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Enzymatic Redox Chemistry 147
Iron is the only metal utilised in haem-dependent mono-oxygenases.
However, metal-dependent mono-oxygenases are found which involve other
redox-active metal ions such as copper, which can access the þ1 and þ2 oxidation
states, and hence also has the ability to interact with molecular oxygen.
6.9 a-Ketoglutarate-dependent dioxygenases
Dioxygenases are enzymes that incorporate both atoms of dioxygen into the
product(s) of their enzymatic reactions. The Wrst class of dioxygenases that we
shall consider catalyse hydroxylation reactions that at Wrst glance seem similar
to the P 450 -dependent mono-oxygenases. However, there are two diVerences:
(1) these enzymes use a-ketoglutarate as a co-substrate, which they convert
into succinate and carbon dioxide;
(2) they use non-haem iron rather than the haem cofactor.
As in the haem enzymes, the non-haem iron(II) can donate one electron to
oxygen, forming iron(III)-superoxide which can react with the carbonyl group
of a-ketoglutarate, forming a cyclic peroxy intermediate. Decarboxylation of
this intermediate releases succinate and produces an iron(IV)-oxo species. This
species can carry out the hydroxylation reaction via a radical mechanism shown
in Figure 6.36, which is similar to the P 450 mono-oxygenase mechanism.
An important member of this family of enzymes is prolyl hydroxylase,
which catalyses the hydroxylation of proline amino acid residues in developing
General reaction
R H +
– O 2 C
O
dioxygenase
CO – – 2 O 2 C CO –
R OH +
2
O 2 , Fe 2+
+ CO 2
Mechanism
O 2
Fe II
– O 2 C
O
O O O O
O Fe III − O Fe IV
O
O
O
O −
Fe IV
– O 2 C
– CO 2
O 2 C – O 2 C
R OH +
Fe II
R
OH
Fe III
R H
O
O −
O
Fe IV
– O 2 C
Figure 6.36 a-Ketoglutarate-dependent iron(II) dioxygenases.