25.11: Enzyme Regulation
- Page ID
- 22367
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You may have wondered how the proteolytic enzymes such as trypsin, pepsin, chymotrypsin, carboxypeptidase, and others keep from self-destructing by catalyzing their own hydrolysis or by hydrolyzing each other. An interesting feature of the digestive enzymes is that they are produced in an inactive form in the stomach or the pancreas - presumably to protect the different kinds of proteolytic enzymes from attacking each other or other proteins.
The inactive precursors are called trypinogen, pepsinogen, chymotrypsinogen, and procarboxypeptidase. These precursors are converted to the active enzymes by hydrolytic cleavage of a few specific peptide bonds under the influence of other enzymes (trypsin, for example, converts chymotrypsinogen to chymotrypsin). The digestive enzymes do not appear to self-destruct, probably because they are so constructed that it is sterically impossible to fit a part of one enzyme molecule into the active site of another. In this connection, it is significant that chymotrypsin attacks denatured proteins more rapidly than natural proteins with their compact structures of precisely folded chains.
Presumably all enzymes must have some regulatory mechanism that turns them on and off as needed. Less is known about regulation mechanisms than about the enzymatic reactions themselves, but one type of control has been recognized. This occurs when a reaction product inhibits one of the reaction steps producing it by tying up the enzyme as a nonreactive complex (feedback inhibition). As the simplest example, suppose that the product \(\left( \ce{P} \right)\) as well as the substrate \(\left( \ce{S} \right)\) complexes with the enzyme \(\left( \ce{E} \right)\); then we can write the following set of equilibria for the net reaction:
\[\ce{E} + \ce{S} \rightleftharpoons \ce{ES} \rightarrow \ce{E} + \ce{P}\]
\[\ce{E} + \ce{P} \rightleftharpoons \ce{EP}\]
Clearly, a reaction of this type will decrease in rate as the product accumulates. It may stop altogether if the active sites are saturated with the product, and it will start again only on removal of the product.
Contributors and Attributions
John D. Robert and Marjorie C. Caserio (1977) Basic Principles of Organic Chemistry, second edition. W. A. Benjamin, Inc. , Menlo Park, CA. ISBN 0-8053-8329-8. This content is copyrighted under the following conditions, "You are granted permission for individual, educational, research and non-commercial reproduction, distribution, display and performance of this work in any format."