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At least 19 recordsLinked to original sources
PubMed2005

Modification of thiamine pyrophosphate dependent enzyme activity by oxythiamine in Saccharomyces cerevisiae cells.

Oxythiamine is an antivitamin derivative of thiamine that after phosphorylation to oxythiamine pyro phosphate can bind to the active centres of thiamine-dependent enzymes. In the present study, the effect of oxythiamine on the viability of Saccharomyces cerevisiae and the activity of thiamine pyrophosphate dependent enzymes in yeast cells has been investigated. We observed a decrease in pyruvate decarboxylase specific activity on both a control and an oxythiamine medium after the first 6 h of culture. The cytosolic enzymes transketolase and pyruvate decarboxylase decreased their specific activity in the presence of oxythiamine but only during the beginning of the cultivation. However, after 12 h of cultivation, oxythiamine-treated cells showed higher specific activity of cytosolic enzymes. More over, it was established by SDS-PAGE that the high specific activity of pyruvate decarboxylase was followed by an increase in the amount of the enzyme protein. In contrast, the mitochondrial enzymes, pyruvate dehydrogenase and 2-oxoglutarate dehydrogenase complexes, were inhibited by oxythiamine during the entire experiment. Our results suggest that the observed strong decrease in growth rate and viability of yeast on medium with oxythiamine may be due to stronger inhibition of mitochondrial pyruvate dehydrogenase than of cytosolic enzymes.

Antimetabolites↗
PubMed2003

Effect of oxythiamin on growth rate, survival ability and pyruvate decarboxylase activity in Saccharomyces cerevisiae.

Oxythiamin is one of the antivitamin derivatives of thiamin which, after phosphorylation, can be bound to the catalytic centre of thiamin-dependent enzymes and inhibit these enzymes. In this work the influence of oxythiamin on the growth rate, survival and the activity of pyruvate decarboxylase of Saccharomyces cerevisiae (s288c) was investigated. Oxythiamin decreased both the growth rate and survival ability of yeast cells. Moreover, in three-day-old cultures on a medium with oxythiamin, an increase of pyruvate decarboxylase activity was observed. This unusual effect may be in response to the earlier inhibition of pyruvate decarboxylase. A high concentration of pyruvate in the cell extracts taken from the medium with oxythiamin was found. This accumulation of pyruvate could provide for enhanced biosynthesis of the pyruvate decarboxylase apoform and an increase of enzyme activity.

Antimetabolites↗
PubMed1982

Effect of 4'-oxythiamine on thiamin transport and phosphorylation by everted jejunal sacs, and on thiamin uptake by rat isolated enterocytes.

Two preparations were used for the present investigation. Rat everted jejunal sacs were incubated at 37 degrees C for 1 h in Krebs-Henseleit buffer, pH 7.4, containing 0.2 microM [thiazole-2-14C] -thiamin, with or without 2 microM 4'-oxythiamine. Suspensions of rat isolated enterocytes were incubated at 37 degrees C for 15 min in Ringer-Krebs, pH 7.4, containing 10 mM d-glucose and 0.125 microM [thiazole-2-14C] -thiamin, with or without 1.25 or 12.50 microM 4'-oxythiamine. Radiometric methods were used for the determination of: labeled thiamin net transport, free and phosphorylated thiamin content in the sac walls, total thiamin content in the isolated enterocytes. 4'-oxythiamine, at a molecular ratio with thiamin of 10:1, did not modify labeled thiamin net transport and accumulation by everted jejunal sacs, but caused a slight, statistically insignificant, decrease of labeled phosphorylated thiamin content of the sac walls. 4'-oxythiamine, at a molecular ratio of 10:1 or 100:1, did not inhibit labeled thiamin uptake by isolated enterocytes. Therefore, 4'-oxythiamine, which is known to be unable to inhibit thiamin enzymatic phosphorylation, did not affect thiamin intestinal transport both by everted intestinal sacs and isolated enterocytes. The present results can be interpreted as a further evidence that intracellular thiamin phosphorylation is an important step in thiamin intestinal transport.

