Carbohydrates are a major source of energy for organisms.
The major pathway by which carbohydrates are degraded
is called glycolysis. Starch, glycogen, and other carbohydrates
are converted to the sugar glucose by pathways that
will not be considered here. In glycolysis, glucose, a sixcarbon
sugar, is oxidized and cleaved by enzymes in the
cytoplasm of cells to form two molecules of pyruvate, a
three-carbon compound (see Figs. 3 and 4). The overall
reaction is exergonic and some of the energy released is
conserved by coupling the synthesis of ATP to glycolysis.
|Figure 3 Schematic outline of carbohydrate metabolism. Glucose is oxidized to two molecules of pyruvate by
glycolysis in the cytoplasm. In mitochondria, pyruvate is oxidized by molecular oxygen to CO2 and water. The synthesis
of ATP is coupled to pyruvate oxidation.
Before it may be metabolized, glucose must first be
phosphorylated on the hydroxyl residue at position 6.
Under intracellular conditions, the direct phosphorylation
of glucose by Pi
is an unfavorable reaction, characterized
by a ΔG0'
0 of about 4 kcal/mol, at pH 7.0 and 25°C. (Note
that the biochemist’s standard state differs from that as
usually defined in that the activity of the hydrogen ion is
taken as 10−7 M
, or pH 7.0, rather than 1 M
, or pH 0.0.
pH 7.0 is much closer to the pH in most cells.) This problem
is neatly solved in cells by using ATP, rather than Pi
as the phosphoryl donor:
|Glucose + ATP ↔ Glucose 6-phosphate + ADP.
for this reaction, which is catalyzed by the enzyme
hexokinase, is approximately −4 kcal/mol. Thus the
phosphorylation of glucose by ATP is an energetically favorable
reaction and is one example of how the chemical
energy of ATP may be used to drive otherwise unfavorable
Glucose 6-phosphate is then isomerized to form fructose
6-phosphate, which in turn is phosphorylated by ATP
at the 1-position to form fructose 1,6-bisphosphate. It
seems odd that a metabolic pathway invests 2 mol of ATP
in the initial steps of the pathway when ATP is an important
product of the pathway. However, this investment
pays off in later steps.
Fructose 1,6-bisphosphate is cleaved to form two triose
phosphates that are readily interconvertible. Note that the
oxidation–reduction state of the triose phosphates is the
same as that of glucose 6-phosphate and the fructose phosphates.
All molecules are phosphorylated sugars. In the
next step of glycolysis, glyceraldehyde 3-phosphate is oxidized
and phosphorylated to form a sugar acid that contains
a phosphoryl group at positions 1 and 3. The oxidizing
agent, nicotinamide adenine dinucleotide (NAD+
a weak oxidant (E0´
, at pH 7.0 of −340 mV). The oxidation
of the aldehyde group of glyceraldehyde 3-phosphate
to a carboxylate is a favorable reaction that drives both
the oxidation and the phosphorylation. This is the only
oxidation–reduction reaction in glycolysis.
The hydrolysis of acyl phosphates, such as that of
position 1 of 1,3-bisphosphoglycerate, is characterized
by strongly negative ΔG0'
values. That for 1,3-bisphosphoglycerate
is approximately −10 kcal/mol, which is
significantly more negative than the ΔG0'
for the hydrolysis
of ATP to ADP and Pi
. Thus, the transfer of the acyl
phosphate from 1,3-bisphosphoglycerate to ADP to form
3-phosphoglycerate and ATP is a spontaneous reaction.
Since two sugar acid bisphosphates are formed per glucose
metabolized, the two ATP invested in the beginning
of the pathway have been recovered.
In the next steps of glycolysis, the phosphate on the
3-position of the 3-phosphoglycerate is transferred to the
hydroxyl residue at position 2. Removal of the elements
of water from 2-phosphoglycerate results in the formation
of an enolic phosphate compound, phospho(enol)pyruvate
(PEP). The free energy of hydrolysis of PEP to form the
enol form of pyruvate and Pi
is on the order of −4 kcal/mol.
In aqueous solution, however, the enol form of pyruvate is
very unstable. Thus, the hydrolysis of PEP to form pyruvate
is a very exergonic reaction. The ΔG0'
for this reaction
is −14.7 kcal/mol, which corresponds to an equilibrium
constant of 6.4×1010
. PEP is thus an excellent
phosphoryl donor and the formation of pyruvate is coupled
to ATP synthesis. Since two molecules of pyruvate
are formed per glucose catabolized, two ATP are formed.
Thus the net yield of ATP is two per glucose oxidized to
In some organisms, glycolysis is the only source of ATP.
A familiar example is yeast growing under anaerobic (no
oxygen) conditions. In this case, glucose is said to be fermented
and ethyl alcohol and carbon dioxide (CO2
the end products (Fig. 5). In contrast, all higher organisms
can completely oxidize pyruvate to CO2
and water, using
molecular oxygen as the terminal electron acceptor. The
conversion of glucose to pyruvate releases only a small
fraction of the energy available in the complete oxidation
of glucose. In aerobic organisms, more than 90% of the
ATP made during glucose catabolism results from the oxidation
|Figure 4 A view of glycolysis. Glucose, a six-carbon sugar, is
cleaved and oxidized to two molecules of pyruvate. There is the
net synthesis of two ATP per glucose oxidized and two NADH are
|Figure 5 Fates of pyruvate. In yeasts under anaerobic conditions,
pyruvate is decarboxylated and reduced by the NADH
formed by glycolysis to ethanol. In anaerobic muscle, the NADH
generated by glycolysis reduces pyruvate to lactic acid. When O2 is present, pyruvate is completely oxidized to CO2 and water.