Action Of Thiamine Research Articles

Comprehensive Study of Biological Aspects of Heteroring Annelated Benzothiazoles

Heterocyclic chemicals are chemical structures which include at least a single carbon molecule plus at least one other element, such as sulphur, oxygen, or nitrogen, within the ring structure. Benzothiazoles are discussed in terms of synthesis methodologies, structural changes, chemical reactivity, and possible pharmaceutical effectiveness. This research relied upon secondary data obtained from the sources. The qualitative method was used to provide a section of such an evaluation which looked flawless and accurate. A handy methodology strategy is used in inquiry research. Heterocyclic compounds have been widely exploited in bioorganic and medical research for medication development. Scientists are interested in such compounds because of their various physicochemical and pharmacological properties. Recognizing heterocycles is advantageous in both industrial and biological processes. Benzothiazole, a molecular heterocyclic structure, is being studied as a candidate for such creation of larger, often medicinal chemicals. It is highly durable due to its aromatic components; however, it has reactive services that offer the synthesis method. The benzothiazole ring becomes an important framework for the production of colours used throughout the identification of lanthanide metal cations in aqueous environments. This identical basic N, S heterocycle, benzothiazoles, seems to be abundant; for example, it is required essential thiamine action (vitamin B1). Thiazole compounds could also be discovered in medications such as Nosiheptide. This chemistry group is used for about simply for antibacterial purposes; its distinctive heteroring linked derivatives have attracted the curiosity of scientists due to their various biological or indeed medicinal properties.

Thiamine-dependent regulation of mammalian brain pyridoxal kinase in vitro and in vivo.

Vitamins B1 (thiamine) and B6 (pyridox (al/ine/amine)) are crucial for central nervous system (CNS) function and neurogenesis due to the coenzyme action of their phosphorylated derivatives in the brain metabolism of glucose and neurotransmitters. Here, the non-coenzyme action of thiamine on the major mammalian producers of pyridoxal-5'-phosphate (PLP), such as pyridoxal kinase (PdxK) and pyridoxine 5'-phosphate oxidase (PNPO), is characterized. Among the natural thiamine compounds, thiamine triphosphate (ThTP) is the best effector of recombinant human PdxK (hPdxK) in vitro, inhibiting hPdxK in the presence of Mg2+ but activating the Zn2+ -dependent reaction. Inhibition of hPdxK by thiamine antagonists decreases from amprolium to pyrithiamine to oxythiamine, highlighting possible dysregulation of both the B1 - and B6 -dependent metabolism in the chemical models of thiamine deficiency. Compared with the canonical hPdxK, the D87H and V128I variants show a twofold increase in Kapp of thiamine inhibition, and the V128I and H246Q variants show a fourfold and a twofold decreased Kapp of thiamine diphosphate (ThDP), respectively. Thiamine administration changes diurnal regulation of PdxK activity and phosphorylation at Ser213 and Ser285, expression of the PdxK-related circadian kinases/phosphatases in the rat brain, and electrocardiography (ECG). In contrast to PdxK, PNPO is not affected by thiamine or its derivatives, either in vitro or in vivo. Dephosphorylation of the PdxK Ser285, potentially affecting mobility of the ATP-binding loop, inversely correlates with the enzyme activity. Dephosphorylation of the PdxK Ser213, which is far away from the active site, does not correlate with the activity. The correlations analysis suggests the PdxK Ser213 to be a target of kinase MAP2K1 and phosphatase Ppp1ca. Diurnal effects of thiamine administration on the metabolically linked ThDP- and PLP-dependent enzymes may support the brain homeostatic mechanisms and physiological fitness.

Insights Into Thiamine Supplementation in Patients With Septic Shock.

