Adenosine Triphosphate Molecules Research Articles

Thioflavin-T-Incorporated Cerium-ATP Coordination Polymer Nanoparticles: A Promising System for Detection of Uranyl Ion (UO22+) in Aqueous Medium.

Lanthanide-based coordination polymer nanoparticles (Ln-CPNs) are studied for analytical and biomedical sensing, mainly utilizing the luminescent properties of lanthanides. However, the inclusion of fluorescent guest molecules within the nanoparticles can lead to a stimuli-responsive system with modulated photo-physical properties that can be useful for detecting analytes. In this work, we have synthesized cerium(III) coordination polymer nanoparticles using adenosine triphosphate (ATP) molecules as the ligands. The porous polymeric structure enables CPNs for reversible inclusion and release of thioflavin-T (ThT), which is a weakly emissive dye in the free state but becomes highly emissive when incorporated into the Ce-ATP CPNs. Modulation of the photo-physical properties of ThT-incorporated CPNs in response to the radiotoxic and environmentally alarming uranyl ion (UO22+) has been used for its detection in aqueous medium in the range of 0-20 μM by fluorimetry with an LOD of 80 ng mL-1 (0.34 μM) in deionized water without interference from the most commonly occurring metal ions. Furthermore, the sensing platform has been successfully utilized for UO22+ determination in seawater sample without any pre-treatment and adjustment of pH.

Ketone Bodies and Brain Metabolism: New Insights and Perspectives for Neurological Diseases.

Ketone Bodies and Brain Metabolism: New Insights and Perspectives for Neurological Diseases.

Evaluation of the Effectiveness of Overheated Dry-Saturated Steam Disinfection in the Control of the Dental Chair Contamination by Bioluminescence Analysis: A Pilot In Vitro Study

This study aimed to evaluate, through Adenosine triphosphate (ATP) bioluminescence analysis, the effectiveness of an overheated dry-saturated steam device (Polti Sani System) in decreasing the superficial microbial contamination on dental chairs’ surfaces after 30 s steam disinfection (T1) in comparison to baseline (T0), i.e., at the end of an aerosol-generating procedure (AGDP), and to investigate any differences in the tested surfaces’ contamination at T0 in relation to the surface’s type. Three dental chair surfaces (scialytic lamp, control button panel, spit bowl), sized 10 × 10 cm each, were swabbed and analyzed before and after steam application. The procedure was repeated 20 times for a total of 60 before–after evaluations. Non-parametric tests were used to analyze Relative Light Unit (RLU) values and categorical data on the ATP molecules’ amount detected on the tested surfaces. Statistically significant differences were found for both RLU and categorical data for all surfaces, and each type of surface evaluated at T0 and T1 (p < 0.05). Differences in RLU among the tested surfaces at T0 were not significant. By reducing the microbial contamination on the evaluated surfaces, the overheated dry-saturated steam system was an effective measure for the disinfection of the dental chair’s surfaces after AGDPs, potentially reducing the risk of cross-infections.

Water-Soluble Conjugated Polyelectrolytes for Adenosine Triphosphate (ATP) Detection

Facile detection of adenosine triphosphate (ATP) at different concentration levels is important for applications such as assessing physiological status and monitoring bacterial and microbial contamination of food. A series of cationic conjugated polymers, PFPE-TEGx-NMe3+, with poly[fluorenyl-alt-p-phenyleneethynylene] (PFPE) as the backbone and different ratios of side chains consisting of a hexyl quaternary ammonium group and triethylene glycol, were synthesized for ATP sensing. Careful calculations based on the integrals of several specific proton peaks in the NMR spectra suggest that the ratios of different side chains of obtained polymers were consistent with the feeding ratios and the quaternization was close to 100%. Sensing application found that the fluorescence of polymers in aqueous solution was quenched upon adding ATP. The limit of detection (LOD) decreased with the increase in cation density on the polymer, which could be as low as 0.25 μM, and the higher the density of the quaternary ammonium group, the higher the sensitivity of polymer to ATP. The sensing system was selective to ATP over other possible interferents. Dynamic light scattering and zeta potential measurements show that ATP molecules were bound to polymer chains mainly through electrostatic interaction, while other interactions also existed, resulting in the formation of aggregates and the consequent fluorescence quenching. Relating the sensing performance to the chemical structures of analytes and fluorescent polymers revealed that the four negative charges combined with the organic part with a π-structure and some other interaction sites, which makes ATP unique compared with those possible interferents. At relatively low densities, the density of cationic groups had a significant effect on LOD and sensitivity, but at high densities, its effect became smaller; this observation is consistent with a sensing mechanism based on multiple interaction synergies dominated by electrostatic interactions. This study provides a general strategy for the design of sensing systems for biomolecules with relatively complex structures.

