2.7 Flashcards
(23 cards)
Where is MFO located?
Smooth ER
What part of the centrifuged medium is the microsomes located?
Bottom Pellet
When not catalyzing a reaction what state is iron in?
3+
Reduction by CYP450 reductases changes iron to what state?
2+
What 2 things happens when CYP450 is in the +2 state?
Binds molecular oxygen
Binds carbon monoxide
Speed of hydroxylation of aromatic compounds?
Relatively slow
What does the oxidation of aromatic compounds (arenes) by MFO’s lead to?
Formation of phenols
Phenolic metabolites undergo conjugation with what type groups?
Water soluble groups
During hydroxylation of aromatic compounds what happens to the fat and water solubility?
Fat solubility decreases
Water solubility increases
What aids in renal excretion?
Fat solubility decreasing
Water solubility increasing
Oxidation of aromatic hydroxylation is believed to proceed?
Via arene oxide intermediate
What rearranges to give a phenol during aromatic hydroxylation?
The arene oxide
How are dihydrodiols formed?
By enzymatic hydration of the arene oxide by microsomal epoxide hydrase or by direct addition of water
What are unstable and may rearrange to afford the phenol or undergo the NIH shift?
Arene Oxide
What was the first evidence for formation of the epoxide intermediate?
NIH shift
What influences aromatic oxidation?
Nature of the functional groups on the aromatic ring.
Steric Factors
Where does hydroxylation occur?
In electron rich rings
At what position does hydroxylation occur?
Normally para
Which is hydroxylated if there is 2 aromatic rings?
The more electron rich ring
What do electron withdrawing groups do to the rate of oxidation?
Decrease it
Olefin (alkene) oxidation
Catalyzed by MFO
Faster than aromatic oxidation
Epoxides more stable than arene oxides
What reaction may be hydrated to give 1.2-dihydrodiols?
Olefin (alkene) oxidation
Benzylic and Allylic Oxidation
Fast Reactions catalyzed by MFO
The alcohol products may be further metabolized or conjugated.
