Chemistry Reference
In-Depth Information
In transamination and racemization reactions, we
have seen loss of a proton from the aldimine, i.e.
breaking of bond
a
. Let us now consider the two
alternatives, namely the breaking of bonds
b
or
c
, to explore further the scope for PLP-dependent
reactions.
c
b
R
H
CO
2
H
a
N
OH
P
O
N
CH
3
H
Breaking of bond
b
accounts for
PLP-dependent
decarboxylations
. Decarboxylation of the intermedi-
ate aldimine is facilitated in the same way as loss of
a proton in the transamination sequence. The pro-
tonated nitrogen acts as an electron sink, and the
conjugated system allows loss of the carboxyl proton,
with subsequent bond breaking and loss of CO
2
.
The resultant imine may subsequently be hydrolysed,
releasing an amine (the decarboxylated amino acid)
and regenerating PLP. There are many examples for
decarboxylation of amino acids (see Box 15.3).
PLP-dependent decarboxylation
O
H
R
H
R
CO
2
H
NH
2
R
H
H
R
R
H
O
H
H
N
restoring
aromaticity
N
N
NH
2
PLP
PLP
decarboxylation
OH
imine
formation
OH
OH
hydrolysis of
imine to aldehyde
and amine
P
O
P
O
P
O
N
CH
3
N
CH
3
N
CH
3
H
H
H
Box 15.3
PLP-dependent amino acid decarboxylations
An important example of
PLP-dependent amino acid decarboxylation
is the conversion of histidine into
histamine.
Histamine
is often involved in human allergic responses, e.g. to insect bites or pollens. Stress stimulates
the action of the enzyme histidine decarboxylase and histamine is released from mast cells. Topical antihistamine
creams are valuable for pain relief, and oral antihistamines are widely prescribed for nasal allergies such as hay
fever. Major effects of histamine include dilation of blood vessels, inflammation and swelling of tissues, and
narrowing of airways. In serious cases, life-threatening anaphylactic shock may occur, caused by a dramatic fall
in blood pressure.
histidine
decarboxyla
s
e
N
N
CO
2
H
NH
2
NH
2
PLP
N
N
L-His
histamine
The
catecholamines noradrenaline
(
norepinephrine
)and
adrenaline
(
epinephrine
) are amines derived
via decarboxylation
of
amino
acids.
Noradrenaline is
a
mammalian
neurotransmitter, and
adrenaline,
the
