24.3 Glycolysis
Sugars
I
+
Fatty acids
Glucose
Amino acids
7t
tion. Many other cells do oxidize other sugars, fatty acids, and amino
acids to obtain energy,however.Certain enzyrnescontained in such cells
degradethesesubstancesto compounds that eventually enter catabolism
through the central core of glucose metabolism. Figure 24.3 shows the
entry points.
Many organisms have the enzymes necessaryto convert galactose,
fructose,and other hexosesinto glucose.Thesesugarsthereforeenter glycolysis as glucose.Fatty acids are oxidized and enter the central core of
glucose catabolism as acetyl CoA. Becauseof the variety of amino acid
structures, their degradation products enter the central core at several
different points: at the tail end of glycolysis as pyruvate, as acetyl CoA, or
as chemical intermediates of the citric acid cycle.
Pyruvate
i
Acetyl CoA
t
tffi
Figure24.3
Proteinsare hydrolyzedto amino
acids;lipids are hydrolyzedto fatty
acidsand glycerol.Above,we see
that the amino acidsand fatty
acidsare convertedto simpler
compoundsthat enterthe main
pathwaysof glucosemetabolism.
24.t Glycolysis
AIM: To list the sfeps in the oerobicglycolysisof one moleculeof
glucose.
The enzymesthat catalyzethe steps of glycolysisare found in the cytoplasm
of cells.This is where glycolysisoccurs. Glycolysisbegins with the phosphorylation of glucoseto glucose6-phosphate.
,rr.
n',.
,rO
C
I
I
H-C-OH
tl
HO-C-H
I
H-C-OH
tl
H-C-OH
I
CH2OH
Glucose
/o
C
H-C-OH
--Z---erp
nnp
HO-C-H
I
H-C-OH
H-C-OH
t^
cH2o_{B)
Glucose6-phosphate
o
(Thesl.rnbol@represents
thephosphorylgroup-il-o
.)
d
One glucosemolecule
produbes two ATP and two
NADH molecules in glycolysis.
The phosphorylation of glucose to
form glucose6-phosphateis so
energetically favorable that essentially all the glucose that enters
the cell is immediatelyphosphorylated.
\
The names and structures of some of the intermediate compounds in\
metabolism are complex.You do not need to memorize them, but they will
be used in the text to make it easierto followwhat is happening.Remember
also that all the steps of these reactions are catalyzedby enzymes.
The phosphoryl group of glucose 6-phosphate comes from AIP This
may seem a little surprising. Since glycolysisis a pathway of catabolism, we
might expectitto produceNlE not to useitlThe important point here is that
the cell is investingAlB just asyou might invest money in the stock market.
Your investment-if you are lucky-will be returned with dividends of more
CHAPTER
24 Carbohydratesin Living Organisms
money. The cell's investment will be repaid with dividends of more AIP The
glucose G-phosphateis converted to fructose 6-phosphate.
HO
\/
C
I
H-C-OH
I
HO-C-H
,l
+
QHzOH
tC:O
HO-C-H
I
I
I
H-C-OH
H-C-OH
H-C-OH
H-C-OH
I
cHro-@
It ^
cH2o-Qg)
Glucose 6-phosphate
Fructose 6-phosphate
Fructose 6-phosphate undergoes phosphorylation to fructose 1,6-bisphosphate at the expenseof another molecule ofAIP invested. .
QHrOn
CH,O-(F)
C:O
C:O
t-
I
I
I
--Z---
HO-C-H
HO-C-H
I
H-C-OH
H-C-OH
I
H-C-OH
H-C-OH
cHro-@
CH,O-@
Fructose G-phosphate
_Fructose
1,6-bisphosphate
The cell has now invested two molecules of AIPf,or every molecule of glucose to be degraded. The conversion offructose 6-phosphate to fructose
1,6-bisphosphate is an important control step in glycolysis.Once fructose
1,6-bisphosphate is formed, it cannot escapq the glycolytic pathway. The
phosphorylation of fructgse G-phosphate to fructose 1,6-bisphosphate is
called the committed step of glycolysis.
Fruct6se 1,6-bisphosphateis now cleavedto give a pair of three-carbon
compounds, dihydroxyacetone phosphate and. glyceraldehyde 3-phosphate.
