Publications by authors named "Iu M Parkhomenko"

Oral administration of antituberculosis drugs to rats for 60 days in doses that are equivalent to clinical ones, causes changes in mRNA levels expression of liver cytochrome P-450 isoforms CYP3A2, CYP2C23, CYP2E1 and pro- and antioxidant state. Experimental composition "Metovitan" given with anti-TB drugs provided a correction of these abnormalities, that is evidenced by modulation of the level of CYP3A2, CYP2C23, CYP2E1 gene expression and antioxidant activity, inhibition of lipid peroxidation. "Metovitan" normalizes the enzymatic activity and content of total billirubin in the blood serum, shows high hepatoprotective properties, exceeding the efficiency of methionine.

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The data available in literature about formation, properties, possible biological role and practical application of the oxidized derivatives of B1 vitamin (thiamine) is first generalized and analysed in the review. It is known that at the values of pH > 7.0 the molecule of thiamine is able to undergo two-phase reaction of opening of thiazole ring with formation of anion of thiol form of thiamine and unstable tricyclic form.

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The current work is aimed at understanding the structure and functionality of thiamine binding protein (TBP) in neural cells plasma membranes. The influence of thiamine triphosphate on thiamine binding by TBP in synaptic plasma membranes (SPM) isolated from the rat brain was investigated. It was shown that thiamine triphosphate inhibits thiamine binding activity of SPM in concurrent manner (K(i) = 1.

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The kinetic parameters of the ThTP hydrolysis by synaptic plasma membranes isolated from rat brain were investigated. It was shown that the ThTPase reaction pH optimum was 7.4, the apparent K(m) was 52 microM and the apparent affinity constant for Mg2+ was 1.

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The influence of the chronic consumption of alcohol on biochemical reactions of thiamine metabolism in the rat brain is investigated. It is shown that the content of thiamine diphosphate (ThDP) in the brain tissue does not change at these conditions, though there is an essential decrease in the thiamine-kinase activity. The ability of the isolated nerve terminals (synaptosomes) to absorb labelled thiamine also decreases under this condition.

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In the researches carried out on rats with models of chronic alcoholism and alcohol abstinence the most vulnerable to chronic action of alcohol biochemical parameters are revealed: a level of reduced glutathione (it was estimated by the content of free SH-groups in tissues), the content of thiamine diphosphate and thiaminekinase activity in a brain, the content of folic acid in the blood, the content of ubiquinone in the cardiac muscle, RNA/DNA relation in the liver. The data obtained demonstrate first of all the negative influence of alcohol on metabolism of sulfur-containing substances and processes of transmethylation. The results of our investigation have also shown that the part of metabolic changes caused by long-term usage of alcohol, can be caused by direct influence of ethanol or its metabolites on those or other enzymatic proteins or receptors, and their functions can quickly be normalized after the abolition of alcohol (NAD+ contents, alpha-ketoglutarate dehydrogenase activity and some others).

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Results of the study of the provision with vitamins and some micro- and macroelements of limited groups of people, who suffered from the accident at the Chornobyl nuclear power plant (ChNPP), which have been carried out by Ukrainian and Russian scientists during various periods after the accident, are generalized in the paper. Persons which participated in liquidation of the accident and lived during the accident in the territory, adjoining to Pripyat (the Kyiv region, town of Slavutich), people which worked at the object "Shelter" and ChNPP were involved in the inspection. It was noted, that in 1-4 years after the ChNPP accident in blood of liquidators the biochemical parameters displaying security of their organism by vitamins A and B1, remain lower in comparison with the same parameters in a group of relatively healthy persons which were not affected by the accident (control), that testifies to stable metabolic disturbance in the organism of people under irradiation influence.

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Herein we review the main stages of life and scientific work of Rostislav Vsevolodovich Chagovets, prominent biochemist and vitaminologist, Member of the Academy of Sciences of Ukrainian SSR, professor and talanted pedagogue. As a founder of scientific school of vitaminologists and researcher in the field of muscle biochemistry, nutrition and vitamins he made a valuable contribution to development of the national and world biochemistry. This work reflects the main trends of fundamental scientific investigations and developments of vitaminological school founded by R.

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The distribution of thiamine-binding and thiamine triphosphatase activity typical of thiamine-binding proteins was studied in intracellular structures of rats liver and kidneys. It was found that the fraction of microsomes has the highest rate of specific thiamine-binding activity amide fractions of subcellular structures that was isolated using differential centrifugation in the both organs. Hydrolysis of thiamine triphosphate (pH 7.

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The study of thiamine-binding proteins (ThBP) isolated from liver and kidneys of rats was held in order to find out the peculiarities and physiological role of the ThBP isolated earlier from the rat brain. It was demonstrated that ThBP from liver and kidneys of rats as well as ThBP from rat brain described earlier, were bifunctional: on an equal footing with ability to bind thiamine specifically, they show an ability to hydrolyse the phosphoric esters of thiamine selectively. The ThBP of these tissues (liver, kidneys and brain) didn't differ by the molecular weight, but differed by the enzymatic activities.

