[The different notions about beta-oxidation of fatty acids in peroxisomes, peroxisomes and ketonic bodies. The diabetic, acidotic coma as an acute deficiency of acetyl-CoA and ATP].

The mechanisms of beta-oxidation of fatty acids developed more than a century before have no compliance with actual physical chemical data. The oxidation of long-chain C 16:0 palmitic saturated fatty acid occurs not by sequential formation of eight molecules of acetyl-KoA but by force of formation of double bond and its hydrolysis on two short-chain C 8:0 fatty acids. Only short-chain fatty acids can become shorter under "chipping" of C 2-acetate with formation of C 4-butyric acid (butyrate) and its metabolites (beta-hidroxibutirate, acetoacetate, acetone). The critical moment of oxidation is a hydrolysis of acetoacetyl-KoA on two molecules of acetyl-KoA. The molecule of ATP is to be expended on hydrolysis. The foundation of nonspecific biological reaction of stress--ketoacidosis,--is a decrease in mitochondrions of acetyl-KoA pool formed both from glycogen and glucose and fatty acids. The oxalate acetate inputs into Krebs cycle inadequate amount of acetyl-KoA which limits synthesis of ATP. The insulin has no direct involvement into development of ketoacidosis but prepares conditions to facilitate nonspecific etiological factor to initiate diabetic ketoacidosis. These are the pooling of small amount of glycogen in cytozol and the predominance in cytozol of cells and adipocytes of palmitic triglycerides which are slowly hydrolyzed by hormone-dependent lipase to release non-esterified fatty acids into intercellular medium. The increase of their concentration in blood plasma precedes ketoacidosis which is developing in patients without diabetes mellitus too. When cells begin to oxidize unsaturated linoleic and linolenic acids with large number of double binds instead of medium-chain fatty acids, oleinic and palmitic fatty acids to support beta-oxidation in mitochondrions and synthesis of ATP the amount of butyric acid, beta-hidroxibutiryl-KoA and acetoacetyl-KoA increases and of acetyl-KoA decreases. The cause of fatal outcome is the development of metabolic acidosis, hyperhydration of cerebral cells with development of edema and a physiologic respiratory compensation of metabolic acidosis. The decarboxylation of acetoacetate and formation of acetone--initial stage of gluconeogenesis--formation of glucose from fatty acids--is manifested poorly both in primates and humans. From theoretical positions, to arrest ketoacidosis and to restore synthesis of AFT, it is reasonable to apply the infusion of optimal amount of acetyl-KoA which as nonpolar tioester can get over hematoencephalic barrier, plasma membrane and inner membrane of mitochondrions. It is supposed that diabetes mellitus is to be considered primarily as pathology of metabolism of fatty acids and only secondly as pathology of glucose.

[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.

[The content of individual fatty acids and numbers of double bonds, insulin, C-peptide and unesterified fatty acids in blood plasma in testing tolerance to glucose].

The glucose tolerance test demonstrates that content of unesterified fatty acids in blood plasma decreases up to three times and the content of oleic and linoleic acids is more decreased in the pool of fatty acids lipids. Out of resistance to insulin, hormone secretion increases up to three times. The decreasing of level of individual fatty acids occurs in a larger extent. Under resistance to insulin secretion of insulin is increasing up to eight times. The decreasing of level of each fatty acid is less expressed. The effect of insulin reflects decreasing of content of double bonds in blood plasma. The number of double bonds characterizes the degree of unsaturation of fatty acids in lipids of blood plasma. The higher number of double bonds is in the pool of unesterified fatty acids the more active is the effect of insulin. The hyper-secretion of insulin is directly proportional to content of palmitic fatty acid in lipids of blood plasma on fasting. According the phylogenetic theory of general pathology, the effect of insulin on metabolism of glucose is mediated by fatty acids. The insulin is blocking lipolysis in insulin-depended subcutaneous adipocytes and decreases content of unesterified fatty acids in blood plasma. The insulin is depriving all cells of possibility to absorb unesterified fatty acids and "forces" them to absorb glucose increasing hereby number of GLUT4 on cell membrane. The resistance to insulin is manifested in high concentration of unesterfied fatty acids, hyperinsulinemia, hyperalbuminemia and increasing of concentration of C-reactive protein-monomer. The resistance to insulin is groundlessly referred to as a symptom of diabetes mellitus type II. The resistance to insulin is only a functional disorder lasting for years. It can be successfully arrested. The diabetes mellitus is developed against the background of resistance to insulin only after long-term hyper-secretion of insulin and under emaciation and death of ß-cells. The diabetes mellitus type I and not type II is an undesirable outcome of resistance to insulin.

