Aging Aging

120 Barnett and IoannidesFig. 1. Metabolic activation of chemicals.parent compounds often have high affinity. The metabolism of chemicals occursthrough an enzymic process that involves a number of enzyme systems presentin many tissues, the highest concentration being encountered in the liver. Themetabolism of chemicals is generally achieved in two phases. Phase I involvesprimarily the incorporation of an atom of oxygen to the substrate, producing amore hydrophilic, and in most cases biologically inactive, metabolite that cannow participate in Phase II metabolism. During Phase II metabolism, the newlygenerated metabolite is conjugated with endogenous substrates, such as sulfateand glucuronide, to form highly hydrophilic products that can now be veryreadily eliminated.1.1. Metabolic Activation of ChemicalsAlthough metabolism of chemicals is essentially a deactivation process,with certain chemicals one or more metabolic pathways may lead to the generationof reactive intermediates, a phenomenon known as metabolic activationor bioactivation (Fig. 1). Because of their increased chemical reactivity,