Equilibrium preceding catalysis

Br0nsted acid catalysis, the substrate electrophile is reversibly protonated in a pre-equilibrium step, prior to the nucleophilic attack (Scheme 2). In general acid catalysis, however, the proton is (partially or fuUy) transferred in the transition state of the rate-determining step (Scheme 2). Clearly, the formation of a hydrogen bond precedes proton transfer. 

If there is no burst, then either the chemical reaction or a step preceding the chemistry is rate limiting. Alternatively, the internal equilibrium may favor substrates (Ki 1) however, this is less likely due to the principles governing catalysis that tend to bring the equilibrium for a reaction closer to unity at the active site of the enzyme than in solution (78). In addition, a complete kinetic analysis would include examination of the burst in each direction, which could reveal an unfavorable equilibrium in one direction and a full burst amplitude in the opposite direction. 

Observations up to this time have been for systems chosen at random. The chemical reactions observed have been very far from equilibrium, and usually represent one step only of a more complicated situation present when steady state catalysis is proceeding, i.e., when all reactants and products are continually arriving on the surface and desorbing. The much more primitive experiments described below must precede such steady-state studies using LEED as a monitor. It should be remembered that LEED observations are restricted to pressures below 10 Torr because the diffracted beams are severely scattered by gas molecules above this limit. 

This chapter will be concerned mainly with the relation between the equilibrium constants of acid-base reactions and their forward and reverse rates. Relations between equilibrium constants and structure have already been considered in Chapter 6, so that the present discussion also implies relations between rates and structure. Moreover, there are many cases in which rates are easier to measure (though more difficult to interpret) than equilibria and can be compared directly with structures. We shall first consider the general basis and experimental evidence for this type of relation, followed by its molecular interpretation, with special reference to exceptional cases. We have seen in the two preceding chapters that the rates of proton-transfer reactions can be measured either directly, or indirectly through the study of acid-base catalysis, and in the following discussion information from both sources will be used indifferently. 

Nucleotide binding to a second site increases the rate of catalysis of ATP hydrolysis as well as dissociation [24, 25]. An alternative rule for avoiding hydrolysis is simply that binding of the proton and nucleotide bring about dissociation of ATP faster than it reverts to ADP and Pj it is possible that the dissociation of ATP is brought about specifically by ADP and P [11]. There is precedent for such a mechanism in the actin-driven dissociation of ATP in good yield from the equilibrium mixture of M ATP M ADP Pi, which is the analogous reaction in the myosin system [26]. 

Three types of reactions were identified. These are rapid equilibrium binding (1,5 and 7), chemical catalysis (3) and isomerizations (2,4 and 6). There is evidence that steps 4 and S are preceded by an isomerization of the complex. M designates myosin and the stars indicate increase in fluorescence of the protein. 

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