section 22.5
Carbohydrate Homeostasis
501
Glucagon
Epinephrine
"
■
I
...
Inositol triphosphate
Adenylate cyclase
A TP
cAMP
d
Cytosolic
cAMP-dependent
Phosphorylase
protein kinase
kinase
Activated
by
phosphorylation
Activated
allosterically
by C e T
_____ J
Phosphorylase b
Phosphorylase a
Glycogen
Glucose 1-phosphate
II
Glucose 6-phosphate
I
Glucose
FIGURE 22-13
Regulation of hepatic glycogenolysis. Glucagon and epinephrine can
activate hepatic glycogenolysis and lead to glucose release. Glucagon acts
primarily by increasing cytosolic levels of cAMP, whereas epinephrine acts
predominantly by increasing the release of calcium from endoplasmic
reticulum into cytosol. In either circumstance, phosphorylase kinase is
activated. cAMP mediates the phosphorylation of phosphorylase kinase,
while calcium activates phosphorylase kinase allosterically. The result is
the phosphorylation and activation of phosphorylase b. Some overlap
between the two mechanisms occurs.
glucose-producing mechanism. Hepatic glycogenolysis is
also regulated by catecholamines. Catecholamine release
is less sensitive to hypoglycemia than glucagon release
but plays a significant role in stress and high-intensity
exercise. Catecholamines act via stimulation of calcium
release from endoplasmic reticulum along with allosteric
activation of phosphorylase kinase that results in activation
of phosphorylase, degradation of glycogen, and hepatic
glucose output.
Utilization of Skeletal Muscle Glycogen
The muscle of a 70-kg human contains about 300 g
of glycogen, but this glycogen is not readily available
to maintain blood glucose levels because muscle lacks
glucose-
6
-phosphatase. However, the Cori cycle provides
a means for muscle to function anaerobically during
intense exercise. Thus, muscle glycogen contributes to
plasma glucose homeostasis, although its conversion to
lactate is regulated by the metabolic demands of muscle
contraction. The ATP/ADP cycle links muscle contrac-
tion and conversion of muscle glycogen to lactate. Since
there are only limited amounts of adenine nucleotides,
these processes are tightly coupled. The coordination of
muscle glycogen utilization and contraction is presented in
more detail in Figure 22-14.
Regulation occurs because
glucagon and insulin function to regulate glycogen synthe-
sis and degradation that directly reflects the blood glucose
level. In the initial phases of starvation, this is the major
1. ADP is a required substrate for glycolysis
(stoichiometric regulation),
2. Phosphofructokinase catalyzes an irreversible step in
glycolysis and is subject to allosteric inhibition by
Lac ta le
G lu co se
Glycolysis
G lu c o s e
/
kn
Q
/ /
6
-p h o sp h ate
.
' >
'
I
1
A M P A T P
A D P
V *
P h o sp h o rylase
*
*
P y ru vate
G lyco g en
N A D
N A D H
. . - W
. .
Muscular work
FIGURE 22-14
Coordinated regulation of skeletal muscle metabolism by nucleotides.
