Download Glycogen Metabolism USP

Glycogen Metabolism
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.
Liver Cell
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
• 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).
Glucose-6-phosphatase
phosphoglucomutase
phosphoglucomutase
G-1-phosphate uridylyl transferase
Glycogen synthases
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
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 GSActivates 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
Effect of Hormone on Glycogen Metabolism
•
low blood glucose > pancreas release
glucagon
>>>>>>> promotes glycogen degradation
•
1.
2.
•
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
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.
• 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.
• 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.
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
•
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†
0.1-1.5
1.85
Phosphorylase A
12.00
0.09
Phosphofructokinase
12.8
15.21
15.88
19.13
Myoadenylate deaminase
*
Study Questions
1.
What’s the importance of glucose?
2.
What is glucose stored as in the body? Where is it stored?
3.
How much glycogen can be stored?
4.
What’s the significance of glycogen being highly branched?
5.
Is there any difference in the functions performed by the liver and muscle
glycogen? If so what is it?
6.
Define glycogenesis and glycogenolysis?
7.
By the aid of diagrams explain the process of glycogenesis and glycogenolysis.
9.
Which hormones are involved in regulating these processes - glycogenesis and
glycogenolysis?
10.
Why is it important that these processes are rigorously controlled?
11.
How is blood glucose regulated?
12.
What is the energy requirements of the white and red muscles and why is
there a difference in energy requirements in these muscles?
13.
What is glycogen storage disease and discuss one example (cause and
symptoms) of such disease.