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The Neuromuscular Junction
Published in Nassir H. Sabah, Neuromuscular Fundamentals, 2020
Equations 5.27–5.29 represent chemical kinetics on a macroscopic scale, considering a large number of channels. How are they to be interpreted for single channels, as observed under patch clamp? If the rate at which No open channels close is αNo, then α is the mean rate at which a single open channel will close. This means that 1/α is the mean open lifetime of a channel. Although the open lifetimes of individual channels will be randomly distributed, according to an exponential distribution, the mean open lifetime of a large number of channels is 1/α. Identifying 1/α as τo (Equation 5.25), it follows that in a system such as that of Equation 5.26 having a single open state, the mean open lifetime is equal to the reciprocal of the rate constant for channel closing. It should be noted that rate β in Equation 5.26 increases the number of open channels but cannot affect the time a channel remains open. In fact, α can be estimated by taking the mean of observed open lifetimes of a fairly large number of channels. Similar considerations apply to the mean closed lifetime of channels.
Enzyme Kinetics and Drugs as Enzyme Inhibitors
Published in Peter Grunwald, 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.
Analytical and mechanistic modeling
Published in Issam El Naqa, A Guide to Outcome Modeling in Radiotherapy and Oncology, 2018
Vitali Moiseenko, Jimm Grimm, James D. Murphy, David J. Carlson, Issam El Naqa
The LQ model, while providing a versatile formalism to account for time-dose-fractionation, in particular for isoeffect calculations, does not explicitly describe the production of primary lesions (DSB), their repair and misrepair, and the production of lethal lesions. The kinetic reaction rate model describes the processes of the production of primary lesions and their processing using equations of chemical kinetics, hence the name kinetic. The repair-misrepair (RMR) and lethal-potentially-lethal (LPL) models [283, 284] formulated in the mid 1980s serve as a benchmark. These two models contained binary exchanges as a pathway of lethal lesion production which has become an integral feature of refined models. Overall, reaction rate models follow the pathways outlined in table 7.1, at least as far as binary exchanges are concerned [285]. Notably, interpretation of the events which downstream lead to the linear term in dose-response remains uncertain. Although our knowledge of DNA damage, repair mechanisms and pathways of cell lethality are much more advanced compared to the 1980s, we still know more about behavior of the linear term, α, as a function of radiation quality, and how it varies between cell lines, rather than how it comes about [286].
Approaches to modeling chemical reaction pathways in radiobiology
Published in International Journal of Radiation Biology, 2022
The author has offered above a mixture of elementary chemical kinetics, logic, advice, observations, critique, and hindsight, in an effort to help those aiming to model chemical reaction pathways in radiobiology. It is, of course, much easier to identify deficiencies in a putative chemical model than it is to construct a model where the response of interest has been identified or hypothesized, the chemical pathways in both model and cell or tissues plausibly defined, rate constants and concentrations of all relevant reactions and reactants at the microscopic level well-characterized, and computational methodology available that can reliably simulate reactions in the complex environment of cells and tissues.
Physicochemical stability of bioadhesive thermoresponsive platforms for methylene blue and hypericin delivery in photodynamic therapy
Published in Pharmaceutical Development and Technology, 2020
Fernanda Belincanta Borghi-Pangoni, Mariana Volpato Junqueira, Marcos Luciano Bruschi
Drug degradation reactions occur at set speeds and are usually from chemical nature in which the principles of chemical kinetics apply. Using this methodology, the results obtained from storage conditions can be extrapolated to predict stability. In many cases, the reaction order can be defined and prediction of shelf-life of the tested product can be established (Lachman et al. 2001; Wu et al. 2009). The decrease of Hyp content of system submitted to the three different stress conditions occurred according to the pseudo first-order reaction.
A critical review of the kinetic direct peptide reactivity assay (kDPRA) for skin sensitizer potency assessment – taking it forward
Published in Critical Reviews in Toxicology, 2021
First plot ln(100-DP) versus t for each initial concentration [E] of test chemical then, if these plots meet linearity criteria, plot the slopes against [E]. The slope of this plot is the second order rate constant k. This is more in line with conventional practice in chemical kinetics and has the benefit of more easily detecting and interpreting deviations from ideal second-order behavior. In particular, involvement of reactive impurities is more straightforward to detect and interpret.