromatosis plaques and the atherothrombosis of coronary arteries and rarer of carotids. Concurrently, the increase of lipoproteins content in blood plasma is supposed to be the test of proliferation of cells in vivo, the smooth muscle cells of medium in particular. The simultaneous detection of content of secretory associated with lipoproteins phospholipase A2 and lipoprotein (a) can be considered as a valid risk factor of atherosclerosis and atherothrombosis--atheromatosis of intima of arteries with the formation of "soft" plaques in the intima, their laceration and thrombosis of coronary arteries and clinical presentation of cardiac infarction. The diagnostic triad of formation of soft plaques in the intima can be composed of the higher level of triglycerides, the content of protein of phospholipase A2 and lipoprotein (a).

[The individual fatty acids in blood plasma, erythrocytes and lipoproteins. The comparison of tests results of patients with ischemic heart disease and volunteers].

According to the generally accepted theory, the atherosclerosis is a kind of disorder of metabolism of lipids which chemically are the ethers of fatty lipids with spirits. Hence, the atherosclerosis is fatty acids pathology. In conformity with the biologic classification, among fatty acids it is functionally valid to distinguish saturated fatty acids without double bonds; monoenic fatty acids with one double bond; unsaturated fatty acids with two or three double bonds and polyenic fatty acids with four of six double bonds in chain. The saturated and monenic fatty acids are the substrates for cells to groundwork energy, ATP The unsaturated fatty acids in vivo are needed to form membranes. The polyenic fatty acids are essential since they are precursors of cell synthesis of humoral regulators--eicosanoids (prostanoids and leukotrienes). To clarify the pathogenesis of the "metabolic pandemics" most prevalent in human population, the quantitative determination of individual fatty acids in blood plasma and erythrocytes using gas chromatography technique is needed. It is necessary to evaluate the content of medium chain fatty acids; palmitic and stearic saturated fatty acids; oleic monoenic fatty acid and its transforms--linoleic, linolenic and dihomo-gamma-linolenic unsaturated fatty acids; essential polyenic omega-6 arachidonic, omega-3 eicosapentaenoic and docosahexaenoic fatty acids. The higher is in food the content of palmitic saturated fatty acid, palmitoleic and trans-vaccenic monoenic fatty acids, the more is in patient diet of beef meat and products of fat cow's milk. The higher is ratio of palmitic/oleic fatty acids the lower is the risk of formation of atheromatosis of arteries intima and development of ischemic heart disease and vice versa. The decrease of ratio of omega-3/omega-6 essential polyenic fatty acids is undesirable in prognostic sense. The metabolism of these acids differs and functional activity of omega-3 eicosanoid type 3 is higher In case of deficiency of omega-3 and omega-6 polyenic fatty acids in cells eicosanoids are synthesized from unsaturated dihomogamma-linolenic fatty acid and their influence turns out to be aphysiologic. This condition is a pathogenic foundation of atherosclerosis. There is a diagnostic reason to detect fatty acids in case of diabetes mellitus, obesity, metabolic syndrome and partially arterial hypertension.