Drugs that target enzymes

Enzyme inhibitors (I) may have either a reversible or irreversible action. Reversible inhibitors tend to bind to an enzyme (E) by electrostatic bonds, hydrogen bonds and van der Waals forces, and so tend to form an equilibrium system with the enzyme. A few reversible inhibitors bind by weak covalent bonds, but this is the exception rather than the rule. Irreversible inhibitors 

These are inhibitors that form a dynamic equilibrium system with the enzyme. The inhibitory effects of reversible inhibitors are normally time dependent because the removal of unbound inhibitor from the vicinity of its site of action by natural processes will disturb this equilibrium to the left. As a result, more enzyme becomes available, which causes a decrease in the inhibition of the process catalysed by the enzyme. Consequently, reversible enzyme inhibitors will only be effective for a specific period of time. 

Non-competitive inhibitors bind reversibly to an allosteric site (see Appendix 7) on the enzyme. In pure non-competitive inhibition, the binding of the inhibitor to the enzyme does not influence the binding of the substrate to the enzyme. However, this situation is uncommon, and the binding of the inhibitor usually causes conformational changes in the structure of the enzyme, which in turn affects the binding of the substrate to the enzyme. This is known as mixed noncompetitive inhibition. The fact that the inhibitor does not bind to the active site of the enzyme means that the structure of the substrate cannot be used as the basis of designing new drugs that act in this manner to inhibit enzyme action. 

SELECTED EXAMPLES OF DRUG ACTION AT SOME COMMON TARGET AREAS 

Uncompetitive inhibitors are believed to form a complex with the enzyme substrate complex. The formation of this complex prevents the substrate reacting to form its normal product(s). 

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We have concentrated on drugs that target enzymes, but already there are drugs that target DNA instead, and this approach could grow in the future. 

Another point of interest is that the brain expresses more of the total genetic information in its DNA than does any other organ, perhaps 10-20 times as much. Thus, in addition to the metabolic and maintenance machinery shared by most cell types, neurons contain many unique macromolecules, including enzymes, ion channels, neurotransmitters, and receptors that are not found in other cells. Drugs that target these sites produce selective changes in nervous system activities that are directly related to altered behavior. In some cases the effect is desired while in others this is obviously not the case. 

Synaptic transmission is the transfer of biological information across synapses. Drugs that influence synaptic transmission play an eminent role in therapy, for two reasons. First, the nervous system controls all tissues. Second, with few exceptions synaptic transmission is chemical, operating by means of transmitter substances, and synapses therefore provide a large number of drug targets, such as the enzymes that synthesize the transmitter. However, the importance of... 

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