Biotransformation Flashcards
Xenobiotic
A chemical found in an organism which is not normally produced or expected to be in it
4 properties of pharmacokinetics
Absorption, Distribution, Metabolism, Excretion
What crosses membranes more readily, polar molecules or non-polar molecules?
Non-polar molecules
What types of molecules tend to get filtered at the glomerulus?
Small, charged, non-protein bound molecules
Where do most metabolic enzymes in the liver appear and what are these enzymes called?
In the membranes of the smooth ER (also a little bit in microsomal fraction of tissue homogenate and thus are called microsomal enzymes)
What is the underlying purpose of drug metabolism?
To make less polar drugs into more polar drugs so that they can be eliminated via the kidneys
What type of compounds are most readily excreted by the kidneys, hydrophilic or hydrophobic?
Hydrophilic (polar)
Phase I metabolism
Reactions to introduce or expose a functional group (typically oxidation, reduction, or hydrolysis)
Where does Phase I metabolism usually occur?
ER
What type of proteins are cytochrome p450s?
Heme-thiolate proteins
How does the activity of CYPs involved in drug metabolism tend to differ from that of CYPs involved in synthesis?
Metabolic CYPs tend to have broad specificity, synthetic CYPs tend to be very specific for substrates
Reactions catalyzed by CYP (types of chemical reactions)
Aliphatic hydroxylation, aromatic hydroxylation, N-,O-,or S-dealkylation, Oxidative deamination, dehalogenation, N- and S-oxidation
What are the most important CYP in terms of mass of enzyme and number of drugs metabolized?
3A4 and 3A5
What CYP is absent in 7% of caucasians while 33% of Ethiopians and Saudia Arabians are ultrarapid metabolizers?
2D6
Which CYP is responsible for generation of reactive acetaminophen metabolite and resultant toxicity?
2E1
