UNIT II:

Bioenergetics and
Carbohydrate
Metabolism

CHAPTER 11: GLYCOGEN

METABOLISM
 I. OVERVIEW
• A constant source of blood glucose is an absolute requirement for
human life.
• Glucose is the greatly preferred energy source for the brain, and the
required energy source for cells with few or no mitochondria such as
mature RBCs.
• Glucose is also essential as an energy source for exercising muscle,
where it is the substrate for anaerobic glycolysis.
• Blood glucose can be obtained from three primary sources:
• the diet,

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• degradation of glycogen,
• and gluconeogenesis.
• Dietary intake of glucose and glucose precursors, such as starch (a
polysaccharide), disaccharides, and monosaccharides, is sporadic
and, depending on the diet, is not always a reliable source of blood
glucose.
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 I. OVERVIEW
• In contrast, gluconeogenesis can provide sustained synthesis of
glucose, but it is somewhat slow in responding to a falling
blood glucose level
• Therefore, the body has developed mechanisms for storing a
supply of glucose in a rapidly mobilizable form, namely,
glycogen.
• In the absence of a dietary source of glucose, this sugar is
rapidly released from liver and kidney glycogen.
• Similarly, muscle glycogen is extensively degraded in

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exercising muscle to provide that tissue with an important
energy source.
• Figure 11.1 shows the reactions of glycogen synthesis and
degradation as part of the essential pathways of energy
metabolism.
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Figure 11.1: Glycogen synthesis

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and degradation shown as a part of the
essential pathways of energy
metabolism. P = phosphate; UDP =
uridine diphosphate.

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 II. STRUCTURE AND FUNCTION OF
GLYCOGEN
• The main stores of glycogen are found in skeletal muscle and
liver, although most other cells store small amounts of
glycogen for their own use.
• The function of muscle glycogen is to serve as a fuel reserve
for the synthesis of adenosine triphosphate (ATP) during
muscle contraction.
• That of liver glycogen is to maintain the blood glucose

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concentration, particularly during the early stages of a fast
(Figure 11.2).

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Figure 11.2: Functions of muscle and liver glycogen. P =
phosphate; Pi = inorganic phosphate.
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 II. STRUCTURE AND FUNCTION OF GLYCOGEN
A. Amounts of liver and muscle glycogen
• Approximately 400 g of glycogen make up 1%–2% of the fresh
weight of resting muscle, and approximately 100 g of glycogen
make up to 10% of the fresh weight of a well-fed adult liver.
• What limits the production of glycogen at these levels is not
clear.
• However, in some glycogen storage diseases ([GSDs] the
amount of glycogen in the liver and/or muscle can be

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significantly higher.

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 II. STRUCTURE AND FUNCTION OF GLYCOGEN
B. Structure of glycogen
• Glycogen is a branched-chain polysaccharide made exclusively
from α-D-glucose.
• The primary glycosidic bond is an α(1→4) linkage.
• After an average of eight to ten glucosyl residues, there is a
branch containing an α(1→6) linkage (Figure 11.3).
• A single glycogen molecule can have a molecular weight of up
to 108 Da.

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• These polymers of glucose exist in discrete cytoplasmic
granules that also contain most of the enzymes necessary for
glycogen synthesis and degradation.

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 Dr. M. Alzaharna 2016
Figure 11.3: Branched
structure of glycogen,
showing α(1→ 4) and α(1→
6) glycosidic bonds.
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 II. STRUCTURE AND FUNCTION OF GLYCOGEN
C. Fluctuation of glycogen stores
• Liver glycogen stores increase during the well-fed state and are
depleted during a fast
• Muscle glycogen is not affected by short periods of fasting (a
few days) and is only moderately decreased in prolonged
fasting (weeks)
• Muscle glycogen is synthesized to replenish muscle stores after
they have been depleted following strenuous exercise.

