Life of all forms depends on the acceleration of the rate of chemical reactions by enzymes. It is now known that many enzymes function by lowering the free-energy barrier to a reaction. This preferential binding of the enzyme to the transition state is a concept credited to Pauling.1 It is the origin of the extraordinary potency of transition-state inhibitors.2 It has recently been recognized that in some enzymes, the action of the enzyme includes coupling of the dynamic motions of the protein backbone to progress along the reaction coordinate.3 These effects have been deemed to be especially important in the case of tunneling reactions. In such a case, the geometry of the barrier may well be as important a determining feature of rate as the height of the barrier. This is because it is far easier to tunnel through a thin barrier than through a thick one. Thus, evolution has crafted enzymes to force reactants in close proximity to each other and a vibrational enhancement of the rate of light particle transfer. Understanding of light particle transfer in enzymatic systems had its origin in anomalous experimental signatures of tunneling behavior - kinetic isotope effects (KIEs). These experiments however, are complex to interpret rarely does evidence for tunneling come in the form expected - the primary KIE. Usually such indications must be found in more physically removed signatures such as KIEs in secondary and tertiary positions and temperature dependence of isotope effects.
|Original language||English (US)|
|Title of host publication||Isotope Effects in Chemistry and Biology|
|Number of pages||24|
|Publication status||Published - Jan 1 2005|
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)