Introduction to Enzyme and Coenzyme Chemistry - E-Library Home

232 Chapter 10
H S
C 6 H 13
HN
His 70
H R
N
O
− AEnz
H AEnz
H AEnz H
O
O
SR
C 6 H 13
SR
C 6 H 13
SR
*H H
H
HN N
HN N
His 70
His 70
Figure 10.8 Mechanism for b-hydroxydecanoyl thioester isomerase.
a 1,3-hydrogen migration; and we have encountered 1,3-migrations of allylic
pyrophosphates in the terpene cyclase reactions of Section 7.9. There are many
allylic isomerases which operate in many diVerent areas of biological chemistry:
I will brieXy mention two examples that are important for the cellular assembly
of fatty acids and terpenoid natural products, respectively.
In Section 8.2 we met the enzyme b-hydroxydecanoyl thioester dehydratase,
which catalyses the elimination of b-hydroxy-thioesters in fatty acid assembly.
This enzyme also catalyses the isomerisation of the trans-2,3-alkenyl thioester
to the cis-3,4-alkenyl thioester, as shown in Figure 10.8. The dehydration
reaction catalysed by this enzyme utilises an active site histidine base, His-70
(see Section 8.2). This base is also thought to be involved in the isomerisation
reaction. The reaction involves the transfer of the C-4 proR hydrogen to the C-2
proS position. This is deWned as a 1,3-suprafacial hydrogen shift, since the
hydrogen is transferred across the same face of the molecule. It is thought
that His-70 mediates this transfer via an enediol intermediate as shown in
Figure 10.8. However, it is worthy of note that no intramolecular hydrogen
transfer is observed in this case, unlike examples such as ketosteroid isomerase,
suggesting that the protonated histidine exchanges readily with solvent water.
Isopentenyl pyrophosphate isomerase catalyses the interconversion of isopentenyl
pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP), the
two Wve-carbon building blocks for the assembly of terpene natural products
(also see Section 7.9). The enzymatic reaction involves stereospeciWc removal of
the proR hydrogen at C-2, and delivery of a hydrogen onto the re-face of the
4,5-double bond. The stereochemistry was established by conversion of a
stereospeciWcally labelled substrate in 2 H 2 O (as shown in Figure 10.9), generating
a chiral methyl group of R conWguration at C-4. This reaction is deWned as a
D +
isopentenyl PP
H
isomerase
OPP
H
OPP
T HS
H R
D 2 O
D T
Figure 10.9 Stereochemistry of isopentenyl pyrophosphate isomerase.