Septic shock is associated with unacceptably high mortality rates, mainly in developing countries. New adjunctive therapies have been explored to reduce global mortality related to sepsis. Considering that metabolic changes, mitochondrial dysfunction and increased oxidative stress are specific disorders within the path of septic shock, several micronutrients that could act in cellular homeostasis have been studied in recent decades. Thiamine, also known as vitamin B1, plays critical roles in several biological processes, including the metabolism of glucose, synthesis of nucleic acids and reduction of oxidative stress. Thiamine deficiency could affect up to 70% of critically ill patients, and thiamine supplementation appears to increase lactate clearance and decrease the vasopressor dose. However, there is no evident improvement in the survival of septic patients. Other micronutrients such as vitamin C and D, selenium and zinc have been tested in the same context but have not been shown to improve the outcomes of these patients. Some problems related to the neutrality of these clinical trials are the study design, doses, route, timing, length of intervention and the choice of endpoints. Recently, the concept that multi-micronutrient administration may be better than single-micronutrient administration has gained strength. In general, clinical trials consider the administration of a single micronutrient as a drug. However, the antioxidant defense is a complex system of endogenous agents in which micronutrients act as cofactors, and the physiological interactions between micronutrients are little discussed. In this context, the association of thiamine, vitamin C and corticoids was tested as an adjunctive therapy in septic shock resulting in a significant decrease in mortality. However, after these initial results, no other study conducted with this combination could reproduce those benefits. In addition, the use of low-dose corticosteroids is recommended in patients with septic shock who do not respond to vasopressors, which can affect the action of thiamine. Therefore, given the excellent safety profile, good biologic rationale and promising clinical studies, this review aims to discuss the mechanisms behind and the evidence for single or combined thiamine supplementation improving the prognosis of patients with septic shock.

Daytime Dependence of the Activity of the Rat Brain Pyruvate Dehydrogenase Corresponds to the Mitochondrial Sirtuin 3 Level and Acetylation of Brain Proteins, All Regulated by Thiamine Administration Decreasing Phosphorylation of PDHA Ser293.

Coupling glycolysis and mitochondrial tricarboxylic acid cycle, pyruvate dehydrogenase (PDH) complex (PDHC) is highly responsive to cellular demands through multiple mechanisms, including PDH phosphorylation. PDHC also produces acetyl-CoA for protein acetylation involved in circadian regulation of metabolism. Thiamine (vitamin B1) diphosphate (ThDP) is known to activate PDH as both coenzyme and inhibitor of the PDH inactivating kinases. Molecular mechanisms integrating the function of thiamine-dependent PDHC into general redox metabolism, underlie physiological fitness of a cell or an organism. Here, we characterize the daytime- and thiamine-dependent changes in the rat brain PDHC function, expression and phosphorylation, assessing their impact on protein acetylation and metabolic regulation. Morning administration of thiamine significantly downregulates both the PDH phosphorylation at Ser293 and SIRT3 protein level, the effects not observed upon the evening administration. This action of thiamine nullifies the daytime-dependent changes in the brain PDHC activity and mitochondrial acetylation, inducing diurnal difference in the cytosolic acetylation and acetylation of total brain proteins. Screening the daytime dependence of central metabolic enzymes and proteins of thiol/disulfide metabolism reveals that thiamine also cancels daily changes in the malate dehydrogenase activity, opposite to those of the PDHC activity. Correlation analysis indicates that thiamine abrogates the strong positive correlation between the total acetylation of the brain proteins and PDHC function. Simultaneously, thiamine heightens interplay between the expression of PDHC components and total acetylation or SIRT2 protein level. These thiamine effects on the brain acetylation system change metabolic impact of acetylation. The changes are exemplified by the thiamine enhancement of the SIRT2 correlations with metabolic enzymes and proteins of thiol-disulfide metabolism. Thus, we show the daytime- and thiamine-dependent changes in the function and phosphorylation of brain PDHC, contributing to regulation of the brain acetylation system and redox metabolism. The daytime-dependent action of thiamine on PDHC and SIRT3 may be of therapeutic significance in correcting perturbed diurnal regulation.

