Enzyme Inhibition
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Enzyme Inhibition

There are ways of inhibiting the activity of enzymes. Denaturing or destroying the enzyme protein is one way of doing this irreversibly. This can be done by heating, changing the pH, or by reaction with a variety of chemicals.

Competitive Inhibition

Each enzyme is designed to bind only its intended substrate. However, it is possible in many cases for a different molecule that is sufficiently similar to the substrate to bind to the active site of the enzyme. If this similar molecule is present in a concentration comparable to the concentration of the substrate, it will compete with the substrate for bonding sites on the enzyme and it will interfere with the catalytic action of the enzyme and the substrate. This phenomenon is known as competitive inhibition because the enzyme is inhibited by the inactive substrate, or competitor, so called because it competes with the real substrate for the active site.

Feedback Inhibition

Another kind of inhibition is called feedback inhibition. In feedback inhibition, there is a second binding site on the enzyme where the inhibitor binds, so that the inhibitor is not necessarily similar in structure to the substrate.

The absence or presence of the inhibitor at this second binding site activates or deactivates the enzyme, presumably by changing the conformation of the enzyme so that the active site is made available or unavailable to the substrate. (Or perhaps in other ways.) The inhibitor is usually the product of a reaction farther on down the metabolic pathway.

This diagram (shown more clearly in Example 12 in your workbook) shows schematically a series of five reactions, each catalyzed by its own enzyme, which converts L-threonine to L-isoleucine. Enzyme one, which catalyzes the reaction which involves the removal of the amino group from L-threonine, is called L-threonine deaminase. This enzyme is strongly inhibited by the ultimate product of the five reactions, L-isoleucine. L-isoleucine is quite specific as an inhibitor; other amino acids or related compounds do not inhibit that enzyme. In this way the cell regulates the amount of isoleucine produced. When the concentration of isoleucine begins to get high, the whole chain of reactions is shut down by the inhibition of the first reaction in the series.

Reaction sequence from workbook (example 12) showing feedback inhibition. [68073.jpg]


The entire process of respiration is also regulated by feedback inhibition. Recall that the process involves converting glucose to CO2 and water and forming ATP in the process. Glucose is first converted to pyruvate or pyruvic acid, which then forms acetyl CoA and enters the citric acid (TCA) cycle.

The first step in the citric acid (TCA) cycle involves combining acetyl CoA with a molecule of oxaloacetate or oxaloacetic acid to form a molecule of citric acid or citrate.

68074.jpg (16490 bytes)

The enzyme which catalyzes this step, citrate synthase, is inhibited by ATP. When the cell has a low concentration of ATP, in other words, is low in energy, the citric acid (TCA) cycle operates, feeds the electron transport chain, and ATP is produced. As the energy store of the cell builds up and the concentration of ATP increases, the TCA cycle or citric acid cycle shuts down because the ATP inhibits the citrate synthase and stops the formation of citrate (or citric acid) which is needed for the cycle to operate.

Comparing Competitive and Feedback Inhibition

There are some important differences between competitive inhibition and feedback inhibition.

In competitive inhibition the inhibitor is similar in structure to the substrate and binds to the enzyme at the active site, preventing the substrate from binding. In feedback inhibition, the inhibitor binds to the enzyme at a site away from the active site and acts by altering the shape of the enzyme in such a way that it is incapable of catalyzing the reaction.
Feedback inhibition is a natural part of the process by which an organism regulates the chemical reactions that take place in its cells. In that sense it is done on purpose. Competitive inhibition usually involves inhibitors, commonly called poisons, that do not belong in the cell.


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