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Glycogen metabolism andGlycogen metabolism and
controlcontrol
Reading:
Harper’s Biochemistry Chapter 20
OBJECTIVESOBJECTIVES
To understand how glycogen is synthesized
and degraded in liver and muscle.
To understand how hormone...
Glycogen is the major storage form of carbohydrate
in animals and corresponds to starch in plants.
Occurs mainly in liver ...
Biomedical ImportanceBiomedical Importance
Muscle glycogen acts as a convenient source of
hexose units for glycolysis with...
Glycogenesis- glycogen synthesisGlycogenesis- glycogen synthesis
Occurs mainly in muscle and liver.
Glucose is phosphoryla...
Uridine diphosphate glucose (UDPGlc)
UDP-glucose is the immediate donor of glucose residues
in the reaction catalyzed by glycogen synthase, which
promotes the ...
Glycogen synthase cannot make the (α1→6) bonds
found at branch points of glycogen. This is done by
the glycogen-branching ...
Initiation of a glycogen particleInitiation of a glycogen particle
Because glycogen synthase
requires a primer, a new
glyc...
Glycogenolysis- glycogen breakdownGlycogenolysis- glycogen breakdown
Glycogen can enter the glycolytic pathway as glucose ...
GlycogenGlycogen
breakdown near abreakdown near a
branch pointbranch point
This requires a
“debranching enzyme” -
amylo(1→...
Glucose 1-phosphate, the end product of the
glycogen phosphorylase reaction, is converted to
glucose 6-phosphate by phosph...
Cyclic AMP integrates the regulation ofCyclic AMP integrates the regulation of
glycogenolysis and glycogenesisglycogenolys...
Cyclic AMP activates muscleCyclic AMP activates muscle
phosphorylasephosphorylase
Epinephrine (adrenaline) activates the β...
Activation of phosphorylase kinase inActivation of phosphorylase kinase in
musclemuscle
Phosphorylase kinase is also activ...
Control of phosphorylase in muscle. The sequence of
reactions arranged as a cascade allows amplification of the
hormonal s...
Glycogen SynthaseGlycogen Synthase
Glycogen synthase is also regulated by reversible
phosphorylation, but in this case, th...
In muscle, when PKA is active and glycogenolysis is
promoted, glycogen synthase is maintained inactive by
the same pathway
SUMMARYSUMMARY
1. Glycogen represents the principal storage form of
carbohydrate in the mammalian body, present mainly
in ...
SUMMARYSUMMARY
4. Cyclic AMP integrates the regulation of
glycogenolysis and glycogenesis by promoting the
simultaneous ac...
Glycogen Metabolism and Control
Glycogen Metabolism and Control
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Glycogen Metabolism and Control

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Reading:
Harper Biochemistry Chapter 20

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Glycogen Metabolism and Control

