Why is uncompetitive inhibition so rare?. A possible explanation, with implications for the design of drugs and pesticides

Abstract

Uncompetitive inhibition is much less common in nature than consideration of enzyme structure and mechanism might lead one to expect. A possible explanation may be that uncompetitive inhibition of an enzyme in a metabolic pathway can have enormously larger effects on the concentrations of metabolic intermediates than competitive inhibition, under circumstances where their effects on the kinetics of the isolated enzyme are very similar. The severely toxic effects that an uncompetitive inhibitor might be expected to have may have caused enzymes to have evolved in such a way that there has been selection against structures that might favour uncompetitive inhibition. Enzyme kinetics Uncompetitive inhibition Catastrophic response Pesticide design. © 1986.