scholarly journals New thermodynamic activity-based approach allows predicting the feasibility of glycolysis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Thorsten Greinert ◽  
Kristina Vogel ◽  
Thomas Maskow ◽  
Christoph Held

AbstractThermodynamic feasibility analyses help evaluating the feasibility of metabolic pathways. This is an important information used to develop new biotechnological processes and to understand metabolic processes in cells. However, literature standard data are uncertain for most biochemical reactions yielding wrong statements concerning their feasibility. In this article we present activity-based equilibrium constants for all the ten glycolytic reactions, accompanied by the standard reaction data (standard Gibbs energy of reaction and standard enthalpy of reaction). We further developed a thermodynamic activity-based approach that allows to correctly determine the feasibility of glycolysis under different chosen conditions. The results show for the first time that the feasibility of glycolysis can be explained by thermodynamics only if (1) correct standard data are used and if (2) the conditions in the cell at non-equilibrium states are accounted for in the analyses. The results here will help to determine the feasibility of other metabolisms and to understand metabolic processes in cells in the future.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jee-Yun Park ◽  
Hee-Young Sohn ◽  
Young Ho Koh ◽  
Chulman Jo

AbstractCurcumin, a phytochemical extracted from Curcuma longa rhizomes, is known to be protective in neurons via activation of Nrf2, a master regulator of endogenous defense against oxidative stress in cells. However, the exact mechanism by which curcumin activates Nrf2 remains controversial. Here, we observed that curcumin induced the expression of genes downstream of Nrf2 such as HO-1, NQO1, and GST-mu1 in neuronal cells, and increased the level of Nrf2 protein. Notably, the level of p62 phosphorylation at S351 (S349 in human) was significantly increased in cells treated with curcumin. Additionally, curcumin-induced Nrf2 activation was abrogated in p62 knockout (−/−) MEFs, indicating that p62 phosphorylation at S351 played a crucial role in curcumin-induced Nrf2 activation. Among the kinases involved in p62 phosphorylation at S351, PKCδ was activated in curcumin-treated cells. The phosphorylation of p62 at S351 was enhanced by transfection of PKCδ expression plasmid; in contrast, it was inhibited in cells treated with PKCδ-specific siRNA. Together, these results suggest that PKCδ is mainly involved in curcumin-induced p62 phosphorylation and Nrf2 activation. Accordingly, we demonstrate for the first time that curcumin activates Nrf2 through PKCδ-mediated p62 phosphorylation at S351.


2019 ◽  
Vol 20 (12) ◽  
pp. 3062 ◽  
Author(s):  
William E. Antholine ◽  
Charles R. Myers

An electron paramagnetic resonance (EPR) method was used to determine the concentration of the antitumor agent Triapine in BEAS-2B cells when Triapine was bound to iron (Fe). Knowledge of the concentration of Fe-Triapine in tumor cells may be useful to adjust the administration of the drug or to adjust iron uptake in tumor cells. An EPR spectrum is obtained for Fe(3+)-Triapine, Fe(3+)(Tp)2+, in BEAS-2B cells after addition of Fe(3+)(Tp)2+. Detection of the low spin signal for Fe(3+)(Tp)2+ shows that the Fe(3+)(Tp)2+ complex is intact in these cells. It is proposed that Triapine acquires iron from transferrin in cells including tumor cells. Here, it is shown that iron from purified Fe-transferrin is transferred to Triapine after the addition of ascorbate. To our knowledge, this is the first time that the EPR method has been used to determine the concentration of an iron antitumor agent in cells.


