582    D I G E S T I V E s y ste m

muscle fibers rely on glycolysis for energy production during
periods of active contraction. Most cells can survive brief peri-
ods of hypoxia (low oxygen levels) by using the small supplies
of ATP provided by glycolysis alone. When oxygen is readily
available, however, mitochondrial activity provides most of the
ATP cells require.
Energy Production Within Mitochondria
Glycolysis yields an immediate net gain of two ATP molecules
for the cell. However, a great deal of additional energy is still
stored in the chemical bonds of pyruvate. The cell’s ability
to capture that energy depends on the presence of oxygen. If
oxygen supplies are adequate, mitochondria will absorb the
pyruvate molecules and break them down completely. The
hydrogen atoms of pyruvate are removed by coenzymes and
are ultimately the source of most of the cell’s energy gain.
transports the pyruvate from the intermembrane space into
the mitochondrial matrix.
Once inside the mitochondrion, each pyruvate molecule
takes part in a reaction leading to a sequence of enzymatic re-
actions called the citric acid cycle (Figure 17-4). This reaction
sequence is also known as the tricarboxylic (trī-kar-bok-SIL-ik)
acid (TCA) cycle, and the Krebs cycle. We use citric acid cycle as
the preferred term, because citric acid is the first substrate of
the cycle. The role of the citric acid cycle is to remove hydrogen
atoms from organic molecules and transfer them to coenzymes.
The Citric Acid Cycle
In the mitochondrion, a pyruvate molecule takes part in a
complex reaction involving NAD and another coenzyme
called coenzyme A (or CoA). This reaction yields one molecule
each of carbon dioxide, NADH, and acetyl-CoA (AS-e-til-KO-a).
.

The carbon and oxygen atoms are removed and released as Acetyl-CoA consists of a 2-carbon acetyl group (CH3CO) bound
carbon dioxide. to coenzyme A. When the acetyl group is transferred from CoA
Recall that a double membrane surrounds each mitochon- to a 4-carbon molecule, a 6-carbon molecule called citric acid
drion. p. 73 The outer membrane is permeable to ions and is produced.
small organic molecules such as pyruvate. Such substances As citric acid is produced, CoA is released to bind with
easily enter the intermembrane space between the outer and another acetyl group. A complete revolution, or turn, of the
inner membranes. A carrier protein in the inner membrane citric acid cycle removes the two added carbon atoms, regen-
erating the initial 4-carbon molecule. (This is
Figure 17-4  The Citric Acid Cycle. Within mitochondria, the citric acid cycle breaks why this reaction sequence is called a cycle.) The
down pyruvate molecules produced by glycolysis (and other catabolic pathways). This two removed carbon atoms become part of two
overview of the citric acid cycle shows the distribution of carbon, hydrogen, and oxygen
molecules of carbon dioxide (CO2), a metabolic
atoms through one complete turn.
waste product. The hydrogen atoms of the acetyl
Pyruvate group are removed by coenzymes.
NAD Coenzyme A The only immediate energy benefit of one
revolution of the citric acid cycle is the for-
CO2 NADH mation of a single molecule of GTP (guanosine
Acetyl-CoA Coenzyme A triphosphate). This high-energy compound is
readily converted into ATP. The real value of
the citric acid cycle can be seen by following the
4-carbon Citric acid fate of the hydrogen atoms that are removed by
6-carbon the coenzymes NAD and FAD (flavine adenine
CO2 H NADH dinucleotide). The two coenzymes form NADH
H
CITRIC and FADH2 and transfer the hydrogen atoms to
17
5-carbon ELECTRON the electron transport system.
2H
ACID TRANSPORT
SYSTEM
CYCLE CO2
The Electron Transport System
H NADH
The electron transport system (ETS) is em-
4-carbon
bedded in the inner mitochondrial membrane
ATP (by GTP)
(Spotlight Figure 17-5). The ETS consists of four
FADH2 respiratory protein complexes (I–IV), coenzyme Q,
NADH and an electron transport chain made up of a

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 Spotlight Figure 17-5
Electron Transport System and ATP Formation
The final step in aerobic ATP production involves the transfer of energy from
the high-energy electrons carried by NADH and FADH2 to ATP molecules.
This energy transfer occurs in the electron transport system (ETS).
The ETS is located in the inner mitochondrial membrane.

The ETS consists of four respiratory complexes (I–IV), coenzyme Q, and an electron
transport chain of cytochrome molecules (b, c, a, and a3). Except for cytochrome c
(Cyt c), these molecules are associated with respiratory complexes III and IV. The
hydrogen atoms delivered by NADH and FADH2 are first split into electrons (e–) and
protons (H+). The high-energy electrons are passed along the protein complexes, such
that their energy is released in a series of small steps. This energy is used to pump H+
into the intermembrane space. The result is a H+ concentration gradient across the
inner membrane. This H+ gradient is used to generate ATP through ATP synthase. The
red line with the arrowhead indicates the paths and destination of the electrons.

CYTOSOL

Outer
membrane
H+ H+
H+
ATP synthase
with hydrogen
Intermembrane Cyt c ion channel
space
b IV
Q III
I a a3

II _
Inner
H+ 2 e
membrane H+ + ADP + P
NADH 1/2 O2 + 2 H
H+

NAD
FADH2 FAD + H+
H2O ATP

MITOCHONDRIAL
MATRIX

1 The electrons from

2 The electrons
3 The electrons are
4 The electrons trans-
5 H+ pass through
NADH pass from from FADH2 transferred from ferred to respiratory hydrogen ion
respiratory are transferred coenzyme Q to complex IV release channels into
complex I to to respiratory respiratory their remaining energy the matrix.
coenzyme Q (Q). complex II complex III. More to pump H+ into the Their movement
The energy released and then electron energy intermembrane space. provides the
by the electrons is directly to is released and The electrons are energy for the
used to pump H+ coenzyme Q. used to pump released into the ATP synthase
from the matrix into H+ into the matrix and combine complex to
the intermembrane intermembrane with oxygen and H+ to combine ADP
space. space. form water molecules. and P into ATP.