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 III. SYNTHESIS OF GLYCOGEN
(GLYCOGENESIS)
• Glycogen is synthesized from molecules of α -D-glucose.
• The process occurs in the cytosol and requires energy supplied
by ATP (for the phosphorylation of glucose) and uridine
triphosphate (UTP)

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 III. SYNTHESIS OF GLYCOGEN (GLYCOGENESIS)
A. Synthesis of uridine diphosphate
glucose
• α-D-Glucose attached to uridine diphosphate (UDP) is the source
of all the glucosyl residues that are added to the growing glycogen
molecule.
• UDP-glucose (Figure 11.4) is synthesized from glucose1-phosphate
and UTP by UDP-glucose pyrophosphorylase (Figure 11.5).
• Pyrophosphate (PPi), the second product of the reaction, is
hydrolyzed to two inorganic phosphates (Pi) by pyrophosphatase.
• The hydrolysis is exergonic, ensuring that the UDP-glucose

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pyrophosphorylase reaction proceeds in the direction of UDP-
glucose production.
• Note: Glucose 1-phosphate is generated from glucose 6-phosphate
by phosphoglucomutase.
• Glucose 1,6-bisphosphate is an obligatory intermediate in this
reversible reaction (Figure 11.6)
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 Dr. M. Alzaharna 2016
Figure 11.4: The structure of UDP-glucose, a nucleotide
sugar.
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Figure 11.5: Glycogen synthesis. UTP = uridine triphosphate;
UDP = uridine diphosphate; PPi = pyrophosphate; Pi = inorganic
phosphate.
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Figure 11.6: Interconversion of glucose 6-phosphate and
glucose 1-phosphate by phosphoglucomutase. P = phosphate.

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 III. SYNTHESIS OF GLYCOGEN (GLYCOGENESIS)
B. Synthesis of a primer to initiate
glycogen synthesis
• Glycogen synthase makes the α(1→4) linkages in glycogen.
• This enzyme cannot initiate chain synthesis using free glucose
as an acceptor of a molecule of glucose from UDP-glucose.
• Instead, it can only elongate already existing chains of glucose
and, therefore, requires a primer.
• A fragment of glycogen can serve as a primer in cells whose
glycogen stores are not totally depleted.

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• In the absence of a glycogen fragment, a protein called
glycogenin can serve as an acceptor of glucose residues from
UDP -glucose (see Figure 11.5).

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 III. SYNTHESIS OF GLYCOGEN (GLYCOGENESIS)
B. Synthesis of a primer to initiate
glycogen synthesis
• The side-chain hydroxyl group of a specific tyrosine in the
protein serves as the site at which the initial glucosyl unit is
attached.
• Glycogenin then catalyzes the transfer of the next few
molecules of glucose from UDP-glucose, producing a short,
α(1→4)-linked glucosyl chain.
• This short chain serves as a primer that is able to be elongated

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by glycogen synthase as described below

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 III. SYNTHESIS OF GLYCOGEN (GLYCOGENESIS)
C. Elongation of glycogen chains by
glycogen synthase
• Elongation of a glycogen chain involves the transfer of glucose from
UDP-glucose to the nonreducing end of the growing chain, forming
a new glycosidic bond between the anomeric hydroxyl group of
carbon 1 of the activated glucose and carbon 4 of the accepting
glucosyl residue (Figure 11.5).
• Note: The nonreducing end of a carbohydrate chain is one in which
the anomeric carbon of the terminal sugar is linked by a glycosidic
bond to another compound, making the terminal sugar nonreducing.

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• Note: The UDP released when the new α(1→4) glycosidic bond is
made can be phosphorylated to UTP by nucleoside diphosphate
kinase (UDP + ATP  UTP + ADP).

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 III. SYNTHESIS OF GLYCOGEN (GLYCOGENESIS)
D. Formation of branches in glycogen
• If no other synthetic enzyme acted on the chain, the resulting
structure would be a linear (unbranched) chain of glucosyl residues
attached by α(1→4) linkages.
• Such a compound is found in plant tissues and is called amylose.
• In contrast, glycogen has branches located, on average, eight
glucosyl residues apart, resulting in a highly branched, tree-like
structure (Figure 11.3) that is far more soluble than the unbranched
amylose.

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• Branching also increases the number of nonreducing ends to which
new glucosyl residues can be added (and also, as described later,
from which these residues can be removed), thereby greatly
accelerating the rate at which glycogen synthesis can occur and
dramatically increasing the size of the glycogen molecule
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 III. SYNTHESIS OF GLYCOGEN (GLYCOGENESIS)
D. Formation of branches in glycogen
1. Synthesis of branches:
• Branches are made by the action of the branching enzyme, amylo-α(1→4)
→ α(1→6)-transglucosidase
• This enzyme removes a set of six to eight glucosyl residues from the
nonreducing end of the glycogen chain, breaking an α(1→4) bond to
another residue on the chain, and attaches it to a nonterminal glucosyl
residue by an α(1→6) linkage, thus functioning as a 4:6 transferase
• The resulting new, nonreducing end (see “j” in Figure 11.5), as well as the
old nonreducing end from which the six to eight residues were removed
(see “o” in Figure 11.5), can now be further elongated by glycogen

