ABSTRACT
When xenobiotics enter the body they can be metabolized by enzymes that (happen to) have sufficient affinity and activity towards these compounds. Both Phase I (oxidative, reductive or hydrolytic), and Phase II (conjugative) reactions may compete for the same substrate. Even for a simple structure like paminosalicylic acid, several pathways compete for biotransformation (Figure 3.1). For example, enzymes may compete for conversion of different groups in the molecule, while at the same time there is also competition for conversion of the same group. The outcome usually is a whole array of metabolites that are excreted mainly in urine or faeces, in a species-and dosedependent pattern. Further metabolism of a primary metabolite (for instance, a glutathione conjugate which is converted in several steps to a mercapturate) may lead to additional metabolites. Several factors determine the outcome of this interplay between enzymes, substrates, co-substrates, the organs in which these processes take place, and the pharmacokinetics of distribution and elimination of the substrates. Obviously the chemical structure of the substrate determines all subsequent events.
