Rate-limiting step, change

As with simple imines, the identity of the rate-limiting step changes with solution pH.. s the pH decreases, the rate of the addition decreases because protonation of the amino compound reduces the concentration of the nucleophilic unprotonated form. Thus, whereas the dehydration step is normalfy rate-determining in neutral and basic solution, addition becomes rate-determining in acidic solutions. 

Studies leading to the proposal of a mechanism for NADH-cytochrome fas reductase were carried out with the snake venom-extracted enzyme, i.e., the catalytic domain. In Section VII,C, work will be described showing that this mechanism obtains for the enzyme bound to microsomes except that the rate limiting step changes because of a presumed restriction in the diffusion rate in the lipid milieu as compared to an aqueous medium (341, 343). 

Under normal circumstances, the pH dependence of kcat/ A follows the titration curve of the active site of the free enzyme. However, a special complication arises when the rate-limiting step changes considerably with pH (Reaction (14.31)). 

In a catalytic reaction, the total number of active sites is constant. When the reaction cycle is completed for a particular molecule, the surface reaction site is regenerated. The order of the reaction depends on the fraction of sites that is occupied. A maximum in the rate as a function of temperature is usually found. It indicates that the rate-limiting step changes. The conversion in a catalytic reaction can never be higher than thermodynamics predicts. 

Theoretical models available in the literature consider the electron loss, the counter-ion diffusion, or the nucleation process as the rate-limiting steps they follow traditional electrochemical models and avoid any structural treatment of the electrode. Our approach relies on the electro-chemically stimulated conformational relaxation control of the process. Although these conformational movements179 are present at any moment of the oxidation process (as proved by the experimental determination of the volume change or the continuous movements of artificial muscles), in order to be able to quantify them, we need to isolate them from either the electrons transfers, the counter-ion diffusion, or the solvent interchange we need electrochemical experiments in which the kinetics are under conformational relaxation control. Once the electrochemistry of these structural effects is quantified, we can again include the other components of the electrochemical reaction to obtain a complete description of electrochemical oxidation. 

To summarize, the surface kinetics (or near surface kinetics) is the limiting step at lower temperature and diffusion is the rate limiting step at higher temperature. It is possible to switch from one rate-limiting step to the other by changing the temperature. This is illustrated in Fig. 2.9, where the Arrhenius plot (logarithm of the deposition rate vs. the reciprocal temperature) is shown for several reactions leading to the deposition of silicon,... 

Fluorouracil Inhibition of the enzyme thymidylate synthase, the rate-limiting step in thymidine formation. Dose-limiting Myelosuppression and mucositis with bolus administration Diarrhea and hand-foot syndrome with continuous infusion Additional toxicities Skin discoloration, nail changes, photosensitivity, and neurologic toxicity... 

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