[Alloxan cytotoxicity: a new aspect of the problem]. / Tsitotoksichnost' alloksana: novyi aspekt problemy.

The effect of alloxan on human intact erythrocytes (in the suspension and whole blood) was studied using an original potentiometric apparatus permitting continuous registration of the flow rate of reducing equivalents ('RE) through a plasmatic membrane. Acceleration of RE flow from erythrocytes due to the activation of hexosomonophosphate shunt (HMPS) was established. This effect was inhibited by P-chlormercury benzoate proving the involvement of the SH-groups of erythrocyte membrane proteins in the interaction of alloxan with erythrocytes. Oxygen consumption after adding alloxan was recorded by polarography that indicated the "start" of the alloxan----dialuric acid (A in equilibrium with DA) cycle. Enhanced RE production in erythrocytes may be caused by H2O2 and free radicals forming in this cycle. It was shown that HMPS activation i.e. transition to a more intense stationary regimen was maintained for a period exceeding the calculated period of alloxan "halt--life". This residual effect of alloxan "depleted" erythrocyte protective mechanisms that was expressed in a decrease in maximum capacity of HMPS of rat whole blood after receiving by the animals a diabetogenic dose of alloxan (150 mg/kg body mass). Thus a specific cumulation of the effect of alloxan expressed in the transition of the RE generation system to a more intense stationary regimen, was revealed. In investigating the mechanism of alloxan cytotoxicity one should take into account this peculiarity of alloxan along with the factor of affinity and conditions for initiation of the A in equilibrium with DA cycle.

[Cause of dehydroascorbic acid accumulation in the blood of patients with insulin-dependent diabetes mellitus]. / O prichine nakopleniia degidroaskorbinovoi kisloty v krovi bol'nykh insulinzavisimym sakharnym diabetom.

It is known that dehydroascorbic acid (DHAA) produces a diabetogenic effect and its content in the blood increases in diabetes mellitus. It was previously established that the generation of reducing equivalents (RE) in the course of hexosemonophosphate shunt, CO2 production and SH-glutathione regeneration in erythrocytes with and without moderate and maximum oxidation load in vitro were not disturbed in diabetes. The authors have proposed a procedure to study blood and erythrocyte DHAA reductase activity in suspension in health and in insulin-dependent diabetes mellitus by means of redoxstatometry using a device of original design. A significant acceleration of RE transfer through the erythrocyte membrane was detected in diabetes. A lowered participation in this process of the AA in equilibrium DHAA "shuttle" system was recorded in the blood of patients with diabetes mellitus what was mostly expressed under the conditions of acidosis in vitro. Probably "shuttle" function in diabetes was provided by some other redox system which might be located in the plasma. The predominant functioning of this redox system and a decrease of DHAA reductase activity in diabetes resulted in the accumulation of DHAA in the blood of patients with type I diabetes mellitus.

[Blood thyroid hormones in ischemic heart disease (a comparison with coronary angiographic data, severity of stenocardia and blood lipid level)]. / Tireoidnye gormony krovi u bol'nykh ishemicheskoi bolezn'iu serdtsa (sopostavlenie s dannymi koronarografii, tiazhest'iu stenokardii i urovnem lipidov krovi).

The blood concentration of the thyroid hormones, thyroid stimulating hormone and lipids were estimated in 67 patients with ischemic heart disease (IHD), 12 patients with hypothyroidism (H) and 19 normal controls. H was diagnosed in 9% of the patients with IHD. There were similar changes of the blood lipid concentrations in the patients with IHD (without H) and the patients with H (without IHD): increased level of the total cholesterol, triglycerides, cholesterol of the low and very low density lipoproteins. The blood level of cholesterol of high density lipoproteins (C-HDL) was significally higher in the patients with H than in the patients with IHD. There was correlation of the level of thyroxine in the blood and clinical severity of angina pectoris among the euthyroid patients with IHD having the same degree of coronary atherosclerosis.