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148 Chapter 6
HO
H
N
N
O
O
H
N
prolyl hydroxylase
Fe 2+ , O 2 , αKG
(ascorbate) red
H
N
N
O
O
H
N
HO
OH
O
O
HO
OH
O
O
HO
OH
O
O
− O OH Fe 3+ Fe 2+ O OH Fe 3+ Fe 2+ O O
reduced ascorbate ascorbate radical oxidised ascorbate
Figure 6.37 Prolyl hydroxylase and the role of ascorbate as a reducing agent.
collagen Wbres to 4-hydroxyproline. Collagen is a very important structural
protein found in skin, teeth, nail and hair, and the presence of hydroxyproline is
necessary for maintenance of the tertiary structure of the protein. This enzyme
also uses ascorbic acid – vitamin C – as a cofactor, and this is one of the major
functions of vitamin C in the body. The overall reaction does not apparently
require any further redox equivalents, but ascorbic acid is required in nonstoichiometric
amounts for full activity. The probable role of ascorbic acid is to
maintain the iron cofactor in the reduced iron(II) state in cases where the
catalytic cycle is not completed. For example, if superoxide is released from
the enzyme active site an inactive iron(III) form of the enzyme is generated.
Ascorbic acid has the ability to reduce iron(III) to iron(II), generating a stable
ascorbate radical shown in Figure 6.37. Thus in the absence of vitamin C the
body’s machinery for making collagen is impaired, leading to the symptoms of
the dietary deWciency disease scurvy.
6.10 Non-haem iron-dependent dioxygenases
There are a number of further non-haem iron-dependent dioxygenase enzymes,
of which I shall introduce two: the catechol dioxygenases and the aromatic
R
dihydroxylating
dioxygenase
O 2 , Fe 2+ ,
NADH
R
OH
OH
dihydrodiol
dehydrogenase
NAD +
R
intradiol
dioxygenase
O 2 , Fe 3+
OH
OH
extradiol
dioxygenase
O 2 , Fe 2+
R
CO −
2
CO −
2
R
O
CO −
2
OH
Figure 6.38 Aromatic hydroxylation/cleavage reactions.