Feedback Inhibition in Metabolic Pathways


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This diagram shows a metabolic pathway in which three enzymes convert a substrate, in three steps, into a final product. The final product inhibits the first enzyme in the pathway.
Metabolic pathways are a series of reactions that multiple enzymes catalyze. Feedback inhibition, where the pathway’s end product inhibits an upstream step, is an important regulatory mechanism in cells.

Source: OpenStax Biology 2e

OpenStax Biology 2e

Molecules can regulate enzyme function in many ways. However, a major question remains: What are these molecules and from where do they come? Some are cofactors and coenzymes, ions, and organic molecules. What other molecules in the cell provide enzymatic regulation, such as allosteric modulation, and competitive and noncompetitive inhibition? The answer is that a wide variety of molecules can perform these roles. Some include pharmaceutical and non-pharmaceutical drugs, toxins, and poisons from the environment. Perhaps the most relevant sources of enzyme regulatory molecules, with respect to cellular metabolism, are cellular metabolic reaction products themselves. In a most efficient and elegant way, cells have evolved to use their own reactions’ products for feedback inhibition of enzyme activity.¬†Feedback inhibition¬†involves using a reaction product to regulate its own further production. The cell responds to the abundance of specific products by slowing down production during anabolic or catabolic reactions. Such reaction products may inhibit the enzymes that catalyzed their production through the mechanisms.

– What bind to a site on a protein other than the substrate binding site and induce a conformational change that increases the binding affinity of the protein for the target substrates?

Producing both amino acids and nucleotides is controlled through feedback inhibition. Additionally, ATP is an allosteric regulator of some of the enzymes involved in sugar’s catabolic breakdown, the process that produces ATP. In this way, when ATP is abundant, the cell can prevent its further production. Remember that ATP is an unstable molecule that can spontaneously dissociate into ADP. If too much ATP were present in a cell, much of it would go to waste. Alternatively, ADP serves as a positive allosteric regulator (an allosteric activator) for some of the same enzymes that ATP inhibits. Thus, when relative ADP levels are high compared to ATP, the cell is triggered to produce more ATP through sugar catabolism.

– What is the physiological value around which the normal range fluctuates?

The physiologic effects of hormones depend largely on their concentration in blood and extracellular fluid. Almost inevitably, disease results when hormone concentrations are either too high or too low, and precise control over circulating concentrations of hormones is therefore crucial. The concentration of hormone as seen by target cells is determined by three factors namely rate or production, rate of delivery, and rate of degradation.

Source:

Clark, M., Douglas, M., Choi, J. Biology 2e. Houston, Texas: OpenStax. Access for free at: https://openstax.org/details/books/biology-2e

https://www.sciencedirect.com/topics/medicine-and-dentistry/allosteric-modulator

http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/basics/control.html


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