Introduction of H2O
Hydrolysis
Esterases:
esters
Hydrolysis Peptidases/amidases:
amides
Responsible for the majority of oxidation reaction.
CYTOCHROME P450
CYTOCHROME P450 (abbreviated as
P450 or CYP
CYTOCHROME P450 found in
liver
Derived from the spectral properties of this
hemoprotein
In its reduced (ferrous) form, it binds carbon monoxide to give
a complex that absorbs light maximally at
450 nm
The relative abundance of P450’s compared with that of the
(blank) in the liver, contributed to making (blank), a rate limiting step in hepatic drug oxidations.
reductase, 450 heme
reduction
Microsomal drug oxidations require
P450, P450 reductase,
NADPH and molecular oxygen.
Identified numerous P450 isoforms CYP:
1A2, 2A6, 2B6,2C8,2C9,2C18,2C19,2D6,2E1,3A4,3A5,4A11,
and 7) in the human liver
Most Important Forms:
CYP1A2, CYP2A6,CYP2B6,CYP2C9,CYP2D6,CYP2E1 and
CYP3A4
CYP1A2,
14%,
CYP2A6
4%
,CYP2B6
1%
,CYP2C9,
20%
CYP2D6,
5%
CYP2E1
10%
CYP3A4
0%
They are responsible for catalyzing the bulk of the
hepatic
drug and xenobiotic metabolism