Simple Enzyme Substrate Interactions
John C. Matthews in Fundamentals of Receptor, Enzyme, and Transport Kinetics, 2017
If we plot the reaction rate vs. [R] (or [S] for substrate concentration for an enzyme-catalyzed reaction we get the relationship shown in Figure 76. Here we see that -d[S]/dt and [S] are not linearly related. The difference between an enzyme-catalyzed reaction and a reaction that is not enzyme-catalyzed is that the reactant (or substrate) must form a complex (or bind) with the enzyme before the reaction can occur. Therefore, the actual reactant species is not S, but rather it is the enzyme-substrate complex (ES). In the enzyme-catalyzed reaction the amount of enzyme is constant and we reach a point as we increase [S] where [S] becomes so high that nearly all the enzyme is in the ES form all the time. Further increases in [S] cannot increase the rate of the reaction beyond this point since the enzyme is working to catalyze the reaction at its maximum capacity. The enzyme has reached saturation.
On Biocatalysis as Resourceful Methodology for Complex Syntheses: Selective Catalysis, Cascades and Biosynthesis
Peter Grunwald in Pharmaceutical Biocatalysis, 2019
In this chapter, we want to illustrate various modes of utilizing biocatalysis including biosynthesis, which can be applied for the production of pharmaceuticals or other high value products. We will start with simple single-step conversions, which might be carried-out by isolated enzymes but also by living, starving, or dead—permeabilized—cells (see Fig. 21.2). More complex processes are multi-step conversions combining various steps, which do not necessarily need to be biocatalysts but also chemical catalysts or even uncatalyzed chemical steps in combination. Although the processes might be more complex in terms of optimizing the individual rates of each step as well as finding compatible reaction conditions for all reactants, the main advantage of multi-step conversions is the reduction of downstream processing operations, which tends to be the most time-consuming and expensive part of a process. The most complex type of biocatalysis is biosynthesis. The biocatalyst is here a living being—an organism, a cell. Thus, it could be considered as the perfect situation for the employed enzymes: perfect environment, cofactor-supply, (re-)folding assistance, and a continuous regeneration of the biosynthesis machinery. But also, biosynthesis has to cope with some drawbacks like transport limitations, toxic intermediates, and product metabolization. Nevertheless, biocatalysis offers a wide range of methods for the selective formation of complex molecules, which reduces the overall number of steps and makes such syntheses more effective. This chapter will lay a focus on the biosynthetic methods and will only highlight the principal ideas from single-step conversions to cascade reactions.
General concepts for applied exercise physiology
Nick Draper, Helen Marshall in Exercise Physiology, 2014
Enzymes are, with the exception of RNA ribozymes (a specialised type of enzyme), proteins that accelerate (catalyse) biochemical reactions without being altered by the process. They catalyse nearly all reactions within the body, increasing the speed of reaction. For instance, during maximal exercise ATP is required at a rate that would be impossible to supply without the action of enzymes.
An update on late-stage functionalization in today’s drug discovery
Published in Expert Opinion on Drug Discovery, 2023
Andrew P. Montgomery, Jack M. Joyce, Jonathan J. Danon, Michael Kassiou
The final challenge is to overcome the unique issues facing the lesser-developed reaction manifolds. Unlocking the full potential of these reaction modes will enable access to completely new reactivity and broaden the scope of their applications. Dual photochemical/metal-catalyzed C–H functionalization has been demonstrated as a formidable technique for invoking radical initiation, however, the application of metallophotocatalysis to generate other reactive intermediates known to be accessible under mild light irradiation (e.g. anions, cations, carbenes, etc.) remains underdeveloped [22]. Despite the significant achievements of electrochemical-mediated transition metal catalysis in pharmaceutical development, applications of robust and transferable C–H functionalization remain limited, inhibiting the incorporation of electrochemical LSF in drug discovery [23]. Biocatalysis has significant potential in medicinal chemistry and process chemistry as enzymatic optimization improves; however, previous examples of transformations possessing high reaction selectivity have also sustained a reduction in scope due to biocatalyst specialization [24]. Future developments in protein engineering and genome mining are poised to overcome this barrier and bring biocatalytic manifolds closer to true LSF applications, while current efforts in metallophotoredox and electrochemical catalysis are expanding the functionality and breadth of LSF transformations step-by-step.
The SNAP-tag technology revised: an effective chemo-enzymatic approach by using a universal azide-based substrate
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2021
Rosa Merlo, Diego Caprioglio, Michele Cillo, Anna Valenti, Rosanna Mattossovich, Castrese Morrone, Alberto Massarotti, Franca Rossi, Riccardo Miggiano, Antonio Leonardi, Alberto Minassi, Giuseppe Perugino
SNAP-tag® technology is essentially based on BG-substrates: although many of them are commercially available, the possibility of conjugation of infinite desired molecules to the 4-position on BG leads to the synthesis of ad hoc substrates. This is generally possible through the crosslinking reaction of the so-called “BG-building block” (such as the amine-reactive BG-NH2) with NHS-ester derivative compounds. The main disadvantage is the need to purify the final compounds before the reaction with the enzyme, increasing the times and costs of the experiments (Figure 1(A)). Furthermore, the presence of chemical groups conjugated to the benzyl moiety of the BG could affect the reaction efficiency of the SNAP-tag®29–33, sometimes making this enzyme not fully applicable to particular requests.
Recent advances in the development of polyethylenimine-based gene vectors for safe and efficient gene delivery
Published in Expert Opinion on Drug Delivery, 2019
Cuiping Jiang, Jiatong Chen, Zhuoting Li, Zitong Wang, Wenli Zhang, Jianping Liu
As the substances that are inherently present in the human body, biological molecules draw growing interests as promising triggering motifs in the design of smart PEI-based gene vectors. Among different classes of biological components, ATP, enzyme, glucose, and antigen are the most attractive endogenous stimuli that enable biomolecule-responsive release. As we all know, enzymes are potent catalysts during almost all biological processes, and enzyme catalysis is highly selective towards specific substrates under mild conditions. Using tumor as an example again, several enzymes (i.e. proteases, lipase, hyaluronidase (HAase), etc.) have great potential to be specific stimuli in a controlled gene delivery system [117]. For instance, Yin et al. [118] reported an HA-conjugated PEI polymer for the active tumor targeting via interaction of HA with CD44 receptor. Once the nanocarrier reached the tumor extracellular matrix, the surface layer of HA would be deshielded under the catalysis of HAase, leading to the enhanced cellular uptake owing to the exposure of positive charges.
Related Knowledge Centers
- Catalysis
- Chemical Reaction
- Enzyme Catalysis
- Metabolic Pathway
- Molecule
- Protein
- Metabolism
- Substrate
- Product
- Cell