BIOLOGY Volume 1 - A Guide to General Biology - 2004

4. ENZYMES

4.4. Enzyme Inhibition

4.4.4. Allosteric Enzymes

One of the most common ways to regulate metabolic pathways is through allosteric Enzymes. Enzymes whose action intrinsically involves A change in shape are called allosteric (from the Greek állos meaning 'other' and stereós meaning 'solid' or 'shape'). The activity of such enzymes is regulated by substances that act similarly to non-Competitive Inhibitors. These molecules bind to specific sites on the enzyme located away from the Active Site, thereby altering enzyme activity by inducing a reversible change in The Structure of the active site.

As a result, the substrate's affinity for the enzyme is also altered (which distinguishes this phenomenon from standard non-competitive inhibition; see Section 4.4.2). Substances operating in this manner are referred to as allosteric inhibitors. Fig. 4.14 illustrates The Mechanism of allosteric inhibition.

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Fig. 4.14. Allosteric inhibition.

A classic example of this phenomenon occurs during Glycolysis, which is a stage of cellular Respiration. Cellular respiration serves as the primary source of ATP. When ATP concentration is high, ATP acts as an allosteric inhibitor, suppressing the activity of one of the glycolytic enzymes. Conversely, when cellular METABOLISM accelerates—and consequently, ATP is consumed and its overall concentration drops—the inhibitor dissociates, and the metabolic pathway resumes operation. This also serves as a prime example of end-product inhibition.

End-product inhibition (negative feedback inhibition / feedback inhibition)

When the end product of a metabolic pathway begins to accumulate, it can act as an allosteric inhibitor on the enzyme that controls the initial step of that pathway. Thus, as the product accumulates, it halts its own further synthesis. This process is self-regulating: as soon as the product is depleted, its production restarts. This phenomenon—end-product inhibition—is a classic example of a mechanism operating via a negative feedback loop (Fig. 4.15) (see also Chapter 19).

Fig. 4.15. End-product inhibition. Specific enzymes catalyzing individual steps of the metabolic pathway are designated by letters e₁– e₄.

4.5. The branched metabolic pathway is shown below:

a) It is known that e₁ is specific for A and that the end product X inhibits e₁. Given this, what can be deduced about the sites on the enzyme molecule where A and X bind?

b) How can an excess of X regulate this metabolic pathway?

c) What is the term for the type of regulation operating in this system?