[Effects of chronic radiation exposure on erythrocyte metabolism and functioning].

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].

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 coenzymes in the regulation of cellular metabolism in various types of diabetes].

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.

[Inhibition of the transport of citrate during ADP-ribosylation of inner membrane proteins of the mitochondria].

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.

[Citrate transport in submitochondrial particles of the rat liver].

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.

[Enzyme systems of the substrate and cofactor supply of hyperlipogenesis in non-insulin-dependent diabetes].

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].

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].

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].

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.

[Sorbitol pathway of glucose metabolism in streptozotocin diabetes of varying duration and severity].

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.

[Study of the role of nicotinamide coenzymes in the regulation of glyceroneogenesis from pyruvate in rat epididymis fat tissue].

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.

[Redox state of free nicotinamide coenzymes and phosphoenolpyruvate synthesis in rat and guinea pig liver].

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.

[Possible mechanisms of the inhibiting effect of nicotinamide on lipogenesis in rat liver].

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.

[Nicotinamide inhibition of 2-14C acetate incorporation into free fatty acids and lipids of rat tissues].

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].

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.

[Gluconeogenesis in the liver of rats receiving 1,3-butanediol in their diet].

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].

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.

[Dinitroorthocresol dissociation of oxidative phosphorylation in the rat liver perfused in situ].

Perfusion of the rat liver in situ for 150 min provides for maintaining optimal values of acid-base balance for the following indexes: surplus of bases, content of standard bicarbonate, buffer bases pH, pO2, pCO2, HbO2, the level of bile secretion, content of lactate, pyruvate, ATP, ADP, that evidences for a high functional activity in the tissue. Introduction of dinitro-ortho-cresol (DNC) into the perfusion liquid causes development of acidosis. DNC results in dissociation of oxidative phosphorylation: the content of ATP and intensity of inorganic phosphorus utilization decrease, oxygen uptake intensifies.

[Redox state of the hepatic cells in rats kept on a diet containing 1,2-propanediol].

A comparative characterization of the redox condition and phosphate potential of the hepatic cells in rats kept on two experimental diets (low- and high-carbohydrate) is given. Intensification of the glucogenesis in the liver of rats kept on a low-carbohydrate diet is determined by lower values of the ratios /NAD+/: (NADH/ and /ATP/:/ADP/P1, the cells acquiring more marked reducting properties. Incorporation of 1,2-propanediol, as a source of metabolized energy, in the composition of the low-carbohydrate diet (20 per cent of the fat content) produces a rise in the level of glycogen and a fall of the liver lipids.

[Dynamics of the intake and utilization of orally administered 1,2-propanediol in glycogen synthesis in the rat liver].

The possibility of an isocaloric substitution of 1,2-propandiol for carbohydrates in the food ration of rats was investigated. The inclusion of propandiol as a synthetic source of food energy in the alimentation in an amount comprising 20 per cent of the overall calorific value of carbohydrates does not affect adversely the growth intensity, nor does it produce any materials upsets in the metabolism of test animals. With its oral introduction in a dose of 1 g per 100 g of weight 1,2-propandiol is quickly absorbed, its level reaching the maximum in the blood and liver after a lapse of 1 hour with complete metabolization in the organism over a period of 12 hours.