The modulator action of thiamine against pentylenetetrazole-induced seizures, apoptosis, nitric oxide, and oxidative stress in rats and SH-SY5Y neuronal cell line

Accumulating evidences indicate that thiamine plays a vital role in the nervous system. However, questions exist as to how it causes epilepsy, neuronal damage, and antiepileptic mechanisms. The study looked at how the thiamine supplement impacted pentylenetetrazole (PTZ)-induced seizures in rats and pentylenetetrazole-induced neurotoxicity in the SH-SY5Y cell line. We used twenty-four male rats and they were randomly divided into 4 groups as control, saline (1 mL/kg/day serum physiologic) + PTZ, thiamine (50 mg/kg/day) + PTZ, and thiamine (50 mg/kg/day) for 10 days. PTZ (45 mg/kg) was given to activate the seizure on day 10. Memory efficiency was measured by using passive avoidance. The brain levels of 8-hydroxy-2′-deoxyguanosine (8-OHdG), caspase-3, nitric oxide (NO), and cyclic guanosine monophosphate (cGMP) were analyzed by using ELISA kits. SH-SY5Y cells were treated with/without thiamine for 1 h, followed by PTZ (30 μm) at a medium level to trigger neurotoxicity. Cell viability, total antioxidant status, total oxidant status, and apoptosis were assayed in the SH-SY5Y cells. Thiamine delayed the initiation of epileptic seizures and increased memory damage. In addition, 8-OHdG, caspase-3, NO, and cGMP levels were significantly reduced in the brain and prevented pentylenetetrazole-induced neurotoxicity, apoptosis, enhanced antioxidant, and reduced oxidant in SH-SY5Y cells. Thiamine dramatically altered seizures, memory loss, oxidative stress, and apoptosis. Thiamine has a preventative effect on PTZ-induced seizures in rats and PTZ-induced neurotoxicity in SH-SY5Y neuroblastoma cells. It could prevent oxidative stress and signaling of NO/cGMP. Thiamine supplement could be used as an additional therapeutic agent in epilepsy.

Regulation of Malate Dehydrogenases and Glutamate Dehydrogenase of Mammalian Brain by Thiamine in vitro and in vivo.

To study the mechanisms of the non-coenzyme action of thiamine and its diphosphate (ThDP) on brain proteins, proteins of acetone extract of bovine brain synaptosomes or the homogenate of rat brain cortex were subjected to affinity chromatography on thiamine-modified Sepharose. In the step-wise eluates by thiamine (at pH 7.4 or 5.6), NaCl, and urea, the occurrence of glutamate dehydrogenase (GDH) and isoenzymes of malate dehydrogenase (MDH) along with the influence of thiamine and/or ThDP on the enzymatic activities were characterized using mass spectrometry and kinetic experiments. Maximal activation of the malate dehydrogenase reaction by thiamine is observed after the protein elution with the acidic thiamine solution, which does not elute the MDH1 isoenzyme. Effects of exogenous thiamine or ThDP on the GDH activity may depend on endogenous enzyme regulators. For example, thiamine and/or ThDP activate the brain GDH in eluates from thiamine-Sepharose but inhibit the enzyme in the crude preparations applied to the sorbent. Inhibition of GDH by ThDP is observed using the ADP-activated enzyme. Compared to the affinity chromatography employing the elution by thiamine at pH 7.4, the procedure at pH 5.6 decreases the activation of GDH by thiamine (but not ThDP) in the eluates with NaCl and urea. Simultaneously, the MDH2 content and total GDH activity are higher after the affinity elution at pH 5.6 than at pH 7.4, suggesting the role of the known interaction of GDH with MDH2 in stabilizing the activity of GDH and in the regulation of GDH by thiamine. The biological potential of thiamine-dependent regulation of the brain GDH is confirmed in vivo by demonstration of changes in regulatory properties of GDH after administration of a high dose of thiamine to rats. Bioinformatics analysis of the thiamine-eluted brain proteins shows a specific enrichment of their annotation terms with "phosphoprotein", "acetylation", and "methylation". The relationship between thiamine and the posttranslational modifications in brain may contribute to the neuroprotective effects of high doses of thiamine, including the regulation of oxidation of the major excitatory neurotransmitter in brain - glutamate.

