Cellular Structure, Proteins, and Metabolism
81
C
COO
CH
3
O
O
H
C
Lactate
Pyruvate
COO
cycle
Reaction 6
(anaerobic)
(aerobic)
H
2NADH + 2H
+
2NAD
+
Glucose
CH
3
Krebs
22
Figure 3–42
Under anaerobic conditions, the coenzyme NAD
+
utilized in the
glycolytic reaction 6 (see Figure 3–41) is regenerated when it transfers
its hydrogen atoms to pyruvate during the formation of lactate.
Pyruvate, upon entering mitochondria from the cyto-
sol, is converted to acetyl CoA and CO
2
(
Figure 3–43
). Note
that this reaction produces the fi
rst molecule of CO
2
formed
thus far in the pathways of fuel catabolism, and that the reac-
tion also transfers hydrogen atoms to NAD
+
.
The Krebs cycle begins with the transfer of the acetyl
group of acetyl CoA to the four-carbon molecule, oxaloace-
tate, to form the six-carbon molecule, citrate (
Figure 3–44
).
At the third step in the cycle a molecule of CO
2
is produced,
and again at the fourth step. Thus, two carbon atoms entered
the cycle as part of the acetyl group attached to CoA, and two
carbons (although not the same ones) have left in the form of
CO
2
. Note also that the oxygen that appears in the CO
2
is not
derived from molecular oxygen, but from the carboxyl groups
of Krebs cycle intermediates.
In the remainder of the cycle, the four-carbon molecule
formed in reaction 4 is modifi ed through a series of reactions
to produce the four-carbon molecule oxaloacetate, which
becomes available to accept another acetyl group and repeat
the cycle.
Now we come to a crucial fact: In addition to produc-
ing carbon dioxide, intermediates in the Krebs cycle generate
hydrogen atoms, most of which are transferred to the coen-
zymes NAD
+
and FAD to form NADH and FADH
2
. This
hydrogen transfer to NAD
+
occurs in each of steps 3, 4, and 8,
and to FAD in reaction 6. These hydrogens will be transferred
from the coenzymes, along with the free H
+
, to oxygen in the
next
stage
of
fue
l
metabo
l
ism—oxidative
phosphory
lation
.
Because oxidative phosphorylation is necessary for regenera-
tion of the hydrogen-free form of these coenzymes,
the Krebs
cycle can operate only under aerobic conditions.
There is no
pathway in the mitochondria that can remove the hydrogen
from these coenzymes under anaerobic conditions.
So far we have said nothing of how the Krebs cycle con-
tributes to the formation of ATP. In fact, the Krebs cycle
directly
produces only one high-energy nucleotide triphosphate. This
Table 3–8
Characteristics of Glycolysis
Entering substrates
Glucose and other monosaccharides
Enzyme location
Cytosol
Net ATP production
2 ATP formed directly per molecule of glucose entering pathway can be produced in the absence of
oxygen (anaerobically)
Coenzyme production
2 NADH + 2 H
+
formed under aerobic conditions
Final products
Pyruvate—under aerobic conditions
Lactate—under anaerobic conditions
Net reaction
Aerobic:
Glucose + 2 ADP + 2 P
i
+ 2 NAD
+
⎯⎯→
2 pyruvate + 2 ATP + 2 NADH + 2 H
+
+ 2 H
2
O
Anaerobic:
Glucose + 2 ADP + 2 P
i
⎯⎯→
2 lactate + 2 ATP + 2 H
2
O
NAD
+
NADH + H
+
Pyruvic acid
Acetyl coenzyme A
O
C
COOH
CH
3
O
C
CH
3
CO
2
CoA
CoA
S
+
SH
+
Figure 3–43
Formation of acetyl coenzyme A from pyruvic acid with the
formation of a molecule of carbon dioxide.
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