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synthase .
2. Synthesis of additional branches:
• After elongation of these two ends has been accomplished, their terminal
six to eight glucosyl residues can be removed and used to make additional
branches
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 IV. DEGRADATION OF GLYCOGEN
(GLYCOGENOLYSIS)
• The degradative pathway that mobilizes stored glycogen in
liver and skeletal muscle is not a reversal of the synthetic
reactions.
• Instead, a separate set of cytosolic enzymes is required.
• When glycogen is degraded, the primary product is glucose 1-
phosphate, obtained by breaking α(1→4) glycosidic bonds.
• In addition, free glucose is released from each α(1→6)–linked

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glucosyl residue (branch point).

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 IV. DEGRADATION OF GLYCOGEN (GLYCOGENOLYSIS)
A. Shortening of chains
• Glycogen phosphorylase sequentially cleaves the α(1→4)
glycosidic bonds between the glucosyl residues at the
nonreducing ends of the glycogen chains by simple
phosphorolysis (producing glucose 1-phosphate) until four
glucosyl units remain on each chain before a branch point
(Figure 11.7).
• The resulting structure is called a limit dextrin, and
phosphorylase cannot degrade it any further (Figure 11.8)

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 Dr. M. Alzaharna 2016
Figure 11.7: Cleavage of
an α(1→4)-glycosidic bond.
PLP = pyridoxal phosphate;
Pi = inorganic phosphate; P
= phosphate.

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 IV. DEGRADATION OF GLYCOGEN (GLYCOGENOLYSIS)
B. Removal of branches
• Branches are removed by the two enzymic activities of a single
bifunctional protein, the debranching enzyme (Figure 11.8).
• First, oligo- α(1→4) →α(1→4)-glucantransferase activity removes
the outer three of the four glucosyl residues attached at a branch.
• It next transfers them to the nonreducing end of another chain,
lengthening it accordingly.
• Thus, an α(1→4) bond is broken and an α(1→4) bond is made, and
the enzyme functions as a 4:4 transferase.

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• Next, the remaining glucose residue attached in an α(1→6) linkage
is removed hydrolytically by amylo- α (1→6)-glucosidase activity,
releasing free glucose.
• The glucosyl chain is now available again for degradation by
glycogen phosphorylase until four glucosyl units in the next branch
are reached
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Figure 11.8: Glycogen
degradation, showing some
of the glycogen storage
diseases (GSDs). [Note: A
GSD can also be caused by
defects in branching
enzyme, an enzyme of

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synthesis, resulting in Type
IV: Andersen disease and
causing death in early
childhood from liver
cirrhosis.] Pi = inorganic
phosphate; P = phosphate.
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 Dr. M. Alzaharna 2016
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 Dr. M. Alzaharna 2016
Figure 11.8 (cont’d)
Glycogen degradation, showing some of the glycogen storage
diseases (GSDs).

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 IV. DEGRADATION OF GLYCOGEN (GLYCOGENOLYSIS)
C. Conversion of glucose 1-phosphate to
glucose 6-phosphate
• Glucose 1-phosphate, produced by glycogen phosphorylase, is
converted in the cytosol to glucose 6-phosphate by
phosphoglucomutase (Figure 11.6).
• In the liver, glucose 6-phosphate is transported into the endoplasmic
reticulum (ER) by glucose 6-phosphate translocase.
• There it is converted to glucose by glucose 6-phosphatase (the same
enzyme used in the last step of gluconeogenesis).
• The glucose then is transported from the ER to the cytosol.
• Hepatocytes release glycogen-derived glucose into the blood to help

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maintain blood glucose levels until the gluconeogenic pathway is
actively producing glucose.
• Note: In the muscle, glucose 6-phosphate cannot be
dephosphorylated and sent into the blood because of a lack of
glucose 6-phosphatase
• Instead, it enters glycolysis, providing energy needed for muscle
contraction
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 IV. DEGRADATION OF GLYCOGEN (GLYCOGENOLYSIS)
D. Lysosomal degradation of glycogen
• A small amount (1%–3%) of glycogen is continuously
degraded by the lysosomal enzyme, α (1→4)-glucosidase (acid
maltase).
• The purpose of this pathway is unknown. However, a
deficiency of this enzyme causes accumulation of glycogen in
vacuoles in the lysosomes, resulting in the serious glycogen
storage disease (GSD) Type II: Pompe disease (see Figure
11.8).

