Biochemistry II lectures 5&6 Flashcards
What are some functions of Cytochrome P450?
-drug metabolism
-steroid hormone synthesis
-fatty acid metabolism
-monooxygenases
-production of vitamin A and D
What is the importance of CYP3A4?
-estimated to act on 30-50% of known drugs
-major player in drug metabolism
-responsible for poor oral bioavailability of some drugs
location: liver
describe the structure of Cytochrome P450
-has a heme group (site for oxidation)
-located in membrane (either ER or mitochondria)
What are the three possible outcomes of metabolism of xenobiotics?
-inactivation (drug metabolism)
-activation (prodrug conversion)
-formation of a highly toxic metabolite (Benzopyrene from coal burning, cigarettes, charcoal briquettes)
what type of drug-drug interactions occur with Cytochrome P450?
-induction of P450 (increased P450 activity)—leads to decreased drug plasma levels
-Inhibition of P450—-leads to increased drug plasma levels
What occurs in CYP3A4 induction?
increases rate of metabolism of many drugs cleared through the liver
-Rifampicin
-St. John’s wort
What occur in CYP3A4 inhibition?
-activity is enzymatically inhibited by one drug, which affects metabolism of many other drugs
-erythromycin and ketoconazole inhibit which causes high blood plasma levels to increase of terfenadine
What are electrochemical-potential-driven transporters?
-does not require ATP (passive transportation)
-direction of transport is determined by electrochemical potentials; down concentration gradient
what is an example of electrochemical gradient transporter?
-Na+/glucose cotransporter (SGLT)
-transport is driven by Na+ (electrochemical gradient)
Which is not a possible outcome from metabolism of xenobiotics and drugs?
1. activation
2. increased structure rigidity
3. inactivation
4. formation of a highly toxic metabolite
5. increased. substrate solubility
- increased structure rigidity
