PRINCIPLES OF TOXICOLOGY

3.2 BIOTRANSFORMATION REACTIONS
There 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 single
site (e.g., sulfation and glucuronidation of the phenolic group of acetaminophen), and more than one
enzyme/isozyme capable of catalyzing a single reaction at a single site. An example of the complexity
of possible metabolism of a relatively simple hypothetical chemical is shown in Figure 3.7. From
considerations in this chapter so far, it can be seen that the subcellular location of a metabolic reaction does
not dictate the nature of the reaction. Both oxidations and hydolyses, albeit by different enzymes, occur in the
cytoplasm and endoplasmic reticulum. Likewise, so do conjugations when considered collectively, but a
specific form of conjugation may occur only in a single fraction (e.g., sulfation in the cytoplasm). The enzymes
are 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; Oxidations
3.2 BIOTRANSFORMATION REACTIONS 65
Microsomal Microsomal oxidations are predominantly catalyzed by a group of enzymes called
mixed-function oxidases or monooxygenases. The terminal oxidase is generally a hemoprotein called
cytochrome P450 but can be a flavoprotein.
Figure 3.7 Possible metabolic conversions of a simple hypothetical xenobiotic.