Enzymes

Enzymes are closely related to receptors in their structure and related functional properties. Many receptors have enzymatic actions (e.g. Na+K+ATPase in the cell membrane). They possess binding sites that bind substrates with low energy bonds. Enzymes are proteins sometimes linked with co-enzymes such as vitamins or ions. They provide a low energy pathway that facilitates a reaction so that equilibrium is reached more rapidly. Enzymes do not alter the final product nor alter the position of the equilibrium. The effects of an enzyme are similar to that of providing energy in other ways such as thermal energy, but avoid the obvious tissue damage that this would entail. Enzymic processes may be synthetic or destructive. Enzyme kinetics, which bear a strong resemblance to receptor kinetics are outlined below. Thus for a synthetic reaction:

The law of mass action indicates that the reaction rate in each direction is proportional to the product of the concentrations on each side. x and y represent numbers of substrate molecules A and B; AxBy is the product of the reaction. The relative concentrations at equilibrium are defined by the equilibrium constant (Keq).

The equilibrium constant is a feature of the reaction itself regardless of whether or not an enzyme is present. Therefore, an additional concept is required to compare enzymatic function. This is the initial velocity of the enzyme-catalysed reaction, the velocity of the reaction when negligible substrate has reacted.

The equation for initial velocity is based on the reaction:

SiilKtrjtr (S) +■ ILiiJTvnic * I'^xJuG"! (¡'} + liiwyiiLC

which may be expressed as follows: where:

V = initial velocity

Vmax = maximum initial velocity

Km = concentration at which the initial velocity is half the maximum initial velocity

Note that this is identical in structure to key equation 3 describing receptor interactions and, therefore, describes a rectangular hyperbola (Figure PD.12).

Some caution should be exercised when alluding to the similarities. While drug and substrate concentrations are comparable terms and Vmax and the initial velocity of the substrate-enzyme interaction might be compared with the efficacy and response of the drug-receptor interaction, Km is not an equilibrium constant. With this in mind, the equations and plots used in the drug-receptor interactions described above can be used to understand the inhibition of enzyme reactions and their plots. Semilogarithmic plots could be used in exactly the same way as with the receptor interactions and similar features would be apparent, but by convention the double reciprocal (Lineweaver-Burk) plot is favoured.

Enzyme inhibition may be competitive (reversible) or non competitive which may be reversible or irreversible. Neostigmine provides an example of a competitive enzyme inhibitor. Ecothiopate and monoamine oxidase inhibitors are a non reversible enzyme inhibitors.

False substrates compete for the binding site and in addition have a product, so they are reversible and competitive. Methyldopa is a false substrate for the enzyme dopamine decarboxylase. Inhibition of the enzyme will be the result of more prolonged binding to the enzyme during the reaction. Although neostigmine is a competitive inhibitor of acetyl cholinesterase and is hydrolysed by plasma cholinesterase of which it is a substrate, it is also slowly hydrolysed by the acetylcholinesterase and is, therefore, a false substrate for this enzyme.

0 200 400 6Û0 800 lOOO 1300 MQ0

Substrata coficonirctiQn |S|

0 200 400 6Û0 800 lOOO 1300 MQ0

Substrata coficonirctiQn |S|

Figure PD. 12 Plot of initial velocity against substrate concentration

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