BL/CH 401 Lecture #15A
Introduction to Enzyme Mechanisms -- Part II
Part II. Chemical Bond Rearrangement During a Reaction.
One way to understand enzyme catalysis- all chemical reactions occur via bond rearrangements. For example, in ester hydrolysis water splits the ester into acid and alcohol.
Figure 2. Ester Hydrolysis.
This reaction is slow at neutral pH, but faster at acidic pH. Acid catalyzes ester hydrolysis. But how does H+ catalyze the reaction? The organic chemist answers this question by hypothesizing a 'mechanism' for the reaction, which explains how acid increases bond rearrangement. First, a hypothesis for the mechanism fo the reaction in the absence of a catalyst. This mechanism is a plausible idea for how the bonds rearrange during the reaction between the ester and water. Thus, the mechanism of the reaction illustrates a likely course for the bond rearrangements to take during the reaction.
Figure 3. Mechanism of Ester Hydrolysis in Absence of Catalyst.
Figure 3A. Attack of the Water Molecule on the Ester.
Figure 3B. Decomposition of the Ester-Water Intermediate into Acid and Alcohol.
The molecules shown in brackets are hypothesized intermediates in the reaction, which are very difficult to actually demonstrate by chemical analysis such as spectroscopy or NMR (nuclear magnetic resonance). The actual bond rearrangements take place in the intermediates in the reaction, which are shown by arrows illustrating the movement of electron pairs to form the new bonds of the products. In this case, the slowest step is the attack of the water molecule on the ester, which is illustrated by the 'free' electrons of the oxygen in water attacking an electron-deficient center in the ester (Fig. 3A). It has become known that the most electron deficient atom in an ester is the carbonyl's carbon. Thus, the hypothesis is developed based on this idea and water attack on the ester leads to plausible intermediates based on bond rearrangements which logically follow from the first step in the reaction, which is the slowest or rate-dtermining step. Then the intermediates rapidly rearrange bonds resulting in a good suggestion for how the ester-water complex breaksdown to form the products, which happens very fast after the slow reaction where the water attacks the ester is done.
©Wilbur H. Campbell, 1995; wcampbel@mtu.edu