Introduction to Enzyme and Coenzyme Chemistry - E-Library Home

130 Chapter 6
one-electron transfer reactions, whereas NAD is restricted to two-electron
hydride transfers. This seemingly minor point has far-reaching consequences,
since it allows Xavin to react with the most powerful oxidising agent in biological
systems: molecular oxygen.
In the reactions of Xavin-dependent dehydrogenases and oxidases, a pair of
hydrogen atoms is transferred from the substrate to the Xavin nucleus, generating
reduced FADH 2 (or FMNH 2 ). A few examples of reactions catalysed by
these enzymes are shown in Figure 6.13. Since oxidised FAD is required for the
next catalytic cycle, the enzyme-bound FADH 2 must be oxidised in situ. In
the Xavin-dependent dehydrogenases this is done by external oxidants, which
in vivo are electron carriers such as cytochromes. In vitro the reduced Xavin can
be oxidised by chemical oxidants such as benzoquinone.
In the case of the Xavin-dependent oxidases the regeneration of oxidised
Xavin is carried out by molecular oxygen, which is reduced to hydrogen peroxide.
Since the ground state of molecular oxygen contains two unpaired electrons (in
its p 2px,y molecular orbitals) it is spin-forbidden to react with species containing
paired electrons. However, reduced Xavin is able to transfer a single electron to
dioxygen to give superoxide and Xavin semiquinone. Recombination of superoxide
with the Xavin semiquinone followed by fragmentation of the peroxy
adduct generates oxidised Xavin and hydrogen peroxide as shown in Figure 6.14.
How does the Xavin nucleus carry out the dehydrogenation reaction
A number of possible mechanisms have been proposed for Xavin-catalysed
dehydrogenation, which have been much debated in the literature. The four
main possibilities are illustrated in Figure 6.15: hydride transfer from the
O
acyl CoA dehydrogenase
O
R
SCoA
FAD
FADH 2
R
SCoA
− O 2 C
CO 2
−
succinate dehydrogenase
− O 2 C
CO 2
−
FAD
FADH 2
R
NH 3
+
CO 2
−
+ H 2 O
D-amino acid oxidase
FAD
O 2 H 2 O 2
R
O
CO 2
−
+ NH 4
+
R
NH 3
+
+ H 2 O
monoamine oxidase
FAD
O 2 H 2 O 2
R
O
+ NH 4
+
Figure 6.13 Flavin-dependent dehydrogenases and oxidases.