CHAPTER 1
 BIOTRANSFORMATION AND ITS IMPORTANCE INT THE DETOXIFICATION OF
 XENOBIOTIC S

 The exposure of biological systems to environmental compounds which may be

potentially toxic to these systems has spurred the evolution of an elaborate, protective

biochemical system whereby these xenobiotics are eliminated from cells and whole

organisms, usually via chemical transformation (or biotransformation). This system is

composed of a multitude of enzymes, which while being distributed in many tissues and

organs, are principally located in organs such as liver, intestine and lungs. This is of

physiological significance since these tissues represent major routes of xenobiotic entry

into organisms. Within cells, biotransformation enzymes also display a level of

organization in that while some are soluble and found in the cytosol (e.g.

sulfotransferases (SULT), glutathione-S-transferases), others are relatively immobile and

membrane-bound (e.g. UDP-glucuronosyltransferases (UGT) and cytochrome P450s

(CYP) in the endoplasmic reticulum).

 Since it is highly improbable that the organism has a substrate-specific enzyme for

metabolizing every potential xenobiotic, biotransformation enzymes are generally non-

specific, acting on a broad range of structurally unrelated substrates. In addition, several

isoforms of the same enzyme (or more than one enzyme) may catalyze product formation

from the same substrate, albeit at different rates and with different affinities. Enzymes in

the same superfamily as those that act upon xenobiotics can also biotransform

endogenous substances, indicating an equally important regulatory role for these