[Effects of chronic radiation exposure on erythrocyte metabolism and functioning]. / Vliianie khronicheskogo vozdeistviia rentgenovskogo izlucheniia na metabolizm i funktsioniirovanie éritrotsitov.

The structural and functional state of blood erythrocytes in people exposed to radiation during Chernobyl NPP accident was studied two or six years later. The changes in oxygen transport system of erythrocytes and in the ratio between some organic phosphate fractions were observed. The beta-carotene per os administration to rats during low-level irradiation increased hemolytic stability and activity of glycolytic enzymes, that bears witness to the increasing of organism adaptive reactions at provitamin administration during irradiation.

[Correcting effect of nicotinamide on hemoglobin glycosylation in streptozotocin diabetes in rats]. / Korrigiruiushchii éffekt nikotinamida na protsessy glikozilirovanniiagemoblogina pri streptozototsinovom diabete u krys.

Streptozotocin induced diabetes in rats was accompanied by development of hyperglycemia, by increase in the rate of hemoglobin and albumin glycosylation in blood and by elevation of 2,3-diphosphoglycerate content in erythrocytes. Alterations of the dissociation properties and the decrease in Hb P50 value suggested the reduced affinity of hemoglobin to oxygen. Injection of nicotinamide, which is involved in NAD+ biosynthesis, caused a decrease of glucose content in blood, stabilized the content of 2,3-diphosphoglycerate and of glycosylated hemoglobin in erythrocytes. Nicotinamide appears to decrease the rate of hemoglobin glycosylation and enhanced the tissue oxygen utilization under hypoxic conditions.

[Nicotinamide coenzymes in the regulation of cellular metabolism in various types of diabetes]. / Nikotinamidnye kofermenty v reguliatsii kletochnogo metabolizma pri raznykh tipakh diabeta.

Hypoglycemic and hypolipidemic effects of nicotinamide in insulin-dependent and noninsulin-dependent types of diabetes have been investigated. Hypoglycemic effect of nicotinamide in alloxan- and streptozotocin-induced diabetes resulted in activation of NAD+ biosynthesis and corresponding alterations in the redox state of free nicotinamide coenzymes. Increase in the free NAD+/NADH ratio was accompanied by inhibition of key gluconeogenic enzymes and by a decrease in the rate of 2-14C-incorporation into glucose in liver tissue and by inhibition of sorbitol formation in lens tissue. Nicotinamide exhibited hypolipidemic effect in db/db mice with noninsulin-dependent diabetes. The agent inhibited the enzyme of primary steps of lipogenesis, altered the structure of intercellular CoA pool and lowered the rate of lipid biosynthesis in liver tissue, thus normalizing blood lipoprotein compositions.

[Inhibition of the transport of citrate during ADP-ribosylation of inner membrane proteins of the mitochondria]. / Ingibirovanie transporta tsitrata pri ADP-ribozilirovanii belkov vnutrennikh membran mitokhondrii.

The ability of rat liver submitochondrial particles to catalyze NAD+ hydrolysis with a transfer of ADP-ribose residues to protein membranes has been demonstrated ADP-ribosylation is directly dependent on NAD+ concentration upon saturation with 1 mM NAD+ and is inhibited by physiological compounds (e.g., ATP, 10 mM; nicotinamide, 10 mM); besides, it is an artificial acceptor of ADP-ribose, arginine methyl ester. It was found that ADP-ribose is accepted by inner mitochondrial membrane protein, whose molecular masses amount to 25-30 kDa. The fact that 5'-AMP is a product of ADP-ribose degradation by snake venom phosphodiesterase suggests that the inner membrane vesiculate proteins are modified by mono(ADP-ribose). Covalent modification of membrane proteins by ADP-ribose leads to citrate transport inhibition in inner membrane vesicles the [14C]citrate uptake is significantly decreased thereby. The ability of ADP-ribosylation inhibitors to restore the citrate transport rate is suggestive of a direct regulatory effect of NAD+-dependent ADP-ribosylation on the activity of citrate-translocating system of inner mitochondrial membranes.

[Citrate transport in submitochondrial particles of the rat liver]. / Transport tsitrata v submitokhondrial'nykh chastitsakh pecheni krys.