9H'o-@
I
C:O
I
HO-C-H
H-C-OH
I
- H \O/ .
cHro-@
+
I
C:O.
I
cH2oH
+
f
H-C-OH
tcHro-@
\
H-C-OH
cHro @
Fructose
1,6-bisphosphate
I
-)
Dihydroxyacetone
phosphate
Glyceraldehyde
3-phosphate
Only glyceraldehyde3-phosphate will be used in futttt"t steps of glycolysis.
24.5 Clycolysis 7t5
The dihydroxyacetone is not wasted. Nature is economical, and cells have
an enzyrne that promotes the conversion of dihydroxyacetone phosphate
to glyceraldehyde3-phosphate.
CH,O-O
I
(1 u-v
CH,O-(D
I
t'\
H-C-OH
I
I
C
//\
HO
CH2OH
Dihydroxyacetone
phosphate
Glyceraldehyde
3-phosphate
Since one molecule of glucosehas provided two molecules of glyceraldehyde 3-phosphate, we will have to take this into account in our future
bookkeeping. From now on, we will have to multiply the reactants and
products of our reactionsby 2.
An enzyme next convertsglyceraldehyde3-phosphateto l,3-bisphosphoglycerate in the first energy-yielding oxidation reaction of glucose
catabolism.
o.o
OH
\,/
C
I
\/'
C
I
2p.
2 H-C-OH
------\,
2 H-C-OH
t^
zNAD*
cHro-e)
t^
2NADH
cHro-e)
1,3-Bisphosphoglycerate
Glyceraldehyde
3-phosphate
The enzSrmeuses NAD+ as a cofactor. The NAD+ is reduced to NADH-it
receives two electrons and a proton from the aldehyde substrate-in the
course of the reaction.The new phosphoryl group of the organic product
comes from inorganic phosphate ions present in the cytoplasm, so no ATP
is expended here. In fact, I,3-bisphosphoglycerateis itself a high-energy
compound-a mixed anhydride of a carboxylic acid and phosphoric acid
(see Sec.23.7) that can transfer its newphosphoryl group to ADP (The
phosphorylation ofADP to AIP outside oxidative phosphorylation is called
substrate-leuelphosphorylation.) This transfer occurs in the next step for
glycolysis.TWoATP molecules are gained.
\
.,/
C
I
2 H-C-OH
I
cHro-@
1,3-Bisphosphoglycerate
o
\.,
I
--Z---,LDP
zH-C-OH
2Arp
|
^
cHro-@
3-Phosphoglycerate
Since the cell invested two ATP molecules and now has two back, it is even
in the AIP stock market. AnyATP produced from this point on is profit.
CHAPIER24 Carbohydratesin Living Organisms
The next step in glycolysis is a shift of the phosphoryl group of 3phoglycerate.
oo-oo\./
CC
tl
2H-C-OH
\./
,
I
) 2H-C-O-@
."r",;T'r?;T*
,nn",o1TlXl",.,"
The product of this reaction, 2-phosphoglycerate,loses a molecule of water
to give phosphoenolpymvate.
oVo-
oo-
C
\./
C
Hro
I
2c-o--@
tl
2 H-g-o--@
I
CHrOH
CHt
2-Phosphoglycerate
2-PhosphoenolpSrnrvate
Phosphoenolpyruvale is another energy-rich phosphate molecule capable
of passing its phosphoryl group to ADP in another substrate-level phosphorylation. TwoATP molecules are gained.
oo-
oo-
\./
C
29-o--@
CH2
\./
C
__z____
ZATP
2ADP
2C:O
I
CHs
Pyruvate
2-Phosphoeno
Since the degradation. of one glueose molecule eventually produces two
molecutes of phosphoenolpyruvate, two molecules of ADP can be phosphorylated to AIP when the phosphoenolpyruvate frorn one molecu,le of
glucose is converted to pyruvate. These two molecules of ATP are the ATP
dividends eamed in glycolysis.
The formation of pyruvate is the flnal step of aerobic glycolysis. Here is
what has happened in the oxidation of one milecule of gluiose:
I . TWomolecules of pymvate have been formed.
