[Effect of hydroxylated pyrimidine derivatives on activities of thiamine-dependent enzymes and some parameters of lipid metabolism in mice]. / Vliianie gidroksilirovannykh proizvodnykh pirimidina na aktivnost' tiaminzavisimykh fermentov i nekotorye pokazateli obmena lipidov u myshei.

It has been found that hydroxylated pyrimidine derivatives actively participate in metabolic proceeds related to functioning of vitamin B1-dependent enzymes (transketolase, 2-oxo acid dehydrogenase). Hydroxypyrimidines also induce a significant increase in the levels of total lipids and cholesterol in the mice liver, not changing the phospholipid content.

[Spectroscopic study of the structure and intramolecular mobility of yeast pyruvate decarboxylase]. / Spektroskopicheskie issledovaniia struktury i vnutrimolekuliarnoi podvizhnosti drozhzhevoi piruvatdekarboksilazy.

Steady-state and time-resolved fluorimetry were used to study the properties of holo- and apopyruvate decarboxylase (EC 4.1.1.1, PDC) from Brewer's yeast after interaction with substrate (pyruvate), cofactor (thiamine diphosphate, ThDP) and Mg2+ ions. The analysis of the enzyme's intrinsic fluorescence as well as of its complex with the probe 2-(p-toluidinylnaphthalene)-6-sulphonate (TNS) revealed that ThDP was found at the polar region of the PDC active sites, inducing a decrease in the mobility of the protein's nearest surroundings. The fluorescent probe had three different sites of binding to the protein apoform, two of which being located at the catalytic site and having different rotation freedom. The study of the PDC complex with thiochrome pyrophosphate, a ThDP structural analogue, pointed to the occurrence of a non-polar region of the enzyme active site for pyruvate absorption besides the polar region. The binding of pyruvate to the protein does not depend upon the cofactor's binding. On the basis of the fluorescent studies a model of the ThDP and pyruvate arrangement at the PDC active site is suggested.

[Antivitamin activity of oxythiamine disulfide nicotinate]. / Antivitaminnaia aktivnost' oksitiamindisul'fidnikotinata.

The B1-antivitamin activity of oxythiamine disulphide nicotinate has been determined in experiments on albino mice and it is shown that in the liver this derivative exerts the equal action while in the blood and heart--a more profound and prolonged inhibitory action on the transketolase activity in comparison with oxythiamine disulphide. Like the initial compound oxythiamine disulphide nicotinate does not penetrate through hemato-encephalic barrier and does not inhibit the brain transketolase.

[Nonenzymatic reduction of methemoglobin by free radical forms of NADH and riboflavin]. / Neénzimaticheskoe vosstanovlenie metgemoglobina svobodnoradikal'nymi formami NADH i riboflavina.

Nonenzymatic reduction of methemoglobin (met-Hb) is effectively catalyzed by NADH and riboflavin (RF). At low concentrations of met-Hb the EPR spectra of the ternary complex are characterized by an increased, whereas those at high met-Hb concentrations--by a decreased intensity of the RF semiquinone signal, which suggests that the met Hb reduction by a Leu-form of RF proceeds at a higher rate than that by the RF semiquinone radical. Riboflavin also accelerates the met-Hb reduction by a NADH-Fe2+ or NADH-Fe(2+)-EDTA mixture. It was found that the rate of met-Hb reduction by the organic radical increases in the following order: NAD. < RF H. < RF H2.

[Features of thiamine diphosphate-dependent enzyme inhibition by oxodihydrothiochrome and its phosphorylated derivatives]. / Osobennosti ingibirovaniia tiamindifosfatzavisimykh fermentov oksodigidrotiokhromom i ego fosforilirovannymi proizvodnymi.

Anticoenzyme action of new derivatives of thiamine: oxodihydrothiochrome and its mono- and diphosphoric esters has been studied in the experiments on mice. It is shown that the given compounds exert an inhibiting action on transketolase and pyruvate dehydrogenase and do not change activity of 2-oxoglutarate dehydrogenase in the animal organism. Antivitamin effect of the studied inhibitors is observed with the lower doses and in the earlier terms as compared with the other known inhibitors of thiamine-diphosphate-dependent enzymes. The preparations inhibit activity of the yeast pyruvate-decarboxylase by the mixed (with respect to thiamine-diphosphate) type (Ki for oxodihydrothiochrome and its mono- and diphosphoric esters: 2.3 x 10(-3), 7.2 x 10(-4), 5.6 x 10(-5) M, respectively). Possible mechanisms of the action of the mentioned compounds as thiamine antimetabolites are discussed.

[Comparative antivitamin activity of oxythiamine disulfide and its monosulfoxide]. / Sravnitel'naia antivitaminnaia aktivnost' oksitiamindisul'fida i ego monosul'foksida.

