Zero-point energy enzymes

This estimate of the barrier effectively includes zero-point energy and tunneling effects since it is obtained from experimental data. In typical EVB studies of enzymatic reactions it is usually assumed that these quantum-mechanical effects do not differ significantly between the water and enzyme environments. This assumption has been verified by implementation of the path integral method [51] within the EVB framework [52,53]. 

Isotope effects are used to probe chemical processes, as isotopic substitution generally alters only the mass of the reacting groups without changing the electronic properties of the reactants. In this fashion, isotope effects can be used as subtle probes of mechanism in chemical transformations. This section will discuss how to use isotope effects to probe for tunneling effects on enzymes. The basic criteria for tunneling are experimental isotope effects that have properties that deviate from those predicted within the semi-classical transition state model, which includes only zero-point energy effects (we refer to this as the bond stretch model ). 

The free energy change in phosphorolysis compared to hydrolysis is much closer to zero, and thus the known phosphorolytic enzymes catalyze biosynthetic reactions as well as catabolic changes. They are implicated chiefly in the synthesis of starch by plants and glycogen by animals. Recent work by Kornberg and his associates has pointed to a pyro-phosphorylase in yeast and hog liver that catalyzes the following general reaction ... 

From the point of view of thermodynamics, the stationary distribution of enzyme molecules between states E and Ex is concomitant with thermodynamic equilibrium. To understand this, let us assume that the average energies of a free enzyme, a free molecule X, and the complex Ex are Se,< x, and i ex, respectively. Further assume that, in order for an enzyme and a molecule X to bind, their combined energies need to surpass an energy threshold ( th > e, x, ex, which can be assumed zero without loss of generality. Thus, the energy landscape for this reaction will look like the one sketched in Fig. 5.1, while the scape rates from E + X to Ex and vice versa are... 

---