Glycogen metabolism and it’s regulation

Glycogen metabolism and it’s regulation

1. GLYCOGEN METABOLISM
AND ITS REGULATION
By GurjeenkaurSarao
HarnoorSekhon
HargunnKaur
HarjashanNoorKaur
HarmanpreetKaur

2. INTRODUCTION
•Glycogen is the storage form of glucose
•It is stored in liver and muscles as fuel reserve
•Why store glycogen as fuel reserve?
It can be easily mobilised
It generates energy in the absence of oxygen
Brain depends on continuosglucose supply
which is fulfilled by glycogen.
•The stored muscle glycogen serves as the fuel
reserve for the supply of ATP during muscle
contraction.

3. STRUCTURE OF GLYCOGEN

4. GLYCOGENESIS
•The process of synthesis of glycogen from
glucose is known as glycogenesis.
•Site of glycogenesis-Cytosol
•Requirements-ATP, UTP,Glucose
•Steps-1.UDP glucose formation
2.Requirement of primer to initiate
glycogenesis
3.Glycogen synthesis by glycogen
synthase
4.Formation of branches in glycogen

5. Formation of UDP glucose

6. Requirement of primer and glycogen
synthase

7. Branching in Glycogen

8. Glycogenolysis
•The degradation of stored glycogen in liver and
muscles constitutes glycogenolysis.
•Site of enzymes-Cytosol
•Steps-1.Action of glycogen phosphorylase
causing shortening of the chain
2.Action of debranchingenzyme
3.Formation of glucose-6-phosphate
and glucose

9. Shortening of glycogen chain

10. Action of debranchingenzyme and
phosphoglucomutase

11. Regulation
•Glycogenesisand gylcogenolysisare controlled
by enzymes glycogen synthaseand glycogen
phosphorylase
•3 mechanisms:-1. allostericregulation
2. Hormonal regulation
3. Influence of calcium

12. Allostericregulation of glycogen
metabolism
•Certain metabolites that allostericallyregulate
the activities of glycogen synthaseand glycogen
phosoporylase
•The glycogen synthesis is increased when
substrate availability and energy levels are high
•Glycogen breakdown is enhanced when glucose
concentration and energy levels are low
•In well fed state, the availability the glucose-6-
phosphate is high which allostericallyactivates
glycogen synthasefor more glycogen synthesis

13. Hormonal regulation
•Hormones like epinephrine,norepinephrineand
glucagon activate adenylatecyclaseto increase
production of Camp .
•Enzyme phosphodiesterasebreaks down cAMP.
•Insulin increases phosphodiesteraseactivity in
liver and lowers cAMPlevels.

14. Regulation of glycogenesisby cAMP

15. Glycogen storage diseases
•These are the metabolic defects concerned with
glycogen synthesis and degradation.
•In these disorders there is deposition of normal
or abnormal type of glycogen in tissues.

16. Von Gierke’sDisease Type I
•It is transmitted by autosomalrecessive trait
•Enzyme deficiency-Glucose-6-phosphatase
•The enzyme is absent in live cells and intestinal
mucosa
•Liver cells, intestinal mucosa and renal tubular
cells are loaded with glycogen

17. Clinical and Biochemical features
•Fasting hypoglycemia
due to defect in the enzyme glucose-6-phosphatase,
enough free glucose is not released from the liver
causing hypoglycemia.
•Lactic acidemia
glucose is not synthesized from lactate produced
in liver and muscles, hence lactate level increases in
blood and pH is lowered causing acidosis

18. Hyperlipidemia
There is blockade in gluconeogenesis. Hence
more fat is mobilisedto meet the energy
requirements of the body, this causes increased
plasma free fatty acids and ketonebodies

19. Hyperuricemia
•glucose-6-phosphate that accumulates is
diverted to HMP shunt pathway leading to
increased synthesis of ribose phosphates and
enhance the metabolism of purinenucleotides to
uric acid. Elevated plasma levels of uric acid are
often associated with gouty arthritis.

20. Various other diseases are
GSD Enzyme defect
1. Pompe’sdiseaseLysosomalalpha-1,4glucosidase
2. Her’sdiseaseLiver glycogen phosphorylase
3. Anderson’s diseaseGlucosyl4-6 transferase
4. Cori’s diseaseAmyloalpha-1,6glucosidase
5. Tarui’sdiseasePhosphofructokinase

21. Questions
•What is the effect of calcium on glycogenolysis?
•Biochemical manifestations of Von Gierkes
disease?
•Compare the effect of glucagon and insulin in
glycogen metabolism
•Compare insulin’s effect on glycogen synthase
with its effect on glycogen phosphorylase.
•Expalinallostericregulation of glycogen
metabolism.