Generalized microscopic reversibility, kinetic co-operativity of enzymes and evolution

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Abstract
Generalized microscopic reversibility implies that the apparent rate of any catalytic process in a complex mechanism is paralleled by substrate desorption in such a way that this ratio is held constant within the reaction mechanism. The physical and evolutionary significances of this concept, for both polymeric and monomeric enzymes, are discussed. For polymeric enzymes, generalized microscopoc reversibility of necessity occurs if, within the same reaction sequence, the substrate stabilizes one type of conformation of the active site only. Generalized microscopic reversibility suppresses the kinetic co-operativity of the slow transition model. This situation is obtained if the free-energy difference between the corresponding transition states of the 2 enzyme forms is held constant along the reaction co-ordinate. This situation implies that the extra costs of energy (required to pass each energy barrier) that are not covered by the corresponding binding energies of the transition states vary in a similar way along the the 2 reaction co-ordinates. The regulatory behavior of monomeric enzymes is discussed in the light of the concept of catalytic perfection proposed by Albery and Knowles: An enzyme will be catalytically perfect when its catalytic efficiency is maximum. If this situation occurs for a monomeric enzyme obeying either the slow transition or the mnemonical model, the kinetic co-operativity disappears. Kinetic co-operativity of a monomeric enzyme is paid for at the expense of catalytic efficiency, and the monomeric enzyme cannot be simultaneously co-operative and catalytically very efficient. This was found experimentally in a number of cases.