Animals↗
PubMedDate not supplied

[Specific and metabolic effect of oxythiamine].

Increasing doses of oxythiamine were studied as exerting the effect on transketolase inactivation in rat tissues. A conclusion is made that in the process of synthesis de novo there is a transient form of the enzyme accessible for interaction with oxythiamine pyrophosphate. Injection of oxythiamine in the increasing doses are accompanied by a decrease in the glycogen amount, increase in the intracellular level most of the studied intermediates of glycolysis and pentose cycle as well as cAMP. The probable biochemical mechanism of the oxythiamine action is connected with the activation of processes dependent on cAMP.

Animals↗
PubMed1984

Effect of oxythiamine on adrenal thiamine pyrophosphate-dependent enzyme activities.

The effect of parenterally administered low doses of oxythiamine (0.5 mumol/100 g body weight every 12 h) on rat adrenal transketolase, pyruvate dehydrogenase ( PDC ) and 2-oxoglutarate dehydrogenase complex ( OGDC ) activities was studied. It was found that the transketolase and the PDC activities decreased after 12, 16, and 20 injections. When the activities were measured in the absence of exogenous thiamine pyrophosphate (TPP), the PDC inhibition was significant after 20 oxythiamine injections. The OGDC activity was resistant to oxythiamine administration. The oxythiamine effects seem to be due to its being phosphorylated to yield diphosphate ester which, as kinetic studies on highly purified PDC from bovine adrenals have shown, is a strong competitive inhibitor (Ki = 0.07 microM) with respect to TPP (Km = 0.11 microM). The data obtained provide evidence for the possibility of a partial selective in vivo inhibition of the adrenal TPP-dependent enzymes.

Adrenal Glands↗
PubMed1982

[Some features of [1-14C] leucine exchange in rat liver during acute oxythiamine avitaminosis].

The leucine content in rat liver and blood serum under acute oxythiamine avitaminosis is decreased. Simultaneously oxythiamine inhibits the activity of alpha-ketoisocaproate dehydrogenase resulting in a decrease of leucine catabolism in the liver. The level of total tRNA in hepatocyte cytosol is lowered, the radioactivity of leucine in aminoacyl-tRNA on the 6th min after injection of [1-14C]leucine is increased approximately 1.5-fold as compared to normal. The radioactivity of leucine in blood serum and aminoacyl-tRNA is directly significantly correlated with the content of leucine incorporated into the proteins, while the level of intracellular [14C]leucine is not correlated with the protein radioactivity (r=-0.154,p greater than 0.5) or with blood serum amino acid radioactivity (r=-0.184, p greater than 0.5). The results obtained thus indicate that 1) in acute oxythiamine avitaminosis when the labelled amino acid is incorporated within 3-6 min the label is "concentrated" in blood serum resulting in increased specific radioactivity of the protein in rat liver; 2) in blood serum leucine is predominantly utilized during protein biosynthesis; 3) acute oxythiamine avitaminosis has no significant effect on protein biosynthesis in rat liver; 4) specific radioactivity of the protein cannot serve as an index of protein synthesis rate.

Animals↗
PubMedDate not supplied

[Influence of oxythiamine on the fatty acid composition of rat liver total lipid fraction and phospholipids].

Changes in the content of individual fatty acids in the total lipid fraction and phospholipids of the liver occurring under the effect of oxythiamine were studied. The fatty acids composition was determined by the method of gas chromatography. A single introduction of oxythiamine in a dose of 0.4 g/kg produced in 24 hours a deficit of essential fatty acids of the liver. Similar results were obtained with daily administration of oxythiamine at the rate of 500 gamma per animal a day, for a space of 10 days. The participation of thiamine as a substrate at one of the stages marking transformation of linolic acid and inhibition of this nonspecific function of thiamine by oxythiamine are presumed.

Animals↗
PubMedDate not supplied

Effects of pyrithiamin and oxythiamin on acetylcholine levels and utilization in rat brain.