583

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 584    D I G E S T I V E s y ste m
series of cytochrome molecules (b, c, a, and a3). The cytochromes
are proteins with iron-containing heme groups. The ETS does
not produce ATP directly. Instead, it creates the conditions
necessary for ATP production.
The hydrogen atoms from the citric acid cycle do not enter
the ETS intact. Only their high-energy electrons enter the ETS.
Their protons are released into the mitochondrial matrix. The
electrons that travel along the ETS release energy as they pass
from coenzyme Q and along the electron transport chain of
cytochrome molecules.
The red lines in Spotlight Figure 17-5 show the paths and
destinations of electrons. Those from NADH go from respira-
tory protein complex I to coenzyme Q. The electrons from
FADH2 enter the ETS at respiratory protein complex II and are
passed to coenzyme Q. As a result, the electrons carried by
NADH enter the ETS at a higher energy level than those car-
ried by FADH2. The electrons from both paths are passed from
coenzyme Q to respiratory protein complex III, which contains
the first cytochrome (b) in the electron transport chain. From
there, the electrons are shuttled by cytochrome c to additional
cytochromes within respiratory protein complex IV.
The energy released at each of several steps drives hydrogen
ion pumps in respiratory protein complexes I, III, and IV. These
pumps move hydrogen ions from the mitochondrial matrix
into the intermembrane space (between the two mitochondrial
membranes). This pumping creates a large concentration gradi-
ent of hydrogen ions across the inner membrane. The concen-
tration gradient provides the energy to convert ADP to ATP.
Despite the concentration gradient, hydrogen ions cannot
diffuse into the matrix because they are not lipid soluble. How-
ever, hydrogen ion channels in the inner membrane permit
H + to enter the matrix. These ion channels and attached pro-
teins make up a membrane enzyme called ATP synthase. The
kinetic energy of the passing hydrogen ions is used to attach
a phosphate group to ADP, forming ATP. This overall process is
called chemiosmosis (kem-e-oz-MO-sis), a term that links the
.
.
chemical formation of ATP with transport across a membrane.
At the end of the ETS, an oxygen atom accepts two electrons
from respiratory protein complex IV and combines with two
hydrogen ions to form a molecule of water.
17
The electron transport system is the most important pro-
cess for generating ATP. It provides roughly 95 percent of
the ATP needed to keep our cells alive. Stopping or slowing
the rate of mitochondrial activity will usually kill a cell. For
­example, if the cell’s supply of oxygen is cut off, mitochondrial
ATP production will cease because the ETS will be unable to
pass along its electrons. With the last reaction in the chain
stopped, the entire ETS comes to a halt, like a line of cars at a
washed-out bridge. When the ETS stops, NADH and FADH2
M17_MART8845_07_SE_C17_577-603.indd 584
can’t drop off their hydrogen atoms, so the citric acid cycle
stops as well. The affected cell quickly dies of energy depriva-
tion. If many cells are affected, the individual may die.
Energy Yield of Glycolysis
and Cellular Respiration
For most cells, the main method of generating ATP is the com-
plete reaction pathway, beginning with glucose and ending
with carbon dioxide and water. Figure 17-6 summarizes the
process in terms of energy gained:
⦁ During glycolysis in the cytosol, the cell gains two mol-
ecules of ATP and two NADH for each glucose molecule
broken down to pyruvate.
⦁ Inside the mitochondria, the two pyruvate molecules de-
rived from each glucose molecule are fully broken down
in the citric acid cycle. Two revolutions of the citric acid
cycle, each yielding a molecule of ATP, provide a gain
of two additional molecules of ATP. An additional eight
NADH and two FADH2 are also formed.
⦁ For each molecule of glucose broken down, a total of ten
NADH and two FADH2 deliver their high-energy electrons
to the electron transport system in the inner mitochon-
drial membrane. Overall, each NADH yields 2.5 ATP and
each FADH2 yields 1.5 ATP. So, the ten NADH yield 25
ATP and the two FADH2 yield 3 ATP, for a total of 28 ATP.
Adding the two ATP generated in glycolysis and the two
ATP from the citric acid cycle gives a total of 32 molecules
of ATP. That total assumes that the cell expends no
energy in transporting the hydrogen atoms from the
two NADH formed during glycolysis into a mitochon-
drion. Because the energy requirements of different
transport processes vary, it is estimated that up to two ATP
are used to transport the two NADH. Subtracting those two
ATP then, leaves us a minimal total of 30 ATP.
Summing up, for each glucose molecule processed, a typi-
cal cell gains 30–32 molecules of ATP. All but two of them are
produced within mitochondria.
Gluconeogenesis (Glucose Synthesis)
Some of the steps in the breakdown of glucose, or glycolysis,
are not reversible. For this reason, cells cannot generate glu-
cose simply by using the same enzymes and reversing the steps
in glycolysis (Figure 17-7). Glycolysis and the production of
glucose require different sets of regulatory enzymes. As a result,
the two processes are independently regulated.
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