Cellular Structure, Proteins, and Metabolism
three-carbon molecules into the other. Thus, at the end of
reaction 5 we have two molecules of 3-phosphoglyceralde-
hyde derived from one molecule of glucose. Keep in mind,
then, that from this point on,
molecules of each inter-
mediate are involved.
The fi rst formation of ATP in glycolysis occurs during
reaction 7, when a phosphate group is transferred to ADP to
form ATP. Since two intermediates exist at this point, reac-
tion 7 produces two molecules of ATP, one from each inter-
mediate. In this reaction, the mechanism of forming ATP
is known as
substrate-level phosphorylation
because the
phosphate group is transferred from a substrate molecule to
A similar substrate-level phosphorylation of ADP occurs
during reaction 10, where again two molecules of ATP are
formed. Thus, reactions 7 and 10 generate a total of four mol-
ecules of ATP for every molecule of glucose entering the path-
way. There is a net gain, however, of only two molecules of
ATP during glycolysis because two molecules of ATP are used
in reactions 1 and 3.
The end product of glycolysis, pyruvate, can proceed in
one of two directions, depending on the availability of molecu-
lar oxygen, which, as we stressed earlier, is
utilized in any of
the glycolytic reactions themselves. If oxygen is present—that
is, if
conditions exist—pyruvate can enter the Krebs
cycle and be broken down into carbon dioxide, as described in
the next section. In contrast, in the absence of oxygen (
conditions), pyruvate is converted to
(the ionized
form of lactic acid) by a single enzyme-mediated reaction. In
this reaction (
Figure 3–42
), two hydrogen atoms derived
from NADH
+ H
are transferred to each molecule of pyru-
vate to form lactate, and NAD
is regenerated. These hydro-
gens were originally transferred to NAD
during reaction 6 of
glycolysis, so the coenzyme NAD
shuttles hydrogen between
the two reactions during anaerobic glycolysis. The overall
reaction for anaerobic glycolysis is:
Glucose + 2 ADP + 2 P
2 Lactate + 2 ATP + 2 H
As stated in the previous paragraph, under aerobic con-
ditions pyruvate is not converted to lactate but instead enters
the Krebs cycle. Therefore, the mechanism just described for
regenerating NAD
from NADH
+ H
by forming lactate
does not occur. The hydrogens of NADH are transferred to
oxygen during oxidative phosphorylation, regenerating NAD
and producing H
O, as described in detail in the discussion
that follows.
In most cells, the amount of ATP glycolysis produces
from one molecule of glucose is much smaller than the amount
formed under aerobic conditions by the other two ATP-gen-
erating pathways—the Krebs cycle and oxidative phosphory-
lation. In special cases, however, glycolysis supplies most, or
even all, of a cell’s ATP. For example, erythrocytes contain the
enzymes for glycolysis but have no mitochondria, which are
required for the other pathways. All of their ATP production
occurs, therefore, by glycolysis. Also, certain types of skeletal
muscles contain considerable amounts of glycolytic enzymes
but few mitochondria. During intense muscle activity, glycol-
ysis provides most of the ATP in these cells and is associated
with the production of large amounts of lactate. Despite these
exceptions, most cells do not have suffi cient concentrations of
glycolytic enzymes or enough glucose to provide, by glycoly-
sis alone, the high rates of ATP production necessary to meet
their energy requirements.
Our discussion of glycolysis has focused upon glucose
as the major carbohydrate entering the glycolytic pathway.
However, other carbohydrates such as fructose, derived from
the disaccharide sucrose (table sugar), and galactose, from the
disaccharide lactose (milk sugar), can also be catabolized by
glycolysis because these carbohydrates are converted into sev-
eral of the intermediates that participate in the early portion
of the glycolytic pathway.
Table 3–8
summarizes the major
characteristics of glycolysis.
Krebs Cycle
Krebs cycle,
named in honor of Hans Krebs, who worked
out the intermediate steps in this pathway (also known as the
citric acid cycle
tricarboxylic acid cycle
), is the second
of the three pathways involved in fuel catabolism and ATP
production. It utilizes molecular fragments formed during
carbohydrate, protein, and fat breakdown, and it produces
carbon dioxide, hydrogen atoms (half of which are bound to
coenzymes), and small amounts of ATP. The enzymes for this
pathway are located in the inner mitochondrial compartment,
the matrix.
+ P
Fats and
Krebs cycle
Figure 3–40
Pathways linking the energy released from the catabolism of fuel
molecules to the formation of ATP.
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