Activation Free Energy, Substrate Binding Free Energy, and Enzyme Efficiency Fall in a Very Narrow Range of Values for Most Enzymes

Enzymes are responsible for controlling many biological processes, catalyzing different reactions using substrates with diverse complexity, size, and chemistry. How enzymes work and achieve their catalytic efficiency are some of the fundamental questions of life. Most studies have focused on specific enzymes to elucidate their reaction mechanisms and rate acceleration. No study, to our knowledge, has performed systematic analyses of the available properties of all six classes of enzymes. Here, we have systematically analyzed three parameters pertinent to enzyme catalysis, viz. activation free energy, substrate-binding free energy, and enzyme efficiency, which were estimated using the turnover number and the K M value at a given temperature for each enzyme. By correlating these parameters with structural/biological information, including the presence/absence of inorganic and/or organic cofactors, the enzyme’s oligomerization state, the monomer size, the cellular location, and the substrate specificity/promiscuity, we show that, despite the chemical, structural, and reaction diversity of the enzymes analyzed, the activation free energies, substrate-binding free energies, and enzyme efficiencies of most enzymes fall in a very characteristic narrow range of values. Various strategies are used by enzymes to confine the values of the catalytic parameters to such a narrow range. These include their location, their monomeric size or oligomeric state, their specificity, the environmental conditions, and the use of cofactors.