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242 Chapter 11
CH 2
Co III
Ad
H OH
OH
H H* CH 2
Co II
Ad
H OH
OH
CH 2
H*
Co II
Ad
H
H
O
OH
CH 2
H*
Co II
Ad
*H H
O
OH
H
H
O
H*
CH 2 Ad
Co II
OH
H
OH
H* CH 2
Co II
Ad
H
OH
OH
*H CH 2
Co II
Ad
Figure 11.3 Mechanism for propanediol dehydrase.
ates in the reaction by stopped Xow electron spin resonance (ESR) spectroscopy
studies.
The proposed mechanism for propanediol dehydrase is shown in Figure
11.3. Initiation of the reaction by homolysis of the carbon–cobalt bond generates
an adenosyl radical, which abstracts the C-1 proS hydrogen, to give a
substrate-derived radical. Migration of the OH group then occurs, from C-2 to
C-1, probably through a cyclic transition state, to give a product radical. The
reaction is completed by abstraction of H . from the 5 0 -deoxy-adenosyl group,
and regeneration of the B 12 cofactor. The hydrate product is then dehydrated
stereospeciWcally, losing the migrating hydroxyl group to give the product
aldehyde.
The methylmalonyl CoA mutase reaction is also initiated by formation of
the 5 0 -deoxy-adenosyl radical. This abstracts a hydrogen atom from the substrate
methyl group as shown in Figure 11.4. Intramolecular ring closure of this
primary radical onto the thioester carbonyl forms a cyclopropyl-oxy radical
intermediate. Fragmentation of this strained intermediate by cleavage of a
diVerent C2C bond generates a more stable secondary radical adjacent to the
carboxylate group. Attachment of the abstracted hydrogen atom gives the
succinyl CoA product, and regenerates the vitamin B 12 cofactor. There is
convincing precedent for this mechanism from organic reactions that perform
this type of rearrangement via free radical intermediates. The X-ray crystal
structure of methylmalonyl CoA mutase has been determined, and is shown in
Figure 11.5.
There are a small number of other vitamin B 12 -dependent rearrangements
that can be also rationalised by the cyclisation of a radical intermediate onto an
sp 2 carbon centre. The reaction catalysed by glutamate mutase, however,
cannot be rationalised in this way, since the migrating group is an sp 3 centre,
the a-carbon of glutamic acid. An alternative radical mechanism has been