Although the catalytic properties of enzymes may seem almost magical, it is simply chemistry the breaking and making of bonds that gives enzymes their prowess. This chapter will explore the unique features of this mechanisms of thousands of enzymes have been studied in at least some detail. In this chapter, it will be possible to examine only a few of these. | Chapter 16 Mechanisms of Enzyme Action to accompany Biochemistry, 2/e by Reginald Garrett and Charles Grisham All rights reserved. Requests for permission to make copies of any part of the work should be mailed to: Permissions Department, Harcourt Brace & Company, 6277 Sea Harbor Drive, Orlando, Florida 32887-6777 Outline Stabilization of the Transition State Enormous Rate Accelerations Binding Energy of ES Entropy Loss and Destabilization of ES Transition States Bind Tightly - Types of Catalysis Serine Proteases Aspartic Proteases Lysozyme Stabilizing the Transition State Rate acceleration by an enzyme means that the energy barrier between ES and EX‡ must be smaller than the barrier between S and X‡ This means that the enzyme must stabilize the EX‡ transition state more than it stabilizes ES See Eq. Large Rate Accelerations See Table Mechanisms of catalysis: Entropy loss in ES formation Destabilization of ES Covalent catalysis General acid/base catalysis Metal ion catalysis Proximity and orientation Binding Energy of ES Competing effects determine the position of ES on the energy scale Try to mentally decompose the binding effects at the active site into favorable and unfavorable The binding of S to E must be favorable But not too favorable! Km cannot be "too tight" - goal is to make the energy barrier between ES and EX‡ small Entropy Loss and Destabilization of ES Raising the energy of ES raises the rate For a given energy of EX‡, raising the energy of ES will increase the catalyzed rate This is accomplished by a) loss of entropy due to formation of ES b) destabilization of ES by strain distortion desolvation Transition State Analogs Very tight binding to the active site! The affinity of the enzyme for the transition state may be 10 -15 M! Can we see anything like that with stable molecules? Transition state analogs (TSAs) do pretty well! Proline racemase was the first case . | Chapter 16 Mechanisms of Enzyme Action to accompany Biochemistry, 2/e by Reginald Garrett and Charles Grisham All rights reserved. Requests for permission to make copies of any part of the work should be mailed to: Permissions Department, Harcourt Brace & Company, 6277 Sea Harbor Drive, Orlando, Florida 32887-6777 Outline Stabilization of the Transition State Enormous Rate Accelerations Binding Energy of ES Entropy Loss and Destabilization of ES Transition States Bind Tightly - Types of Catalysis Serine Proteases Aspartic Proteases Lysozyme Stabilizing the Transition State Rate acceleration by an enzyme means that the energy barrier between ES and EX‡ must be smaller than the barrier between S and X‡ This means that the enzyme must stabilize the EX‡ transition state more than it stabilizes ES See Eq. Large Rate Accelerations See Table Mechanisms of catalysis: Entropy loss in ES formation Destabilization of ES .
