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142 Chapter 6
neither has a stable semiquinone form, so are capable of only two-electron
transfers. In these respects their chemistry is more similar to nicotinamide than
riboXavin. 1-DeazaXavin on the other hand behaves more like riboXavin in terms
of its redox potential and its ability to carry out one-electron redox chemistry.
Factor F 420 is used as a cofactor in a Ni 2þ -dependent hydrogenase enzyme
found in methanogenic bacteria which uses hydrogen gas to reduce carbon
dioxide to methane. Its role appears to be as one component of a complex
chain of electron carriers in this multi-enzyme complex. The redox potential
of F 420 is ideally suited for its role in this enzyme, since at 0:36 V it is higher
than the redox potential for hydrogen ( 0:42 V) but lower than the redox
potentials of other redox cofactors such as NADH and Xavin. Therefore F 420 is
able to accept electrons from hydrogen and transfer them to NAD þ or FAD.
The pterin cofactor is used in a number of redox enzymes, in particular a
small family of mono-oxygenase enzymes which hydroxylate aromatic rings.
Phenylalanine hydroxylase catalyses the conversion of l-phenylalanine to
l-tyrosine, using tetrahydropterin as a cofactor. The enzyme incorporates one
atom of oxygen from dioxygen into the product, similar to the Xavin-dependent
mono-oxygenases. However, unlike the Xavin-dependent mono-oxygenases,
there is no hydroxyl group present in the ortho- orpara- positions of the
substrate.
Conversion of phenylalanine labelled with deuterium at C-4 of the ring by
phenylalanine hydroxylase gives 3- 2 H-tyrosine, indicating that a 1,2-shift
(known historically as the ‘NIH shift’, since this startling result was discovered
at the National Institute of Health research laboratories) is taking place during
the reaction. It is likely that a pterin hydroperoxide is formed upon reaction with
dioxygen, as found with Xavin. The mammalian phenylalanine hydroxylase
requires iron(II) for activity, and it is believed that a high-valent iron-oxo species
is formed which carries out substrate hydroxylation. The NIH shift could result
upon formation either of an epoxide intermediate or a carbonium ion intermediate,
shown in Figure 6.28. Although rearrangement is observed with the [4- 2 H]
substrate, there is no kinetic isotope eVect observed with this substrate, implying
that the rearrangement occurs after the rate-determining step of the reaction.
6.7 Iron–sulphur clusters
We have seen in the case of Xavin how single electron transfer is an important
process in biological systems. The most common type of one-electron carrier
found in biological systems is the family of iron–sulphur clusters. They are
inorganic clusters of general formula (FeS) n , where n is commonly 2 or 4. The
[2Fe2S] and [4Fe4S] clusters shown in Figure 6.29 are commonly found in
biological electron carriers known as ferredoxins, and are also found in a
number of redox enzymes. They have the ability to accept a single electron
from a single electron donor such as Xavin, and transfer the single electron to