All of the thousands of drug biotransformation reactions (as well as all normal metabolic processes) are catalysed by enzymes. The drug substance that is acted on by an enzyme is called the substrate of that enzyme. On the other hand, the enzyme, representing a compound that increases the rate or velocity of a biochemical reaction is called the catalyst. Several aspects should be emphasised from the outset: most (but not all) biological catalysts are proteins (these are called enzymes); a catalyst, though it participates in the reaction process, is unchanged by it, at the end of reaction being found again in exactly the same state as before, ready for another cycle of biotransformation; catalysts change rates of processes but do not affect the position of equilibrium of a reaction. This means that a thermodynamically favourable process is not made more favourable, nor is an unfavourable process made favourable, by the presence of a catalyst. Instead, the equilibrium state is simply approached more rapidly. It being generally accepted that for a reaction to take place energy is needed, we present an explanation of how enzymes function.

The barrier preventing a chemical reaction from occurring is called the activation energy and refers to a high-energy transition state that a reactant molecule has to pass through in order to form products. Catalysts function by lowering this activation energy, binding the substrate in an intermediate conformation that resembles the transition state but which has a lower energy. In enzyme catalysis, one or more substrates are bound at the active site of an enzyme to form the enzyme-substrate complex, which is a highly reactive species that promotes the reaction and releases the product(s). It is important to stress the fact that the active site portion of the enzyme molecule is not one continuous sequence of the protein. Because of the coiling of the molecule, portions of the amino acid sequence that are far removed from one another if the protein were to be stretched linearly come into close proximity when the molecule folds into its proper conformation

The reaction rate of the enzyme and (indirectly) the amount of enzyme present in the biological material under study can be estimated. Usually, in measuring the rate of reaction, one determines the amount of product formed and divides by the time required to form that amount of material. Inspection of Eq.4.1 shows that each molecule of substrate must combine with a molecule of enzyme to form a molecule of product. However, in measuring enzyme activity, we assume that that there are many more substrate molecules than enzyme molecules. In this situation, each enzyme molecule will bind substrate and convert it, then accept another substrate molecule for further reaction, and so on. It follows that the substrate cannot be converted any faster than the number of enzyme molecules present allows. The enzyme level is therefore said to be ‘rate-limiting’. However, when an enzyme reaction is studied, several parameters are involved.

Best Regards,
Nancy Ella
Associate Managing Editor
Drug Designing: Open Access