Ordered equilibrium ternary complex mechanism

Scheme 5.5 Ordered equilibrium ternary complex mechanism.

Q. This finding eliminates a truly rapid equilibrium random mechanism, for which k and k must be much smaller than fc 4, k-i, k, and k-2, since the two exchange rates must then be equal. In fact, the differences between the two exchange rates show that the dissociation of A and/or P from the ternary complexes must be slow compared with that of B and/or Q, and also slow relative to the interconversions of the ternary complexes (32). This means that in at least one direction of reaction the dissociation of products in the overall reaction is essentially ordered for all these enzymes, the coenzymes dissociating last, as in the preferred pathway mechanism (Section I,B,4). With malate, lactate, and liver alcohol dehydrogenases, the NAD/NADH exchange rate increased to a... 

This brings us to the final mechanism we need to consider for a 2-substrate reaction, namely a random-order mechanism. We have assumed that we would be alerted to the possibility of a steady-state random-order mechanism by non-linear primary or secondary plots, but it is possible to get linear kinetics with a random-order mechanism. If we make the assumption that the further reaction of the ternary complex EAB is much slower than the network of reactions connecting E to EAB via EA and EB, then there are only 4 kinetically significant complexes and their concentrations are related to one another by substrate concentrations and dissociation constants. This is the rapid-equilibrium random-order mechanism, and the assumption made is analogous to the Michaelis-Menten equilibrium assumption for a 1-substrate mechanism. 

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