Download Panel 13–2 The complete citric acid cycle

Panel 13–2 The complete citric acid cycle
NAD+
NADH + H
+
HS CoA
O
CH3 C
The complete citric acid cycle. The two
carbons from acetyl CoA that enter this
turn of the cycle (shadowed in red ) will
be converted to CO2 in subsequent turns
of the cycle: it is the two carbons
shadowed in blue that are converted to
CO2 in this cycle.
COO–
CO2
pyruvate
O
acetyl CoA (2C)
CH3 C S CoA
NADH + H
COO–
COO–
H2O
COO–
CH2
HO C COO–
Step 1
oxaloacetate (4C)
Step 2
CH2
COO–
COO–
C O
CH2
COO–
Step 8
H C OH
CH2 malate (4C)
COO–
C O
CH2
COO–
+
NAD+
HS CoA
COO–
next cycle
HC COO–
oxaloacetate (4C)
HO CH
COO–
CITRIC ACID CYCLE
NAD+
Step 3
H2O
α-ketoglutarate (5C)
COO–
CH
CH
COO–
COO–
H2O
Step 5
CH2
CH2
Step 4
GTP
HS CoA
CO2
COO–
NAD+
C O
GDP
+
Pi
CH2
C O
CH2
CH2
COO–
FAD
COO–
NADH + H
CH2
succinyl CoA (4C)
succinate (4C)
Step 6
FADH2
+
COO–
fumarate (4C)
Step 7
isocitrate (6C)
CH2
citrate (6C)
HS CoA
S CoA
NADH + H
+
CO2
Details of the eight steps are shown below. 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 CH3 group on
acetyl CoA, the negatively O
C S CoA
charged CH2– forms a
bond to a carbonyl carbon
CH3
of oxaloacetate. The
subsequent loss by
hydrolysis of the
coenzyme A (CoA) drives
the reaction strongly
acetyl CoA
forward.
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.
COO–
C
+
O
O
citrate
synthase
COO–
oxaloacetate
COO–
C
H
HO
C
COO–
H
C
H
H
COO–
citrate
S CoA
COO–
H2O
CH2
CH2
HO
CH2
C
C
COO–
HO
CH2
COO–
COO–
COO–
H
aconitase
H2O
+ HS CoA + H+
COO–
CH2
S-citryl-CoA
intermediate
H2O
C
citrate
COO–
H2O
C
H
H
C
H
C
COO–
H
C
COO–
C
H
HO
C
H
COO–
cis-aconitate
intermediate
H2O
COO–
isocitrate
COO–
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
CO2 while still bound to
the enzyme.
COO–
isocitrate
dehydrogenase
C
H
H
C
COO–
HO
C
H
H
H
H
NAD+ NADH + H
COO–
+
H
H
C
H
C
COO–
H
C
H
C
O
C
O
H
+
H
H
a-ketoglutarate
C
COO–
H
C
H
C
O
a-ketoglutarate dehydrogenase complex
+ HS CoA
NAD+
NADH + H
C
H
H
C
H
C
O
S CoA
CO2
a-ketoglutarate
succinyl-CoA
COO–
H
C
H
H
C
H
C
O
COO–
succinyl-CoA synthetase
H
C
H
H
C
H
COO–
GDP
Pi
COO–
H
C
H
COO–
C
H
FAD
COO–
fumarate
COO–
fumarase
HO
C
H
H
C
H
COO–
HO
C
H
H
C
H
COO–
H2O
fumarate
COO–
H
C
FADH2
C
malate
H
succinate dehydrogenase
H
COO–
Step 8
H
GTP
succinate
C
C
succinate
COO–
Step 7
H
COO–
H2O
S CoA
Step 6
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.
H
+
succinyl-CoA
The addition of
water to fumarate places a
hydroxyl group next to a
carbonyl carbon.
COO–
oxalosuccinate
intermediate
COO–
Step 5
In the third
oxidation step in the cycle,
FAD removes two hydrogen
atoms from succinate.
CO2
COO–
Step 4
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.)
C
COO–
isocitrate
The a-ketoglutarate
dehydrogenase complex closely
resembles the large enzyme
complex that converts pyruvate
to acetyl CoA (pyruvate
dehydrogenase). It likewise
catalyzes an oxidation that
produces NADH, CO2, and a
high-energy thioester bond to
coenzyme A (CoA).
COO–
malate
COO–
malate dehydrogenase
C
O
CH2
+
NAD
NADH + H
+
COO–
oxaloacetate
+ HS CoA