Flexibility of enzymatic transitions as a hallmark of optimized enzyme steady-state kinetics and thermodynamics.

We investigate the relations between the enzyme kinetic flexibility, the rate of entropy production, and the Shannon information entropy in a steady-state enzyme reaction. All these quantities are maximized with respect to enzyme rate constants. We show that the steady-state, which is characterized by the most flexible enzymatic transitions between the enzyme conformational states, coincides with the global maxima of the Shannon information entropy and the rate of entropy production. This steady-state of an enzyme is referred to as globally optimal. This theoretical approach is then used for the analysis of the kinetic and the thermodynamic performance of the enzyme triose-phosphate isomerase. The analysis reveals that there exist well-defined maxima of the kinetic flexibility, the rate of entropy production, and the Shannon information entropy with respect to any arbitrarily chosen rate constant of the enzyme and that these maxima, calculated from the measured kinetic rate constants for the triose-phosphate isomerase are lower, however of the same order of magnitude, as the maxima of the globally optimal state of the enzyme. This suggests that the triose-phosphate isomerase could be a well, but not fully evolved enzyme, as it was previously claimed. Herein presented theoretical investigations also provide clear evidence that the flexibility of enzymatic transitions between the enzyme conformational states is a requirement for the maximal Shannon information entropy and the maximal rate of entropy production.