Alternative product inhibition

Rate experiments that are typically carried out in the presence of different concentrations of an alternative product (or product analog) while using the normal substrates . This approach can be particularly useful when the normal product cannot be used because it is unstable, insoluble, or ineffective (the latter indicated by a very high Ki value). Moreover, the normal product may be consumed as an essential substrate in a coupled assay system for the primary enzyme. Fromm and Zewe used the alternative product inhibition approach in their study of hexokinase. Wratten and Cleland later applied this procedure to exclude the Theorell-Chance mechanism for liver alcohol dehydrogenase. See Abortive Complexes... 

ALTERNATIVE PRODUCT INHIBITION ABORTIVE COMPLEXES ALTERNATIVE SUBSTRATES COMPETITIVE INHIBITOR ABORTIVE COMPLEXES MAPPING SUBSTRATE INTERACTIONS USING KINETIC DATA MEMBRANE TRANSPORT ENERGY OF ACTIVATION Old... 

Many examples of product inhibition are to found. Some dehydrogenases are inhibited by NADH (a co-product of the reaction), e.g. PDH and isocitrate dehydrogenase (ICD), which are involved with the glycolysis and the TCA cycle are two such examples. Hexokinase isoenzymes in muscle (but not liver) and citrate synthase are inhibited by their products, glucose-6-phosphate and citrate respectively offering a very immediate fine tuning of reaction rate to match cellular requirements and possibly allowing their substrates to be used in alternative pathways. 

If product inhibition occurs, either a stirred-tank reactor in batch or a plug-flow reactor should be used. In these two reactors, the product concentration increases with time. Alternatively a reactor with integrated product separation (membrane, solvent, etc.) is preferable. 

Similar considerations apply to processes occurring on the surface of the catalyst i.e., the rate of dissociation of ethyl radicals to ethylene molecules will be equal to the rate of the reverse reaction. An alternative method of describing the kinetic behavior of an exchange reaction is to treat it as an example of a catalytic reaction where the products inhibit the reaction as they compete on equal terms with the reactants for the available surface. 

Many glycosyltransferases have been employed in the in vitro synthesis of oligosaccharides [124,125]. Since the nucleoside mono- or diphosphates released during the reaction, e. g. UDP, usually cause product inhibition, in situ regeneration cycles have been developed in which they are transformed back to the sugar nucleotides [126]. Alternatively, the nucleoside mono- or diphosphates may be degraded by use of alkaline phosphatase [127]. 

Kinetic studies with calcineurin yielded a modest solvent isotope effect of 1.35, and a proton inventory and fractionation factor data that were most consistent with a mechanism involving a single proton transfer from a water molecule coordinated to a metal ion.136 No transphosphorylation products were found in the presence of alternate nucleophiles, consistent with direct phosphoryl transfer to a metal-coordinated water.137 No calcineurin-catalyzed oxygen exchange of 180 labeled water with phosphate could be detected.138 In a study using / NPP as the substrate, product inhibition studies found that both phosphate and p-nitrophenol are... 

One of the limiting factors in obtaining efficient esterase antibodies is the observation of product inhibition by the carboxylate product. Non-phosphonate haptens have been used to induce esterase activity in antibodies [17]. Alternatively, taking carbonates as substrates instead of esters provides an elegant solution to the problem of product inhibition, as demonstrated in a kinetic resolution experiment [18]. This might be the most practical approach to obtain preparatively useful esterase catalytic antibodies in the future for kinetic resolu-... 

Benzaldehyde can be produced from benzoyl formate with whole cells of Pseudomonas putida ATCC 12633 as biocatalyst119 201 (Fig. 16.6-5). Alternatively, but less effectively, mandelic acid can be used as starting material. A pH of 5.4 was found to be optimal for benzaldehyde accumulation. At this proton concentration, partial inactivation of the benzaldehyde dehydrogenase isoenzymes and activation of the benzoyl formate decarboxylase are reported. Fed-batch cultivation prevented substrate inhibition. In situ product removal is necessary to prevent product inhibition. 

The technique of alternate substrate inhibition, which was pioneered by Fromm (38), involves the use of alternate substrates (that produce alternate products) as inhibitors of the formation of the specific product from the variable... 

In the case of ethanol, extraction with water is undesirable due to the dilution of the ethanol, whereas direct pressing gives poor yields [184]. Direct distillation from the fermented solids performs relatively poorly, although distillation is economically feasible if combined with animal feed production from the solid wastes [217,218]. As an alternative, forced gas circulation can be used to strip ethanol from the substrate. This has been shown for a gas-solid fluidized bed and for a stirred bed [90, 219, 220]. A further advantage is that continuous stripping during the fermentation, rather than simply recovering the ethanol at the end of the fermentation, avoids the product inhibition... 

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