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• Note: Type II: Pompe disease is the only GSD that is a
lysosomal storage disease.

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V. REGULATION OF GLYCOGENESIS AND GLYCOGENOLYSIS

• Because of the importance of maintaining blood glucose levels, the

synthesis and degradation of its glycogen storage form are tightly
regulated.
• In the liver,
• glycogenesis accelerates during periods when the body has been well fed,
• whereas glycogenolysis accelerates during periods of fasting.
• In skeletal muscle, glycogenolysis occurs during active exercise, and
glycogenesis begins as soon as the muscle is again at rest.
• Regulation of glycogen synthesis and degradation is accomplished
on two levels.

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• First, glycogen synthase and glycogen phosphorylase are hormonally
regulated (by phosphorylation/dephosphorylation) to meet the needs of
the body as a whole.
• Second, these same enzymes are allosterically regulated (by effector
molecules) to meet the needs of a particular tissue

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Figure 11.9: Stimulation and inhibition of glycogen degradation. AMP = adenosine
monophosphate; cAMP = cyclic AMP; GTP = guanosine triphosphate; P = phosphate;
PPi = pyrophosphate; R = regulatory subunit; C = catalytic subunit.
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 V. REGULATION OF GLYCOGENESIS AND GLYCOGENOLYSIS
A. Activation of glycogen degradation
• The binding of hormones, such as glucagon or epinephrine, to
plasma membrane G protein–coupled receptors (GPCRs)
signals the need for glycogen to be degraded, either to elevate
blood glucose levels or to provide energy for exercising
muscle.

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 V. REGULATION OF GLYCOGENESIS AND GLYCOGENOLYSIS
A. Activation of glycogen degradation
1. Activation of protein kinase A:
• Binding of glucagon or epinephrine to their specific hepatocyte GPCR, or
of epinephrine to a specific myocyte GPCR, results in the G protein–
mediated activation of ade nylyl cyclase.
• This enzyme catalyzes the synthesis of cyclic adenosine monophosphate
(cAMP), which activates cAMP -dependent protein kinase A (PKA)
(Figure 11.9).
• PKA then phosphorylates several enzymes of glycogen metabolism,
affecting their activity.

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• Note: When cAMP is removed, the inactive tetramer, R2C2, is again
formed.

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 V. REGULATION OF GLYCOGENESIS AND GLYCOGENOLYSIS
A. Activation of glycogen degradation
2. Activation of phosphorylase kinase:
• Phosphorylase kinase exists in two forms:
• an inactive “b” form and an active “a” form.
• Active PKA phosphorylates the inactive “b” form of phosphorylase
kinase, producing the active “a” form (Figure 11.9).
3. Activation of glycogen phosphorylase:
• Glycogen phosphorylase also exists in two forms:
• the dephosphorylated, inactive “b” form and the phosphorylated, a ctive “a”

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form.
• Active phosphorylase kinase is the only enzyme that phosphorylates
glycogen phosphorylase b to its active “a” form, which then begins
glycogenolysis (see Figure 11.9)

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 V. REGULATION OF GLYCOGENESIS AND GLYCOGENOLYSIS
A. Activation of glycogen degradation
4. Summary of the regulation of glycogen degradation:
• The cascade of reactions listed above results in glycogenolysis.
• The large number of sequential steps serves to amplify the effect of the
hormonal signal (that is, a few hormone molecules binding to their receptors
results in a number of PKA molecules being activated that can each activate
many phosphorylase kinase molecules).
• This causes the production of many active glycogen phosphorylase a
molecules that can degrade glycogen.
5. Maintenance of the phosphorylated state:
• The phosphate groups added to phosphorylase kinase and phosphorylase in