The B1-antivitamin activity of oxythiamine disulphide monosulphoxide has been determined in experiments on albino mice. It is shown that this derivative is less toxic and exerts a more profound and prolonged inhibitory action on the pyruvate dehydrogenase and transketolase activity in the animal body in comparison with initial oxythiamine disulphide.

[Optimization of hydroxythiamine administration regimen in vitaminological research]. / Optimizatsiia rezhima ispol'zovaniia oksitiamina v vitaminologicheskikh issledovaniiakh.

A correlation between the different doses and inhibitory effect of hydroxythiamine relative to the activity of main thiamine pyrophosphate-dependent enzymes is studied in experiments on animals. It is established that the maximal inhibitory effect on the transketolase and oxoglutarate dehydrogenase activities is at a dose of antivitamin of 0.35 mmol/kg and that of pyruvate dehydrogenase of 0.55 mmol/kg. At lower doses of hydroxythiamine the inhibition of enzyme activities occurred in a dose-dependent manner.

[Interaction of pyruvate dehydrogenase complex from the heart muscle with thiamine diphosphate and its derivatives]. / Vzaimodeistvie piruvatdegidrogenaznogo kompleksa iz serdechnoi myshtsy s tiamindifosfatom i ego proizvodnymi.

Inhibitory effects of 23 thiamin derivatives on the bovine heart pyruvate dehydrogenase complex (PDC) were studied. Oxythiamin diphosphate and tetrahydroxythiamin diphosphate exhibited the most pronounced effect on the PDC activity, affecting the complex by a competitive type of inhibition for thiamin diphosphate (TDP). The apparent affinity of TDP and the anticoenzyme derivatives for apo PDC depended on presence of phosphate and divalent metal ions. Phosphate considerably increased the Km values for TDP (up to 0.17 microM) and the Ki values for oxythiamin diphosphate (0.40 microM) as well as for tetrahydroxythiamin diphosphate (0.23 microM). In presence of Mn2+, Km value for TDP was 3.5-fold lower as compared with Mg2+ containing medium.

[Antivitamin activity of O-acyloxythiamine disulfides]. / Antivitaminnaia aktivnost' O-atsiloksitiamindisul'fidov.

B1-antivitamin activity of symmetrical oxythiamine disulphide esters with succinic and o-phthalic acids has been studied in experiments on albino mice. It is shown that O-acyloxythiamine disulphides exert more profound and prolonged inhibitory effect on the transketolase activity in the animal body in comparison with the known antagonist of vitamin B1, oxythiamine, and the initial oxythiamine disulphide.

[Advantages of oxythiamine bromide as a specific inhibitor of activity of thiamine-dependent enzymes]. / Preimushchestva oksitiaminbromida kak spetsificheskogo ingibitora aktivnosti tiaminzavisimykh fermentov.

Production of hydrogen bromide salt of hydroxythiamine (Ht. HBr) from thiamine bromide was developed its toxic and inhibitory properties towards transketolase and pyruvate dehydrogenase were studied as compared with commercial preparation hydroxythiamine chloride (HT. HCl). As compared with HT. HCl, synthesis of HT. HBr was more simple, the higher yield and purity of the end product were achieved. At the same time, the preparation was less toxic and exhibited the antivitaminous activity similar to the commercial chloride form.

[Comparative evaluation of the action of oxythiamine and its derivatives on animals with Erhlich's ascitic cancer]. / Sravnitel'naia otsenka deistviia oksitiamina i nekotorykh ego proizvodnykh na zhivotnykh s astsitnym rakom Erlikha.

It is found that hydroxythiamine ester with sebacic acid surpassed hydroxythiamine in its antitumour effect on Ehrlich ascites tumour in albino mice. A linear correlation is observed between the values of activity coefficients of hydroxythiamine and its esters with dicarboxylic acids and some morphometric data.

[Changes in the permeability of the blood-brain barrier to oxythiamine]. / Ob izmenenii pronitsaemosti gematoéntsefalicheskogo bar'era dlia oksitiamina.

Activity of transketolase was distinctly inhibited in mice brain after simultaneous administration of hydroxythiamine and 3,3-dimethyl-l-phenyl-l-phthalyl acetic acid. The rate of the enzyme inhibition correlated with an increase of the acid concentration in the mixture studied. The data obtained suggest that permeability of blood-brain barrier for hydroxythiamine was altered in simultaneous administration of the vitamin with some biologically active preparations.

[Selective inhibition of pyruvate dehydrogenase in the liver and heart of mice by triphosphate esters of thiochrome and tetrahydrothiamine]. / Izbiratel'noe ingibirovanie piruvatdegidrogenazy pecheni i serdtsa myshei trifosfornymi éfirami tiokhroma i tetragidrotiamina.

In experiments with white mice it was shown that in contrast to hydroxythiamine and other known vitamin B1 antagonists, triphosphate esters of thiochrome and tetrahydrothiamine possess a selective anticoenzyme activity with respect to the only one of the thiamine pyrophosphate-dependent enzymes, i.e. pyruvate dehydrogenase.