Renal and Cardiovascular Metabolic Impact Caused by Ketogenesis of the SGLT2 Inhibitors.

Sodium-glucose cotransporter type 2 inhibitors (SGLT2i) are glycosuric drugs that were originally developed for the treatment of type 2 diabetes mellitus (T2DM). There is a hypothesis that SGLT2i are drugs that are capable of increasing ketone bodies and free fatty acids. The idea is that they could serve as the necessary fuel, instead of glucose, for the purposes of cardiac muscle requirements and could explain antihypertensive effects, which are independent of renal function. The adult heart, under normal conditions, consumes around 60% to 90% of the cardiac energy that is derived from the oxidation of free fatty acids. In addition, a small proportion also comes from other available substrates. In order to meet energy demands with respect to achieving adequate cardiac function, the heart is known to possess metabolic flexibility. This allows it to switch between different available substrates in order to obtain the energy molecule adenosine triphosphate (ATP), thereby rendering it highly adaptive. It must be noted that oxidative phosphorylation in aerobic organisms is the main source of ATP, which is a result of reduced cofactors. These cofactors include nicotine adenine dinucleotide (NADH) and flavin adenine dinucleotide (FADH2), which are the result of electron transfer and are used as the enzymatic cofactors that are involved in the respiratory chain. When there is an excessive increase in energy nutrients-such as glucose and fatty acids-which occur in the absence of a parallel increase in demand, a state of nutrient surplus (which is better known as an excess in supply) is created. The use of SGLT2i at the renal level has also been shown to generate beneficial metabolic alterations, which are obtained by reducing the glucotoxicity that is induced by glycosuria. Together with the reduction in perivisceral fat in various organs, such alterations also lead to the use of free fatty acids in the initial stages of the affected heart. Subsequently, this results in an increase in production with respect to ketoacids, which are a more available energy fuel at the cellular level. In addition, even though their mechanism is not fully understood, their vast benefits render them of incredible importance for the purposes of further research.

Association of adenosine triphosphate with lipid headgroups measured by NMR spectroscopy.

Adenosine triphosphate (ATP) is the energy currency of biological processes because of its central role in energy conversion in biological cells. Given the complexity and the molecular disorder of the cellular environment, the mechanism of energy conversion into useful work still poses challenging questions in molecular biophysics. Using nuclear magnetic resonance spectroscopy and dynamic light scattering, we show that ATP molecules have a measurable affinity to phosphatidylcholine lipid headgroups. The adenosine and ribose groups of the ATP molecule insert into the headgroup region of the membrane as seen by 2D NOESY spectra. Based on 31P NMR measurements, the most likely orientation for the phosphate chain is away from the membrane surface into the water space and the interaction of ATP with lipid headgroups leads to electrostatic charging of membrane surfaces. The interaction of adenosine triphosphate with lipid membranes has relevance to biophysical and biochemical studies of energy conversion in biological cells. In particular, the affinity of ATP to lipid headgroups can affect the interaction with specialized receptors present in biological cells. The observed association of ATP with membrane surfaces primarily through the adenosine group allows phosphate chains to participate in hydrolysis reactions consistent with biochemical data.