Mechanisms of Non-coenzyme Action of Thiamine: Protein Targets and Medical Significance.

Thiamine (vitamin B1) is a precursor of the well-known coenzyme of central metabolic pathways thiamine diphosphate (ThDP). Highly intense glucose oxidation in the brain requires ThDP-dependent enzymes, which determines the critical significance of thiamine for neuronal functions. However, thiamine can also act through the non-coenzyme mechanisms. The well-known facilitation of acetylcholinergic neurotransmission upon the thiamine and acetylcholine co-release into the synaptic cleft has been supported by the discovery of thiamine triphosphate (ThTP)-dependent phosphorylation of the acetylcholine receptor-associated protein rapsyn, and thiamine interaction with the TAS2R1 receptor, resulting in the activation of synaptic ion currents. The non-coenzyme regulatory binding of thiamine compounds has been demonstrated for the transcriptional regulator p53, poly(ADP-ribose) polymerase, prion protein PRNP, and a number of key metabolic enzymes that do not use ThDP as a coenzyme. The accumulated data indicate that the molecular mechanisms of the neurotropic action of thiamine are far broader than it has been originally believed, and closely linked to the metabolism of thiamine and its derivatives in animals. The significance of this topic has been illustrated by the recently established competition between thiamine and the antidiabetic drug metformin for common transporters, which can be the reason for the thiamine deficiency underlying metformin side effects. Here, we also discuss the medical implications of the research on thiamine, including the role of thiaminases in thiamine reutilization and biosynthesis of thiamine antagonists; molecular mechanisms of action of natural and synthetic thiamine antagonists, and biotransformation of pharmacological forms of thiamine. Given the wide medical application of thiamine and its synthetic forms, these aspects are of high importance for medicine and pharmacology, including the therapy of neurodegenerative diseases.

Long-term treatment with thiamine as possible medical therapy for Friedreich ataxia.

Thiamine (vitamin B1) is a cofactor of fundamental enzymes of cell energetic metabolism; its deficiency causes disorders affecting both the peripheral and central nervous system. Previous studies reported low thiamine levels in cerebrospinal fluid and pyruvate dehydrogenase dysfunction in Friedreich ataxia (FRDA). We investigated the effect of long-term treatment with thiamine in FRDA, evaluating changes in neurological symptoms, echocardiographic parameters, and plasma FXN mRNA levels. Thirty-four consecutive FRDA patients have been continuously treated with intramuscular thiamine 100mg twice a week and have been assessed with the Scale for the Assessment and Rating of Ataxia (SARA) at baseline, after 1month, and then every 3months during treatment. Thiamine administration ranged from 80 to 930days and was effective in improving total SARA scores from 26.6±7.7 to 21.5±6.2 (p<0.02). Moreover, deep tendon reflexes reappeared in 57% of patients with areflexia at baseline, and swallowing improved in 63% of dysphagic patients. Clinical improvement was stable in all patients, who did not show worsening even after 2years of treatment. In a subgroup of 13 patients who performed echocardiogram before and during treatment, interventricular septum thickness reduced significantly (p<0.02). Frataxin mRNA blood levels were modestly increased in one-half of treated patients. We suppose that a focal thiamine deficiency may contribute to a selective neuronal damage in the areas involved in FRDA. Further studies are mandatory to evaluate thiamine role on FXN regulation, to exclude placebo effect, to verify our clinical results, and to confirm restorative and neuroprotective action of thiamine in FRDA.

Characterization of thiamine uptake and utilization in Candida spp. subjected to oxidative stress.

