A.

FED STATE METABOLISM

Just after consuming a meal DIGESTION: (GLYCOGEN)
Nutrients are stored 1. Glycogen phosphorylase catalyzes phospholytic GLYCOGEN - readily metabolized storage form of glucose
During glycogen synthesis reaction on (α1→4) glycosidic linkage generating glucose Linked by α-1,4 (linear) and α -1,6 (branched) glycosidic
 bonds
1-phosphate
GLUCOSE IN FED STATE Storage Features
Trapped in the cell by phosphorylation at C6 2. Stops when it reaches (α1→6) branch point; Liver Glycogen Muscle Glycogen
(Glucose-6- phosphate) before entering mitochondria debranching enzyme removes the branching glucose Major storage site Fuel reserve for ATP production
Entrapment – for maintenance of normal blood glucose 1-phosphate converted to glucose 6- phosphate by Depleted after 12- 1-2% of muscle weight
level and good source of energy phosphoglucomutase 18 hrs. of fasting
Undergoes glycolysis to produce 2 mol. of pyruvate from 10% of liver
cytoplasm to translocate inside the mitochondria Monosaccharides enter glycolytic pathway at several weight
Pyruvate is: points Glucose reserve for Lacks G6 Phosphatase and most
1. Converted to acetyl CoA by pyruvate dehydrogenase maintenance of glucose formed is catabolized
2. Enters the Krebs cycle (aerobic oxidation) Blood glucose Good muscle mass stores glucose
3. Produces citrate (a tricarboxylic acid) Concentration as glycogen - does not replenish
End products of the Krebs cycle: CO2 and water blood glucose levels but only

Entry of Carbohydrates from diet into Glycolysis Why is glucose stored in glycogen?
Significant residues: Glucose is more osmotically active and can cause osmotic
Storage polysaccharides (glycogen and starch), lysis of cells. On the other hand, glycogen is more inert
Disaccharides (maltose, lactose, trehalose, and sucrose), and will not cause osmotic pressure problems to the cell
Monosaccharides (fructose, mannose, galactose).
HYDROLYSIS converts ALL to monosaccharides. STRUCTURE
Linked by α-1,4-glycosidic bonds.
DIGESTION: (STARCH) Branches are created by α-1,6-glycosidic bonds.
>>Mouth: salivary α-amylase hydrolyses internal Branching is IMPORTANT
(α1→4) glycosidic linkage of starch It increases the solubility of glycogen.
>>Stomach: salivary α-amylase is inactive Creates a large number of terminal residues, the sites of
>>Intestine: secondary salivary α-amylase secreted action of glycogen phosphorylase and synthase.
By the pancreas continues the process yielding maltose, Increases the rate of glycogen synthesis and
maltotriose, and dextrins: enzymes in the intestinal brush degradation.
border to glucose degrade maltose and dextrins Glycogen branching requires a single transferase
activity. Phosphoenzyme is reformed and glucose 6-phosphate is synthesis through inactivating glycogen synthase
Glycogen debranching requires two enzyme produced kinase (enzyme that maintains glycogen synthase in its
activities: a transferase and an α-1,6 glucosidase. phosphorylated, inactive state)
GLYCOGENESIS
Glycogenin - Primer protein mol. for glycogen synthesis; -
GLYCOGEN SYNTHASE Active for glycogenesis as its key
- Required for the addition of 4 to 8 glycosyl units enzyme and inactive for glycogenolysis Steps of Insulin Action
Self-glycosylating enzyme which uses UDP-glucose Isoforms: a (active) Dephosphorylated and b (inactive) 1. Insulin binds to a receptor tyrosine kinase (RTK)
(activated glucose) to link glucose to one of its own 2. Insulin-receptor substrates (IRS) phosphorylates that
tyrosine residues Ways of Regulation initiates the insulin cascade.
Activated glucose + Glycogenin = Glycosylated glycogenin
(Inactive b isoform) >> Phosphoprotein phosphatase or 3. Intracellular domain of the RTK phosphorylates,
(Autoglycosylation) Protein phosphatase 1 >[dephosphorylated]>> active a Protein kinase is activated >> then phosphorylates
Glycogenin’s glycosyl residues >> glycogen synthase isoform 4. Inactivates glycogen synthase kinase
>> UDP glucose (activated glucose) 5. Protein phosphatase 1 (PP1) is activated >>
Glycosylated glycogenin form α- 1, 4 glycosidic bonds
Protein Kinase A (activation of PKA) initiates the cascade dephosphorylate >> activate Glycogen Synthase
Branching enzymes form α- 1, 6 glycosidic bonds. of kinase enzyme (phosphorylating enzymes) 6. Glycogen reserves are restored.
↑cAMP levels[phosphorylation] inactivate a to b isoform
GLUCOSE ACTIVATION Cascade of Regulation - prevent the wasteful depletion of
breakdown of glycogen also occurs
Glucose enters the cell >> hexokinase or glucokinase glycogen after energy needs have been met:
Glucagon and Epinephrine
(liver) [phosphorylation of carbon 6, invest 1 ATP] (1) Phosphorylase kinase and glycogen phosphorylase
hormones initiate the cascade during fasted-state
>>Form Glucose-6-phosphate >>phosphoglucomutase are dephosphorylated and inactivated.
[transfer phosphoryl group from carbon 6 to 1] (2) Simultaneously, glycogen synthesis is activated.
INSULIN AT FED-STATE
>> Form Glucose-1-phosphate
↑Insulin level - normalizes blood glucose levels Initiating hormone is no longer present:
Glucose-1-Phosphateuridyl transferase + UTP(as Glucose will go inside the cell, Excess is stored in the cell. >> deactivation of glycogen phosphorylase
donor) >> UDP-glucose Uridine Diphosphate Glucose inactivation of Glycogen Synthase Kinase 3 (GSK3) (inherent GTPase activity)converts the bound GTP into
- Active form of glucose > inactivation of casein kinase I & II leads inactive GDP
required by glycogen synthesis >>Dephosphorylation of glycogen synthase phosphodiesterases converts cycLic AMP into AMP
added to the nonreducing end of glycogen molecules HIGH LEVELS OF GLUCOSE-6-PHOSPHATE Protein kinase A - shutdown of glycogen degradation
at fed-state, direct activation of glycogen synthase via by adding a phosphoryl group to the c subunit of PK after
Steps in catalyzing reaction of phosphoglucomutase receptor within the enzyme first phosphorylating the 3 subunit
1. Enzyme donates phosphoryl group to glucose 1- PO4 -Causes the same glucagon- and epinephrine-triggered
2. C1 phosphoryl group at glucose 1,6-bisphosphate is REGULATION BY INSULIN cAMP cascades to shut off glycogen synthesis
transferred back to the enzyme. ↑blood-glucose levels = insulin stimulates glycogen
 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