Chemistry Reference
In-Depth Information
CYP450 is bound within a haem co-factor and can exist in a number of
oxidation states, of which Fe
2
(ferrous) and Fe
3
(ferric) are the most
important.
A detailed description of the (fascinating) molecular mode(s) of
action of this important enzyme system is beyond the scope of this topic
and the interested reader should consult textbooks of biochemistry, phar-
macology, or medicinal chemistry for more information. What is important
is that a student should understand the functional group interconversions
brought about by CYP450 and appreciate the metabolic effects of these
changes on the physicochemical properties of drugs.
The oxidations brought about by CYP450 may be simple oxidation of
a part of the drug molecule, e.g. a side-chain or aromatic ring, or may
involve more complicated transformations in which a functional group is
lost from the molecule in the course of the oxidation reaction. Examples of
this type of transformation are
O
- and
N
-dealkylations (in which an alkyl
group is lost) and deaminations (in which an amino group is lost). A list of
the types of transformation catalysed by CYP450s is shown in Table 5.1.
This list is not intended to be exhaustive; it merely indicates the range of
chemical interconversions catalysed by this enzyme system.
Table 5.1
Oxidative biotransformations catalysed by CYP450
Substrate
Product(s)
1. Side-chain oxidation
O
CH
3
O
CH
3
CH
3
CH
3
OH
HN
HN
CH
3
CH
3
O
O
O
N
H
O
N
H
Pentobarbital
CH
3
OH
CH
3
CH
3
CH
3
CH
3
COOH
COOH
Ibuprofen
CH
3
CH
3
CH
3
HO
COOH
(continued)
