Course Description
Considerations of the biochemical mechanisms for the biotransformation of drugs and foreign compounds. Includes reaction mechanisms, ultrastructural considerations, induction mechanisms, methodology, kinetics of inhibition and activation, steroid and amine metabolism. Course is offered jointly with PHCOL 527 on odd years.
Course Schedule
| Date | Topic | Instructor |
|---|---|---|
| Jan 7 | Introduction | Rettie/Thummel |
| Jan 9 | P450 I: Basics- Nomenclature, Substrate Specificity | Rettie |
| Jan 11 | P450 II: Structure-Function | Rettie |
| Jan 14 | P450 III: Reaction Mechanisms A | Totah |
| Jan 16 | P450 IV: Reaction Mechanisms B | Totah |
| Jan 18 | Non-Heme Oxygenases | Rettie |
| Jan 21 | HOLIDAY | |
| Jan 23 | Hydrolysis and Reduction | Rettie |
| Jan 25 | Literature Critique I (20) | Totah |
| Jan 28 | Acetylation/Methylation | Rettie |
| Jan 30 | Exam 1 (80) | |
| Feb 1 | Glucuronidation/Sulfation | Atkins |
| Feb 4 | Glutathione Conjugation | Atkins |
| Feb 6 | Drug Transporters I | Prasad |
| Feb 8 | Drug Transporters II NOTE: Class canceled due to weather |
Prasad |
| Feb 11 | P450 Inhibition I (Reversible) | Kunze |
| Feb 13 | P450 Inhibition II (Irreversible) | Kunze |
| Feb 15 | Activation | Atkins |
| Feb 18 | HOLIDAY | |
| Feb 20 | Exam 2 (70) | |
| Feb 22 | P450 Induction (Nuclear Receptors, Stabilization) | Thummel |
| Feb 25 | P450 Induction (Clinical, Pathophysiological Effects) | Thummel |
| Feb 27 | Pharmacogenomics I | Thummel |
| Mar 1 | Pharmacogenomics II | Rettie |
| Mar 4 | Literature Critique II (20) | Rettie |
| Mar 6 | Safety Considerations in Drug Development | Wienkers |
| Mar 8 | Cellular Toxicity | Totah |
| Mar 11 | Chemical Toxicity | Totah |
| Mar 13 | Toxicity: Avoidance Strategies | Totah |
| Mar 15 | Model Systems: Aristolochic Acid Case Study | Kelly |
| Mar 19 | FINAL EXAM (80) |
Useful Readings
- Correlating Structure and Function of Drug-Metabolizing Enzymes: Progress and Ongoing Challenges (PDF)
- FDA Table of Substrates, Inhibitors and Inducers (PDF)
- Sligar, Stephen G. "Glimpsing the Critical Intermediate in Cytochrome P450 Oxidations." Science 330, 924 (2010). (PDF)
- Rittle J, et al. "Cytochrome P450 Compound I: Capture, Characterization, and C-H Bond Activation Kinetics." Science 330, 933 (2010). (PDF)
- Im S, Waskell L. "The Interaction of Microsomal Cytochrome P450 2B4 With its Redox Partners, Cytochrome P450 Reductase and Cytochrome b5." Archives of Biochemistry and Biophysics (2010). (PDF)
- Isin EM, Guengerich FP. "Substrate Binding to Cytochromes P450." Anal Bioanal Chem. 392:1019-1030 (2008). (PDF)
- Testa B, Pedretti A, Vistoli G. "Reactions and enzymes in the metabolism of drugs and other xenobiotics." Drug Discovery Today 17:549-560 (2012). (PDF-1)
- Testa B, Kramer SD. "Biochemistry of Drug Metabolism - An Introduction." Chemistry & Biodiversity 4:257-332 (2007). (PDF-2)
- Testa B, Kramer SD. "Biochemistry of Drug Metabolism." Chemistry & Biodiversity 4:333-405 (2007). (PDF-3)
- Pryde DC, Dalvie D, Hu Q, Jones P, Obach RS, Tran TD. "Aldehyde Oxidase: An Enzyme of Emerging Importance in Drug Discovery." J. Med. Chem. 53: 8441-8460 (2010). (PDF)