Download rll 24.5 The citric ocid cycle

75,8
CHAPTER
24 Carbohydratesin Living Organisms
thiamine pyrophosphate, lipoic acid, FAD, NAD*, and coenzyme A-are
also present.Thiamine was mentioned previously (Sec.21.B)asvitamin 81.
Now we see that there is a need for it, as its pyrophosphate, in converting
pyruvate to acetyl CoA.
H
NH,
I
I
*//
NZc-c-cH, -N'
rll
CH3-C\.
C-S
\l
|
I
o-
o-
C:C-CH,CH,O-P-O-P-O_
/.C
l-tl
CH.
Thiamine pynophosphate
Lipoic acid is not classifled as a vitamin. Evidently humans can make their
ornmlipoic acid. No caseof lipoic acid deficiency in a human being has ever
been reported.
HO
( ) < l l -cH2cH2cH2cH2c-oH
\
/
S-S
Lipoicacid
PRACTICE
EXERCISE
24.I
Acetyl CoA is often considered an energy-rich compound
Explainwhy.
like ATP
24.5 Thecitric ocid cycle
AIM: To list the stepsfor the degradotionof one ocetylgroup in
the citric ocid cycle.
Focus
'
The oxidation of glucose
carbons is completed in the
citric acid cycle.
The two molecules of acetyl CoA from one molecule of glucosenow pass
into the citric acid cycle. Figure 24.4 shows the complete cycle,which rbkes
place in the mitochondria of eukaryotic cells. As in other metabolicfathways, all the reactions of the citric acid cycle are catalyzed by enzymes.
Some of the necessaryenzyrnesare located in the fluid contained inside the
mitochondrial inner membrane; others are attached to the inner surface of
the interior membrane. As we go through the steps of the cycle, be especially alert to the fates of the carbons of the reacting molecules, the various
types of transformations that are occurring, and the production of NADH,
FADH2,andAIP
24.5 The Citric Acid Cycle
o
il
CH.-C-S-CoA
Acetyl CoA
Uttvr^/Wt
CO,-
o:c
tftvl
I-
\,/s-coA
'ft'
tl,o
(
lLu+ar
,io"cts,1luL
CH,
t-
CH,
CO,
t'
neP
CO2
Oxaloacetate
(or-
Cot-
t-
HO -C-
HC-OH
Ma]ate
\n,
CO;
I
tz
,rA
-l
Hro
l-
,
Citric acid cycle
l
COr-
COr-
,
l'
cis-Aconitate
HC
tl
t:
CH2
.c- co,tl
CH Fumarate
cot
i
felHa
CO2-
Citrate.
co^'\
I
t fl
9Ht
l-
H-CH
o '' u i
o'
Citryl CoA
I
-t"q4t7
ior.^
CH
y*'
Hzoo.'
"--.\
,_4j:"succinate
cr-Ketoglutarate
COrI
CH,
t.fHz
NAD*
,/l
Hto
#
Figure24.4
Thecitricacidcyclebeginsat the l2 o'clockposition.Aswe followthe fateof the
carbonatomsof the acetylgroupof acetylCoA"we seethat they arenot the ones
Iostascarbondioxidein oneturn of the cycle.Wll eitherof thesecarbonatomsbe
oxidizedto carbondioxideduringtheirsecondpassthroughthe cycle?
l^ -
,4O
CHAFIER24 Carbohydratesin Living Organisms
' The citric acid cycle begins when an acetyl-group of acetyl
CoA condenses with a molecule of oxaloacetate to give a niolecule of citryl CoA.
O
S-CoA
\ .'c
/
9o'I
O:C
O
till
CH,
+ CH3-C-S-CoA
9H,
t,.l
i.---. HO-Q-COz-
co'-
f",
Cozoxaloacetate-
AcetldcoA
tcoeffirl$o",1t ut"l
The thioester bond of citryl CoA is rapidly hydrolyzed to give citrate and
CoA.
O. .S-CoA
\./
c
co,-
CH,
CH,
+
t-
ll
HO-C-CO2tl
CH,
+ HzO i-
HO-C-COzCH,
t-
t-
cor-
coz-
Citryl CoA
.
+ HS-CoA
Citrate
The early discovery of citrate is the reason the pathway is called the.citric
""*rT"'?"ostep
of the rycle involves the dehydration of citrate to c,s-
aconitate.
-tt
co,l-r-
co,-
t",
f",
tl
HO-C-CO2-:
ttl
H-C-H
tl
,
cozCitrate
9-COr- + 4rO
CH
cozcls-Aconitate
Water
\
Now a hydration reaction occurs in which water is added to the Ao,[Ut"
bond. Isocitrate is the product of the rehydration. ,
Qor-
?o'.l
f"'
f-"o,CH
rl
cozcis-Aconitate
fo,-
f",
+H2o.-H-?-corHC-OH
cozIsocitrate
24.5 TheCitricAcidCycle
741
At this point the production of reducing power andAIP is about to begin as
isocitrate is oxidized to a-ketoglutarate.
CozCOr
I
I
CH,
CH,
I
HC-CO2I
HC-OH
I
9H,
I
--Z---NAD.
NADH
+ CO2
C:O
I
I
Coz-
Coza-Ketoglutarate
Isocitrate
NAD+ is the coen4rme in the reaction, and for every molecule of isocitrate
oxidized, one molecule of NAD+ is reduced to NADH. The oxidation also
involves the loss of a molecule of carbon dioxide, but notice that the carbon
dioxide comes from the oxaloacetate and not from the acetyl group that
entered the cycle.
