Metabolism of Xenobiotics


Toxication and Detoxication: Must consider both parent and metabolites:

Metabolism may either decrease or increase toxicity.Toxicants can be formed in a variety of ways:

A) Parent compound toxic. Metabolites non-toxic.

B) Parent compound non-toxic. Metabolites toxic.


ABSORPTION/ELIMINATION:

  1. CHARACTERISTICS OF XENOBIOTICS?
  1. HOW ELIMINATE?

Xenobiotic metabolism consists of two phases:

  1. Phase I -- Polar reactive groups introduced
  2. Phase II -- Covalent "conjugation" to endogenous substances:

Generalizations

1. Changes activity of xenobiotics

2. Phase I products most often more polar and less lipophilic

3. Phase II reactions most often abolish biological activity and add to polarity

4. Biotransformation requires energy or energy equivalents

5. Enzyme systems are inducible

6. Enzyme systems are saturable, frequently by depletions of cofactors

7. Systems are age, gender, and species dependent and are affected by exgogenous environmental factors


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