What Is Feedback Inhibition and Why Is It Important in Regulating Enzyme Activity?

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At the cellular level, most of life is generally driven by reactions in which the help of enzymes is critical. During a reaction, inputs, or substrates, are converted into outputs, or products. In a biological system such as a human cell, these reactions could theoretically occur in a spontaneous manner as long as the reactants have a higher inherent energy than the products; such reactions give off energy in the form of heat and are considered exothermic. (Reactions that require an input of energy, in contrast, are called endothermic.)

Without the help of enzymes, most of these exothermic reactions would occur so slowly that the cell would not be able to function properly as it would run out of fuel. These special proteins are capable of speeding up reactions, but if there were no way to control their activity, the results would be just as catastrophic for the cell as a lack of enzymes would be. Feedback inhibition is one of the methods a cell can use to hinder unnecessary enzymatic activity.

Function of Enzymes

In a laboratory setting, many reactions can be performed without enzymes by heating a solution full of substrates, which adds energy to the system and increases the chances of the substrates randomly bumping into each other in the exact positions necessary to produce the desired product. Living cells do not have this option, so they produce enzymes to bring substrates together and facilitate the reaction between the different compounds. Enzymatic reactions still require energy, but not nearly as much as would be needed in the absence of the catalytic enzyme.

Enzyme Regulation

There are generally three ways a cell can control the activity of its enzymes. It could control how much enzyme is produced, how much is destroyed, or some combination, but these methods are heavy-handed and not as useful to a cell whose growth requires a finer degree of control.

The third method, feedback inhibition, is a form of feedback regulation that can be used to immediately react to cellular conditions. Feedback inhibition occurs when one of the products of a chain of reactions hinders the activity of an enzyme at the beginning or in the middle of the chain. This kind of negative feedback is a reversible process. When concentration of the inhibiting compound falls, it will dissociate from the enzyme, allowing it to catalyze reactions again.

This often occurs via allosteric regulation, wherein the product inhibits the enzyme by interacting with a site distant from the enzymatically active site.

Case Study: Glucose Metabolism

One of the most critical reaction chains in eukaryotic cells includes glycolysis and the citric acid cycle. When glucose enters a cell, a chain of 20 different enzymes plus several protein complexes in the mitochondria work together to transform the glucose into adenosine triphosphate (ATP), an energy carrier necessary to drive cellular life.

If animal cells could not control this enzyme chain, glucose would be continuously drawn from the bloodstream, lowering blood sugar levels to a dangerous level. Without inhibition, enzyme chains would constantly produce compounds the cell does not currently need. This would be a massive waste of cellular resources.

Feedback Inhibition in Glucose Metabolism

ATP, the end product of glucose metabolism, is the key feedback inhibitor for the enzyme chain. When the cell has an abundance of free ATP molecules – meaning it has plenty of energy reserves and does not need to produce more – the compound binds with several enzymes along the chain, most notably phosphofructokinase (PFK) and pyruvate kinase.

ATP inhibition occurs at critical, irreversible points in the process. Glucose metabolism is therefore put on hold until the cell runs low on ATP, at which point the energy molecules break away from the enzymes, allowing them to continue metabolizing sugar into energy.

References

About the Author

Robert Mullis is is a graduate of Liberty University with a bachelor's degree in biochemistry and a second degree in accounting. As a writer, he specialized in math, biology, chemistry, literature, and business.

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