PRINCIPLES OF TOXICOLOGY - Biology East Borneo

3.2 BIOTRANSFORMATION REACTIONS 653.2 BIOTRANSFORMATION REACTIONSThere is multiple redundancy in metabolism. There may be more than one site of attack on a xenobiotic(e.g., amine and ester group of cocaine), there may be more than one metabolic reaction at a singlesite (e.g., sulfation and glucuronidation of the phenolic group of acetaminophen), and more than oneenzyme/isozyme capable of catalyzing a single reaction at a single site. An example of the complexityof possible metabolism of a relatively simple hypothetical chemical is shown in Figure 3.7. Fromconsiderations in this chapter so far, it can be seen that the subcellular location of a metabolic reaction doesnot dictate the nature of the reaction. Both oxidations and hydolyses, albeit by different enzymes, occur in thecytoplasm and endoplasmic reticulum. Likewise, so do conjugations when considered collectively, but aspecific form of conjugation may occur only in a single fraction (e.g., sulfation in the cytoplasm). The enzymesare therefore considered in the following paragraphs by the nature of the chemical reaction that they catalyze,and only for phase I oxidations is the subcellular location used as a convenient subdivision.Phase I; OxidationsMicrosomal Microsomal oxidations are predominantly catalyzed by a group of enzymes calledmixed-function oxidases or monooxygenases. The terminal oxidase is generally a hemoprotein calledcytochrome P450 but can be a flavoprotein.Figure 3.7 Possible metabolic conversions of a simple hypothetical xenobiotic.