Chemistry of Fe Flashcards
Where are cytochrome P450s found?
Liver
What type of molecules are cytochrome P450s?
Oxidising molecules
What do cytochrome P450s do to aromatic rings?
Add OH
What do cytochrome P450s do to heterocycles?
Add OH to them
What do cytochrome P450s do to methyl groups?
Change to an alcohol
What do cytochrome P450s do to alkenes?
Form epoxide
How many phases is there in drug metabolism?
2
What is Phase I of drug metabolism?
Functionalisation
What phase are cytochrome P450s part of?
Phase I
What happens in Phase II of drug metabolism?
Conjugation
Describe Phase I (oxidation)
Addition of O
Cytochrome P450
Require cofactors
Whay are examples of cofactors?
NADH
NADPH
O
What is the general equation for cofactors in Phase I oxidation?
R-H + NADPH + O2 + H+ —-> R-OH + NADP+ + H2O
What are cytochrome P450s?
Heme-containing enzymes
What are similar about cytochrome P450s?
Catalytically + structurally similar
Describe iron containing porphyrin
Fe2+/3+ ion at active site
Ligated by 4 N atoms
Sharing of non-bonding e- with metal
Why is there N in iron containing porphyrin?
N holds metal ion on specific position
Metals have preferred geometry
What is the shape of iron containing porphyrin?
Planar = sp2
Describe what happens to iron containing porphyrin prodrug (clopidogrel)
Cytochrome P450 adds O
Then hydrolase adds H2O
Describe what happens to iron containing porphyrin prodrug (clopidogrel)
MORE DETAIL
Reduced to coordinated hydroperoxide (0)
H2O relays cleavage of O-O bond
Highly oxidising intermediate formed (I)
Abstract H, radical forms
OH, transfers from II
Enzyme back to start
Describe cytochrome P450 cycle
Fe3+
Then shunting of e-
Fe2+
Addition of O = radical
Fe3+ -O-O.
Addition of e- via NADPH = no longer radical
Fe3+-O-O
2H+ remove additional O
Fe3+-O
C-H bond cleaved by adding OH
R-OH removed