Introduction to Enzyme and Coenzyme Chemistry - E-Library Home

132 Chapter 6
(a)
R
N
H +
N
O
R
N
H
N
O
N
H
O
NH
H −
transfer
N
H
O
NH
'R
XH
'R
X
(b)
R
R H +
N N O
N N O
NH attack of X
NH
N
N
H + at C-4a
O
H
X
XH
O
H
R'
H
R'
(c)
R
N
H +
N
O
R
N
H
N
O
N
O
NH
attack of
carbanion
at N-5
H +
'R
N
O
XH
NH
'R
XH
1e − transfer
(d)
R
N
H
N
O
R
N
H
N
O
'R
N
XH
O
NH
1e − , H +
OR
H transfer
Figure 6.15 Possible mechanisms for Xavin-catalysed dehydrogenation. (a) Hydride transfer from
the substrate to oxidised Xavin; nucleophilic attack by the substrate on the Xavin nucleus by a
heteroatom at C-4a (b); by a substrate carbanion at N-5 (c); (d) radical mechanism involving single
electron transfer.
The monoamine oxidase reaction is a very important medicinal target for
the mammalian nervous system, since it is responsible for the deamination of
several neuro-active primary amines. Inhibitors of monoamine oxidase therefore
have potential clinical applications as antidepressants. Monoamine oxidase
is rapidly inactivated by trans-2-phenylcyclopropylamine (marketed as the
antidepressant Tranylcypromine) via a radical mechanism shown in Figure
6.18. This behaviour indicates that an amine radical cation intermediate is
'R
N
H
X
O
NH