Candida species are associated with an increasing number of life-threatening infections (candidiases), mainly due to the high resistance of these yeast-like fungi to antifungal drugs and oxidative stress. Recently, thiamine (vitamin B1) was found to alleviate stress responses in Saccharomyces cerevisiae; however, thiamine influence on defense systems in pathogenic fungi has never been investigated. The current work was aimed to elucidate the role of thiamine in stress reactions of C. albicans, C. glabrata, C. tropicalis and C. dubliniensis, subjected to hydrogen peroxide treatment. As compared to S. cerevisiae, Candida strains exposed to oxidative stress showed: (i) a much higher dependence on exogenous thiamine; (ii) an increased demand for thiamine diphosphate (TDP) and TDP-dependent enzyme, transketolase; (iii) no changes in gene expression of selected stress markers - superoxide dismutase and catalase - depending on thiamine availability in medium; (iv) a similar decrease of reactive oxygen species (ROS) generation in the presence of thiamine. Moreover, the addition of therapeutic doses of thiamine to yeast culture medium revealed differences in its accumulation between various Candida species. The current findings implicate that the protective action of thiamine observed in S. cerevisiae differs significantly form that in pathogenic Candida strains, both in terms of the cofactor functions of TDP and the effects on fungal defense systems.

Evidence for altered thiamine metabolism in diabetes: Is there a potential to oppose gluco- and lipotoxicity by rational supplementation?

Growing prevalence of diabetes (type 2 as well as type 1) and its related morbidity due to vascular complications creates a large burden on medical care worldwide. Understanding the molecular pathogenesis of chronic micro-, macro- and avascular complications mediated by hyperglycemia is of crucial importance since novel therapeutic targets can be identified and tested. Thiamine (vitamin B1) is an essential cofactor of several enzymes involved in carbohydrate metabolism and published data suggest that thiamine metabolism in diabetes is deficient. This review aims to point out the physiological role of thiamine in metabolism of glucose and amino acids, to present overview of thiamine metabolism and to describe the consequences of thiamine deficiency (either clinically manifest or latent). Furthermore, we want to explain why thiamine demands are increased in diabetes and to summarise data indicating thiamine mishandling in diabetics (by review of the studies mapping the prevalence and the degree of thiamine deficiency in diabetics). Finally, we would like to summarise the evidence for the beneficial effect of thiamine supplementation in progression of hyperglycemia-related pathology and, therefore, to justify its importance in determining the harmful impact of hyperglycemia in diabetes. Based on the data presented it could be concluded that although experimental studies mostly resulted in beneficial effects, clinical studies of appropriate size and duration focusing on the effect of thiamine supplementation/therapy on hard endpoints are missing at present. Moreover, it is not currently clear which mechanisms contribute to the deficient action of thiamine in diabetes most. Experimental studies on the molecular mechanisms of thiamine deficiency in diabetes are critically needed before clear answer to diabetes community could be given.

Synthesis of stable analogues of thiamine di- and triphosphate as tools for probing a new phosphorylation pathway.

Thiamine (vitamin B1) is an essential nutritional factor metabolized inside the body in its mono-, di-, and triphosphate forms. Although the action of thiamine and thiamine diphosphate have been intensely investigated, many questions remain unanswered and the role of thiamine triphosphate is still especially unknown. To probe recent hypotheses on the implication of thiamine triphosphate in a new phosphorylation pathway involving synaptic proteins, we synthesized a series of thiamine di- and triphosphate analogues that are resistant to both enzymatic and chemical hydrolyses. The key step in the preparation of the title compounds is the coupling of thiamine propyl disulfide with adequately protected methylenebis-phosphonic acid, the corresponding triphosphate analogue, and difluoromethylenebisphosphonic acid.

