Theorell-Chance mechanism systems

Different abortives may be formed with alternative products or substrates. Such procedures can be useful in helping to distinguish Theorell-Chance mechanisms from ordered systems with abortive complexes . In the case of lactate dehydrogenase, the E-pyruvate-NAD+ and E-lactate-NADH abortive complexes may play a regulatory roles in aerobic versus anaerobic metabolism. 

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... 

The value of R varies from zero for a Theorell-Chance mechanism to 1.0 for a RapidEquUibrium OirieiedBi Bi system. If V, and Va are unequal, R indicates the rate-limiting step in the slower direction only. In this case, R gives the fraction of the total enzyme present as the central complexes when both substrates for the slower direction are saturating. The ratio/ /(1-R)then gives the ratio of the central complexes to aU other enzyme species present. 

There are two possible bisubstrate systems that combine the enzyme feature of the Ping Pong sequence with the hit-and-mn feature of the Theorell-Chance mechanism. These are in fact the hmiting cases of the common Ping Pong Bi Bi system, in which one of two central complexes has extremely short life. The reaction sequences are shown below ... 

A system for describing kinetic mechanisms for enzyme-catalyzed reactions . Reactants (ie., substrates) are symbolized by the letters A, B, C, D, eto., whereas products are designated by P, Q, R, S, etc. Reaction schemes are also identified by the number of substrates and products utilized (i.e.. Uni (for one), Bi (two), Ter (three occasionally Tri), Quad (four), Quin (five), etc. Thus, a two-substrate, three-product enzyme-catalyzed reaction would be a Bi Ter system. In addition, reaction schemes are identified by the pattern of substrate addition to the enzyme s active site as well as the release of products. For a two-substrate, one-product scheme in which either substrate can bind to the free enzyme, the enzyme scheme is designated a random Bi Uni mechanism. If the substrates bind in a distinct order (note that, in such cases, A binds before B for ordered multiproduct release, P is released prior to Q, etc.), the scheme would be ordered Bi Uni. If the binding scheme is different than the release of product, then that information should also be provided for example, a two-substrate, two-product reaction in which the substrates bind to the enzyme in an ordered fashion whereas the products are released randomly would be designated ordered on, random off Bi Bi scheme. If one or more Theorell-Chance steps are present, that information is also given (e.g., ordered Bi Bi-(Theorell-Chance)), with the prefixes included if there is more than one Theorell-Chance step. 

A sequential enzyme-catalyzed binding mechanism for a two substrate-two product system in which substrates A and B have to bind in a certain order but either P or Q can be released in a Theorell-Chance step upon the binding of B. Following this step, the other substrate is... 

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