Essential Cell Biology 5th edition

The Breakdown and Utilization of Sugars and Fats
443
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 –
H C H
isocitrate
dehydrogenase H C H
H
HO
C
C
COO
H
H C
C
COO –
O
COO – NAD + NADH +
COO –
isocitrate
oxalosuccinate
intermediate
H + COO –
H C H
H C H
C O
CO 2
COO –
α-ketoglutarate
STEP 4
COO –
COO –
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).
H C H
H C H
C O
COO –
α-ketoglutarate
+
HS
CoA
α-ketoglutarate dehydrogenase complex
NAD + NADH + H +
CO 2
H C H
H C
C
H
O
S CoA
succinyl CoA
STEP 5
An inorganic phosphate
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 GDP GTP
H
H
COO –
C H
C H
COO –
+
HS
CoA
succinyl CoA
succinate
STEP 6
In the third oxidation step of 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.
COO –
HO C H
H C H
COO –
malate
H + H +
malate dehydrogenase
NAD + NADH +
COO –
C O
CH 2
COO –
oxaloacetate
ECB5 Panel 13.02b