Effect of the Neck Linker on Processive Stepping of Kinesin Motor

Kinesin motor protein, which is composed of two catalytic domains connected together by a long coiled-coil stalk via two flexible neck linkers (NLs), can step processively on a microtubule towards the plus end by hydrolyzing adenosine triphosphate (ATP) molecules. To understand what the role is that the NL plays in the processive stepping, the dynamics of the kinesin motor are studied theoretically here by considering the mutation or deletion of an N-terminal cover strand that contributes to the docking of the NL in kinesin-1, the extension of the NL in kinesin-1, the mutation of the NL in kinesin-1, the swapping of the NL of kinesin-2 with that of kinesin-1, the joining of the stalk and neck of Ncd that moves towards the minus end of MT to the catalytic domain of kinesin-1, the replacement of catalytic domain of kinesin-1 with that of Ncd, and so on. The theoretical results give a consistent and quantitative explanation of various available experimental results about the effects of these mutations on motor dynamics and, moreover, provide predicted results. Additionally, the processive motility of kinesin-6 MKLP2 without NL docking is also explained. The available experimental data about the effect of NL mutations on the dynamics of the bi-directional kinesin-5 Cin8 are also explained. The studies are critically implicative to the mechanism of the stepping of the kinesin motor.

Bi-enzyme competition based on ZIF-67 co-immobilization for real-time monitoring ofexocellular ATP.

Monitoring exocellular adenosine-5'-triphosphate (ATP) is a demanding task but the biosensor development is limited by the low concentration and rapid degradation of ATP. Herein, we developed a simple yet effective biosensor based on ZIF-67 loaded with bi-enzymes of glucose (GOx) and hexokinase (HEX) for effective detectionof ATP. In the confined space of the porous matrix, the bi-enzymes competed for the glucose substrate in the presence of ATP, facilitating the biosensor to detect low ATP concentrations down to the micromole level (3.75μM) at working potential of 0.55V (vs. Ag/AgCl). Furthermore, ZIF-67 with cobalt served as a porous matrix to specifically adsorb ATP molecules, allowing it to differentiate isomers with sensitivity of 0.53 nA/μM, RSD of 5.4%, and recovery rate of 93.3%. We successfully applied the fabricated biosensor to measure ATP secreted from rat PC12 cells in the pericellular space thus realizingtime-resolving measurement. This work paved the path for real-time monitoring of ATP released by cells, which will aid in understanding tumor cell glycolysis and immune responses.

Conversion of Mevalonate to Isoprenol Using Light Energy in Escherichia coli without Consuming Sugars for ATP Supply.

Bioconversion of key intermediate metabolites such as mevalonate into various useful chemicals is a promising strategy for microbial production. However, the conversion of mevalonate into isoprenoids requires a supply of adenosine triphosphate (ATP). Light-driven ATP regeneration using microbial rhodopsin is an attractive module for improving the intracellular ATP supply. In the present study, we demonstrated the ATP-consuming conversion of mevalonate to isoprenol using rhodopsin-expressing Escherichia coli cells as a whole-cell catalyst in a medium that does not contain energy cosubstrate, such as glucose. Heterologous genes for the synthesis of isoprenol from mevalonate, which requires three ATP molecules for the series of reactions, and a delta-rhodopsin gene derived from Haloterrigena turkmenica were cointroduced into E. coli. To evaluate the conversion efficiency of mevalonate to isoprenol, the cells were suspended in a synthetic medium containing mevalonate as the sole carbon source and incubated under dark or light illumination (100 μmol m-2 s-1). The specific isoprenol production rates were 10.0 ± 0.9 and 20.4 ± 0.7 μmol gDCW-1 h-1 for dark and light conditions, respectively. The conversion was successfully enhanced under the light condition. Furthermore, the conversion efficiency increased with increasing illumination intensity, suggesting that ATP regenerated by the proton motive force generated by rhodopsin using light energy can drive ATP-consuming reactions in the whole-cell catalyst.

Impact of the Cellular Environment on Adenosine Triphosphate Conformations.

