A.

FED STATE METABOLISM

Just after consuming a meal
Nutrients are stored
During glycogen synthesis

GLUCOSE IN FED STATE

Trapped in the cell by phosphorylation at C6
(Glucose-6- phosphate) before entering
mitochondria
Entrapment for maintenance of normal blood
glucose level and good source of energy
Undergoes glycolysis to produce 2 mol. of
pyruvate from cytoplasm to translocate inside
the mitochondria
Pyruvate is:
1. Converted to acetyl CoA by pyruvate
dehydrogenase
2. Enters the Krebs cycle (aerobic oxidation)
3. Produces citrate (a tricarboxylic acid)
End products of the Krebs cycle: CO2 and water
Entry of Carbohydrates from diet into Glycolysis
Significant residues:
Storage polysaccharides (glycogen and starch),
Disaccharides (maltose, lactose, trehalose, and
sucrose),
Monosaccharides (fructose, mannose,
galactose).
HYDROLYSIS converts ALL to monosaccharides.
DIGESTION: (STARCH)
>>Mouth: salivary -amylase hydrolyses
internal
(14) glycosidic linkage of starch

>>Stomach: salivary -amylase is inactive

>>Intestine: secondary salivary -amylase
secreted
By the pancreas continues the process yielding
maltose, maltotriose, and dextrins: enzymes in
the intestinal brush border to glucose degrade
maltose and dextrins
DIGESTION: (GLYCOGEN)
1. Glycogen phosphorylase catalyzes
phospholytic reaction on (14) glycosidic
linkage generating glucose 1-phosphate
2. Stops when it reaches (16) branch point;
debranching enzyme removes the branching
glucose 1-phosphate converted to glucose 6phosphate by phosphoglucomutase
Monosaccharides enter glycolytic pathway at
several points

GLYCOGEN - readily metabolized storage form of

glucose
Linked by -1,4 (linear) and -1,6 (branched)
glycosidic bonds
Storage Features
Liver Glycogen
Muscle Glycogen
Major storage
Fuel reserve for ATP
site
production
Depleted after
1-2% of muscle weight
12-18 hrs. of
fasting
10% of liver
weight
Glucose reserve
Lacks G6 Phosphatase and
for maintenance
most glucose formed is
of Blood glucose
catabolized
Concentration
Good muscle mass stores
glucose as glycogen - does
not replenish blood glucose
levels but only
Why is glucose stored in glycogen?
Glucose is more osmotically active and can
cause osmotic lysis of cells. On the other hand,
glycogen is more inert and will not cause
osmotic pressure problems to the cell

STRUCTURE
Linked by -1,4-glycosidic bonds.
Branches are created by -1,6-glycosidic bonds.
Branching is IMPORTANT
It increases the solubility of glycogen.
Creates a large number of terminal residues, the
sites of action of glycogen phosphorylase and
synthase.
Increases the rate of glycogen synthesis and
degradation.
Glycogen branching requires a single
transferase
activity.
Glycogen debranching requires two enzyme
activities: a transferase and an -1,6
glucosidase.
GLYCOGENESIS
Glycogenin - Primer protein mol. for glycogen
synthesis; - Required for the addition of 4 to 8 glycosyl
units
Self-glycosylating enzyme which uses UDPglucose (activated glucose) to link glucose to
one of its own tyrosine residues
Activated glucose + Glycogenin = Glycosylated
glycogenin
(Autoglycosylation)
Glycogenins glycosyl residues >> glycogen
synthase
>> UDP glucose (activated glucose)
Glycosylated glycogenin form - 1, 4 glycosidic
bonds

Branching enzymes form - 1, 6 glycosidic

bonds.

Isoforms: a (active) Dephosphorylated and b

(inactive)

GLUCOSE ACTIVATION
Glucose enters the cell >> hexokinase or
glucokinase (liver) [phosphorylation of carbon
6, invest 1 ATP]
>>Form Glucose-6-phosphate
>>phosphoglucomutase
[transfer phosphoryl group from carbon 6 to 1]
>> Form Glucose-1-phosphate

Ways of Regulation
(Inactive b isoform) >> Phosphoprotein
phosphatase or Protein phosphatase 1
>[dephosphorylated]>> active a isoform

GLYCOGEN SYNTHASE Active for glycogenesis

as its key enzyme and inactive for
glycogenolysis

REGULATION BY INSULIN
blood-glucose levels = insulin stimulates
glycogen

Protein Kinase A (activation of PKA) initiates the

cascade of kinase enzyme (phosphorylating
enzymes)
cAMP levels[phosphorylation] inactivate a to b
Glucose-1-Phosphateuridyl transferase + UTP(as isoform
donor) >> UDP-glucose Uridine Diphosphate
breakdown of glycogen also occurs
Glucose
Glucagon and Epinephrine
- Active form of glucose
hormones initiate the cascade during fasted required by glycogen synthesis
state
added to the nonreducing end of glycogen
molecules
INSULIN AT FED-STATE
Insulin level - normalizes blood glucose levels
Steps in catalyzing reaction of
Glucose will go inside the cell, Excess is stored
phosphoglucomutase
in the cell.
1. Enzyme donates phosphoryl group to glucose inactivation of Glycogen Synthase Kinase 3
1- PO4
(GSK3)
2. C1 phosphoryl group at glucose 1,6> inactivation of casein kinase I & II leads
bisphosphate is transferred back to the enzyme. >>Dephosphorylation of glycogen synthase
Phosphoenzyme is reformed and glucose 6HIGH LEVELS OF GLUCOSE-6-PHOSPHATE
phosphate is produced
at fed-state, direct activation of glycogen
synthase via receptor within the enzyme

synthesis through inactivating glycogen

synthase
k
inase (enzyme that maintains glycogen
synthase in its
phosphorylated, inactive state)
Steps of Insulin Action
1. Insulin binds to a receptor tyrosine kinase
(RTK)
2. Insulin-receptor substrates (IRS)
phosphorylates that initiates the insulin cascade.
3. Intracellular domain of the RTK
phosphorylates, Protein kinase is activated >>
then phosphorylates
4. Inactivates glycogen synthase kinase
5. Protein phosphatase 1 (PP1) is activated >>
dephosphorylate >> activate Glycogen
Synthase

6. Glycogen reserves are restored.

Cascade of Regulation - prevent the wasteful
depletion of glycogen after energy needs have
been met:
(1) Phosphorylase kinase and glycogen
phosphorylase are dephosphorylated and
inactivated.
(2) Simultaneously, glycogen synthesis is
activated.
Initiating hormone is no longer present:
>> deactivation of glycogen phosphorylase
(inherent GTPase activity)converts the bound
GTP into inactive GDP
phosphodiesterases converts cycLic AMP into
AMP
Protein kinase A - shutdown of glycogen
degradation by adding a phosphoryl group to

the c subunit of PK after first phosphorylating

the 3 subunit
-Causes the same glucagon- and epinephrinetriggered cAMP cascades to shut off glycogen
synthesis
adds a phosphoryl group to phophorylase
kinase, activating that enzyme and initiating
glycogen breakdown.
adds a phosphoryl group to glycogen
synthase, but this phosphorylation leads to a
decrease in enzymatic activity.
Glycogen synthase kinase, helps inactive the
synthase.
GLYCOGENOLYSIS