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All enzymes are able to use alternative substrates. When these are naturally occurring metabolites, an 'underground reaction' takes place. Examples are presented in which underground metabolism of this sort produces an observable phenotype. Although biological processes can be remarkably accurate, evolution has selected error rates far from perfect. It is suggested here that a certain level of metabolic inaccuracy, in addition to saving energy, may also confer an evolutionary advantage, for example by providing metabolic plasticity. Since underground reactions are unpredictable from DNA sequence data, caution is in order when interpreting correlations between genetic disorders and pathological syndromes.
D’Ari et al. (Sun,) studied this question.