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

106 PANEL 2–9: The Complete Citric Acid Cycle
NAD + NADH + H + coenzyme A
O
HS CoA
Overview of the complete citric acid cycle.
CH 3 C
COO – The two carbons from acetyl CoA that
enter this turn of the cycle (shadowed in
pyruvate CO 2 acetyl CoA (2C)
red ) will be converted to CO
O
2 in
subsequent turns of the cycle: it is the two
CH 3 C S CoA
carbons shadowed in blue that are
converted to CO
HS CoA
2 in this cycle.
COO – H 2 O
next cycle
C O
COO –
CH 2
CH 2
NADH + H + HO C COO –
COO –
COO – Step 1
NAD + Step 2
oxaloacetate (4C)
CH 2
C O
COO –
COO –
CH 2
COO – isocitrate (6C)
Step 8 CH 2
citrate (6C)
COO –
HC COO –
H C OH
oxaloacetate (4C)
HO CH
CH
COO –
2 malate (4C)
COO –
CITRIC ACID CYCLE
NAD +
Step 3
H 2 O
COO –
NADH + H +
fumarate
Step 7 COO –
(4C)
α-ketoglutarate (5C)
CH 2
CO 2
succinyl CoA (4C)
CH
CH
2
succinate (4C)
C O
CH
COO –
COO – Step 4
Step 6
H 2 O
COO –
COO –
CH 2
CH Step 5
2
CH 2
CH 2
NAD +
COO –
C O
FADH 2
HS CoA
FAD
GDP S CoA
+ H +
GTP
NADH
+
HS CoA P i
CO 2
Details of these eight steps are shown below. In this part of the panel, for each step, the part of the molecule that undergoes
a change is shadowed in blue, and the name of the enzyme that catalyzes the reaction is in a yellow box.
Step 1 After the
enzyme removes a proton
from the CH 3 group on
acetyl CoA, the negatively
charged CH – 2 forms a
bond to a carbonyl carbon
of oxaloacetate. The
subsequent loss by
hydrolysis of the coenzyme
A (HS–CoA) drives the
reaction strongly forward.
O
COO –
O C S CoA H 2 O COO –
citrate
synthase CH
C S CoA C O
2
CH 2
+
HO C COO –
COO – + HS CoA +
HO C
H +
CH 3 CH 2
COO –
CH 2 CH 2
COO – COO –
acetyl CoA
oxaloacetate
S-citryl-CoA
intermediate
citrate
Step 2 An isomerization
reaction, in which water is
first removed and then
added back, moves the
hydroxyl group from one
carbon atom to its neighbor.
H
HO
H
COO –
C H
C COO –
C H
COO –
aconitase
H 2 O
H 2 O
H
COO –
C H
C COO –
C H
COO –
H 2 O
H 2 O
H
H
HO
COO –
C H
C COO –
C H
COO –
citrate cis-aconitate intermediate isocitrate