Cellular Structure, Proteins, and Metabolism
83
ATP is derived from the energy released when hydrogen ions
combine with molecular oxygen to form water. The hydrogen
comes from the NADH + H
+
and FADH
2
coenzymes gener-
ated by the Krebs cycle, by the metabolism of fatty acids (see
the discussion that follows), and, to a much lesser extent, dur-
ing aerobic glycolysis. The net reaction is:
1
2
O
2
+ NADH + H
+
⎯→
H
2
O + NAD
+
+ Energy
Unlike the enzymes of the Krebs cycle, which are sol-
uble enzymes in the mitochondrial matrix, the proteins that
mediate oxidative phosphorylation are embedded in the inner
mitochondrial membrane. The proteins for oxidative phos-
phorylation can be divided into two groups: (1) those that
mediate the series of reactions that cause the transfer of hydro-
gen ions to molecular oxygen, and (2) those that couple the
energy released by these reactions to the synthesis of ATP.
Most of the fi rst group of proteins contain iron and cop-
per cofactors, and are known as
cytochromes
(because in
pure form they are brightly colored). Their structure resem-
bles the red iron-containing hemoglobin molecule, which
binds oxygen in red blood cells. The cytochromes form the
components of the
electron transport chain,
in which two
electrons from the hydrogen atoms are initially transferred
either from NADH + H
+
or FADH
2
to one of the elements
in this chain. These electrons are then successively transferred
to other compounds in the chain, often to or from an iron or
copper ion, until the electrons are fi nally transferred to molec-
ular oxygen, which then combines with hydrogen ions (pro-
tons) to form water. These hydrogen ions, like the electrons,
come from free hydrogen ions and the hydrogen-bearing
coenzymes, having been released early in the transport chain
when the electrons from the hydrogen atoms were transferred
to the cytochromes.
Importantly, in addition to transferring the coenzyme
hydrogens to water, this process regenerates the hydrogen-free
form of the coenzymes, which then become available to accept
two more hydrogens from intermediates in the Krebs cycle,
glycolysis, or fatty acid pathway (as described in the discussion
that follows). Thus, the electron transport chain provides the
aerobic
mechanism for regenerating the hydrogen-free form
of the coenzymes, whereas, as described earlier, the
anaerobic
mechanism, which applies only to glycolysis, is coupled to the
formation of lactate.
At each step along the electron transport chain, small
amounts of energy are released. Because this energy is released
in small steps, it can be coupled to the synthesis of several mol-
ecules of ATP in a controlled manner.
ATP is formed at three points along the electron trans-
port chain. The mechanism by which this occurs is known as
the
chemiosmotic hypothesis.
As electrons are transferred
from one cytochrome to another along the electron transport
chain, the energy released is used to move hydrogen ions (pro-
tons) from the matrix into the compartment between the inner
and outer mitochondrial membranes (
Figure 3–45
), thus pro-
ducing a source of potential energy in the form of a hydrogen-
ion gradient across the membrane. At three points along the
chain, a protein complex forms a channel in the inner mito-
chondrial membrane, allowing the hydrogen ions to fl ow back
to the matrix side and, in the process, transfer energy to the for-
mation of ATP from ADP and P
i
. FADH
2
has a slightly lower
chemical energy content than does NADH + H
+
and enters
the electron transport chain at a point beyond the fi rst site of
ATP generation (see Figure 3–45). The process is not perfectly
stoichiometric, however, and thus the transfer of electrons to
oxygen produces approximately 2.5 and 1.5 molecules of ATP
for each molecule of NADH + H
+
and FADH
2
, respectively.
In summary, most ATP formed in the body is produced
during oxidative phosphorylation as a result of processing
hydrogen atoms that originated largely from the Krebs cycle
during the breakdown of carbohydrates, fats, and proteins.
The mitochondria, where the oxidative phosphorylation and
the Krebs cycle reactions occur, are thus considered the power-
houses of the cell. In addition, most of the oxygen we breathe
is consumed within these organelles, and most of the carbon
dioxide we exhale is produced within them as well.
Table 3–9
Characteristics of the Krebs Cycle
Entering substrate
Acetyl coenzyme A—acetyl groups derived from pyruvate, fatty acids, and amino acids
Some intermediates derived from amino acids
Enzyme location
Inner compartment of mitochondria (the mitochondrial matrix)
ATP production
1 GTP formed directly, which can be converted into ATP
Operates only under aerobic conditions even though molecular oxygen is not used directly in this pathway
Coenzyme production
3 NADH + 3 H
+
and 2 FADH
2
Final products
2 CO
2
for each molecule of acetyl coenzyme A entering pathway
Some intermediates used to synthesize amino acids and other organic molecules required for special cell
functions
Net reaction
Acetyl CoA + 3 NAD
+
+ FAD + GDP + P
i
+ 2 H
2
O
⎯→
2 CO
2
+ CoA + 3 NADH + 3 H
+
+ FADH
2
+ GTP
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