The next step in the cycle results in the loss of carbon dioxide, reduction
of a second NAD+, and phosphorylation of ADP to AIP (a substrate-level
phosphorylation). Succinate is the product. Note that once again the carbon dioxide comes from oxaloacetateinstead of acetyl CoA. A second
NADH and oneAIP are produced.
co,I
CozI
CHz
CHt
ATP
ADP+ 4
I
I
CH,
CH,
I
Coz-
I
C:O
I
+ co2
CorSuccinate
d-Ketoglutarate
Succinate is next oxidized to fumarate. Recall that oxidation-reduction
enzyrnesthat catalyzethe formation of carbon-carbon double bonds usually use FAD as the coenzyrne.That is the case here, where one FADH2 is
produced.
coz-
coztl
HC
HC-H
I
--Z----=
H-!H
I
eio
enbH,
coz-
CH
I
corFumarate
Succinate
A second hydration reaction now occurs as fumarate is converted to
malate.
Corcort-
I
HC-OH
HC
CH
I
CozFumarate
+ HrO =-
I
H-CH
Cot-
742
CHAPTER
24 Carbohydratesin Living Organisms
Malate is oxidized back to oxaloacetate in the final step of the cycle, and
NAD+ is simultaneously reduced. A third NADH is produced.
CO,
COr
I
HC-OH
I
CHr
t-
Cor-
--z--NAD*
Malate
NADH'H
I
c- o
I
Yii,
I
CorOxaloacetate
The oxaloacetate molecule is now available to start another turn of the
cycle by reacting with another molecule of acetyl CoA.
This is what happens in the citric acid cycle:
1. Acetyl CoA and oxaloacetatecombine to form citrate.
2. Citric acid eventually loses two carbon atoms as carbon dioxide. The
carbons in the two molecules of carbon dioxide are not the same carbons that entered the citric acid cycle as acetyl groups of acetyl CoA.
Nevertheless, the net effect of the cycle is the same as if these carbons
were oxidized.
3. At the end of the pathway, a molecule of oxaloacetateremains, which is
why the pathway is called a cycle. (The original oxaloacetate molecule
could have come from several places in metabolism, but we need not
worry about that here.)
4. Each turn of the citric acid cycle yields three molecules of NADH, one of
FADH2,and one of AIP
PRACTICE
EXERCISE
24.4
Write a net equation that summarizes one turn of the citric acid cycle.
24.6ATPyield
AIM: Togive on occountingof the ATPproducedby the complete
oxidation of o moleculeof glucose.
\
Focus
The complete oxidation of
I molecule of glucose yields
38ATP molecules.
Two turns of the citric acid cycle are necessaryto oxidize completelir the
equivalent of two molecules of acetyl CoA (obtained from one molecule of
glucose) to four molecules of carbon dioxide. Using this information,
alongwith the yields ofATP and NADH obtained in glycolysis,we can calculate the total amount of ATP generatedby the aerobic catabolism of one
molecule of glucose.Remember that each NADH molecule can generate
three ATP molecules and each FADH2 molecule can generate two ATP
molecules by oxidative phosphorylation. TabIe 24.2 summarizes the
24.7 LacticFermentation 74t
of
AerobicCatabolism
from Complete
Table24.2ATPProduction
Molecule
OneGlucose
Pathway
Burning a mole of glucoseto
form CO2and H2Oproduces686
kcal of energy. \v\rhenwe oxidize
a mole of glucose,the 38 mol of
ATPrepresents 277 kcal of stored
energy.Our bodies,then, are
about277 kcal/686 kcal x 100 :
40% efficient.
glycolysis (4ATPgenerated minus 2 invested)
citric acid cycle (2 acetyl groups of acetyl CoA
oxidized to carbon dioxide)
oxidative phosphorylation:
2NADH from glycolysis
2NADH from acetyl CoA formation
6NADH from the citric acid cycle
zFADH2from the citric acid rycle
ATPyield
2
2
6
6
1B
A
3B
results.The data show that enough of the energyreleasedin the complete
oxidation of I molecule of glucoseis trapped by aerobic cells to generate
3BAIP molecules.
24.7 LacticFermentstion
AIM: To exploin why cells sometimesuseloctic fermentotionfor
energyproduction.
Focus
Aerobic cells switch to lactic or
alcoholic fermentation in the
absenceofoxygen.
So far our discussion of glucose metabolism has assumed that the cell
doing the metabolism has plenty of oxygen available.\Mhat if it does not?
We know that the mitochondria of aerobic cells need oxygen so that the
electron transport chain can opelate. \Mhen there is no oxygen available
to drain electrons from NADH and FADH2 in respiration, the electron
carriers of the electron transport chain become completely reduced.
More electrons cannot be passed down the chain, and oxidative phosphorylation stops. However,the levels of NADH and FADH2in the mitochondrion increase as the citric acid cycle continues to operate. Soon,
not enough NAD+ and FAD are regeneratedby respiration to sustain the
operation of the citric acid cycle, and the mitochondrial power plant
shuts down
,/
Now the only place that ATP is being produced is in the cytoplasm.
Here,two molecules ofATP are produced for every glucosemolecule converted to two molecules of pyruvate in glycolysis. Cytoplasmic NAD+ is
also being reduced to NADH, and NAD+ is needed for glycolysisto continue. (It is needed to change glyceraldehyde3-phosphateto 1,3-bisphosphoglycerate.)If there were no way to regenerateNAD+, glycolysis too
would stop.With no energyproduction, the cell would die'
In such an emergency,the cells of many aerobic organismsregenerate
NAD+ from the NADH formed in glycolysis by using the NADH to reduce