Author(s):  
YUTAKA KAGAYA ◽  
HIROAKI ISAGO

Rapid reactions of tetra(tert-butyl)phthalocyanine, H 2( tbpc ), and its zinc complex, [ Zn ( tbpc )], with tellurium tetrachloride ( TeCl 4) in non-aqueous solutions have been investigated. Upon mixing respective solutions containing the reactants, drastic spectral changes occurred in chloroform and toluene even at room temperature. The electronic spectra of the products indicated that the reactions involved an acid-base equilibrium where the phthalocyanines and tellurium tetrachloride acted as a Lewis base and a Lewis acid respectively. By monitoring the spectral changes based on various initial molar ratios of the reactants, the compositions of the products for each system have been determined. [ Zn ( tbpc )] formed a 1:1 ( tbpc : TeCl 4) adduct in both chloroform and toluene, showing the same spectra close to those of the known monoprotonated phthalocyanines. On the other hand, H 2( tbpc ) formed a 1:1 adduct in chloroform but a 1:3 adduct in toluene even though both products showed essentially the same spectra close to those of the known diprotonated phthalocyanines. Equilibrium constants have been calculated for the four systems. Magnetic circular dichroism (MCD) spectra of conjugated acids of phthalocyanines have been studied for the first time.


2018 ◽  
Vol 73 (3) ◽  
pp. 259-263
Author(s):  
Alexander B. Salyulev ◽  
Alexei M. Potapov

AbstractThe electrical conductivities of molten KCl-ZrCl4 and CsCl-ZrCl4 mixtures, including their heterogeneous (melt+crystals) ranges, were measured for the first time. The concentration ranges were 65–72 and 66–75 mol.% of ZrCl4, and the temperature ranges were 482–711 and 548–735 K, respectively. The measurements were carried out in cells of an original design.


2021 ◽  
Author(s):  
Francois Iv ◽  
Carla Silva Martins ◽  
Gerard Castro-Linares ◽  
Cyntia Taveneau ◽  
Pascale Barbier ◽  
...  

Septin GTP-binding proteins contribute essential biological functions that range from the establishment of cell polarity to animal tissue morphogenesis. Human septins in cells form hetero-octameric septin complexes containing the ubiquitously expressed SEPT9. Despite the established role of SEPT9 in mammalian development and human pathophysiology, biochemical and biophysical studies have relied on monomeric SEPT9 thus not recapitulating its native assembly into hetero-octameric complexes. We established a protocol that enabled the first-time isolation of recombinant human septin octamers containing distinct SEPT9 isoforms. A combination of biochemical and biophysical assays confirmed the octameric nature of the isolated complexes in solution. Reconstitution studies showed that octamers with either a long or a short SEPT9 isoform form filament assemblies, and can directly bind and cross-link actin filaments, raising the possibility that septin-decorated actin structures in cells reflect direct actin-septin interactions. Recombinant SEPT9-containing octamers will make it possible to design cell-free assays to dissect the complex interactions of septins with cell membranes and the actin/microtubule cytoskeleton.


1979 ◽  
Vol 57 (9) ◽  
pp. 1080-1088 ◽  
Author(s):  
James Bouquant ◽  
Alain Maujean ◽  
Josselin Chuche

A method for the determination of the intrinsic parameters K and Δ for lanthanide–substrate complexes has been extended to conformationally mobile molecules. These parameters, determined for a series of secondary cyclohexane alcohols (cyclohexanol and 2-methylcyclohexanol) and for tertiary alcohols (1-methylcyclohexanol and 1-ethylcyclohexanol) complexed with Eu(DPM)3 and Yb(DPM)3 lead to the determination of the conformational equilibrium constants between) the free species on one part and the complexed species on the other.The results obtained for the free species are in good agreement with those obtained by other physicochemical methods. For the complexed species an appreciable shift of conformational equilibrium is noted for low values of the association constants.For the first time, the tert-butyl group of Yb(DPM)3 has been used as a conformational probe. [Journal translation]


Author(s):  
Gennadiy Vladimirovich Zhizhin

The process of formation of spirals (right and left) in the DNA molecule is described for the first time. Representations of the higher dimensionality of the constituent DNA molecules (D-ribose and phosphoric acid ion), developed in the previous works of the author, are used. Images of a DNA molecule with elements of higher dimension are presented. The higher dimensionality of the constituent DNA molecules, which allows to describe mathematically the structure of DNA, requires reconsidering the issues of tight packing of DNA molecules in cells, viruses and bacteria, provided that the DNA chains necessary for the preservation and transfer of genetic information are complementary.