The submitochondrial particles (SMP, inverted inner membrane vesicles of mitochondria of the turned out vesicles in internal mitochondrial membranes) of the rat liver are characterized for their ability to incorporate [14C]citrate depending on the concentration of exogenic citrate, temperature and time of incubation. The rate of citrate incorporation into SMP does not depend on the addition of the oxidation substrate into the medium, however in the presence of malate and phosphate it is sharply activated. 1,2,3-benzene tricarboxylase (1,2,3-BTC) is an active inhibitor of the citrate transport into SMP. The citrate transport is determined by the protonation-deprotonation processes of the carrier protein on the outer and inner side of the membrane. A decrease in the pH of the medium favours protonation of the carrier protein on the outer side of the membrane and intensifies [14C]citrate incorporation into SMP, whereas the pH increase inhibits this process. The effect of pH changes is less pronounced in the presence of K+ ions. Valinomycin in the K+ medium activates incorporation of [14C]citrate increasing the carrier protein deprotonation rate on the inner side of the SMP membrane. Protonophore separators intensify conductivity for H+ ions and remove the stimulating influence of valinomycin on the rate of [14C]citrate incorporation into SMP.

[Enzyme systems of the substrate and cofactor supply of hyperlipogenesis in non-insulin-dependent diabetes]. / Fermentnye sistemy substratnogo i kofaktornogo obespecheniia giperlipogeneza pri insulinnezavisimom diabete.

Enzymatic systems of hepatic hyperlipogenesis supply by substrate (acetyl-CoA) and cofactors (NADPH and ATP) were studied in experiments on diabetic C57Bl/Ks J mice (db/db) that served as a model of non-insulin dependent diabetes. The rise in acetyl-CoA synthetase activity catalyzing the primary step of lipogenesis from acetate has been found, while pyruvate dehydrogenase complex activity did not differ from the control and ATP-citrate lyase activity was lowered. Hyperlipogenesis in non-insulin dependent diabetes was induced by the activation of cellular energy supply revealed in enhanced 2-oxoglutarate dehydrogenase activity and elevated ATP level, as well as changes in the activity ratio of NADPH supply and utilization and the rise in fructose-1,6-diphosphate, allosteric effector of fatty acid synthetase, which resulted in the increase of the enzyme activity and created wider potentials of NADPH utilization as a reducing equivalent in lipogenesis.

[Hypoglycemic effect of nicotinamide in diabetes mellitus]. / Gipoglikemicheskii éffekt nikotinamida pri sakharnom diabete.

Administration of nicotinamide (NA) is followed by a pronounced hypoglycemic effect with a simultaneous decrease of glucose content in the lens, sciatic nerve and aorta at manifest streptozotocin-induced diabetes and also by a complete normalization of parameters of the intraperitoneal glucose-tolerance test in rats with a "diabetic" type of glucose tolerance. A 14-day NA treatment of patients with diabetes mellitus results in the improvement of the glycemic profile, a decrease of glucosuria and the blood serum level of protein-bound hexoses as well as positive shifts in the condition of the cardiovascular and nervous systems.

[Nicotinamide coenzyme regulation of the sorbitol pathway of glucose metabolism in the aorta of rats with streptozotocin diabetes]. / Reguliatsiia nikotinamidnymi kofermentami sorbitolovogo puti obmena gliukoza v aorte krys so streptozototsinovym diabetom.

Increase in content of glucose in aorta as well as in reducing properties of NAD and NADP coenzymes and alteration in content of cofactor of the sorbitol pathway led to accumulation of sorbitol in streptozotocin-diabetic rats. Administration of nicotinamide into diabetic animals induced an increase in the ratios of NAD+/NADH and NADP+/NADPH, accompanied by a decrease in sorbitol formation occurring in the reaction catalyzed by aldose reductase and stimulation of the sugar oxidation in the reaction catalyzed by sorbitol dehydrogenase. Possible use of nicotinamide for prevention and treatment of vascular lesions in diabetes is discussed.

[Nicotinamide nucleotides as factors of lipogenesis regulation]. / Nikotinamidnye nukleotidy kak faktory reguliatsii lipogeneza.

Data are analyzed on a regulatory effect of the redox state of NAD- and NADP-couples (the free NAD+-/NADH, NADP+/NADPH ratios) on certain enzymic links of lipogenesis. A concept is formulated on coordination of the activity of lipogenesis key enzymes by a common signal, supposedly by changes in the NAD+/NADH and NADP+/NADPH values in cytoplasm and mitochondria of the rat liver cells. High values of the NAD- and NADP-couples ratios, activation of the citrate transport from mitochondria to cytoplasm and of enzymic systems supplying lipogenesis with a substrate--acetyl-CoA, reducing equivalents (NADPH) determine the maximal lipid synthesis rate observed in adaptive hyperlipogenesis. The inhibitory action of nicotinamide on lipogenesis is realized at the level of systems providing a high metabolic pool of acetyl-CoA and dehydrogenases, producing NADPH in cytoplasm of liver cells.

