Introduction to Enzyme and Coenzyme Chemistry - E-Library Home

252 Chapter 11
cofactor is involved in the catalytic mechanism, and in each case the formation
of the novel cofactor is likely to involve oxidative radical chemistry.
Problems
(1) The enzyme methyleneglutarate mutase requires vitamin B 12 as a cofactor.
(a) Write a mechanism for this reaction involving cyclisation of a substrate
radical intermediate. (b) Also suggest an alternative mechanism involving
C2C fragmentation of a radical intermediate.
− O 2 C
CO 2
−
methyleneglutarate
mutase
vit B 12
− O 2 C
CO 2
−
(2) The plant alkaloid hyoscyamine is generated by an enzyme-catalysed intramolecular
rearrangement of littorine, as shown below. The stereochemistry
of the conversion is also shown. It was previously thought that this reaction
involved vitamin B 12 as a cofactor; however, plants are thought not to
contain vitamin B 12 . (a) Suggest a radical mediated mechanism for this
transformation. (b) If vitamin B 12 is not involved, how else might a radical
intermediate be generated
Me
N
Me
N
H H*
O
O
HO T OH
H
O
O
T
H*
littorine
hyoscyamine
(3) The enzyme benzylsuccinate synthase catalyses the addition of toluene to
succinate, as shown below. The enzyme is thought to contain a glycyl
radical at its active site. Suggest a catalytic mechanism involving the
glycyl radical.