By using carbon monoxide as a reagent for releasing oxygen from blood solutions (instead of the customary potassium ferricyanide) and by combining the techniques of the Van Slyke constant-volume gasometric apparatus and the Scholander gas analysis apparatus, a precise method has been devised of estimating oxygen content and carbon monoxide capacity simultaneously on one and the same sample of blood solution. The procedure eliminates various errors inherent in the determination of oxygen percentage saturation, when oxygen content and capacity are successively measured on separate samples. The method has been extensively tested on sheep blood solutions containing 3 to 4 g haemoglobin/100 ml. and is considered to give an accuracy of ± 0.5 in the oxygen percentage saturation of such solutions. In its present form the method is only applicable to solutions containing a negligible amount of dissolved nitrogen, but it is probable that this restriction could be removed by the simple addition to the technique suggested in the text. Modifications are also described in the usual tonometer technique for equilibrating blood solutions with various pressures of oxygen, and for transferring the equilibrated blood solution to the Van Slyke apparatus for analysis. The techniques of the present paper have been specially used for obtaining oxyhaemoglobin dissociation curve data of higher accuracy than hitherto available. From these improved data it has for the first time been possible to calculate directly, and in many cases with fair precision, the values o f the equilibrium constants of the four successive reactions of haemoglobin with oxygen.


2020 ◽  
Author(s):  
Juri Habicht ◽  
Ashley Mooneyham ◽  
Asumi Hoshino ◽  
Mihir Shetty ◽  
Xiaonan Zhang ◽  
...  

AbstractIn invertebrates, UNC-45 regulates myosin stability and functions. Vertebrates have two distinct isoforms of the protein: UNC-45B, expressed in muscle cells only and UNC-45A, expressed in all cells and implicated in regulating both Non-Muscle Myosin II (NMII)- and microtubule (MT)-associated functions. Here we show for the first time that: a) in vitro UNC-45A binds to the MT lattice and weakens its integrity leading to MT bending, breakage and depolymerization, b) in cells, UNC-45A overexpression causes loss of MT mass and increase in MT breakages, c) both in vitro and in cells, UNC-45A destabilizes MTs independent of its NMII C-terminal binding domain and destabilization occurs even in presence of the NMII inhibitor blebbistatin. These findings are consistent with a not mutually exclusive but rather dual role of UNC-45A in regulating NMII activity and MT stability.Because many human diseases, from cancer to neurodegenerative diseases, are caused by or associated with deregulation of MT stability our findings have profound implications in both, the biology of MTs as well as the biology of human diseases and possible therapeutic implications for their treatment.


2021 ◽  
Vol 64 (10) ◽  
pp. 768-777
Author(s):  
L. A. Makrovets ◽  
O. V. Samoilova ◽  
G. G. Mikhailov ◽  
I. V. Bakin

Phase diagram of the ternary oxide system FeO - SrO -Al2O3 was constructed for the first time. In this system, the following compounds can be formed: hercynite FeAl2O4 and five strontium aluminates - Sr4Al2O7 , Sr3Al2O6 , SrAl2O4 , SrAl4O7 , SrAl12O19 . According to the calculations performed, solid solutions of oxides are not formed in the system, as it is confirmed by the literature data. In the course of modeling, the optimal energy parameters of the theory of subregular ionic solutions were selected for the components of the oxide melt (FeO, SrO, Al2O3 ). Thermodynamic analysis of strontium deoxidizing ability in liquid iron at presence of aluminum was carried out using the technique for constructing the surface of solubility of strontium and aluminum in metal for steelmaking temperatures (1550 and 1600 °C) and carbon concentrations of 0.1 and 0.4 %. The equilibrium constants of the reactions of formation of strontium aluminates Sr3Al2O6 and SrAl2O4 from the components of the metal melt were calculated for the temperature range of 1550 - 1650 °C. It was found that the rest of strontium aluminates can be formed in liquid metal only at temperatures above 1750 °C. The base of thermodynamic data for the studied systems is given: temperature dependences of equilibrium constants for reactions occurring between components; values of interaction parameters of the first order (according to Wagner) for elements in liquid iron; values of energy parameters of the theory of subregular ionic solutions (for oxide melt). It follows from the calculations that the formation of strontium monoaluminate SrAl2O4 and corundum Al2O3 is most probable as the interaction products in Fe -Al - Sr - O and Fe -Al - Sr - C - O systems.


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