Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

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Step 3 In the first of
four oxidation steps in the
cycle, the carbon carrying
the hydroxyl group is
converted to a carbonyl
group. The immediate
product is unstable, losing
CO 2 while still bound to
the enzyme.
– COO –
COO –
COO –
H C H
isocitrate
dehydrogenase H C H
H C H
H C COO H C COO –
H C H
HO C H
C O
C O
COO – NAD + NADH + H + COO –
H + CO 2
COO –
isocitrate
oxalosuccinate intermediate
α-ketoglutarate
Step 4 The α-ketoglutarate
dehydrogenase complex closely
resembles the large enzyme
complex that converts pyruvate
to acetyl CoA, the pyruvate
dehydrogenase complex in
Figure 13–10. It likewise
catalyzes an oxidation that
produces NADH, CO 2 , and a
high-energy thioester bond to
coenzyme A (CoA).
COO –
H C H
H C
C
H
O
COO –
α-ketoglutarate
+
HS
CoA
α-ketoglutarate dehydrogenase complex
NAD + NADH + H +
CO 2
COO –
H C H
H C
C
H
O
S CoA
succinyl-CoA
Step 5 A phosphate
molecule from solution
displaces the CoA, forming a
high-energy phosphate
linkage to succinate. This
phosphate is then passed to
GDP to form GTP. (In bacteria
and plants, ATP is formed
instead.)
H
H
COO –
C H
C H
C O
S CoA
H 2 O
succinyl-CoA synthetase
P i
GDP GTP
H
H
COO –
C H
C H
COO –
+
HS
CoA
succinyl-CoA
succinate
Step 6 In the third oxidation
step in the cycle, FAD accepts two
hydrogen atoms from succinate.
H
H
COO –
C H
C H
COO –
succinate dehydrogenase
FAD
FADH 2
H
COO –
C H
C
COO –
succinate
fumarate
Step 7 The addition of
water to fumarate places a
hydroxyl group next to a
carbonyl carbon.
H
COO –
C H
C
COO –
fumarase
H 2 O
HO
H
COO –
C H
C H
COO –
fumarate
malate
Step 8 In the last of four
oxidation steps in the cycle, the
carbon carrying the hydroxyl
group is converted
to a carbonyl group,
regenerating the oxaloacetate
needed for step 1.
HO
H
COO –
C H
C H
COO –
malate dehydrogenase
NAD + NADH + H +
COO –
C O
CH 2
COO –
malate
oxaloacetate