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Metabolism of Xenobiotics
Dr Rupali Sengupta
Coordinator-MScCND
Dr BMN College of Home Science
Affiliated to SNDT women’s University
338 R.A.Kidwai Road Matunga
Xenobiotics
• A xenobiotic (Gk xenos "stranger") is a
compound that is foreign to the body.
• Types of Xenobiotics:
• Exogenous & Endogenous
Types of Xenobiotics
• Exogenous- The foreign molecules which gain
entry through dietary food stuffs, or in the
form of certain medicines/ drugs used for a
therapeutic cause or are inhaled through
environment .
• Examples: Drugs, food additives, pollutants,
insecticides,etc
• Endogenous
These are synthesized in the body or are
produced as metabolites of various processes in
the body.
Examples-Bilirubin, Bile acids, Steroids,
Eicosanoids and certain fatty acids.
Metabolism of Xenobiotics
• Metabolism of xenobiotics occurs in two phases-
• Phase 1, the major reaction involved is hydroxylation. In addition to
hydroxylation, a wide range of reactions also take place including-
 Deamination,
 Dehalogenation,
 Desulfuration,
 Epoxidation,
 Peroxygenation,
 Reduction
• Phase 2, the hydroxylated or other compounds produced in
phase 1 are converted by specific enzymes to various polar
metabolites by conjugation with-
 Glucuronic acid,
 Sulfate, acetate,
 Glutathione, or
 Certain amino acids,
 By methylation.
Detoxification Reactions
 All the biochemical reactions involved in the
conversion of foreign, toxic and water insoluble
molecules to non toxic, water soluble and excretable
forms are called Detoxification / Biotransformation
reactions
 The overall purpose of the two phases of metabolism of
xenobiotics is to increase their water solubility
(polarity) and thus excretion from the body.
• Significance
– Converts lipophilic to hydrophilic compounds
– Facilitates excretion
• Consequences
– Changes in solubility characteristics
– Detoxification
– Metabolic activation
Function of Liver
 Main organ involved-Liver
 Hepatocytes contain wide variety of enzymes to
process xenobiotics
 Enzymes are present in cytosol, endoplasmic reticulum
and to lesser extent in other organelles
 Each enzyme represents a large family of gene product
Phase 1 reactions can also convert xenobiotics from inactive to
biologically active compounds.
Phase 2/conjugation reactions can convert the active products of phase 1
reactions to less active or inactive species, which are subsequently excreted in
the urine or bile.
Factors affecting Biotransformation of drugs
 Prior administration of the drug or Co administration of other drugs
 Diet
 Hormonal status
 Genetics
 Disease (e.g., decreased in cardiac and pulmonary disease)
 Age and developmental status
 Functional status of Liver and Kidney
Effects of Xenobiotics
References
• Review of Biochemistry .Harold A.Harper.30th
Edition.ISBN 9780870410376.
• Biochemistry . Dawn B.Marks. ISBN 978068305979.
• www.pubmed.com

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Xenobiotics Metabolism

  • 1. Metabolism of Xenobiotics Dr Rupali Sengupta Coordinator-MScCND Dr BMN College of Home Science Affiliated to SNDT women’s University 338 R.A.Kidwai Road Matunga
  • 2. Xenobiotics • A xenobiotic (Gk xenos "stranger") is a compound that is foreign to the body. • Types of Xenobiotics: • Exogenous & Endogenous
  • 3. Types of Xenobiotics • Exogenous- The foreign molecules which gain entry through dietary food stuffs, or in the form of certain medicines/ drugs used for a therapeutic cause or are inhaled through environment . • Examples: Drugs, food additives, pollutants, insecticides,etc
  • 4. • Endogenous These are synthesized in the body or are produced as metabolites of various processes in the body. Examples-Bilirubin, Bile acids, Steroids, Eicosanoids and certain fatty acids.
  • 5. Metabolism of Xenobiotics • Metabolism of xenobiotics occurs in two phases- • Phase 1, the major reaction involved is hydroxylation. In addition to hydroxylation, a wide range of reactions also take place including-  Deamination,  Dehalogenation,  Desulfuration,  Epoxidation,  Peroxygenation,  Reduction
  • 6. • Phase 2, the hydroxylated or other compounds produced in phase 1 are converted by specific enzymes to various polar metabolites by conjugation with-  Glucuronic acid,  Sulfate, acetate,  Glutathione, or  Certain amino acids,  By methylation.
  • 7. Detoxification Reactions  All the biochemical reactions involved in the conversion of foreign, toxic and water insoluble molecules to non toxic, water soluble and excretable forms are called Detoxification / Biotransformation reactions  The overall purpose of the two phases of metabolism of xenobiotics is to increase their water solubility (polarity) and thus excretion from the body.
  • 8. • Significance – Converts lipophilic to hydrophilic compounds – Facilitates excretion • Consequences – Changes in solubility characteristics – Detoxification – Metabolic activation
  • 9. Function of Liver  Main organ involved-Liver  Hepatocytes contain wide variety of enzymes to process xenobiotics  Enzymes are present in cytosol, endoplasmic reticulum and to lesser extent in other organelles  Each enzyme represents a large family of gene product
  • 10. Phase 1 reactions can also convert xenobiotics from inactive to biologically active compounds. Phase 2/conjugation reactions can convert the active products of phase 1 reactions to less active or inactive species, which are subsequently excreted in the urine or bile.
  • 11. Factors affecting Biotransformation of drugs  Prior administration of the drug or Co administration of other drugs  Diet  Hormonal status  Genetics  Disease (e.g., decreased in cardiac and pulmonary disease)  Age and developmental status  Functional status of Liver and Kidney
  • 13. References • Review of Biochemistry .Harold A.Harper.30th Edition.ISBN 9780870410376. • Biochemistry . Dawn B.Marks. ISBN 978068305979. • www.pubmed.com