[Sorbitol pathway of glucose metabolism in streptozotocin diabetes of varying duration and severity]. / Sorbitolovyi put' obmena gliukozy pri streptozototsinovom diabete raznoi dlitel'nosti i tiazhesti.

The degree of accumulation of sorbitol pathway metabolites by the lens, sciatic nerve and aorta is determined by the duration and gravity of experimental diabetes. As the blood glucose content (indicating experimental diabetes gravity) rises, the aldose reductase activity in the tissues increases, the content of sorbitol and fructose ascends. The sorbitol-dehydrogenase activity does not depend on diabetes gravity. An increase of aldose reductase and a decrease in the sorbitol-dehydrogenase activity occur within the first two weeks after diabetes induction, which correlates with the maximal rate of sorbitol and fructose accumulation. The conclusion is made on the necessity of a strict compensation for diabetes to prevent the development of chronic complications.

[Study of the role of nicotinamide coenzymes in the regulation of glyceroneogenesis from pyruvate in rat epididymis fat tissue]. / Izuchenie reguliatsii nikotinamidnymi kofermentami glitseroneogeneza iz piruvata v épididimal'noi zhirovoi tkani krys.

The paper deals with a regulatory effect of the redox state of nicotinamide coenzymes on glyceroneogenesis in the epididymal fatty tissues involving incorporation of [2-14C] pyruvate into synthetized de novo blood glucose, glycerol and fatty acids of triacyglycerines. Large values of the NAD+/NADH and NADP+/NADPH ratios in cytoplasm and mitochondria promote a high rate of lipogenesis and glucose oxidation processes, which is pronounced in a more intense 14C incorporation into fatty acids than in triacylglycerol glycerols. A decrease in the NAD+/NADH ratio and an increase in the reducing ability of NAD-pairs under fasting intensify glyceroneogenesis in the fatty tissue. The incorporation of [14C] pyruvate into blood glucose in 3.6 times as high, the radioactivity of fatty acids lowers. Nicotinamide administered to animals after fastening inhibits glyceroneogenesis in the fatty tissue, lowering considerably the incorporation of [14C] pyruvate into triacylglycerol glycerol and blood glucose.

[Possible mechanisms of the inhibiting effect of nicotinamide on lipogenesis in rat liver]. / Izuchenie vozmozhnykh mekhanizmov ingibiruiushchego deistviia nikotinamida na lipogenez v pecheni krys.

The activity of some NAD- and NADP-dependent dehydrogenases involved in generation of the reducing equivalents for lipogenesis and the activity and some kinetic parameters of ATP-citrate (pro-3S)-lyase from rat liver, i. e. the enzyme involved in the formation of CoASAc, the primary substrate of fatty acid biosynthesis, were studied. The changes in the activity of NADP-dependent dehydrogenase and ATP-citrate(pro-3S)-lyase, as well as the affinity of the latter for sitrate and CoA and the rate of lipogenesis in starved rats and in rats kept on a carbohydrate-rich diet after starvation appeared to be parallel. Nicotinamide decreased the activity of all NADP-dependent dehydrogenases under study, which was especially well-pronounced after nicotinamide addition against increased lipogenesis. The affinity of ATP-citrate(pro-3S)-lyase for citrate and CoA decreased simultaneously with the decrease in the concentration of the latter. These changes can possibly induce the decrease of lipogenesis rate in rat liver after addition of nicotinamide.

[Redox state of free nicotinamide coenzymes and phosphoenolpyruvate synthesis in rat and guinea pig liver]. / Okislitel'no-vosstanovitel'noe sostoianie svobodnykh nikotinamidnykh kofermentov i sintez fosfoenolpiruvata v pecheni krys i morskikh svinok.

The paper deals with the redox state of free nicotinamide adenine dinucleotides (the NAD+/NADH ratio) in main compartments of the rat and guinea pig liver cells. NAD-pairs of cytoplasm and mitochondria in guinea pigs liver are shown to be more reduced than those in rats' liver. Stimulation of glucogenesis decreases the NAD+/NADH ratio in both compartments of rat liver and increases it in the guinea pigs' liver mitochondria. The guinea pigs' liver mitochondria synthesize actively phosphoenol pyruvate from oxaloacetate, malate and alpha-ketoglutarate. A decrease in the NAD+/NADH ratio value with introduction of beta-oxybutyrate into the incubation medium inhibits the phosphenolpyruvate synthesis from malate by 73%.