  1. 1. Glycogen metabolism andGlycogen metabolism and controlcontrol Reading: Harper’s Biochemistry Chapter 20
  2. 2. OBJECTIVESOBJECTIVES To understand how glycogen is synthesized and degraded in liver and muscle. To understand how hormones like adrenalin and glucagon affect glycogen synthesis and breakdown.
  3. 3. Glycogen is the major storage form of carbohydrate in animals and corresponds to starch in plants. Occurs mainly in liver and muscle.
  4. 4. Biomedical ImportanceBiomedical Importance Muscle glycogen acts as a convenient source of hexose units for glycolysis within muscle itself. Only depleted significantly after prolonged vigorous exercise. Liver glycogen is largely concerned with storage and export of hexose units for maintenance of blood glucose, particularly between meals. After 12-18h of fasting, the liver becomes nearly depleted of glycogen. Glycogen storage diseases are a group of inherited disorders characterized by deficient mobilization of glycogen or deposition of abnormal forms of glycogen.
  5. 5. Glycogenesis- glycogen synthesisGlycogenesis- glycogen synthesis Occurs mainly in muscle and liver. Glucose is phosphorylated to glucose 6-phosphate as in the first step of glycolysis. Glucose-6-phosphate is converted to glucose-1- phosphate by phosphoglucomutase. In this reaction, the enzyme itself becomes phosphorylated and glucose 1,6- bisphosphate is an intermediate. Glucose 6-phosphate Glucose 1-phosphate The key reaction in glycogen synthesis is the formation of UDP-glucose by the action of UDP-glucose pyrophosphorylase. Glucose 1-phosphate + UTP→ UDP-glucose + PPi This reaction proceeds to the right because PPi is rapidly hydrolyzed to inorganic phosphate.
  6. 6. Uridine diphosphate glucose (UDPGlc)
  7. 7. UDP-glucose is the immediate donor of glucose residues in the reaction catalyzed by glycogen synthase, which promotes the transfer of the glucose residue of UDP- glucose to a non-reducing end of a branched glycogen molecule (primer must have at least 8 glucose residues)
  8. 8. Glycogen synthase cannot make the (α1→6) bonds found at branch points of glycogen. This is done by the glycogen-branching enzyme “amylo (1→4) to (1→6) transglycosylase.” Branching makes glycogen more soluble and provides more non-reducing ends which act as sites for glycogen synthase and glycogen phosphorylase
  9. 9. Initiation of a glycogen particleInitiation of a glycogen particle Because glycogen synthase requires a primer, a new glycogen particle is formed by the protein glycogenin (MV 37kD). Glycogenin becomes glycosylated on a specific tyrosine residue by UDP- glucose. Further glucose molecules are attached in the 1→ 4 position to make a short glucose chain which can then act as a primer for glycogen synthase.
  10. 10. Glycogenolysis- glycogen breakdownGlycogenolysis- glycogen breakdown Glycogen can enter the glycolytic pathway as glucose 6- phosphate following the action of two enzymes: glycogen phosphorylase and phosphoglucomutase. Glycogen phosphorylase releases terminal glucose residues from the non-reducing end of glycogen chains
  11. 11. GlycogenGlycogen breakdown near abreakdown near a branch pointbranch point This requires a “debranching enzyme” - amylo(1→6)glucosidase - which has a transferase and a glucosidase activity
  12. 12. Glucose 1-phosphate, the end product of the glycogen phosphorylase reaction, is converted to glucose 6-phosphate by phosphoglucomutase: glucose 1-phosphate glucose 6-phosphate In liver (and kidney), but not in muscle, there is a specific enzyme, glucose 6-phosphatase, that removes phosphate from glucose 6-phosphate. The glucose formed can diffuse from the cell into the blood.
  13. 13. Cyclic AMP integrates the regulation ofCyclic AMP integrates the regulation of glycogenolysis and glycogenesisglycogenolysis and glycogenesis The principle enzymes controlling glycogen metabolism are glycogen phosphorylase and glycogen synthase. These enzymes are regulated by a complex series of reactions involving both allosteric mechanisms and covalent modification by phosphorylation/dephosphorylation. *Glycogen phosphorylase is activated by phosphorylation *Glycogen synthase is inactivated by phosphorylation
  14. 14. Cyclic AMP activates muscleCyclic AMP activates muscle phosphorylasephosphorylase Epinephrine (adrenaline) activates the β-adrenergic receptor on the surface of muscle cells This activates, via trimeric G proteins, the enzyme adenylate cyclase, which makes cyclic AMP from ATP Cyclic AMP, or cAMP, activates cAMP-dependent protein kinase (PKA) R2C2 (inactive) + 4cAMP R2-(AMP)4 + 2C (active) Active PKA phosphorylates and activates phosphorylase b kinase Active phosphorylase b kinase phosphorylates and activates phosphorylase b, which can now mobilize glycogen
  15. 15. Activation of phosphorylase kinase inActivation of phosphorylase kinase in musclemuscle Phosphorylase kinase is also activated by Ca2+ Subunit structure (αβγδ)2 α,β - phosphorylated by PKA γ - catalytic subunit δ - calmodulin Calmodulin binds Ca2+ Binding of Ca2+ by δ subunit enhances activity of phosphorylase kinase Therefore, Ca2+ synchronizes the activation of phosphorylase with muscle contraction
  16. 16. Control of phosphorylase in muscle. The sequence of reactions arranged as a cascade allows amplification of the hormonal signal at each step (n= number of glucose residues; G6P, glucose 6-phosphate).
  17. 17. Glycogen SynthaseGlycogen Synthase Glycogen synthase is also regulated by reversible phosphorylation, but in this case, the phosphorylated enzyme is inactive. *Glycogen synthase a - active form- dephosphorylated *Glycogen synthase b - inacitve form- phosphorylated
  18. 18. In muscle, when PKA is active and glycogenolysis is promoted, glycogen synthase is maintained inactive by the same pathway
  19. 19. SUMMARYSUMMARY 1. Glycogen represents the principal storage form of carbohydrate in the mammalian body, present mainly in the liver and muscle. 2. In the liver, its major function is to service the other tissues via formation of blood glucose. In muscle, it serves the needs of that organ only, as a ready source of metabolic fuel. 3. Glycogen is synthesized from glucose and other precursors by the pathway of glycogenesis. It is broken down by a separate pathway known as glycogenolysis. Glucose is not exported from muscle due to absence of glucose 6-phosphatase.
  20. 20. SUMMARYSUMMARY 4. Cyclic AMP integrates the regulation of glycogenolysis and glycogenesis by promoting the simultaneous activation of phosphorylase and inhibition of glycogen synthase. Insulin acts reciprocally by inhibiting glycogenolysis and stimulating glycogenesis. 5. Inherited deficiencies in specific enzymes of glycogen metabolism in both liver and muscle are the causes of glycogen storage diseases.
  • bahrambehnam

    Mar. 13, 2020
  • kuruvaanitha

    Aug. 12, 2019
  • LubnaAnsari10

    Oct. 27, 2018

Reading: Harper Biochemistry Chapter 20

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