METABOLISM OF XENOBIOTICS

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METABOLISM OF XENOBIOTICS

• dr Agus Budiman

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• 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.

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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.

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• 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.

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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.

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• 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.

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Conjugation reactions

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

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

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