Regional cerebral acetylcholine (ACh) levels and utilization rate were assessed in vivo in rats rendered thiamin deficient using the thiamin antagonists pyrithiamin or oxythiamin. ACh levels were significantly reduced in all brain regions of pyrithiamin treated rats and in the medulla-pons and striatum of oxythiamin treated rats compared to controls. ACh utilization was significantly reduced in the midbrain, striatum and hippocampus of pyrithiamin treated rats, but was reduced only in the striatum of oxythiamin treated rats compared to controls. Thus, there are some reductions in ACh levels and utilization that are unique to pyrithiamin induced deficiency and as such are distinct from oxythiamin/undernutrition related reductions. Since only pyrithiamin produces neurological symptoms, its unique ACh effects may be related to these symptoms.

Acetylcholine↗
PubMed2005

Zinc(II), cadmium(II) and mercury(II) complexes of the vitamin B1 antagonist oxythiamine.

The reaction of oxythiamine chloride hydrochloride (HOxTCl x HCl) with ZnCl2, CdCl2 and HgCl2 in ethanol yielded the complexes [ZnCl3(HOxT)], [CdCl3(HOxT)] and [HgCl3(HOxT)]. In water, the reaction with CdCl2 afforded [CdCl2(OxT)], but reaction with ZnCl2 or HgCl2 yielded unidentified products. The four new complexes were characterized by mass spectrometry and IR spectroscopy in the solid state and by 1H, 13C and 15N nuclear magnetic resonance (NMR) spectroscopy in hexadeuterated dimethylsulfoxide (DMSO-d6), and three were also studied by X-ray diffractometry. In [ZnCl3(HOxT)] and [HgCl3(HOxT)] the oxythiamine ligand is bound to the metal via N(1') and adopts the V conformation exhibited by thiamine in biological contexts. The infrared (IR) spectrum of [CdCl3(HOxT)] suggests a similar coordination mode. In [CdCl2(OxT)] each OxT zwitterion coordinates to one Cd(II) ion via its N(1') atom and to another via its N(3') and O atoms, giving rise to a polymeric chain along the x-axis. The coordination number of the metal is made up to six by Cdc...Cl interactions, two of which link the polymeric chains in pairs. This seems to be the first metal complex containing the oxythiamine ligand as a zwitterion, with the N(3')-H/O(4'alpha)-H group deprotonated. Neither HOxTCl nor its zinc(II) complex showed any significant activity in vitro against HeLa cells.

Antimetabolites↗
PubMed1995

The effects of thiamine and oxythiamine on the survival of cultured brain neurons.

The effects of treatment with thiamine (Vitamin B1) alone or together with its antagonist oxythiamine on the survival of brain neurons in primary culture were investigated. Treatment with thiamine significantly promoted the survival of hippocampal neurons in high cell density culture, but had no effects on the neuronal survival in low cell density culture. In addition, the survival-promoting activity exerted by thiamine was remarkably decreased by the co-application of oxythiamine, although oxythiamine used alone revealed neither a trophic nor toxic effect on the neurons of examined brain regions. The neurotrophic function of thiamine may be due to its coenzymatic role in a biochemical reaction and/or its specific function on neurotransmission and nerve conduction.

Animals↗
PubMedDate not supplied

[Antivitamin activity of oxythiamine disulfide nicotinate].

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.

Animals↗
PubMedDate not supplied

[The effect of oxythiamine on tumor growth and certain biochemical and genetic characteristics of normal and tumor cells].

The effect of oxythiamine (400 mg/kg) on chromosomal structure of Ehrlich ascites carcinoma cells (EAC, hyperdiploid strain) and bone marrow cells was studied in intact AF mice. The influence of the antivitamin on the rate of tumor growth was investigated in tumor-bearing mice. Oxythiamine decreased transketolase activity in hepatocytes and tumoral cells and markedly inhibited tumor growth. Amount of chromosomes was unaltered both in tumor cells and in bone marrow cells, which could be manifested as increased content of cells with impairment of chromosomal set calculated per a cell. However, the oxythiamine-induced impairment of chromosomal integrity was less distinct as compared with the effect of such mutagens as urethane and cyclophosphamide; hence, the antivitamin might be used in the courses of combined chemotherapy.

