Browse
Submit Data
Databases
API
Help

Dataset Information

21 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Can enzyme proximity accelerate cascade reactions?

ABSTRACT: The last decade has seen an exponential expansion of interest in conjugating multiple enzymes of cascades in close proximity to each other, with the overarching goal being to accelerate the overall reaction rate. However, some evidence has emerged that there is no effect of proximity channeling on the reaction velocity of the popular GOx-HRP cascade, particularly in the presence of a competing enzyme (catalase). Herein, we rationalize these experimental results quantitatively. We show that, in general, proximity channeling can enhance reaction velocity in the presence of competing enzymes, but in steady state a significant enhancement can only be achieved for diffusion-limited reactions or at high concentrations of competing enzymes. We provide simple equations to estimate the effect of channeling quantitatively and demonstrate that proximity can have a more pronounced effect under crowding conditions in vivo, particularly that crowding can enhance the overall rates of channeled cascade reactions.

SUBMITTER: Kuzmak A

PROVIDER: S-EPMC6345930 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Does metabolite channeling accelerate enzyme-catalyzed cascade reactions?

Project description:Metabolite or substrate channeling is a direct transfer of metabolites from one enzyme to the next enzyme in a cascade. Among many potential advantages of substrate channeling, acceleration of the total reaction rate is considered as one of the most important and self-evident. However, using a simple model, supported by stochastic simulations, we show that it is not always the case; particularly at long times (i.e. in steady state) and high substrate concentrations, a channeled reaction cannot be faster, and can even be slower, than the original non-channeled cascade reaction. In addition we show that increasing the degree of channeling may lead to an increase of the metabolite pool size. We substantiate that the main advantage of channeling likely lies in protecting metabolites from degradation or competing side reactions.

| S-EPMC5325314 | biostudies-literature

Multimodal Enzyme-Carrying Suprastructures for Rapid and Sensitive Biocatalytic Cascade Reactions.

Project description:Colloidal assemblies of mesoporous suprastructures provide effective catalysis in an advantageous volume-confined environment. However, typical fabrication methods of colloidal suprastructures are carried out under toxic or harmful conditions for unstable biomolecules, such as, biocatalytic enzymes. For this reason, biocatalytic enzymes have rarely been used with suprastructures, even though biocatalytic cascade reactions in confined environments are more efficient than in open conditions. Here, multimodal enzyme- and photocatalyst-carrying superstructures with efficient cascade reactions for colorimetric glucose detection are demonstrated. The suprastructures consisting of various functional nanoparticles, including enzyme-carrying nanoparticles, are fabricated by surface-templated evaporation driven suprastructure synthesis on polydimethylsiloxane-grafted surfaces at ambient conditions. For the fabrication of suprastructures, no additional chemicals and reactions are required, which allows maintaining the enzyme activities. The multimodal enzymes (glucose oxidase and peroxidase)-carrying suprastructures exhibit rapid and highly sensitive glucose detection via two enzyme cascade reactions in confined geometry. Moreover, the combination of enzymatic and photocatalytic cascade reactions of glucose oxidase to titanium dioxide nanoparticles is successfully realized for the same assay. These results show promising abilities of multiple colloidal mixtures carrying suprastructures for effective enzymatic reactions and open a new door for advanced biological reactions and enzyme-related works.

| S-EPMC8981434 | biostudies-literature

PCR-like cascade reactions in the context of an allosteric enzyme mimic.

Project description:A supramolecular allosteric catalyst that exhibits a PCR-like cascade reaction is reported. The complex is triggered by a reaction with an acetate ion, which turns on a catalytic cascade that exponentially increases acetate ion concentration through an acyl transfer reaction.

| S-EPMC8191497 | biostudies-literature

Encapsulated Hydrogels by E-beam Lithography and Their Use in Enzyme Cascade Reactions.

Project description:Electron beam (e-beam) lithography was employed to prepare one protein immobilized hydrogel encapsulated inside another by first fabricating protein-reactive hydrogels of orthogonal reactivity and subsequently conjugating the biomolecules. Exposure of thin films of eight arm star poly(ethylene glycol) (PEG) functionalized with biotin (Biotin-PEG), alkyne (Alkyne-PEG) or aminooxy (AO-PEG) end-groups to e-beam radiation resulted in cross-linked hydrogels with the respective functionality. It was determined via confocal microscopy that a nominal size exclusion effect exists for streptavidin immobilized on Biotin-PEG hydrogels of feature sizes ranging from 5 to 40 μm. AO-PEG was subsequently patterned as an encapsulated core inside a contiguous outer shell of Biotin-PEG. Similarly, Alkyne-PEG was patterned as a core inside an AO-PEG shell. The hydrogel reactive end-groups were conjugated to dyes or proteins of complementary reactivity, and the three-dimensional (3-D) spatial orientation was determined for both configurations using confocal microscopy. The enzyme glucose oxidase (GOX) was immobilized in the core of the encapsulated Alkyne-PEG core/ AO-PEG shell architecture, and horseradish peroxidase (HRP) was conjugated to the shell periphery. Bioactivity for the HRP-GOX enzyme pair was observed in this encapsulated configuration by demonstrating that the enzyme pair was capable of enzyme cascade reactions.

| S-EPMC4852853 | biostudies-literature

Synergistic Degradation of a Hyperuricemia-Causing Metabolite Using One-Pot Enzyme-Nanozyme Cascade Reactions.

