Lecture 8 (EXAM 3) Flashcards
Why is CYP450 also called a Mixed function Oxidase?
-it mostly performs oxidation reactions, a few reduction reactions
-high variability in substrates
-high variability in products (metabolites)
Why is CYP450 also called Monooxygenase?
Monooxygenase: attaches ONE oxygen atom to a molecule
Why is CYP450 also called a Microsomal enzyme?
What are Microsomes? EXAM!!!
-Microsomes don’t exist in cells
-they are formed from smooth ER of cells after preparing a cell
-Microsomes are artifacts of a cell preparation (it wasn’t there before, but after preparing the cell it forms)
-Microsomes contain CYP450
Which of the CYPs are the most important?
-CYP3A4 and CYP2D6, CYP2C19
-because they have the most substrates
-some CYPs are important for specific drugs (f.e. CYP2C19 for Clopidogrel (prodrug))
What is the effect of CYP inducers?
-increase the amount of CYP enzymes by promoting the CYP gene
-an increase in CYP enzyme activity -> increase of rate of metabolism of drug
How do inducers affect the steady-state curve?
It will decrease
What would happen to CYP substrates if it is taken with CYP inhibitors?
A higher substrate concentration because the inhibitor prevents CYP from metabolizing the substrate
-> decreasing the rate of elimination
How do inducers and inhibitors affect a drug’s position in the therapeutic index?
-an increase in CYP inducer will lead to lower drug concentration, and a decrease in CYP inducer can cause higher drug concentration (riks of TOXICITY)
-an increase in CYP inhibitors can lead to higher drug concentration (risk of TOXICITY), decrease in CYP inhibitors can cause lower drug concentration
Which enzyme adds Glucuronitide to substrates?
-UGT Uridine Glucuronitide Transferase
-most common conjugation!
Which enzyme adds Glutathione to substrates?
-GST glutathione sulfone transferase
Function of NAT, SULTs, and TPMT
-NAT (N-Acetyltransferase): modifies amino group to acetyl group
-SULT (Sulfontransferase): transfer sulfate groups
-TPMT: Thiopurinmethy transferase: transfer methyl groups
How is Acetaminophen metabolized?
-Acetaminophen usually undergoes Phase 2 metabolism
-> Gluthathion addition
What causes Acetaminophen overdose?
-Phase 1 metabolism
if Acetaminophen levels are so high (overdose) that Phase 2 enzymes cant pick up, some will undergo Phase 1 -> producing a free radical causing liver damage
How is Acetaminophen overdose treated?
-by replenishing Sulfate conjugate
-with N-Acetyl cysteine (Mucumist)
Which mechanism does the body use for protection from free radicals?
-S.O.D. Super oxide dismutase
-it converts a free radical (O2*) into hydrogen peroxide (HOOH) –> catalases converts hydrogen peroxide into H2O +O2
