Chapter 3: Enzymes
Enzyme inhibitors Competitive, reversible inhibition
As we have seen, the active site of an enzyme fits one particular substrate perfectly. It is possible, however, for some other molecule to bind to an enzyme’s active site if it is very similar in shape to the enzyme’s substrate. This would then inhibit the enzyme’s function. If an inhibitor molecule binds only briefly to the site, there is competition between it and the substrate for the site. If there is much more of the substrate present than the inhibitor, substrate molecules can easily bind to the active site in the usual way, and so the enzyme’s function is unaffected. However, if the concentration of the inhibitor rises, or that of the substrate falls, it becomes less and less likely that the substrate will collide with an empty site. The enzyme’s function is then inhibited. This is therefore known as competitive inhibition (Figure 3.12a). It is said a Competitive inhibition substrate fits precisely into the enzyme’s active site active site competitive inhibitor has a similar shape to the substrate and fits into the enzyme’s active site
enzyme b Non-competitive inhibition Other molecules may bind elsewhere on the enzyme, distorting its active site.
to be reversible (not permanent) because it can be reversed by increasing the concentration of the substrate. An example of competitive inhibition occurs in the treatment of a person who has drunk ethylene glycol. Ethylene glycol is used as antifreeze, and is sometimes drunk accidentally. Ethylene glycol is rapidly converted in the body to oxalic acid, which can cause irreversible kidney damage. However, the active site of the enzyme which converts ethylene glycol to oxalic acid will also accept ethanol. If the poisoned person is given a large dose of ethanol, the ethanol acts as a competitive inhibitor, slowing down the action of the enzyme on ethylene glycol for long enough to allow the ethylene glycol to be excreted.
Non-competitive, reversible inhibition
A different kind of reversible inhibition takes place if a molecule can bind to another part of the enzyme rather than the active site. While the inhibitor is bound to the enzyme it can seriously disrupt the normal arrangement of hydrogen bonds and hydrophobic interactions holding the enzyme molecule in its three-dimensional shape (Chapter 2). The resulting distortion ripples across the molecule to the active site, making the enzyme unsuitable for the substrate. While the inhibitor is attached to the enzyme, the enzyme’s function is blocked no matter how much substrate is present, so this is an example of noncompetitive inhibition (Figure 3.12b). Inhibition of enzyme function can be lethal, but in many situations inhibition is essential. For example, metabolic reactions must be very finely controlled and balanced, so no single enzyme can be allowed to ‘run wild’, constantly churning out more and more product. One way of controlling metabolic reactions is to use the end-product of a chain of reactions as a non-competitive, reversible inhibitor (Figure 3.13). As the enzyme converts substrate to product, it is slowed down because the endinhibition
active site enzyme 1
substrate
non-competitive inhibitor enzyme
Figure 3.12 Enzyme inhibition. a Competitive inhibition. b Non-competitive inhibition.
enzyme 2
product 1
enzyme 3
product 2
product 3 (end-product)
Figure 3.13 End-product inhibition. As levels of product 3 rise, there is increasing inhibition of enzyme 1. So, less product 1 is made and hence less product 2 and 3. Falling levels of product 3 allow increased function of enzyme 1 so products 1, 2 and 3 rise again and the cycle continues. This end-product inhibition finely controls levels of product 3 between narrow upper and lower limits, and is an example of a feedback mechanism.
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