Drug Metabolism in Drug Design and Development Basic Concepts and Practice

2.5.4 Aldehyde Oxidase and Xanthine Dehydrogenase

These two enzymes are found in the cytosol of the liver (and other tissues) and
also oxidize substrates (Panoutsopoulos et al., 2004; Rajagopalan, 1997), with
a very different stoichiometry and mechanism:

RHþH 2 O!ROHþ2e

The two electrons may be transferred to an oxidized pyridine nucleotide or
to O 2 (yielding H 2 O 2 ).
These enzymes contain flavin, a molybdenum center, and Fe–S clusters in
the ratio 1 : 1 : 4. The pathway of electron flow is from Mo to Fe–S to FAD.

N

H

N

NH

N O

O

O

O

H

NH 2

N

H

N

NH

N O

O

O

H

OH

NH 2

H

N

N

NH

N O

O

OH

NH 2

••

+

•• ••

••

FIGURE 2.6 Proposed mechanism of hydroxylation of activated aromatic ring by
FMO (Frederick et al., 1982).

OXIDATION ENZYMES 23