Introduction to Enzyme and Coenzyme Chemistry - E-Library Home

11 Radicals in Enzyme Catalysis
11.1 Introduction
A special chapter is being devoted to the topic of radical chemistry in enzyme
catalysis because of a series of remarkable discoveries in this area that have
occurred since 1990. Before then, it was known that certain enzymes could
generate free radical intermediates, such as cytochrome P 450 mono-oxygenases
(Section 6.8), certain metallo-enzymes (Sections 6.9, 6.10, 7.10), and certain
Xavo-enzymes (Section 6.3), but that such intermediates were generally shortlived
reaction intermediates, generated Xeetingly in special circumstances. It has
now emerged that enzymes can generate a variety of radical species, some of
which are long-lived, using several diVerent strategies.
11.2 Vitamin B 12 -dependent rearrangements
Vitamin B 12 has the most complex structure of all of the vitamins. The X-ray
crystal structure of vitamin B 12 was solved in 1961 by Hodgkin. The structure,
shown in Figure 11.1, consists of an extensively modiWed porphyrin ring
system, containing a central Co 3þ ion. The two axial ligands are a benzimidazole
nucleotide and an adenosyl group. The cobalt–carbon bond formed with
the adenosyl ligand is weak and susceptible to homolysis, and this is the
initiation step for the radical-mediated vitamin B 12 -dependent reactions.
We shall consider three vitamin B 12 -dependent rearrangements: propanediol
dehydrase, methylmalonyl coenzyme A (CoA) mutase, and glutamate
mutase. Both reactions involve the 1,2-migration of a hydrogen atom, and the
corresponding 1,2-migration of another substituent, either 2OH or 2CO 2 H, as
shown in Figure 11.2.
Propanediol dehydrase catalyses the rearrangement of propane-1,2-diol to
propionaldehyde. There is no incorporation of solvent hydrogens during the
reaction, implying that there is an intramolecular hydrogen transfer. StereospeciWc
labelling studies have shown that the reaction involves the removal of
the proS hydrogen at C-1. This hydrogen atom is transferred speciWcally to the
proS position at C-2, giving an inversion of conWguration at C-2.
Tritium labelling of the C-1 proS hydrogen gives rise to exchange of 3 H into
the adenosyl 5 0 -position. This implies that there is an adenosyl 5 0 -CH 3 intermediate
in the enzyme mechanism formed by homolysis of the adenosyl–cobalt
bond and hydrogen atom transfer from the substrate. Homolysis of the
adenosyl–cobalt bond is further supported by the detection of Co 2þ intermedi-
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