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response to cAMP are maintained because the enzyme that hydrolytically
removes the phosphate, protein phosphatase-1 (PP1), is inactivated by inhibitor
proteins that are also phosphorylated and activated in response to cAMP
(Figure 11.9).
• Note: PP1 is activated by a signal cascade initiated by insulin
• Insulin also activates the phosphodiesterase that degrades cAMP, and, thus,
insulin opposes the effects of glucagon and epinephrine.
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 V. REGULATION OF GLYCOGENESIS AND GLYCOGENOLYSIS
B. Inhibition of glycogen synthesis
• The regulated enzyme in glycogenesis is glycogen synthase.
• It also exists in two forms, the active “a” form and the inactive “b”
form.
• However, for glycogen synthase, in contrast to phosphorylase kinase
and phosphorylase, the active form is dephosphorylated, whereas the
inactive form is phosphorylated (Figure 11.10).
• Glycogen synthase “a” is converted to the inactive “b” form by -
phosphorylation at several sites on the enzyme, with the level of
inactivation proportional to its degree of phosphorylation.

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• Phosphorylation is catalyzed by several different protein kinases that
are regulated by cAMP or other signaling mechanisms
• Glycogen synthase b can be reconverted to the “a” form by PP1
• Figure 11.11 summarizes the covalent regulation of glycogen
metabolism
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Figure 11.10: Hormonal regulation of

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glycogen synthesis. [Note: In contrast to
glycogen phosphorylase, glycogen synthase
is inactivated by phosphorylation.] cAMP
= cyclic adenosine monophosphate; P =
phosphate; PPi = pyrophosphate; R =
regulatory subunit; C = catalytic subunit.
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Figure 11.11: Summary of
the hormone-mediated
covalent regulation of glycogen
metabolism. cAMP = cyclic
AMP; PKA = protein kinase A.

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 V. REGULATION OF GLYCOGENESIS AND GLYCOGENOLYSIS
C. Allosteric regulation of glycogen
synthesis and degradation
• In addition to hormonal signals, glycogen synthase and
glycogen phosphorylase respond to the levels of metabolites
and energy needs of the cell.
• Glycogensis is stimulated when substrate availability and
energy levels are high, whereas glycogenolysis is increased
when glucose and energy levels are low.
• This allosteric regulation allows a rapid response to the needs

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of a cell and can override the effects of hormone-mediated
covalent regulation

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 V. REGULATION OF GLYCOGENESIS AND GLYCOGENOLYSIS
C. Allosteric regulation of glycogen
synthesis and degradation
1. Regulation of glycogen synthesis and degradation
in the well-fed state:
• In the well-fed state, glycogen synthase b in both liver and
muscle is allosterically activated by glucose 6-phosphate,
which is present in elevated concentrations (Figure 11.12).
• In contrast, glycogen phosphorylase a is allosterically
inhibited by glucose 6-phosphate, as well as by ATP, a high-

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energy signal in the cell.
• Note: In liver, but not muscle, nonphosphorylated glucose is
also an allosteric inhibitor of glycogen phosphorylase a,
making it a better substrate for PP1

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Figure 11.12: Allosteric
regulation of glycogen synthesis and
degradation. A. Liver. B. Muscle. P =
phosphate.
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 V. REGULATION OF GLYCOGENESIS AND GLYCOGENOLYSIS
C. Allosteric regulation of glycogen
synthesis and degradation
2. Activation of glycogen degradation by calcium:
• Ca2+ is released into the cytoplasm in muscle in response to neural
stimulation and in liver in response to epinephrine binding to α 1-
adrenergic receptors.
• The Ca2+ binds to calmodulin (CaM), the most widely distributed member
of a family of small, calcium-binding proteins.
• The binding of four molecules of Ca2+ to CaM triggers a conformational
change such that the activated Ca2+–CaM complex binds to and activates
protein molecules, often enzymes, that are inactive in the absence of this
complex (Figure 11.13).

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• Thus, CaM functions as an essential subunit of many complex proteins.
• One such protein is the tetrameric phosphorylase kinase, whose b form
is activated by the binding of Ca2+ to its δ subunit (CaM) without the need
for the kinase to be phosphorylated by P KA.
• Note: Epinephrine at β-adrenergic receptors signals through a rise in
cAMP, not Ca2+
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Figure 11.13: Calmodulin mediates
many effects of intracellular Ca2+.
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 V. REGULATION OF GLYCOGENESIS AND GLYCOGENOLYSIS
C. Allosteric regulation of glycogen
synthesis and degradation
3. Activation of glycogen degradation in muscle:
• Muscle glycogen phosphorylase is active in the presence of the high
adenosine monophosphate (AMP) concentrations that occur under extreme
conditions of anoxia and ATP depletion.
• AMP binds to glycogen phosphorylase b, causing its activation without
phosphorylation (Figure 11.9).
• Note: Recall that AMP also activates phosphofructokinase-1 of glycolysis,
allowing glucose from glycogenolysis to be oxidized.

