GLYCOGENOLYSIS

Gul Muneer 23

Ghulam Mujtaba 102

Fawad Ahmed 20

Sultan Ali 77

Lal malook 38

Abdul Qadir 01

Zubair Mangrio 87

Hussain Solangi 99

Hifz-ur-Rahman 28

Mohammad Junaid 50

Asad Ali 10

Group E

B.S Part-III

Institute of Biochemistry

University of Sindh, Jamshoro

GLYCOGEN OVERVIEW

Homopolysaccharide Homopolymer of α-D-glucose Highly branched

2 GLYCOSIDIC LINKAGES

Linear linkages α(1→4) Branching linkages α(1→6) Branches after once every 8-10 residues Linear 13 glucose residues Branches 12 glucose residues

Storage Storage form of Glucose in animals So called “animal starch” Granular form High in liver (6-8%) and muscles(1-2%) Liver

regulates blood glucose levelsMuscle

Store of glucose as fuel for exercise high intensity exercise dependent on anaerobic glycolysis

Glycogenolysis Degradtion Of stored Glycogen occurs in cytosol triggered by low blood glucose levels why this pathway occurs? =When an organism needs energy quickly =During muscular exercise =can do so anaerobically

1st StepPhosphorolysis

Enzyme: Glycogen phosphorylaseAction: Cleavage of α(1→4)linkagesPosition: non-reducing endsCoenzyme: Pyridoxal phosphate (vit.B6 derivative)Product: glucose-1-phosphateLimits: degrades the Glycogen molecule until 4 glucose residues remain on each chin before a branch point.( Stops at 4 Glucose residue)Result: Limit dextrinNOTE: This cannot further degraded by phosphorylaseInhibitor: a suitable treatment for diabetes (liver phosphorylase)

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2nd StepRemoval of Branches

General name: Debranching enzyme Structure: =2 independent active site =Single polypeptide cleaves branches by 2 enzyme activities (Bifunctional enzyme)Two enzyme activities:

1. Glycosyl 4:4 transferase (oligo α-1,4→1,4 glucan transferase)2. Amylo α-1-6-glucosidase

glycosyl 4:4 transferase: Removes chain of (3 or 4) glucose residue at a branch Transfer them to the non-reducing end of another chain α-1,4 bond is broken and α-1,4 bond is made.

amylo α-1,4 glucosidase: Breaks the α-1,6 bond at branch point Action is hydrolytically Releases a free glucose Skeletal muscle do generate free glucose that could enter bloodstream Hexokinase ―low Km (immediately phosphorylate)

Glycogen Debranching Enzyme

-(1—>4) transglycosylase

Glucose-(1—>6) glucosidase

Limit Branch (4 residues)

(group transfer reaction)

The remaining molecule of glycogen is again available for the action of

phosphorylase and debranching enzyme to repeat the reactions stated in 1 and 2.

3rd step formation of free glucose and glucose-6-phosphate

catalysed by phosphoglucomutase product fate depends on tissue

Glucose-6-phosphate may enter Glycolysis or (mainly in liver) be dephosphorylated for release to the blood. Liver Glucose-6-phosphatase catalyzes the following, essential to the liver's role in maintaining blood glucose: glucose-6-phosphate + H2O glucose + Pi

Most other tissues lack this enzyme.

Glycogen Glucose

Hexokinase or Glucokinase

Glucose-6-Pase Glucose-1-P Glucose-6-P Glucose + Pi Glycolysis Pathway

Pyruvate Glucose metabolism in liver.

Regulation Of Glycogenolysis

Glycogenolysis is controlled by enzyme glycogen phophorylase

Regulation of this enzyme is accompalished by 3 mechanisms:1.Allosteric regulation 2. Hormonal regulation3. Influence of calcium

Allosteric regulationGlycogen breakdown is enhanced:

low glucose conc low energy level

glycogen breakdown inhibited:high Glucose-6-phosphateATPFree glucose in liver

Above metabolites allosterically regulate glycogen phosphorylase.

Hormonal And Ca²⁺ Regulation

Hormonal RegulationLow blood glucose level (fasting)Releases these 2 hormones

GlucagonEpinephrine

Glucogen phosphorylase exists in 2 forms: 1. An active “a” form 2. An inactive “b” formGlucagon and epinephrine both stimulate intracellular pathway via increasing levels of cAMP.

Ca²⁺ Ions InfluenceCa²⁺ regulates glycogen breakdown in muscle.

Release of Ca²⁺ from ER into cytosol of muscle cells causes muscle contraction resulting urgent need of ATP.

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