1. METABOLISM OF XENOBIOTICS
dr Agus Budiman

2. Xenobiotics ( Xenos = strange) are compounds that are foreign to the body.
It includes drugs, food additives, pollutants etc.
Understanding how xenobiotics are handled at the cellular level is important in learning how to cope with the chemical attack.

3. Catabolism of xenobiotics
Metabolism of xenobiotics is considered in:
phase 1: involved hydroxylation, catalyzed by monooxygenases or cytochrome P450( involved by NADPH).
phase 2: conjugation with glucuronic acid,sulfate, acetate, glutathione, or certain amino acids, or by methylation.

4. The overall purpose of the two phases is to increase their water solubility( polarity) and thus excretion from the body.
Xenobiotics are prodrugs or procarcinogens.
Detoxification is usually used as terms to metabolism of xenobiotics.

5. Cytochrome P450 Hemoprotein, like hemoglobin.
Widely distributed across species.
Present in highest amount in liver and small intestines, mainly in the membranes of the smooth endoplasmic reticulum.
Substrate specificity.
NADPH is involved in reaction mechanism in cyt P450.
Lipids also components of cyt P450 system.
Most of cyt P450 are inducible.

6. Certain isoforms of cyt P450 involved in metabolism of PAH( polycyclic aromatic hydrocarbons) and called AHH( aromatic hydrocarbon hydroxylases).
Certain cyt P450 exist in polymorphic forms.

7. Conjugation reactions
Glucuronidation
Sulfation
Conjugation with glutathione
Acetylation e.g. in INH( isohydrazid)
Methylation

8. Activities of xenobiotics metabolism affected by species, genetic factors, gender, age.
Intake phenobarbital or certain hydrocarbons can cause enzyme induction.

9. The goal of xenobiotics metabolism is make xenobiotics less poisonous or nontoxic metabolite.