2. Two molecules of NAD* have been reduced.to NADH.
/
r
3. A net tota[ of two ADP molectrleshave been phosphorylated to AIP (four
AfP molecules gained niinus two invested).
Table 24.Lsummarizes the reactions of glycolysis.
PRACTIGE
EXERGISE
24.I
(
Write a net equation that summarizes glycolysis.
1'
7r7
24.4 Acetyl Coenzyme A
Table24.1TheReactions
of Glycolysis
l.
Glucose --Z---\ATP
Glucose6-phosphate
ADP
Fructose6-phosphate
2. Glucose6-phosphate i-Z---Fructose 1,6-bisphosphate
5. Fructose O-phosphate
Fructose1,6-bisphosphate
I
Dihydroxyacetone phosphate -L
Glyceraldehyde3-phosphate
l,3-Bisphosphoglycerate
Glyceraldehyde3-phosphate + 4 --Z--NAD.
6. l,3-Bisphosphoglycerate --Z--*
2N)P
7. 3-Phosphoglycerate i-
NADH
3-Phosphoglycerate
zATP
2-Phosphoglycerate
8. 2-Phosphoglycerate :-
Phosphoenolpl.n-rvate
-Z---Pyruvate
9. Phosphoenolpyruvate
2ADP
2ATP
EXERCISE
24.2
=,:=PRACTICE
the
moles
of AIP produced when 90 g of glucose is broken
Calculate
t:.,
dor,rrnin glycolysis.The molar mass of glucose is 180 g.
24,4 AcetylcoenzymeA
AIM: To describethe formotion ond functionof ocetyl CoA.
TWocarbons ofpyruvate are
incorporated into acetyl
coenzrrmeA.
\,Vhenan aerobic cell is operating with a good supply of oxygen, pyruvate
molecules flow into the mitochondria. Two of the carbons of each pyruvate
ion end up as aceryl CoA, and one molecule of NAD* is reduced to NADH.
Carbon dioxide is formed as a waste product. This process can be summarized by a single equation:
/--lll
'o'.
o
o)
+ HS-CoA
I CH3-C;C.
.i\
oh'ruvate
--;z----+
NAD*
CH3-C-S-CoA
+ eO2
NADH
Acetyl CoA
An organized assemblyof three dffirent kinds of enzyrnemoleculescalled a
multienzyme complex is responsiblefor the formation of acetyl CoAfrom
pyruuate. This multienrqe complex is named as if it were one enzyrnepJtruuatedehydrogenase.Severalcopies of each type of enzyrne are present
in the pyruvate dehydrogenasemultienzf/me complex. Five coen4/mes-
7ta
CHAPTER
24 Carbohydrates
in LivingOrganisms
thiamine pyrophosphate, lipoic acid, FAD, NAD*, and coenzyme A-are
alsopresent.Thiamine was mentioned previously (Sec.21.8)as vitamin 81.
Now we see that there is a need for it, as its pyrophosphate, in converting
pyruvate to acetyl CoA.
T
TH,
I
C-S
o
o
|
ll
c:c-cH'cH'o-P-o-P-o
ruZc-c-cH,:r(
il-\l
cH3-c\-..,.b
-N-
J".
A A
Thiamine py'rophosphate
Lipoic acid is not classified as a vitamin. Evidently humans.can make their
ornmlipoic acid. No caseof lipoic acid deficiency in a human being has ever
been reported.
o
/,,\t
\
fcn
S-S
2cH2cH2cH2c-oH
Lipoicacid
PRACTICE
EXERCISE
24.'
Acetyl CoA is often considered an energy-rich compound
Explainwhy.
like AIP.
24.5 Thecitricocid cycle
AIM: To list the stepsfor the degrodotionof one ocetylgroup in
the citric ocid cycle.
The oxidation of glucose
carbons is completed in the
citric acid rycle.
The two molecules of acetyl CoA from one molecule of glucose now pass
into the citric acid cycle. Figure 24.4 shows the complete cycle,which pkes
place in the mitochondria of eukaryotic cells. As in other metabolicfathways, all the reactions of the citric acid cycle are catalyzed by enzymes.
Someof the necessaryen4rnes are 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,
FADH,, andAIP