Chapter 23 - Metabolism of Pesticides

Abstract

This chapter focuses on the metabolism or biotransformation of xenobiotics, especially pesticides. The metabolism of xenobiotics generally occurs in two phases. Phase I involves predominantly oxidations, reductions, and hydrolyses, and serves to introduce a polar group into the molecule. Phase II, consisting primarily of conjugation reactions, involves the combination of the products of phase I reactions with one of several endogenous molecules to form water soluble, and hence excretable, products. In the past, the most emphasis has been placed microsomal cytochrome P450 (P450)-dependent oxidations and reductions of pesticides, and they are described in detail in this chapter. With the exception of glutathione conjugation, phase II conjugation reactions involving pesticides are secondary, involving, as substrates, the products of phase I reactions. They include glutathione conjugation, glucoside formation, glucuronic acid formation, sulfate formation, and conjugation with amino acids. This chapter describes various factors affecting the metabolism of xenobiotics, including species differences due to differences in activity of liver microsomal enzymes, gender of the organism, polymorphisms in the expression of the xenobiotic metabolizing enzymes. The terms resistance and tolerance refer to a relative insusceptibility of a population of organisms to the effects of a toxicant.