1. Glycogen Metabolism

2. Glycogen Function
In liver – The synthesis and breakdown of glycogen is regulated to maintain blood glucose levels.
In muscle - The synthesis and breakdown of glycogen is regulated to meet the energy requirements of the muscle cell.

3. Liver Cell

4. Glycogen structure Large molecule
Branch points are frequent (about every fourth residue) – allows glucose residues to be easily added or removed quicker than a linear molecule.
Glucose residues linked by α (1-4) glycosidic bonds into chains & chains branch via α (1-6) linkage

5. Liver glycogen varies with food intake,
with a high level after a meal, and decreasing slowly as it is mobilized to maintain blood glucose levels. (see fig).

6. Glucose-6-phosphatase
phosphoglucomutase
phosphoglucomutase
G-1-phosphate uridylyl transferase
Glycogen synthases

7. Insulin Peptide hormone of 51 aa produced in the pancreas
The stimulation of glycogen synthesis is one of the major physiological responses modulated by insulin
The exact mechanism by which insulin stimulates glycogen synthesis is not known
Insulin:
* Controls uptake and transport of glucose

8. Reciprocal Regulation of Glycogen Synthase and Glycogen Phosphorylase
Glycogen Synthesis and Degradation are Highly Regulated Pathways:
• Glycogen synthase and glycogen phosphorylase are the regulatory enzymes of glycogen synthesis and degradation.
Insulin Induces and activates protein phosphatase-1 (removes p from GS- Activates GS
Feeding results in glycogen synthesis
Glucagon activates Protein kinase A which phosphorylates and inactivates glycogen synthase and activates GP
Little glycogen synthesis during fasting. Lots of breakdown

9. Effect of Hormone on Glycogen Metabolism
low blood glucose > pancreas release glucagon
>>>>>>> promotes glycogen degradation
During stress > release epinephrine (adrenal medulla)
Promotes glucagon release > increase blood glucose
interacts directly with both muscle and liver cells to promote glycogen degradation
High blood sugar > release insulin (B-cells)
>>>>> > glycogen synthesis

10. Exercise and Glycogen Metabolism
Exercise of a muscle triggers mobilization of glycogen to form ATP.
The yield of ATP and the fate of carbons from glycogen depends on whether the muscles is “white” or “red”.
Red muscles are supplied with rich supply of blood, have a large amount of myoglobin, and are packed with mitochondria.

12. In “red” muscles glycogen is converted to pyruvate.
Then pyruvate is converted to CO2 and H2O + ATP
(due to O2 and mitochondria).
“White” muscles have a poorer supply of O2 and
fewer mitochondria.
Glycogen > Lactate primarily
White muscles have more capacity for glycogenolysis and glycolysis than red muscle fibers.

13. In Red muscles glycogen provides energy for longsustained activities
In Red muscles glycogen provides energy for longsustained activities. ( O2 & mitochondria, more ATP)
In White muscles glycogen provides energy for short periods of maximal activity. (glycogen is mobilized rapidly)
In humans most skeletal muscles are a mixture of red and white fibers to provide for both rapid and sustained muscle activity.

14. McArdle's Disease
Glycogen phosphorylase deficient cannot break glycogen > glucose
There is an abnormal accumulation of glycogen in muscle tissue.
Symptoms are exercise intolerance - muscular pain, fatigability - and muscle cramping. Rest relieves the muscle pain and enables exercise to resume

15. Muscle phosphorylase enzyme histochemistry in a control muscle shows the normal checkerboard staining pattern. Phosphorylase staining was absent in the patient's muscle
Assay
Normal* (nmol/min/g)
Patient
Glycogen†
1.85
Phosphorylase A
12.00
0.09
Phosphofructokinase
12.8
15.21
Myoadenylate deaminase
15.88
19.13 *

16. Study Questions What’s the importance of glucose?
What is glucose stored as in the body? Where is it stored?
How much glycogen can be stored?
What’s the significance of glycogen being highly branched?
Is there any difference in the functions performed by the liver and muscle glycogen? If so what is it?
Define glycogenesis and glycogenolysis?
By the aid of diagrams explain the process of glycogenesis and glycogenolysis.
Which hormones are involved in regulating these processes - glycogenesis and glycogenolysis?
Why is it important that these processes are rigorously controlled?
How is blood glucose regulated?
What is the energy requirements of the white and red muscles and why is there a difference in energy requirements in these muscles?
What is glycogen storage disease and discuss one example (cause and symptoms) of such disease.