Impact of the Chemical Analogues of Decarboxylated Ornithine and S-Adenosylmethionine on the Rate of the L-Cells Growth in the Tissue Culture

ABSTRACT The impact of the aliphatic amino-and oxy derivatives decarboxylated ornithine and Sadenosylmethionine on the rate of the L-cells growth in a tissue culture has been investigated. The known specific inhibitors of the polyamine synthesis enzymes (DFMO and MGBG) were used for control and comparison of efficacy of the substances tested. The nature of action of 1-aminooxy-3-aminopropane (APA) and S-(5-deoxyadenosile)-S-methyl--thioethylhydroxylamine (АМА) used separately or combined one with another was similar to the effect of DFMO and MGBG though less expressed. The degree of inhibition of the Lcells growth as of the 4 th day made 50-60%. By the 7 th day the tendency to not only stabilization of the growth rate but also to the recovery thereof manifested itself. This points to the reversible nature of action of the APA and AMA combinations and constitutes the difference from the effect DFMO and MGBG

Конформационные особенности лактатдегидрогеназы: влияние температурного фактора в присутствии малых молекул, математическая модель

The aim of this work was to study the conformational changes of lactate dehydrogenase under the influence of different concentrations of intermediates (pyruvate, oxaloacetate) in the temperature gradient with the  subsequent building of a mathematical model.Materials and methods. Thermolability of lactate dehydrogenase was studied using the method of differential scanning fluorimetry to determine the change in endogenous fluorescence of tryptophan and tyrosine under the conditions of stable concentration of lactate dehydrogenase and changing concentrations of pyruvate and oxaloacetate. Further, a mathematical model was developed for a more in-depth consideration of the behavior of the catalytic protein.Results. We found that pyruvate and oxaloacetate in low concentrations have a thermostabilizing effect on lactate dehydrogenase conformation; the effect of pyruvate is statistically more significant in comparison with oxaloacetate (p < 0.05). The studied ligands in high concentrations reduce the thermal stability of lactate dehydrogenase.Conclusion. Understanding the role of small molecules in the regulation of biological and catalytic processes has long remained in the background of scientific interest, but today the work in this direction is reaching a new level. The data obtained indicate the possibility of small molecules acting as ligands when interacting with enzymes.  Цель. Исследовать конформационные изменения лактатдегидрогеназы под действием различных концентраций интермедиатов (пируват, оксалоацетат) в температурном градиенте с последующим построением математической модели.Материалы и методы. Изучение термолабильности лактатдегидрогеназы проводили с  использованием метода дифференциальной сканирующей флуориметрии по изменению  эндогенной флуоресценции триптофана и тирозина в условиях стабильной концентрации лактатдегидрогеназы и изменяющихся концентраций пирувата и оксалоацетата. Далее была разработана математическая модель для более углубленного рассмотрения поведения каталитического белка.Результаты. Было выявлено, что пируват и оксалоацетат в низких концентрациях оказывают термостабилизирующее воздействие на конформацию лактатдегидрогеназы, влияние пирувата статистически более значимо в сравнении с оксалоацетатом (p < 0,05). Изучаемые лиганды в высоких концентрациях снижают термостабильность лактатдегидрогеназы.Заключение. Понимание роли малых молекул в регуляции биологических и каталитических процессов долгое время оставалось в тени научного интереса, но сегодня работа в данном направлении выходит на качественно новый уровень.  Полученные данные свидетельствуют о возможности малых молекул выступать в качестве лигандов при взаимодействии с каталитическими белками

Specificity of the metabolism response, caused by AB0-belonging on action of biologically active materials

Erythrocytes' quantitative and structurally functional parameters of clinically healthy persons with various АВ0-belonging were studied. Group-specific features of the given cells were revealed. Dependence of the metabolic answer character to action of biologically active materials of an exogenous and endogenous parentage on a AB0-group is studied. It is established, that the most expressed changes of erythrocytes indicators under the influence of a pyruvate, oxaloacetate, ethanol and silistrong are observed at persons with the fourth blood groups. The received results open molecular bases of the specific answer of an organism on action of endogenous and exogenous bioregulators