Ammar Akhtar Roll No.176

8/14/2019 Ammar Akhtar Roll No.176

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GLYCOGENOLYSIS



Outline:

Definition

Steps of glycogenolysis

Diagrammatic representation of

glycogenolysis

Regulation of glycogenolysis

Clinical implification



DEFINITION:

Breakdown of glycogen to

glucose is called glycogenolysis.



STEPS OF

GLYCOGENOLYSIS:

First step: The overall reaction for the first

step

Glycogen + Pi glycogen +(n residues) (n-1 residues)

glucose-1-phosphate

Enzyme used for this step is glycogenPhosphorylase which uses vit. B6 derivative

as co-factor.



Glycogen Phosphorylase breaks down glucose

polymer at alpha-1,4 linkages until 4 glucose

residues left on a branch called limit dextrin.

Second step: Enzyme alpha-1,4 alpha-1,4

glucan transferase transfer trisaccharide from one

side to other exposing alpha,1-6 branch point.

Third step: Hydrolytic splitting of alpha-1,6

glucosidic linkage by debranching enzyme and

one molecule of free glucose is produced.



Fourth step:

Glucose-1-phosphate is

converted to glucose-6-phosphate by

the enzyme phophoglucomutase.



Steps of glycogenolysis



STRUCTURE OF GLYCOGEN PHOSPHORYLASE



glucose-1-phosphate

phosphoglucomutase

glucose-6-phosphate

free glucose glycolysis(in kidney and liver) (in muscles)

energy

Glucose-6-phosphatase

blood



REGULATION OF GLYCOGENOLYSIS

Cyclic AMP dependant protein kinase has

dual effects on glycogenolysis regulation

> activation of Phosphorylase enzyme

> activation of inhibitor-1



> Activation of Phosphorylase



> Activation of inhibitor-1

Inhibitor-1 (inactive)

protein kinase Pi

inhibitor-1-p (active)

This inhibits protein phosphatase-1 which

inhibits the inactivation of Phosphorylase

kinase. As a result more and more

Phosphorylase is converted to active form

ACTIVATION AND INACTIVATION OF MUSCLE



ACTIVATION AND INACTIVATION OF MUSCLEPHOSPHORYLASE:

> phosphorylase(active)+4H2O

Phosphorylase rupturing enzyme

phosphorylase(inactive)+4Pi

phosphorylase(inactive)+4ATP

Phosphorylase kinase

Mg ion

phosphorylase(active)+4ADP



ROLE OF Ca IONS:

Glycogenolysis increase in muscle

contraction immediately after onset of

contraction. This involves rapid activation of

Phosphorylase due to activation of protein

kinase by Ca ions, the same signal that

initiates contraction.



Muscle phosphorylase has 4 types of subunits: alpha, beta, gamma, delta

alpha and beta has serine residueswhich are phosphorylated by cyclic-AMPdependant protein kinase

beta subunit binds 4 Ca ions and isidentical to calmodulin

binding of Ca ions activatescatalytic site of gamma subunit while themolecule remains in dephosphorylatedconfiguration



A second molecule of calmodulin can interact

with phosphorylase kinase causing further activation

So muscle contraction andglycogenolysis are carried out by

same Ca binding protein.



CLINICAL APPLICATION:

GLYCOGEN STORAGE DISEASESGSDs

These are a group of inherited disordersassociated with glycogen metabolism and is

characterized by deposition of normal or abnormal type and large quantity of glycogen intissues.

GSDs also known as glycogenosis.

THE MOST IMPORTANT GSD IS



VON GIERKE’S DISEASE:

DEFICIENT ENZYME:

glucose-6- phosphatase

INHERITANCE:autosomal recessive

SIGN AND SYMPTOMS:

1) Hypoglycemia as very little glucose isderived from liver

2) Fats are used as energy source leading to



2) Fats are used as energy source leading to

ketosis and acidemia.

3) Increase acetyl-CoA causes increase incholesterol level which produces xanthomas.

4) Persistent hypoglycemia has two effects:> decrease insulin secretion which decreases

protein synthesis resulting stunted growth(dwarfism)

> increase secretion of catecholamine causemuscle glycogen to breakdown producing lacticacid causing lactic acidosis



5) Increase blood lactic acid competes with

urate excretion by kidney leading to increaseblood uric acid level. There is also evidence

that there is increased uric acid synthesis in

these children which accumulate in jointsresulting in GOUT

Other GSDs are described in table below:



.



TYPE NAME ENZYMEEFI

CIENCY

CLINICAL FEATURES

II Pompe’s disease Lysosomal

glucosidase

Glycogen accumulate in

lysosomes, death from hearth

failure by age 2, muscle

dystrophy

III Cori’s disease/

Limit

dextrinosis

Debranching

enzyme

Fasting hypoglycemia,

hepatomegaly in infancy

IV Anderson’s

disease/

amylopectinosis

Branching

enzyme

Hepatosplenomegaly, death from

heart or liver failure in first

year of life

V McArdle’s

syndrome

Muscle

Phosphorylase

Poor exercise tolerance, blood

lactate low after exercise.

VI Her’s disease Liver

Phosphorylase

Hepatomegaly, glycogen

accumulate in liver, mild

hypoglycemia



Many other GSDs like type VII, VIII, IX

and X but most common are these six GSDs

REFERENCES:



REFERENCES:

1) Murray, Granner, Rodwell, “Harper’s Illustrated

Biochemistry” 27th

edition Ch:19 Page: 159-166

2) MNChatterjea, Rana Shinde, “Textbook Of

Medical Biochemistry” 7th edition Ch:23 part II

Page: 327-333

3) Lubert Styrer, Tymoczha, Berg,

“W.H.Freemann and Company Biochemistry”

5

th

edition Ch:21 Page:866-8764) wikipedia



ACKNOWLEDGMENTS:1) To Supreme Power ALLAH AL-MIGHTY

2) Head Of Biochemistry DepartmentProf. Dr. Khawaja Fayyaz

3) Mr. Jamshad Iqbal

4) Dr. Safqat Nazir

5) Dr. Huda6) Dr. Sarfaraz

7) Dr. Javaria

8) My Parents

9) Library staff

10) My Seniors of 3rd year

11) Class fellows Safeet, Umair

Ammar Akhtar Roll No.176

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