Chapter 24
Nutrition, Metabolism, and Body Temperature Regulation
919
24
protein. Once in the mitochondrion, the first order of business
is a
transitional phase
that converts pyruvic acid to acetyl CoA.
Tis occurs via a three-step process (
Figure 24.7
, top):
1.
Decarboxylation.
In this step, one of pyruvic acid’s carbons
is removed and released as carbon dioxide gas, a process
called
decarboxylation
. CO
2
diffuses out of the cells into
the blood to be expelled by the lungs. Tis is the first time
that CO
2
is released during cellular respiration.
2.
Oxidation.
Te remaining 2C fragment (acetic acid) is oxi-
dized by removing hydrogen atoms, which are picked up
by NAD
1
.
3.
Formation of acetyl CoA.
Acetic acid is combined with
coenzyme A
to produce the reactive final product,
acetyl
coenzyme A (acetyl CoA)
. Coenzyme A is a sulfur-
containing coenzyme derived from vitamin B
5
.
Acetyl CoA is now ready to enter the Krebs cycle and be bro-
ken down completely by mitochondrial enzymes. Coenzyme A
shuttles the 2-carbon acetic acid to an enzyme that condenses
it with a 4-carbon acid called
oxaloacetic acid
(ok
0
sah-lo
0
ah-
sēt
9
ik) to produce the 6-carbon
citric acid
. Because citric acid
is the first substrate of the cycle, biochemists prefer to call the
Krebs cycle the
citric acid cycle
.
As the cycle moves through its eight successive steps, the at-
oms of citric acid are rearranged to produce different intermediate
molecules, most called
keto acids
(Figure 24.7). Te acetic acid
that enters the cycle is broken apart carbon by carbon (decarboxy-
lated) and oxidized, simultaneously generating NADH
1
H
1
and
FADH
2
. At the end of the cycle, acetic acid has been totally dis-
posed of and oxaloacetic acid, the
pickup molecule
, is regenerated.
What are the products of the Krebs cycle? Because two
de-
carboxylations
and four
oxidations
occur, the products are two
CO
2
molecules and four molecules of reduced coenzymes (3
NADH
1
H
1
and 1 FADH
2
). Te addition of water at certain
steps accounts for some of the released hydrogen. One molecule
of A±P is formed (via substrate-level phosphorylation) during
each turn of the cycle. Te detailed events of each of the eight
steps of the Krebs cycle are described in Appendix D.
Now let’s back up and account for the pyruvic acid molecules
entering the mitochondria. We need to consider the products
of both the transitional phase and the Krebs cycle itself. Alto-
gether, each pyruvic acid yields three CO
2
molecules and five
molecules of reduced coenzymes—1 FADH
2
and 4 NADH
1
H
1
(equal to removing 10 hydrogen atoms). Te products of
glucose oxidation in the Krebs cycle are twice that (remember
1 glucose
5
2 pyruvic acids): six CO
2
, ten molecules of reduced
coenzymes, and two A±P molecules.
Notice that it is these Krebs cycle reactions that produce the
CO
2
evolved during glucose oxidation. Te reduced coenzymes,
which carry their extra electrons in high-energy linkages, must
now be oxidized if the Krebs cycle and glycolysis are to continue.
Although glycolysis is exclusive to carbohydrate oxidation,
breakdown products of carbohydrates, fats, and proteins can
feed into the Krebs cycle to be oxidized for energy. On the other
hand, some Krebs cycle intermediates can be siphoned off to
make fatty acids and nonessential amino acids. Tus, the Krebs
cycle is a source of building materials for anabolic reactions, as
well as the final common pathway for oxidizing food fuels.
are cleaved off, enough energy is captured to form four A±P
molecules. As we noted earlier, formation of A±P this way is
called
substrate-level phosphorylation
.
Te final products of glycolysis are two molecules of
pyru-
vic acid
and two molecules of reduced NAD
1
(which is NADH
1
H
1
). Tere is a net gain of two A±P molecules per glucose
molecule. Four A±Ps are produced, but remember that two are
consumed in phase 1 to “prime the pump.” Each pyruvic acid
molecule has the formula C
3
H
4
O
3
, and glucose is C
6
H
12
O
6
. Be-
tween them the two pyruvic acid molecules have lost four hy-
drogen atoms, which are now bound to two molecules of NAD
1
.
NAD carries a positive charge (NAD
1
), so when it accepts a hy-
drogen pair, NADH
1
H
1
is the resulting reduced product. Al-
though a small amount of A±P has been harvested, the other two
products of glucose oxidation (H
2
O and CO
2
) have yet to appear.
Te fate of pyruvic acid, which still contains most of glucose’s
chemical energy, depends on the availability of oxygen at the
time the pyruvic acid is produced. Because the supply of NAD
1
is limited, glycolysis can continue only if the reduced coen-
zymes (NADH
1
H
1
) formed during glycolysis are relieved
of their extra hydrogen. Only then can they continue to act as
hydrogen acceptors.
When oxygen is readily available, this is no problem. NADH
1
H
1
delivers its burden of hydrogen atoms to the enzymes of the
electron transport chain in the mitochondria, which deliver them
to O
2
, forming water. However, when oxygen is not present in suf-
ficient amounts, as might occur during strenuous exercise, NADH
1
H
1
unloads its hydrogen atoms
back onto pyruvic acid
, reducing
it. Tis addition of two hydrogen atoms to pyruvic acid yields
lactic
acid
(see bottom right of Figure 24.6). Some of this lactic acid dif-
fuses out of the cells and is transported to the liver for processing.
When oxygen is again available, lactic acid is oxidized back
to pyruvic acid and enters the
aerobic pathways
(the oxygen-
requiring Krebs cycle and electron transport chain within the
mitochondria), and is completely oxidized to water and carbon
dioxide. Te liver may also convert lactic acid all the way back
to glucose-6-phosphate (reverse glycolysis) and then store it as
glycogen, or free it of its phosphate and release it to the blood if
blood sugar levels are low.
Except for red blood cells (which typically carry out
only
gly-
colysis), prolonged anaerobic metabolism ultimately results in
acid-base problems. Consequently,
totally
anaerobic conditions
resulting in lactic acid formation provide only a temporary route
for rapid A±P production. ±otally anaerobic conditions can go on
without tissue damage for the longest periods in skeletal muscle,
for much shorter periods in cardiac muscle, and almost not at
all in the brain. Although glycolysis generates A±P rapidly, each
glucose molecule yields only 2 A±P as compared to the 30 to 32
A±P when a glucose molecule is completely oxidized.
Krebs Cycle
Named a²er its discoverer Hans Krebs, the
Krebs
cycle
is the next stage of glucose oxidation. Te Krebs cycle,
which occurs in the mitochondrial matrix, is fueled largely by
pyruvic acid produced during glycolysis and by fatty acids re-
sulting from fat breakdown.
Because pyruvic acid is a charged molecule, it must enter the
mitochondrion by active transport with the help of a transport
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