Enzyme Kinetics and Drugs as Enzyme Inhibitors
Peter Grunwald in Pharmaceutical Biocatalysis, 2019
The term “enzyme kinetics” is in so far somewhat misleading as one might draw the conclusion from it that the basic principles of chemical kinetics are not valid in this area, which is of course not the case. Reactions catalyzed by bioactive material likewise depend on parameters like concentration, temperature, etc.—the peculiarity is that during the reaction an intermediate is involved which is in equilibrium with the reactants. As it is characteristic for catalysts, enzymes catalyze a reaction in both directions, which is of considerable importance for organic synthesis. Irrespective of that, a treatment of enzyme kinetics is based on the interaction between a macromolecule and a small ligand that normally is the substrate but which can also be an inhibitor, an activator, a co-factor, etc. Because of the usually large differences in particle size between enzymes (10 to 100 nm) and substrate molecules (e.g., ~0.7 nm for glucose), enzyme kinetics marks the transition between homogeneous and heterogeneous catalysis and is therefore sometimes named micro-heterogeneous catalysis. As in case of heterogeneous catalysis, enzyme-catalyzed reactions show the phenomenon of substrate saturation.
Beyond Enzyme Kinetics
Clive R. Bagshaw in Biomolecular Kinetics, 2017
Enzyme kinetics dominated the field of biochemical kinetics in the early years primarily because the inherent amplification property of catalytic reactions aided the quantification of product formation in the steady state. Increasing detection sensitivity has opened up the application of kinetic methods to many other biochemical systems. All biological problems have a kinetic element, and this chapter outlines some other topics that are widely studied at the molecular level. Ligand binding by nonenzymic proteins, or to nonactive sites on enzymes, is fundamental to much of biochemistry, but the principles and methodology used are similar to the initial steps of catalysis, and these aspects have been covered in Chapters 2 and 3. Here, we deal with topics that require special considerations.
Answers
Calver Pang, Ibraz Hussain, John Mayberry in Pre-Clinical Medicine, 2017
This question focuses on diabetes. Blood sugar levels in diagnosing diabetes are different dependent on the plasma glucose test. In a random glucose test or a 2-hour postprandial test, a level of 11.1 mmol/L is diagnostic whereas a fasting glucose test level of 7.0 mmol/L or more is diagnostic. Insulin is a hormone that has many physiological effects not only on carbohydrate metabolism but also lipid (increases lipogenesis and decreases lipolysis) and protein (increases protein synthesis and decreases protein degradation) metabolism. Enzyme kinetics is a common exam topic and it is important to appreciate that a competitive inhibitor increases Km but has no effect on Vmax; an uncompetitive inhibitor decreases both Km and Vmax; a non-competitive inhibitor has no effect on Km but decreases Vmax.
Kushenol A and 8-prenylkaempferol, tyrosinase inhibitors, derived from Sophora flavescens
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2018
Jang Hoon Kim, In Sook Cho, Yang Kang So, Hyeong-Hwan Kim, Young Ho Kim
This study confirmed the inhibitory mechanism of compounds 1–4 towards tyrosinase using enzyme kinetics. Enzyme kinetics were performed based on academic methods that examine a variety of substrate concentrations. The results were represented by Lineweaver–Burk plots, which confirmed the inhibition to involve a two-step binding mechanism. The Lineweaver–Burk plots of inhibitors 1, 3 and 4 showed a series of straight lines passing through a point on the negative abscissa (non-competitive inhibitor). In contrast, all of the straight lines produced by different concentrations of inhibitor 2 passed through a point on the axis of ordinates (competitive inhibitor). Finally, the Ki values calculated for inhibitors 1–4 were 0.4±0.4 μM, 2.4±0.1 μM, 16.0±0.3 μM, and 17.1±1.1μM, respectively, on the secondary re-plot (Figure 2(F) and Table 1).
Modeling principles of protective thyroid blocking
Published in International Journal of Radiation Biology, 2022
Alexis Rump, Stefan Eder, Cornelius Hermann, Andreas Lamkowski, Manabu Kinoshita, Tetsuo Yamamoto, Junya Take, Michael Abend, Nariyoshi Shinomiya, Matthias Port
In the case Michaelis-Menten kinetics are used to describe an exchange process between two compartments, it may be convenient to use molar substance amounts instead of concentrations. This requires to know the volume of distribution of the source compartment (Vs in l). In that case C becomes m (= C*Vs in µmol), Km becomes Km# (= Km*Vs in µmol). T and Tmax are also multiplied by Vs and Tmax# expressed in µmol*d−1. The equation with its original units is probably more familiar to most scientists as Michaelis-Menten kinetics are often associated with enzyme kinetics, but the derived variable units are probably more convenient when running computations using a compartment model with Michaelis-Menten kinetics describing a saturable transport process.
Mixed and non-competitive enzyme inhibition: underlying mechanisms and mechanistic irrelevance of the formal two-site model
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2023
Prompted to “write a definition of mixed-type enzyme inhibition”, ChatGPT elaborated the following composition: Mixed-type enzyme inhibition is a form of enzyme inhibition where the inhibitor can bind to both the free enzyme and the enzyme-substrate complex, resulting in distinct effects on both the enzyme’s catalytic activity and its affinity for the substrate. In mixed-type inhibition, the inhibitor can interact with the enzyme at either the active or a separate allosteric site. […]Mixed-type enzyme inhibition is a complex regulatory mechanism that can have important implications in various biological processes and the development of therapeutic strategies targeting enzyme activity. Understanding the nature of mixed-type inhibition is crucial for studying enzyme kinetics, drug discovery, and the design of effective enzyme inhibitors. Because the algorithms of ChatGPT have been trained using a massive amount of text data, the response it provided can be considered as a representative description of mixed inhibition that aligns with the general understanding presented in articles, books and other scientific publications.
Related Knowledge Centers
- Chemical Kinetics
- Chemical Reaction
- Enzyme Catalysis
- Enzyme Inhibitor
- Molecule
- Protein
- Reaction Rate
- Metabolism
- Drug
- Substrate