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178 Chapter 7
HN
N
+
N
H
NH
S
O
OPP
OPP
+ +
RN S
RN
O
− CO 2 HO
S
O−
O
OPP
E
+
RN
S
OPP
RN
S
OPP
O
E
H
Figure 7.27 Mechanism for pyruvate decarboxylation.
OH
E +
(E + = H + or electrophile)
dehydrogenase complex. This reaction follows the mechanism shown in Figure
7.27, but in this case the electrophile is a second cofactor present in the pyruvate
dehydrogenase complex: lipoamide. The structure of lipoamide shown in
Figure 7.28 is simply a Wve-membered ring containing a disulphide linkage
attached via an acyl chain to the e-amino group of a lysine residue. Upon
reaction of the thiamine pyrophosphate–enamine intermediate with oxidised
lipoamide and fragmentation of the linkage with thiamine pyrophosphate, an
acetyl-lipoamide thioester is formed, as shown in Figure 7.28. Transfer of the
acyl group to the thiol group of CoA generates acetyl CoA and reduced
OPP
OPP
RN
S
OH
S
S
Enz
pyruvate
decarboxylase
+
RN S
S
O
H
SH
Enz
lipoamide
dehydrogenase
FAD,
NAD +
SH
O
Enz
HS
S
O
CoAS −
SCoA
Figure 7.28 TPP-dependent production of acetyl CoA using lipoamide.
SH
Enz