Course: Nutrition and Metabolism - National University · 2019-04-04 · Glycogen Storage Disease...

Course: Nutrition and Metabolism

Part (1): Metabolism of Carbohydrates Lecture (6): Glycogenolysis

Rihab SiddigMobile: +249918191982

Uses of Glycogen in Different Organs

• Liver: Glucose for other organs.

Liver cells do not use this glucose for their own energy needs.

• Muscle: Glucose for muscle use during exercise.

WHEN?

• Glycogen degradation

occurs;

1. After some hours without

food; when blood glucose

levels are low ( fasting

state)

2. In muscle during exercise

Functions of

GLYCOGENOLYSIS

• Regulates blood glucose

between meals. Supplies blood

glucose for 12 – 18 hours of

fasting

• Gives muscles energy for

exercise

WHERE?

•In the cytosol of liver

and muscle cells

REACTIONS

OF GLYCOGENOLYSIS

• GLYCOGENOLYSIS starts with glycogen and ends with glucose-6-phosphate or glucose.

Glycogen → → → → Glucose-6-phosphate/glucose

Glycogenolysis is NOT reverse of glycogenesis

glucose

----------

1. Glycogen Phosphorylase

Pyridoxal Phosphate

• Muscle glycogen phosphorylase requires a coenzyme pyridoxal phosphate (PLP)

Glycogen Phosphorylase

• Breaks a α1-4 bonds releasing Glucose-1-P

• Requires PLP

• STOPS four glucoses before a branch point

2. Debranching Enzyme

• The activity of phosphorylase stops 4 glucose residues from the branch point.

• Debranching enzyme contains 2 activities: –glucotransferase–glucosidase

Debranching Enzyme

-(1—>4) transglycosylase

Glucose-(1—>6) glucosidase

Limit Branch (4 residues)

(group transfer reaction)

P

P P P P

P

P

Pphosphorylase

Transferase activity of

Debranching enzyme

-1,6 glucosidase activity of

Debranching enzyme

3. Phosphoglucomutase

Glucose–1–P Glucose–6–P

4. Glucose-6-phosphatase

• Is an enzyme found in liver and kidney cells

Glucose-6-Phosphatase

Glc-6-P --------------> Glucose

• NOT found in muscle cells.

Glc-6-P --------------> GlucoseX

MUSCLE:

Glc-6-P ------ --------> Glucose

LIVER:

Glucose-6-Phosphatase

Glc-6-P --------------> Glucose

Glycolysis

X

Piglycogen

phosphorylase

phosphoglucomutaseglucose-6-phosphatase

Glucose-1-phosphate

Glucose-6-phosphate

Glycogen

Glucose

Xglycolysis

LIVER PATHWAY

Pi

MUSCLE PATHWAY

glycolysis

Pyruvate

Piglycogen

phosphorylase

phosphoglucomutase

Glucose-1-phosphate

Glucose-6-phosphate

Glycogen

GlucoseX

Major Enzymes

Glycogen phosphorylase

and

Glycogen debranching enzyme.

The key enzyme is glycogen

phosphorylase

Glycogenolysis Regulation

1.HORMONAL REGULATION

• GLUCAGON, EPINEPHRINE

–Activate glycogen breakdown

• INSULIN

– Inactivates glycogen breakdown

Active / Inactive form

Key Enzyme Active form

(a form)

Inactive form

(b form)

Glycogen

Phosphorylase

−P

Phosphorylated

form

−OH

Dephosphorylated

form

• Glucagon and epinephrine phosphorylate ( and thus activates) glycogen phosphorylase

Key Enzyme Active form

(a form)

Inactive form

(b form)

Glycogen

Synthase

−OH

Dephosphorylated

form

−P

Phosphorylated

form

Glycogen

Phosphorylase

−P

Phosphorylated

form

−OH

Dephosphorylated

form

Hormonal Regulation

• Insulin dephosphorylates bothenzymes

• Glucagon and epinephrine phosphorylate both enzymes

Reciprocal regulation of glycogen

metabolism

• Insulin activates glycogen synthase and inactivates glycogen phosphorylase

• Glucagon and epinephrine activate glycogen phosphorylase and inactivate glycogen synthase

Glycogenesis vs Glycogenolysis

Glycogen Storage Diseases:

•Enzyme deficiencies that affect glycogen metabolism•They are inherited

Symptoms

Accumulation of glycogen in tissues

• If liver is affected, hypoglycemia results

• If muscle is affected inability to exercise

• In the most severe diseases, death at an early age.

Types of Glycogen Storage Diseases

Type I

Type II

Type III

Type IV

Type V

Type VI

Type VII

Type VIII

Type I (Von Gierke’s Disease)

• due to deficiency of Glucose 6 phosphatase

glycogen

glucose-1-P

Glucose-6-Phosphatase

glucose-6-P glucose + Pi

fructose-6-P

Phosphofructokinase

fructose-1,6-bisP

Glycolysis continued

Type I (Von Gierke’s Disease)

Symptoms of Von Gierke’s Disease

1. liver cells are loaded with glycogen

2. hepatomegally

3. hypoglycemia

Glycogen Storage Disease Symptoms, in addition to

glycogen accumulation

Type I, liver deficiency of

Glucose-6-phosphatase (von

Gierke's disease)

hypoglycemia (low blood

glucose) when fasting, liver

enlargement.

Type IV, deficiency of

branching enzyme in various

organs, including liver

(Andersen's disease)

liver dysfunction and early

death.

Type V, muscle deficiency of

Glycogen Phosphorylase

(McArdle's disease)

muscle cramps with exercise.

Type VII, muscle deficiency of

Phosphofructokinase.

inability to exercise.

Thank you