Project description:Multi-enzyme cascade reactions are frequently found in living organisms, in particular when an intermediate should be eliminated. Recently, enzyme-mimic nanomaterials (nanozymes) received much attention for various applications, because they are usually more stable and cost-effective than enzymes. However, enzyme-nanozyme cascade reations have not been yet extensively exploited. Therefore, in this study, we investigated one-pot enzyme-nanozyme cascade reactions using urate oxidase (UOX) and catalase-mimic gold nanoparticle nanozyme (AuNP) with the ultimate goal of treatment of hyperuricemia. UOX degrades hyperuricemia-causing uric acid, but also generates hydrogen peroxide raising several health concerns. We successfully demonstrated that one-pot UOX-AuNP cascade systems degrade uric acid more than five times faster than UOX alone, by eliminating potentially cytotoxic hydrogen peroxide, similar to enzyme-enzyme reactions.

| S-EPMC5347090 | biostudies-literature

Hyperbaric Oxygen Activates Enzyme-Driven Cascade Reactions for Cooperative Cancer Therapy and Cancer Stem Cells Elimination.

Project description:Tumor starvation induced by intratumor glucose depletion emerges as a promising strategy for anticancer therapy. However, its antitumor potencies are severely compromised by intrinsic tumor hypoxia, low delivery efficiencies, and undesired off-target toxicity. Herein, a multifunctional cascade bioreactor (HCG), based on the self-assembly of pH-responsive hydroxyethyl starch prodrugs, copper ions, and glucose oxidase (GOD), is engineered, empowered by hyperbaric oxygen (HBO) for efficient cooperative therapy against aggressive breast cancers. Once internalized by tumor cells, HCG undergoes disassembly and releases cargoes in response to acidic tumor microenvironment. Subsequently, HBO activates GOD-catalyzed oxidation of glucose to H2 O2 and gluconic acid by ameliorating tumor hypoxia, fueling copper-catalyzed •OH generation and pH-responsive drug release. Meanwhile, HBO degrades dense tumor extracellular matrix, promoting tumor accumulation and penetration of HCG. Moreover, along with the consumption of glucose and the redox reaction of copper ions, the antioxidant capacity of tumor cells is markedly reduced, collectively boosting oxidative stress. As a result, the combination of HCG and HBO can not only remarkably suppress the growth of orthotopic breast tumors but also restrain pulmonary metastases by inhibiting cancer stem cells. Considering the clinical accessibility of HBO, this combined strategy holds significant translational potentials for GOD-based therapies.

| S-EPMC10375084 | biostudies-literature

Oxa-Michael-initiated cascade reactions of levoglucosenone.

Project description:The reactions of aromatic aldehydes and levoglucosenone promoted by methoxide gives bridged α,β-unsaturated ketones, formed by a series of oxa-Michael-initiated cascade reactions in yields of up to 91% (14 examples). A complex series of equilibria operate during the reaction, and the formation of the bridged species is thermodynamically favored, except in the case of 5-methylfurfural and pyrrole-2-carboxaldehyde. This is the first report detailing this type of aldol/Michael cascade involving oxa-Michael initiation.

| S-EPMC9577383 | biostudies-literature

A kinetic description of how interfaces accelerate reactions in micro-compartments.

Project description:A kinetic expression is derived to explain how interfaces alter bulk chemical equilibria and accelerate reactions in micro-compartments. This description, aided by the development of a stochastic model, quantitatively predicts previous experimental observations of accelerated imine synthesis in micron-sized emulsions. The expression accounts for how reactant concentration and compartment size together lead to accelerated reaction rates under micro-confinement. These rates do not depend solely on concentration, but rather the fraction of total molecules in the compartment that are at the interface. Although there are ∼107 to 1013 solute molecules in a typical micro-compartment, a kind of "stochasticity" appears when compartment size and reagent concentration yield nearly equal numbers of bulk and interfacial molecules. Although this is distinct from the stochasticity produced by nano-confinement, these results show how interfaces can govern chemical transformations in larger atmospheric, geologic and biological compartments.

| S-EPMC8163377 | biostudies-literature

Photo-Organocatalytic Enantioselective Radical Cascade Reactions of Unactivated Olefins.

Project description:Radical cascade processes are invaluable for their ability to rapidly construct complex chiral molecules from simple substrates. However, implementing catalytic asymmetric variants is difficult. Reported herein is a visible-light-mediated organocatalytic strategy that exploits the excited-state reactivity of chiral iminium ions to trigger radical cascade reactions with high enantioselectivity. By combining two sequential radical-based bond-forming events, the method converts unactivated olefins and α,β-unsaturated aldehydes into chiral adducts in a single step. The implementation of an asymmetric three-component radical cascade further demonstrates the complexity-generating power of this photochemical strategy.

| S-EPMC6175195 | biostudies-literature

Enzyme-mediated proximity labeling identifies small RNAs in the endoplasmic reticulum lumen

Project description:In eukaryotic cells, the subcellular targeting of RNA controls many fundamental aspects of cellular physiology. RNA molecules are broadly distributed throughout the nucleoplasm and cytoplasm, but are conventionally believed to be excluded from the secretory pathway compartments, including the endoplasmic reticulum (ER). Recent discovery of RNA N-glycan modification (glycoRNAs) has challenged this view, but direct evidence of RNA localization in the ER lumen has been lacking. In this study, we applied enzyme-mediated proximity labeling to profile the ER lumen-localized RNAs in human embryonic kidney 293T cells and rat cortical neurons. Our dataset revealed the presence of small non-coding RNAs in the ER lumen, including U RNAs, sco/sca RNAs and Y RNAs, which partially overlap with glycoRNAs. These findings shed light on novel RNA targeting mechanism and raise interesting questions regarding the biological functions of ER lumenal RNAs.

2024-03-10 | GSE227266 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data