90 ■ CHAPTER 05 How Cells Work
CELLS
supply, at which point your cells switch to glycol-
ysis, as mentioned already. But how do the cells
extract sufficient energy via glycolysis alone?
Under anaerobic conditions, these muscle
cells use a fermentation pathway. Fermen-
tation begins with glycolysis, followed by a
special set of reactions whose only role is to
help perpetuate glycolysis. This process enables
organisms to generate ATP through glycol-
ysis alone, when aerobic ATP production is
constrained by low oxygen levels (Figure 5.12).
If glycolysis cannot be perpetuated, the cells
will run out of ATP and die.
Many species of bacteria that live in places
like oxygen-deficient swamps, sewage, or deep
layers of soil never use oxygen or are actually
poisoned by oxygen. Similar to rock-breathing
microbes, many microbes can utilize other elec-
tron acceptors, such as iron or sulfur compounds.
When these run out, anaerobic organisms use the
fermentation pathway to regenerate molecules
needed to perpetuate glycolysis, and exclusively
generate ATP through glycolysis without ever
using oxygen.
Most eukaryotic cells can perform both aero-
bic and anaerobic ATP production, depending on
the oxygen levels in their environment. Because
the Krebs cycle and oxidative phosphorylation
produce magnitudes more ATP than glycolysis
and the fermentation pathway yield, these cells
always use oxygen and aerobic respiration when
levels permit.
Together, photosynthesis and cellular respira-
tion enable cells to store and utilize energy from
the sun. They are two sides of the same coin; the
products of one reaction are the ingredients for
the other. Photosynthesis, an anabolic process,
requires energy (sunlight) and CO 2 , and releases
O 2 and glucose. Cellular respiration, a catabolic
process, requires O 2 and glucose, and releases
CO 2 and energy.
Unlike the situation with photosynthesis and
cellular respiration—metabolic processes that
have been well studied for decades— researchers
don’t yet know the details of how rock eaters
store and use energy. “There isn’t really any
pathway worked out yet,” says Rowe. “Truthfully,
it’s amazing that it works.” She’s eager to find out
how. Of the 30 species Rowe has isolated, she is
currently focused on 8, working to develop tools
to identify which enzymes are involved in their
metabolism.energy yield from glycolysis is small. For most
eukaryotes, glycolysis is just the first step in
extracting energy from sugars, and the second
and third stages of cellular respiration, which
occur in the mitochondria, help to gener-
ate much more ATP than is possible through
glycolysis alone.
Glycolysis is an anaerobic process; that is,
it does not require oxygen. Cells experiencing
low oxygen levels—such as our muscle cells
during intense exercise or cancer cells in the
interior of a tumor mass—use glycolysis alone
because there is not enough oxygen available
for the later stages of cellular respiration to
proceed.
But when oxygen is present, eukaryotic cells
rely on all three stages of cellular respiration.
After pyruvate is made in the cytoplasm during
glycolysis, it enters the mitochondria, where it is
broken down during the second stage of cellular
respiration: a sequence of enzyme-driven reac-
tions known as the Krebs cycle or citric acid
cycle. The carbon backbone of the pyruvate
molecule is taken apart, releasing carbon diox-
ide (Figure 5.11, bottom left). The breakdown of
carbon backbones by the Krebs cycle produces a
large bounty of energy carriers, including ATP,
NADH, and FADH 2. Essentially, during the
Krebs cycle the remaining chemical energy of
glucose is completely converted to the chemical
energy of these energy carriers.
The largest output of ATP, however, is gener-
ated during the third and last stage of cellular
respiration: oxidative phosphorylation. The
electrons and hydrogen atoms are removed from
NADH and FADH 2 and handed over to molecu-
lar O 2 through an electron transport chain, creat-
ing water (H 2 O). In the process, a large amount
of ATP is generated (Figure 5.11, bottom right).
During oxidative phosphorylation, the chemical
energy of NADH and FADH 2 is converted into
the chemical energy of ATP. In fact, oxidative
phosphorylation can generate 15 times as much
ATP as can glycolysis alone.
ATP production in mitochondria is crucially
dependent on oxygen; that is, the Krebs cycle
and oxidative phosphorylation are strictly aero-
bic processes. Highly aerobic tissues, like your
muscles, have high concentrations of mitochon-
dria and a rich blood supply to deliver the large
amounts of O 2 needed to support their activity.
Even so, intense exercise exhausts this oxygen