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CASE FILES: BIOCHEMISTRY
vigorous exercise, the liver mobilizes its glycogen stores in response to
glucagon and epinephrine and exports glucose into the blood. As glycogen lev-
els are depleted, the liver begins to synthesize glucose via gluconeogenesis. In
addition to a source of carbons to synthesize glucose, which it obtains from
either lactate or the breakdown of amino acids, the liver also needs a source of
energy in the form of ATP. P-Oxidation of fatty acids provides the reducing
equivalents (NADH and FADH2), by which ATP is synthesized through the
action of the electron transport system and oxidative phosphorylation.
The storage form of glucose is glycogen, which is stored in both muscle
and liver. However, the function of stored glycogen is different in these two
tissues. Muscle uses glycogen as a fuel reserve to provide ATP for its own
needs, whereas the liver uses stored glycogen as a reservoir for glucose to
maintain blood glucose levels. When blood glucose concentrations drop,
glucagon and epinephrine are released into the bloodstream and bind to
glucagon and epinephrine receptors on hepatocytes. The binding of the hormones
to the receptors activates adenylate cyclase producing 3',5'-cyclic AMP
(cAMP). When cAMP binds to cAMP-dependent protein kinase (PKA), it is
activated and is able to phosphorylate target proteins. This leads to activation
of glycogen phosphorylase, the enzyme primarily responsible for mobilizing
glucose from glycogen. Phosphorylase, which is stabilized by pyridoxal
phosphate (vitamin B6), catalyzes the phosphorolysis of glycogen; it cleaves
the 1,4-glycosidic bond of a terminal glucose residue from the nonreducing end
of the glycogen molecule using inorganic phosphate (Figure 20-1). The products
are glucose 1-phosphate and glycogen that is shorter by one glucose residue.
Mobilization of glycogen stores also requires the participation of a
debranching enzyme because phosphorylase ceases to cleave a-1,4-glycosidic
linkages four glucosyl residues from an a-1,6-branch site. The debranching
enzyme has two catalytic activities: a transferase activity and a glucosidase
GLYCOGEN
UDP
Glycogen
Synthase a
P h o s p h o ry la s e
a
UDP-glucose
-T "
PPj
G lu t
.
.
yjp
U rid ylyltra h sfe rè se
PPi
G lu c o s e 1-p h o s p h a te
P h o s p h o g lu c o m u ta s e
|
G-6-P
Figure 20-1. Reactions involved in the synthesis and breakdown of glycogen.
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