Theoretical aspects of competitive antagonism

The theory of competitive antagonism has been reexamined and equations derived for characterizing it. It has been shown that the inhibition index¹ is not constant but is a linear function of the reciprocal of the substrate concentration.In applying this relation to results of antimetabolite studies, it has been found that two types of graph result, those with a negative and those with a positive slope. It is suggested that these graphs distinguish two types of antagonist, the true competitive antagonist and the apparent competitive antagonist, the latter, in fact, undergoing the same reaction as the substrate with the formation of an inhibitory product.With the help of equations derived above, the mode of action of sulphanilamide has been examined. The results suggest that sulphanilamide is metabolised in the same way as p-aminobenzoic acid with the formation of an inhibitory analogue of folic acid.A theory to account for growth stimulation by low concentrations of inhibitors has been presented, and the means for testing it outlined. It is based on the postulate that the curve relating the concentration of enzyme-substrate complex to the concentration of enzyme is not hyperbolic but sigmoid, and it is developed by analogy with the known behaviour of carbon monoxide and oxygen towards haemoglobin.