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 VI. Glycogen storage diseases
• These are a group of genetic diseases that result from a defect
in an enzyme required for glycogen synthesis or degradation
• They result either in formation of glycogen that has an
abnormal structure, or in the accumulation of excessive
amounts of normal glycogen in specific tissues as a result of
impaired degradation
• A particular enzyme may be defective in a single tissue, such as
liver, or the defect may be more generalized, affecting liver,

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muscle, kidney, intestine, & myocardium
• Severity of glycogen storage diseases (GSDs) ranges from fatal
in infancy to mild disorders that are not life-threatening

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VII. CHAPTER SUMMARY
• Main stores of glycogen in body are found in skeletal muscle,
where they serve as a fuel reserve for synthesis of ATP during
muscle contraction, & in liver, where glycogen is used to
maintain blood glucose conc, particularly during early stages
of a fast
• Glycogen is a highly branched polymer of α-D-glucose. The
primary glycosidic bond is an α (1→4) linkage. After ~ 8-10
glucose residues, there is a branch containing an α (1→6)
linkage.
• UDP-glucose, building block of glycogen, is synthesized from

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G-1-P & UTP by UDP-glucose pyrophosphorylase
• Glucose from UDP-glucose is transferred to the non-reducing
ends of glycogen chains by glycogen synthase, which makes α
(1→4) linkages

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VII. CHAPTER SUMMARY
• Branches are formed by amylo-α(1→4) → α(1→6)-
transglucosidase, which transfers a chain of 5-8 glucosyl
residues from the non-reducing end of glycogen chain
(breaking an α(1→4) linkage), and attaches it with an α(1→6)
linkage to another residue in the chain
• Glycogen phosphorylase cleaves the α(1→4) bonds between
glucosyl residues at the non-reducing ends of glycogen chains,
producing G-1-P. it requires pyridoxyl phosphate as a
coenzyme.
• This sequential degradation continues until 4 glucosyl units
remain on each chain before a branch point. The resulting

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structure is called a limit dextrin.
• Oligo-α(1→4)→α(1→4)-glucan transferase [common name,
glucosyl (4:4) transferase] removes the outer 3 of the 4
glucosyl residues attached at a branch, & transfers them to the
non-reducing end of another chain where they can be
converted to G-1-P by glycogen phosphorylase.
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VII. CHAPTER SUMMARY

• Next, the remaining single glucose residue attached in an

α(1→6) linkage is removed hydrolytically by the amylo-
α(1→6)-glucosidase activity, releasing free glucose.
• G-1-P is converted to G-6-P by phosphoglucomutase. In the
muscle, G-6-P enters glycolysis. In liver, the P is removed by
glucose-6-phosphatase, releasing free glucose that can be used
to maintain blood glucose levels at beginning of a fast

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• A deficiency of the phosphatase causes glycogen storage
disease type 1 (Von Gierke disease). This disease results in an
inability of liver to provide free glucose to body during a fast.
It affects both glycogen degradation & last step in
gluconeogenesis

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VII. CHAPTER SUMMARY
• Glycogen synthase & glycogen phosphorylase are
allosterically regulated. In well-fed state, glycogen synthase is
activated by G-6-P, as well as ATP
• In liver, glucose also serves as an allosteric inhibitor of
glycogen phosphorylase
• Ca2+ is released from sarcoplasmic reticulum during exercise.
It activates phosphorylase kinase in the muscle by binding to
enzymes calmodulin subunit. This allows the enzyme to
activate glycogen phosphorylase, thereby causing glycogen
degradation

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• Glycogen synthesis & degradation are reciprocally regulated
by the same hormonal signals, namely, an elevated insulin
level results in overall increased glycogen synthesis &
decreased degradation, whereas elevated glucagon (or
epinephrine) level causes increased glycogen degradation &
decreased synthesis.
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VII. CHAPTER SUMMARY

• Key enzymes are phosphorylated by a family of protein

kinases, some of which are cAMP-dependent (a compound
increased by glucagon and epinephrine). Phosphate groups are
removed by protein phosphatase 1 (activated when insulin
levels are elevated).

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