Anti metabolites: antagonistic analogues of coenzymes and enzyme substrates

Abstract

The smallest change in the chemical constitution of a selectively toxic agent often makes an enormous change in its biological activity, and many examples of this have been given in Chapter 2. The present chapter deals in greater detail with one cause of high specificity, namely a close resemblance between (a) the normal substrate (or coenzyme) of an enzyme and (b) an agent which inhibits it. In previous editions, these agents were called ‘metabolite analogues’, but the word metabolite has become broader in meaning. To the biochemist, ‘metabolites’ are the intermediates of metabolism, such as the pyruvate ion, fatty acids, oxygen, and the nucleotides. Many pharmacologists, however, use ‘metabolite’ for the degradation product of a xenobiotic (foreign substance). Here we shall speak of anti-metabolites, meaning antagonistic analogues of coenzymes and the substrates of enzymes. Such substances have also been called ‘metabolic inhibitors’.