Pressure-tuning infrared spectra of the thiamine enzyme ‘active aldehyde’ intermediate 2-(α-hydroxycyclohexylmethyl)thiamine chloride (HCMT · HCl) and its complex with zinc(II), Zn(HCMT)Cl 3

IR spectra of the protonated form of 2-(α-hydroxycyclohexymethyl)thiamine chloride (HCMT · HCl) and the zwitterionic zinc(II) complex, Zn(HCMT)Cl 3, have been recorded at room temperature and various pressures up to ∼30 kbar. The majority of the peaks are blue shifted (towards higher wavenumbers) with increasing pressure; the v(OH) and v(NH) vibrations are red shifted. As for the closely related 2-(α-hydroxybenzyl)thiamine hydrochloride ligand and its metal complexes, the pyrimidine skeletal ring vibrations are quite pressure-sensitive (d v/d P>0.50 cm −1/kbar). In solution, the pyrimidine and thiazolium rings of the HCMT ligand adopt an S conformation with respect to one another and this conformation is apparently retained in the solid-state, even at very high pressures, suggesting that its stability may be important in the enzymatic action of thiamine in the presence of divalent metal ions.

Structural aspects of thiamine, its derivatives and their metal complexes in relation to the enzymatic action of thiamine enzymes

A review is given of the mechanism of the enzymatic action of thiamine (vitamin B 1) enzymes, based mainly on the metal complexes and the crystal structures of the ligand and its derivatives. It consists of three parts. Part 1 is a general introduction. Part 2 emphasizes the role of the pyrimidine and thiazole moities of thiamine and also of the pyrophosphate group and the bivalent metal ions in the enzymatic action, covered in four subsections referred to each of the above labels, the last of which describes the crystal structures of thiamine, its derivatives and their metal complexes. It attempts a correlation of the crystallographic data with the proposed mechanisms of the enzymatic action of thiamine. Part 3 is the conclusion, pointing to the stage of intervention of the metal ions and expanding the importance of the S conformation of the ligand during the enzymatic action of thiamine enzymes.

Solution versus solid state conformation of Group 12 metal complexes of active aldehyde derivatives of thiamine

Molar conductances in water and dimethylformamide and 13C NMR spectra in D2O and (CD3)2SO solutions and solid-state 13C cross polarization magic angle spinning NMR spectra have been measured for the chloride salts of 2-(α-hydroxybenzyl)thiamine (hbt), 2-(α-hydroxycyclohexylmethyl)thiamine (hcmt), their protonated forms [hbt]Cl·HCl and [hcmt]Cl·HCl and zwitterionic complexes of the type [M(hbt)Cl3] and [M(hcmt)Cl3](M = Zn, Cd or Hg). The data affords good evidence for bonding of the metals to the N(1′) atom of the pyrimidine moieties in the ligands, as well as of the S conformation of the ligands in solution. The small chemical shifts observed for the carbon atoms situated adjacent to the N(1′) site [C(2′), C(6′) and 2′-CH3] in the solid-state and solution 13C NMR spectra of the complexes are attributed to the synergic interaction of metal complexation which causes a downfield shift and the accumulation of negative charge at the same position due to [MCl3]– which leads to an opposing upfield shift. The 199Hg NMR spectra of [Hg(hbt)Cl3] and [Hg(hcmt)Cl3] in (CD3)2SO further substantiate these conclusions. Overall, the results strongly support earlier suggestions for the role of metal ions in the enzymatic action of thiamine.

Action of thiamine on auditory evoked potentials in the guinea pig

A technique is proposed for quantifying the effects of physiologically active substances at the periphery of the auditory analyzer. It was found that applying 1×10−11 to 1×10−3 M thiamine to the membrane of guinea pig cochlear round window (fenestra rotunda) produces a rise in the amplitude and a reduction in the latency of the N1 and N2 components of auditory nerve action potentials, waves I and II of brainstem auditory evoked potentials occurring in response to an acoustic stimulus. It is suggested that this effect is produced by facilitated synaptic transmission at synapses between hair cells and spiral ganglia neurons under the action of thiamine penetrating into the cochlea.

Action of thiamine on different synapses

Thiamine at a concentration of 1×10−14 to 1×10−4 M facilitated neuromuscular transmission at the glutaminergic synapse of the crayfish adapter, manifesting as increased amplitude and quantal content of excitatory postsynaptic potentials and raised frequency of miniature excitatory postsynaptic potentials. Thiamine augmented spontaneous electrical activity and the amplitude of synaptic potentials in the longitudinal muscle of guinea pig taenia coli. It was found from studying the effects of thiamine on the membrane potential of rat brain synaptosomes that its presynaptic action is brought about by depolarization of the nerve terminal membrane. Interaction between thiamine and the nerve endings was described by a Hill coefficient of 0.22–0.30, indicating that it has several binding sites within the structure of the receptor concerned.