The cytoplasm is an environment crowded by macromolecules and filled with metabolites and ions. Recent experimental and computational studies have addressed how this environment affects protein stability, folding kinetics, and protein-protein and protein-nucleic acid interactions, though its impact on metabolites remains largely unknown. Here we show how a simulated cytoplasm affects the conformation of adenosine triphosphate (ATP), a key energy source and regulatory metabolite present at high concentrations in cells. Analysis of our all-atom model of a small volume of the Escherichia coli cytoplasm when contrasted with ATP modeled in vitro or resolved with protein structures deposited in the Protein Data Bank reveals that ATP molecules bound to proteins in cell form specific pitched conformations that are not observed at significant concentrations in the other environments. We hypothesize that these interactions evolved to fulfill functional roles when ATP interacts with protein surfaces.

Mathematical modeling of intracellular calcium in presence of receptor: a homeostatic model for endothelial cell.

Calcium is a ubiquitous molecule and second messenger that regulates many cellular functions ranging from exocytosis to cell proliferation at different time scales. In the vasculature, a constant adenosine triphosphate (ATP) concentration is maintained because of ATP released by red blood cells(RBCs). These ATP molecules continuously react with purinergic receptors on the surface of endothelial cells (ECs). Consequently, a cascade of chemical reactions are triggered that result in a transient cytoplasmic calcium (Ca[Formula: see text]), followed by return to its basal concentration. The mathematical models proposed in the literature are able to reproduce the transient peak. However, the trailing concentration is always higher than the basal cytoplasmic Ca[Formula: see text] concentrations, and the Ca[Formula: see text] concentration in endoplasmic reticulum (ER) remains lower than its initial concentration. This means that the intracellular homeostasis is not recovered. We propose, herein, a minimal model of calcium kinetics. We find that the desensitization of EC surface receptors due to phosphorylation and recycling plays a vital role in maintaining calcium homeostasis in the presence of a constant stimulus (ATP). The model is able to capture several experimental observations such as refilling of Ca[Formula: see text] in the ER, variation of cytoplasmic Ca[Formula: see text] transient peak in ECs, the resting cytoplasmic Ca[Formula: see text] concentration, the effect of removing ATP from the plasma on Ca[Formula: see text] homeostasis, and the saturation of cytoplasmic Ca[Formula: see text] transient peak with increase in ATP concentration. Direct confrontation with several experimental results is conducted. This work paves the way for systematic studies on coupling between blood flow and chemical signaling, and should contribute to a better understanding of the relation between (patho)physiological conditions and Ca[Formula: see text] kinetics.

Mapping the per-residue surface electrostatic potential of CAPRIN1 along its phase-separation trajectory

Electrostatic interactions and charge balance are important for the formation of biomolecular condensates involving proteins and nucleic acids. However, a detailed, atomistic picture of the charge distribution around proteins during the phase-separation process is lacking. Here, we use solution NMR spectroscopy to measure residue-specific near-surface electrostatic potentials (ϕENS) of the positively charged carboxyl-terminal intrinsically disordered 103 residues of CAPRIN1, an RNA-binding protein localized to membraneless organelles playing an important role in messenger RNA (mRNA) storage and translation. Measured ϕENS values have been mapped along the adenosine triphosphate (ATP)-induced phase-separation trajectory. In the absence of ATP, ϕENS values for the mixed state of CAPRIN1 are positive and large and progressively decrease as ATP is added. This is coupled to increasing interchain interactions, particularly between aromatic-rich and arginine-rich regions of the protein. Upon phase separation, CAPRIN1 molecules in the condensed phase are neutral (ϕENS [Formula: see text] 0 mV), with ∼five molecules of ATP associated with each CAPRIN1 chain. Increasing the ATP concentration further inverts the CAPRIN1 electrostatic potential, so that molecules become negatively charged, especially in aromatic-rich regions, leading to re-entrance into a mixed phase. Our results collectively show that a subtle balance between electrostatic repulsion and interchain attractive interactions regulates CAPRIN1 phase separation and provides insight into how nucleotides, such as ATP, can induce formation of and subsequently dissolve protein condensates.

ATP-Responsive Strand Displacement Coupling with DNA Origami/AuNPs Strategy for the Determination of Microcystin-LR Using Surface-Enhanced Raman Spectroscopy.

