Dehydrogenases preferred pathway mechanism

The preferred pathway mechanism might be regarded at present as a rather general one for dehydrogenases, in place of the simple ordered 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... 

Perhaps the most important general conclusions from isotope exchange studies, supported by other investigations, are that the preferred pathway mechanism is common to a number of dehydrogenases and that for most, but not all, the formation of the active ternary complex with the second substrate increases the firmness of coenzyme binding, presumably by a protein conformational change. 

The conclusion that even with the best substrate, ethanol, dissociation of NAD occurs from the active ternary complex is consistent with the evidence-from isotope exchange experiments 32), mentioned previously, that the dissociation of coenzyme is not greatly suppressed in the ternary complex compared with the binary complex, in contrast to liver alcohol dehydrogenase. This is also indicated by the initial rate data in another way 4>a/4>o for the preferred pathway mechanism approximates to the dissociation constant for NAD from the ternary complex (Table I), and is reasonably constant for the three primary alcohols and approximately equal to the dissociation constant of E-NAD, determined independently 40). 

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