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Participation of the enzyme which provides the phosphorylation of thiamine to thiamindiphosphate (TDP) thiaminkinase (thiaminpyrophosphokinase, KF 2.7.6.

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The investigation was conducted on provision with vitamins C and B1 of Kyiv inhabitants limited contingent at spring period and efficiency of complex vitamin-mineral preparations in normalisation of the vitamins level in blood of human-subjects. The deficit of vitamin C in 54% and vitamin B1 in 18.5% of the investigated people was revealed.

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Mechanistic model of thiamine-binding protein functioning which is based on the potential role of prototropic groups and hydrophobic environment around 5-beta-hydroxyethyl substituent of ligand has been proposed. As a model the chemical transformations of thiamine and its structural O-acyl substituted analogues in the presence of ferricyanide and phosphatic buffer in pH range 7,2-7,8 were investigated. The oxidation to the thiochrome and thiochrome derivatives is first order in substrate and ferricyanide concentrations.

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Biochemistry of vitamins is one of the leading trends in the fundamental researches of A. V. Palladin Institute of Biochemistry from the moment of its foundation in 1925.

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Thiamine has been shown to be bound specifically by a synaptosomal plasmatic membrane and transported inside to the nervous ending. Apparent K[symbol: see text] and Km for processes of binding and transport have been determined as equal 2.34 +/- 0.

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The levels of vitamins in the blood of persons who suffered from the catastrophe at Chernobyl NPP subject to medically treatment at Kiev clinics at different time periods have been studied. Polyhypovitaminosis has been detected in all the patients groups examined, especially in persons with the diagnosis of acute radiation sickness. The hypovitaminosis status in the organism is regulated by means of an adequate vitamin therapy.

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Inactivation of yeast pyruvate decarboxylase in the presence of substrate and oxidative system containing substituted quinone and ferricyanide has been investigated. It was established that ferricyanide at pH 5.2-6.

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A review of some experimental results as to identification of the specific role of thiamine in functioning of nerve cells is presented. Failure to attribute high neuroactivity of thiamine considering only its known biochemical function as a coenzyme precursor of some key Enzymes of the carbohydrate metabolism has formed conceptions existence of non-coenzyme functions in this vitamin which are realized in nerve cells. The Investigation of this thiamine function has been developing mainly in two principal directions the study of participation of biologically active thiamine derivatives is functioning of the excited membrane ion channels and the study of their role in the synthesis and metabolism of acetylcholine.

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The rate constants of paracatalytic inactivation of pyruvate decarboxylase in the presence of 1,4-naphthoquinones and 1,4-benzoquinones are determined by redox potentials of the oxidant. The logarithm of k2 depends hyperbolically on the redox potential of quinone E0(Q/Q-.) with the coefficient of proportionality which approximates 8.

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The influence of methionine and vitamin E, compounds intensifying thiol metabolism, on thiamine-phosphate level and thiamine-dependent dehydrogenase activity was studied in the liver of rats with varying thiamine providing: in case of its alimentary deficiency, and intensified thiamine consumption due to rat feeding with high-carbohydrate food. Methionine administration to vitamin B1-deficient rats led to a significant rise in thiamine-phosphate content and normalized alpha-ketoacid dehydrogenase acidity and non-protein SH-group level. Combined administration of thiamine with methionine and vitamin E increased the level of parameters studied.

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Changes in the amount of thiamine, reduced glutathione, thiamine diphosphate-dependent dehydrogenase activity has been traced after thiamine injection to thiamine-deficient rats and oxythiamine to normal rats. The obtained data show that a drop in reduced glutathione level was a primary reason of the alpha-keto-acid dehydrogenase activity reduction under conditions of the thiamine deficiency. The existence of immediate connection between thiamine and glutathione metabolism is supposed.

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A thiamine-binding protein (ThBP) with a specific activity of 8.21 nmoles/mg protein was isolated from rat brain synaptosomes by affinity chromatography and gel filtration on Sephadex G-200. The protein was purified 746-fold with a 40.

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The thiamine-binding protein was obtained from rat brain synaptosomes by affinity chromatography and gel-filtration on Sephadex G-200. The protein is homogeneous by the data of SDS gel-electrophoresis, anode electrophoresis and isofocusing between pH 3.5-9.

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The effect of thiamine triphosphate (ThTP) and thiamine diphosphate (ThDP) on the activity of rat liver pyruvate dehydrogenase complex regulatory enzymes (kinase and phosphatase) was studied in experiments with isolated enzyme preparations. It is shown that ThDP caused a pronounced activation of pyruvate dehydrogenase phosphatase (Ka is equal to 65.0 nM).

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