Action of thiamine on neuromuscular transmission in the frog

The action of thiamine on neuromuscular transmission in the frog sartorius muscle was investigated. It was found that thiamine at a concentration of 1×10−14 to 1×10−4 M increases transmitter secretion at the nerve endings. This is demonstrated by the increased frequency, amplitude, and quantal content of miniature endplate potentials, and is due to the enhanced likelihood of transmitter release. The role of thiamine in regulating synaptic transmission and the mechanism of its interaction with thiamine-sensitive receptors are examined.

The action of thiamine and its di- and triphosphates on the slow exponential decline of the ionic currents in the node of Ranvier

Sodium and potassium currents in the node of Ranvier decrease exponentially with time during long lasting voltage clamp experiments. This decline is strongly dependent on temperature (Q 10 approximately 3). Thiamine and, particularly, its di- and triphosphoric acid esters are shown to prevent this exponential decline of the ionic currents. Thiamine acts from the outside and from the inside of the nodal membrane, but more potently from the inside. Thiamine diphosphate prevents the exponential decline of the ionic currents only when applied internally. Thiamine triphosphate, the most effective thiamine derivative was tested from the inside only. Bacterial thiaminases applied externally were not effective, presumably because they do not permeate the nodal membrane. Tetrodotoxin, that has been shown by other investigators to induce a release of thiamine from nerve membranes, does not alter the action of thiamine on the exponential decline of currents and vice versa. It is concluded that: (1) thiamine diphosphate or thiamine triphosphate are the active thiamine compounds in nerve membranes; (2) the site of action is located at the internal surface of the membrane; (3) the reduction of the thiamine concentration in the membrane or in the axoplasm could cause the exponential decline of currents; (4) the release of thiamine from nerve membranes induced by tetrodotoxin is interpreted as a side effect not even related to the mechanism by which tetrodotoxin blocks the sodium channels; (5) thiamine polyphosphates appear to stabilise the intrinsic electric field strength of the nodal membrane in the resting state. Therefore, as a working hypothesis, it is suggested that the thiamine derivatives control the number of functioning ionic channels by stabilising the density of negative surface charges at the inner side of the nerve membrane.

Action of Thiamine on Protein and Nucleic Acid Metabolism, III. Transketolase Activity ofLactobacillus viridescensduring Thiamine Starvation

Article Action of Thiamine on Protein and Nucleic Acid Metabolism, III. Transketolase Activity of Lactobacillus viridescens during Thiamine Starvation was published on January 1, 1973 in the journal Biological Chemistry (volume 354, issue 1).

Action of thiamine and related compounds on isolated clam heart.

1. The action of thiamine and related compounds on the isolated heart of clam (Meretrix meretrix lusoria) was investigated.2. S-benzoylthiamine (SBT) and thiamine propyl disulfide (TPD) among these related compounds displayed a very remarkable positive inotropic action, whereas thiamine, acetylthiamine, thiamine diphosphate, thiamine triphosphate, benzoylthiamine monophosphate and ATP did not practically display any clear action.3. SBT and TPD showed a remarkable antagonistic action against the negative inotropic action of acetylcholine, but have no effect on the action of 5-hydroxytryptamine.4. The positive inotropic action of SBT and TPD was retained in K-free medium, but it completely disappeared in Na-free or Cafree medium. When more or less Na+ or Ca2+ was present in the medium, the action of SBT and TPD appeared as in the normal medium.5. The positive inotropic action of SBT and TPD, therefore, is believed to be closely related to the transport system of the cellular membrane of the clam heart muscle, in which Na+ and Ca2+ are involved.