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Biochemistry Detoxification (Metabolism of Xenobiotics)

Introduction to Xenobiotics

Topic overview

Start with the big picture

The liver, particularly its smooth endoplasmic reticulum and cytosol, is the primary site of xenobiotic biotransformation; the intestine, lungs, kidneys and skin also contribute. The overall aim is to make lipophilic compounds more water-soluble for excretion, commonly through urine or bile. Metabolism is organized into three phases: Phase I modifies or exposes functional groups, Phase II attaches hydrophilic groups, and Phase III transports compounds across membranes for efflux. These processes can be altered by enzyme induction or inhibition, genetic variation, and factors such as age, liver disease or malnutrition. Some Phase I reactions generate reactive intermediates that may contribute to cellular injury, making metabolism clinically relevant to both drug response and toxicity.

Learning objectives

What you'll learn

  • Define xenobiotics and identify common examples.
  • Describe the primary and secondary sites of xenobiotic metabolism.
  • Distinguish the roles of Phase I, Phase II and Phase III.
  • Explain how metabolism can contribute to toxicity as well as elimination.
  • Recognize factors that can alter detoxification capacity.
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