A-5
Glucose-6-phosphate is rearranged and converted to its
isomer, fructose-6-phosphate. Isomers, remember, have the
same number and types of atoms but in different structural
arrangements.
An isomerase enzyme interconverts the 3-carbon sugars,
and if left alone in a test tube, the reaction reaches equilibrium.
This does not happen in the cell, however, because the next
enzyme in glycolysis uses only glyceraldehyde phosphate as its
substrate and not dihydroxyacetone phosphate. This pulls the
equilibrium between the two 3-carbon sugars in the direction of
glyceraldehyde phosphate, which is removed as fast as it forms.
Thus, the net result of steps 4 and 5 is cleavage of a 6-carbon
sugar into two molecules of glyceraldehyde phosphate; each
will progress through the remaining steps of glycolysis.
In this step, still another molecule of ATP is used to
add a second phosphate group to the sugar, producing
fructose-1,6-bisphosphate. So far, the ATP ledger shows a
debit of –2. With phosphate groups on its opposite ends,
the sugar is now ready to be split in half.
This is the reaction from which glycolysis gets its name. An
enzyme cleaves the sugar molecule into two different 3-carbon
sugars: glyceraldehyde 3-phosphate and dihydroxyacetone
phosphate. These two sugars are isomers of one another.
An enzyme now catalyzes two sequential reactions
while
it holds glyceraldehyde phosphate in its active site. First, the
sugar is oxidized by the transfer of H from the number one
carbon of the sugar to NAD
+
, forming NADH + H
+
. Here we
see in metabolic context the oxidation-reduction reaction
described in Chapter 24. This reaction releases substantial
amounts of energy, and the enzyme capitalizes on this by
coupling the reaction to the creation of a high-energy
phosphate bond at the number one carbon of the oxidized
substrate. The source of the phosphate is inorganic phosphate
(P
i
) always present in the cytosol. The enzyme releases
NADH + H
+
and 1,3-bisphosphoglyceric acid as products.
Notice in the figure that the new phosphate bond is
symbolized with a squiggle (~), which indicates that the bond
is at least as energetic as the high-energy phosphate bonds of
ATP.
CH
2
OH
H
HO
O
H
Glucose
OH
OH
ADP
ADP
Hexokinase
Phosphoglucoisomerase
Glucose-6-phosphate
H
OH
H
H
CH
2
O
P
H
HO
O
H
OH
OH
H
OH
H
H
Fructose-6-phos-
phate
H
2
C
O
Phosphofructokinase
Fructose-1,
6-bisphosphate
P
H
O
CH
2
OH
OH
H
OH
H
HO
H
2
C
O
P
P
H
O
CH
OH
H
OH
H
HO
O
CH
2
C O
C O
H
O
P
CH
2
Glyceraldehyde
3-phosphate
1,3-Bisphosphoglyceric
acid (2 molecules)
O
P
C
O
CHOH
O
P
P
~
CH
2
O
CHOH
CH
2
OH
NAD
+
Triose phosphate
dehydrogenase
Aldolase
Dihydroxyacetone
phosphate
Isomerase
P
i
Glucose enters the cell and is phosphorylated by the
enzyme hexokinase, which catalyzes the transfer of a
phosphate group, indicated as
, from ATP to the number six
carbon of the sugar, producing glucose-6-phosphate. The
electrical charge of the phosphate group traps the sugar in the
cell because the plasma membrane is impermeable to ions.
Phosphorylation of glucose also makes the molecule more
chemically reactive. Although glycolysis is supposed to
produce
ATP, ATP is actually consumed in step 1—an energy
investment that will be repaid with dividends later in glycolysis.
P
THE TEN STEPS OF GLYCOLYSIS
Each of the ten steps of
glycolysis is catalyzed by a specific enzyme found dissolved in
the cytoplasm. All steps are reversible. An abbreviated version of
the three major phases of glycolysis appears in the lower
right-hand corner of the next page.
ATP
ATP
NADH+H
+
1
2
3
4
5
6
1
2
3
4
5
6
Two Important Metabolic Pathways
Appendix D
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