[Nicotinamide inhibition of 2-14C acetate incorporation into free fatty acids and lipids of rat tissues]. / Ingibirovanie nikotinamidom vkliucheniia 2-14C atsetata v svobodnye zhirnye kisloty i lipidy tkanei krys.

The synthesis of fatty acids and lipids in the rat tissues is inhibited to a considerable extent during fasting and is activated when feeding highly carobhydrate ration to rats after fasting. Nicotinamide (50 mg/100 g of weight) causes a decrease in intensity of 14C incorporation into free fatty acids and lipids of blood, liver, epididimal and perienal fatty tissues. The degree of nicotinamide inhibition of fatty acids and lipids sythesis is in direct dependence on lipogenesis intensity.

[Hypoglycemic effect of nicotinamide in rats with alloxan diabetes]. / Gipoglikemicheskii effekt nikotinamida pri alloksanovom diabete u krys.

Experimentally-induced alloxan diabetes was characterized in rats by a marked increase in the blood glucose level and by a number of disturbances in the concentration of metabolites and the activity of the enzymes of carbohydrate metabolism in the liver. Stimulation of gluconeogenesis in diabetes was judged by reduction of the redox condition of free NAD- and NADP-couples, by the increase in the concentration of phosphoenolpyruvate, malic oxaloacetate and phosphoenolpyruvate carboxykinase activity of the liver. Nicotinamide in a dose of 50 mg per 100 g of body weight caused a marked reduction in the blood glucose level of diabetic rats. An increase of the [NAD+]/[NADN], [NADP+]/[NADPN] ratio, a reduction of the concentration of phosphoenolpyruvate, malate and phosphoenolpyruvate carboxylase activity pointed to the inhibition of gluconeogenesis and stimulation of glycolysis in the liver of diabetic rats given nicotinamide.

[Gluconeogenesis in the liver of rats receiving 1,3-butanediol in their diet]. / Gliukoneogenez v pecheni krys, poluchavshikh v sostave diety 1,3-butandiol.

Inclusion of 1,3-butandiol as a synthetic source of nutritional energy into the composition of a low-carbohydrate diet produced a fall in the ration of free [NAD+]:[NADN] and [NADP]:[NADPN] calculated for the cytoplasm and mitochondria of the liver cell in rats according to the concentration of oxidated and reduced metabolites and the equilibrium constant of the lactate-dehydrogenase, glutamate-dehydrogenase and malic-fermentative systems. In these conditions the concentration of metabolites, at whose level the conjugation of the carbohydrates decomposition during glycolysis and their synthesis at the time of gluconeogenesis (phosphoenol-pyruvate, malate, oxaloacetate) is realized, as well as the activity of key gluconeogenesis enzymes (phosphoenol-pyruvate carboxykinase, fructose-1,6-diphosphatase) increase. The NADN generation in the course of oxidative metabolism of 1,3-butandiol gives rise to reducing properties of the free NAD-par cytoplasm and mitochondria pool, which leads to the intensification of gluconeogenesis in the liver, attended by a drop of the phosphate potential level.

[Role of the oxidation-reduction state and phosphate potential in regulating rat liver gluconeogenesis during inclusion of 1,3-butanediol in the diet]. / Rol' okislitel'no-vosstanovitel'nogo sostoianiia i fosfatnogo potentsiala v reguliatsii gliukoneogeneza v pecheni krys pr vkliuchenii v dietu, 1,3-butandiola.

Gluconeogenesis was stimulated in rat liver tissues if 38.5% of carbohydrates were substituted in the diet by 1,3-butane diol used as a source of energy. Under these conditions concentration of substrates (phosphoenol pyruvate, malate, oxalacetate), participating in coupling of glycolysis and gluconeogenesis, was increased in liver tissue; activity of gluconeogenesis key enzymes (phosphoenolpyruvate carboxykinase and fructose-1,6-diphosphatase) was also increased. Decrease in the ratio NAD+/NADH showed that the nicotinamide nucleotide pool acquired the most distinct reducing properties of cytoplasma and mitochondria of rats maintained on the diet. The value of phosphate potential (the ration ATP/ADP/Pn) was decreased during the experiment due to increase of ATP utilization in gluconeogenesis.