62 Feedback Inhibition in Metabolic Pathways
Molecules can regulate enzyme function in many ways. The major question remains, however: What are these molecules and where do they come from? Some are cofactors and coenzymes, as you have learned. What other molecules in the cell provide enzymatic regulation such as allosteric modulation, and competitive and non-competitive inhibition? Perhaps the most relevant sources of regulatory molecules, with respect to enzymatic cellular metabolism, are the products of the cellular metabolic reactions themselves. In a most efficient and elegant way, cells have evolved to use the products of their own reactions for feedback inhibition of enzyme activity. Feedback inhibition involves the use of a reaction product to regulate its own further production (Figure 62.1). The cell responds to an abundance of the products by slowing down production during anabolic or catabolic reactions. Such reaction products may inhibit the enzymes that catalyzed their production through the mechanisms described above.
Figure 62.1 Image Description
The diagram shows how feedback inhibition works to regulate a biochemical pathway in a cell. A series of arrows connects several shapes, representing a chain of chemical reactions where each step is catalyzed by a different enzyme. The pathway begins with a starting molecule that is converted step by step into a final product. At the end of the pathway, the product loops back and binds to the first enzyme at a location separate from the active site. When the product binds there, it changes the enzyme’s shape so it can no longer catalyze the first reaction, effectively shutting down the entire pathway. Labels show the enzymes and the product, and an arrow from the product back to the first enzyme is labeled to indicate that this is inhibition by the end product. This illustrates how cells use feedback inhibition to prevent making too much of a product by having the product itself stop the pathway when it is abundant.
The production of both amino acids and nucleotides is controlled through feedback inhibition. Additionally, ATP is an allosteric regulator of some of the enzymes involved in the catabolic breakdown of sugar, the process that creates ATP. In this way, when ATP is in abundant supply, the cell can prevent the production of ATP. On the other hand, ADP serves as a positive allosteric regulator (an allosteric activator) for some of the same enzymes that are inhibited by ATP. Thus, when relative levels of ADP are high compared to ATP, the cell is triggered to produce more ATP through sugar catabolism.
References
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Text adapted from: OpenStax, Concepts of Biology. OpenStax CNX. May 18, 2016. http://cnx.org/contents/b3c1e1d2-839c-42b0-a314-e119a8aafbdd@9.10
