BL/CH 401 Lecture #15A
Introduction to Enzyme Mechanisms -- Part III
Part III. Acid Catalyzed Ester Hydrolysis.
Now, acid catalysis of ester hydrolysis can be hypothesized in a slightly altered mechanism, which shows how the catalyst changes the course of bond rearrangements It is clear at the start that the acid catalyst must accelerate the first step in the reaction, ie the attack of the water molecule on the ester.
Acid Catalyzed Ester Hydrolysis:
Figure 4. Acid Activation of the Ester.
Figure 5. Attack of Water and the Resulting Intermediates.
Figure 6. Decomposition of Ester-Acid-Water Intermediates to Products.
The final step in the process is the regeneration of the acid catalysts (ie the proton is released from organic "acid").
SUMMARY
All the steps in the hypothesized mechanism must fit with know properties of the chemical involved in the mechanism and if possible, chemical evidence for the various bond re-arrangements in the mechanism should be obtained. This simple example of a mechanism of reaction from organic chemistry illustrates what a biochemist must do in order to explain what happens when an enzyme catalyzes a similar reaction such as trypsin catalyzing the hydrolysis of a protein's backbone. In this case, water attacks an amide bond, the peptide bond, which is very similar to the ester hydrolysis illustrated above. Thus, the question is how do the amino acid side chains of an enzyme assist is bond rearrangements? Can a plausible mechanism of action for enzyme catalyzed peptide bond hydrolysis be formulated by the biochemist in a manner similar to that done by the organic chemist? These questions are addressed in the next lecture.
©Wilbur H. Campbell, 1995; wcampbel@mtu.edu