The DNA origami-mediated self-assembly strategy has emerged as a powerful tool in surface-enhanced Raman spectroscopy (SERS). However, these self-assembly approaches typically do not possess high detection specificity. Herein, a novel strategy based on adenosine triphosphate (ATP)-responsive strand displacement (ARSD) coupling with DNA origami/AuNPs for SERS analysis of microcystin-LR (MC-LR) is presented. In the presence of MC-LR and ATP molecules, nucleic acid sensing structures fabricated with anti-MC-LR aptamer (T1) and ATP aptamer (T2) were triggered to release the remaining ATP. In addition, DNA origami-assisted assembly results in the formation of homogeneous plasmonic nanostructures for Raman enhancement via strong plasmonic coupling. After the binding in the gaps of functionalized DNA origami/AuNPs, the Raman shift of the ATP molecules becomes detectable, leading to increased SERS intensity in 734 cm-1. A linear response to MC-LR was obtained in the concentration range of 1.56-50 μg·L-1, and the limit of detection (LOD) was 0.29 μg·L-1. Combined with the solid-phase extraction sample pretreatment for extraction and 10-fold concentration, this proposed method was successfully used to detect MC-LR type in real lake-water samples with good recoveries of 98.4-116% and relative standard deviations of 1.9-6.7%. Furthermore, for the detection of MC-LR in contaminated lake-water samples, the results of the developed method and ultrahigh-performance liquid chromatography-tandem mass spectrometry were found to be in agreement with relative errors between -12 and 2.4%. The proposed strategy provides a sensitive recognition and signal amplification platform for trace MC-LR analysis as well as innovative nucleic acid sensing structures for toxin analysis more generally.

In-situ synthesis of phosphorus-doped graphene paper with adenosine triphosphate and its application for intelligent fire warning

Design of intelligent sensors for detecting early fire warning before combustion is a challenging for the fire safety. Herein, a nacre-biomimetic paper based on graphene oxide (GO) and adenosine triphosphate (ATP) was fabricated via a low-temperature evaporation assembly approach. Then the fire-alarm sensor was designed according to the high temperature thermal reduction properties of GO. The GO-ATP paper exhibited a well-organized ‘‘brick and mortar” structure due to the presence of hydrogen bonds and electrostatic attraction interaction between GO and ATP molecules. The paper containing 50 wt% of ATP presented a rapid flame detection response (1.36 s) and a long continuous alarm time (1300 s) due to in-situ phosphorus doping and the honeycomb-like char forming during fire exposure. Moreover, the GO-ATP-50 also exhibited flexibility, flame retardant performance, heat insulation ability and char-forming properties. This work provides a bright application prospect for fire safety and prevention of combustible materials.

Enhanced Sensing Performance of a Microchannel-Based Electrochemiluminescence Biosensor for Adenosine Triphosphate via a dsDNA Superstructure Amplification Strategy.

The sensing performance of a microchannel-based electrochemiluminescence (ECL) biosensor is related to the change ratio of charge density on the surface of microchannels caused by a target recognition reaction. In this study, adenosine triphosphate (ATP) served as a model target. The dsDNA superstructures containing a capture probe (CP, containing an ATP aptamer sequence) and alternating units of ssDNA probes of P1 and P2, CP/(P1/P2)n, were grafted onto the inner wall of microchannels first. The CP in dsDNA superstructures captured ATP molecules, causing the release of dsDNA fragments containing alternating units of P1 and P2, (P1/P2)n. The target recognition reaction significantly changed the charge density of microchannels, which altered the ECL intensity of the (1,10-phenanthroline)ruthenium(II)/tripropylamine system in the reporting interface. The ECL intensity of the constructed system had a linear relationship with the logarithm of ATP concentration ranging from 1 fM to 100 pM with a detection limit of 0.32 fM (S/N = 3). The biosensor was successfully applied to detect ATP in rat brains.

Free Energy Landscape of the Adenylation Reaction of the Aminoacylation Process at the Active Site of Aspartyl tRNA Synthetase.