Animals↗
PubMedDate not supplied

[Effect of oxythiamine disulfides on the pancreas and thyroid of rats].

Single administration of oxythiamine (200 mg/kg) or an isomolar amount of oxythiamineamyldisulfide to rats does not change the content of insulin in 72 h, whereas oxythiaminehexyldisulfide slightly increases the blood level of the hormone. Oxythiamine and its disulfides cause changes of the thyroid indicating considerable suppression of its function. It is assumed that hormonal mediation of oxythiamine nonspecific metabolic effects results predominantly from the involvement of the thyroid hormones rather than insulin.

Animals↗
PubMed1977

[Biosynthesis of mitochondrial protein in rat liver under conditions of vitamin B 1 deficiency following oxythiamine injection].

The incorporation of labelled precursors into mitochondrial proteins of liver under different duration of oxythiamine (antivitamin B1) effect was studied in the whole organism and in a cell-free system. After 24 hrs following the injection, oxythiamine at a dose of 400 mg/kg of body weight increases the mitochondrial protein synthesis in vivo without changing the protein-synthesizing capacity of isolated mitochondria. After 72 hrs following the injection of the same dose of preparation, a sharp increase in the rate of protein label incorporation into the mitochondria was observed. The protein synthesis in mitochondria in the whole body studies also showed an increase. It is assumed that oxythiamine enhances the inductive synthesis of mitochondrial thiamine phosphate-dependent enzymes or activates the syntheses of other enzymic systems, capable of increasing the utilization of alpha-keto acids accumulated under conditions of thiamine deficiency.

Animals↗
PubMedDate not supplied

[Transketolase inhibitors based on disulfide derivatives of oxythiamine with branched hydrocarbon chains].

The experiments on mice have shown that oxythiamine disulphide derivatives with the branched hydrocarbon chains are less toxic in the organism as compared to oxythiamine and corresponding disulphides with the unbranched hydrocarbon chains and also induce a more pronounced inhibition of transketolase in the liver and other tissues. It is found that under the effect of the above substances the recovery of enzymic activity is slower than in the case with the oxythiamine application.

Animals↗
PubMed2000

Oxythiamine hexafluorophosphate monohydrate, a thiamine antagonist with the same conformation as thiamine.

In the title compound, 3-[(3,4-dihydro-2-methyl-4-oxopyrimidin-5-yl) methyl]-5-(2-hydroxyethyl)-4-methylthiazolium hexafluorophosphate monohydrate,C(12)H(16)N(3)O(2)S(+).PF(6)(-).H(2)O, oxythiamine is a monovalent cation with a neutral oxopyrimidine ring. The molecule assumes the F conformation, which is a common form for thiamine but which is substantially different from the unusual V conformation found in the chloride and hydrochloride salts of oxythiamine. The anion-bridging interaction, C-H...anion...pyrimidine, is emphasized as being important for stabilization of the F conformation.

Crystallography, X-Ray↗
PubMed1977

Effect of thiamine deficiency, pyrithiamine and oxythiamine on pyruvate metabolism in rat liver and brain in vivo.

Rats were fed either a thiamine-deficient diet of diets containing pyrithiamine or oxythiamine. When symptoms of thiamine deficiency appeared, the animals were injected intraperitoneally with [2-14C] pyruvate six to twelve minutes prior to sacrifice. Free glutamic and aspartic acids were isolated from liver and brain and degraded. The results indicate that, in thiamine-deficient or oxythiamine-treated rats, pyruvate metabolism in liver and brain is similar to that in normal animals. In contrast, pyrithiamine drastically decreases the oxidative decarboxylation of pyruvate by rat liver.

Animals↗