242
chapter
13
Carbohydrate Metabolism 1: Glycolysis and TCA Cycle
C oA S H
S u c c in a te
C H ,— C — S — C oA
A cetyl C oA
C O O
c o o
NAI H
C O O
c = o
h o — c — h
K) noil ici»
h .o
HO—c — c o o
_
C O O
C O O
dehydrogenjs®
l-M a la ie
O x a lo a c e ta te
umarat®
C O O
hydratas®
C itrate
C O O
c — c o o
F u m a ra te
f ADH
Succinate
F A D w tlohydrogonase
L
C O O
C O O
Ado- lata
c /s-A co m tate
BMMWMM
C O O
C O O
Succm yl CoA
ynthetas®
GTR-V-'^Cc
C oA SH
H — C — C O O
C O O
HO—C—H
c o o
I'-ocitrato
_ •“’’rf®*"“}
|S0Cltrate
co o
(i Ketoglutarate
c = o
dehydrogenase C O O
NAD
— C oA C O ;
\ m
Af
NADH + H
(H
CoASH
S u ccin y l C oA
Isoc'tiato
H — c — C O O
C H , dtthydrogenasa
NADH
= ° T
c = o
NAD
rC O ,
C O O
c o o
O x a lo su c c m a te
« -K e to g iu ta ra te
FIGURK 13-12
Reaction of the tricarboxylic acid
( T C A )
cycle.
citrate to isocitrate directly. Aconitate dehydratase has an
iron-sulfur center, the exact function of which is not
known. The reaction is considered to be near-equilibrium,
even though under physiological conditions the ratio
of citrate to isocitrate is about 9:1
owing to rapid
conversion of isocitrate to subsequent products of the
cycle.
Although citrate is a symmetrical molecule, its two
-CH
2
COOH groups are not identical with regard to the
orientation of the -OH and -COOH groups. Thus, citrate
reacts in an asymmetrical manner with the enzyme, so
that only the -CH
2
COOH group derived from oxaloac-
etate is modified. A three-point attachment of the enzyme
to the substrate accounts for the asymmetrical nature of
the reaction.
A powerful competitive inhibitor (highly toxic) of
aconitate dehydratase is fluorocitrate, an analogue of
citrate:
C H F — C O O '
I
H O — C H — C O C T
I
C H
2
— C O O '
In vivo,
fluorocitrate can be formed by condensation of
fluoroacetyl-CoA with oxaloacetate by action of citrate
synthase. Fluoroacetyl-CoA itself is synthesized from flu-
oroacetate by acetyl-CoA synthase.