The process of protein biosynthesis is initiated by the aminoacylation process where a transfer ribonucleic acid (tRNA) is charged by the attachment of its cognate amino acid at the active site of the corresponding aminoacyl tRNA synthetase enzyme. The first step of the aminoacylation process, known as the adenylation reaction, involves activation of the cognate amino acid where it reacts with a molecule of adenosine triphosphate (ATP) at the active site of the enzyme to form the aminoacyl adenylate and inorganic pyrophosphate. In the current work, we have investigated the adenylation reaction between aspartic acid and ATP at the active site of the fully solvated aspartyl tRNA synthetase (AspRS) from Escherichia coli in aqueous medium at room temperature through hybrid quantum mechanical/molecular mechanical (QM/MM) simulations combined with enhanced sampling methods of well-tempered and well-sliced metadynamics. The objective of the present work is to study the associated free energy landscape and reaction barrier and also to explore the effects of active site mutation on the free energy surface of the reaction. The current calculations include finite temperature effects on free energy profiles. In particular, apart from contributions of interaction energies, the current calculations also include contributions of conformational, vibrational, and translational entropy of active site residues, substrates, and also the rest of the solvated protein and surrounding water into the free energy calculations. The present QM/MM metadynamics simulations predict a free energy barrier of 23.35 and 23.5 kcal/mol for two different metadynamics methods used to perform the reaction at the active site of the wild type enzyme. The free energy barrier increases to 30.6 kcal/mol when Arg217, which is an important conserved residue of the wild type enzyme at its active site, is mutated by alanine. These free energy results including the effect of mutation compare reasonably well with those of kinetic experiments that are available in the literature. The current work also provides molecular details of structural changes of the reactants and surroundings as the system dynamically evolves along the reaction pathway from reactant to the product state through QM/MM metadynamics simulations.

Autonomous Chemistry Enabling Environment-Adaptive Electrochemical Energy Storage Devices

Autonomous Chemistry Enabling Environment-Adaptive Electrochemical Energy Storage Devices

Biocompatible Chemically Fueled Transient Polymer Nanoparticles for Temporally Programmable in Vivo Imaging

Biocompatible Chemically Fueled Transient Polymer Nanoparticles for Temporally Programmable in Vivo Imaging

The energy cost of repairing photoinactivated photosystem II: an experimental determination in cotton leaf discs.

Summary Photosystem II (PSII), which splits water molecules at minimal excess photochemical potential, is inevitably photoinactivated during photosynthesis, resulting in compromised photosynthetic efficiency unless it is repaired. The energy cost of PSII repair is currently uncertain, despite attempts to calculate it.We experimentally determined the energy cost of repairing each photoinactivated PSII in cotton (Gossypium hirsutum) leaves, which are capable of repairing PSII in darkness.As an upper limit, 24 000 adenosine triphosphate (ATP) molecules (including any guanosine triphosphate synthesized at the expense of ATP) were required to repair one entire PSII complex. Further, over a 7‐h illumination period at 526–1953 μmol photons m−2 s−1, the ATP requirement for PSII repair was on average up to 4.6% of the ATP required for the gross carbon assimilation.Each of these two measures of ATP requirement for PSII repair is two‐ to three‐fold greater than the respective reported calculated value. Possible additional energy sinks in the PSII repair cycle are discussed.

The role of ATP in solubilizing RNA-binding protein fused in sarcoma.

Intrinsically disordered protein (IDP) plays an important role in liquid-liquid phase separation (LLPS). RNA-binding protein fused in sarcoma (FUS) is a well-studied IDP that induces LLPS since its low-complexity core region (FUS-LC-core) is essential for droplet formation through contacts between FUS-LC-cores. Several experimental studies have reported that adenosine triphosphate (ATP) concentrations modulate LLPS-driven droplet formation through the dissolution of FUS. To elucidate the role of ATP in this dissolution, microsecond-order all-atom molecular dynamics (MD) simulations were performed for a crowded system of FUS-LC-cores in the presence of multiple ATP molecules. Our analysis revealed that the adenine group of ATP frequently contacted the FUS-LC-core, and the phosphoric acid group of ATP was exposed to the external solvent, which promoted both hydration and solubilization of FUS.