Metabolism of Xenobiotics
A) Parent compound toxic. Metabolites non-toxic.
B) Parent compound non-toxic. Metabolites toxic.
- Toxic metabolites formed in situ
- Toxic metabolites formed in liver and transported
- e.g., Parathion (nerve poison):
- CHARACTERISTICS OF XENOBIOTICS?
- Penetrate membranes by diffusion
- Transported by lipoproteins in blood
- HOW ELIMINATE?
- Diffusion (limitations?)
- Excrete (limitations?)
- MAKE IT WATER SOLUBLE!!!!!!
- Phase I -- Polar reactive groups introduced
- Phase II -- Covalent "conjugation" to endogenous substances:
- amino acids
- inorganic ions
1. Changes activity of xenobiotics
- Quantitative (detox or activation)
- Qualitative (disposition and effect)
2. Phase I products most often
more polar and less lipophilic
3. Phase II reactions most often abolish biological activity and add to
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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