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CHO_met_2_Biochemistry_21-12-2018.pdf

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GLYCOGENESIS AND GLYCOGENOLYSIS
Glycogen Storage form of glucose in animals. Stored in the liver (6-8%) & muscle (1-2%). Quantity more in the muscle(~250g) than liver(75g) due to higher muscle mass. Stored as granules in the cytosol.
Glycogen vs. Fat as source of energy:- Fat cannot be rapidly metabolised like glycogen. Fat cannot generate energy in the absence of oxygen. Brain requires a continuous supply of glucose, which come from glycogen. Fat cannot produce glucose.
CHO_met_2_Biochemistry_21-12-2018.pdf
Glycogenesis :- Synthesis of glycogen from glucose. Site :- Cytosol Activated Glucose –UDP Glucose
Structure of Glycogen
CHO_met_2_Biochemistry_21-12-2018.pdf
G Glycogen primer or Glycogenin required to initiate Glycogenesis GLUCOKIN ASE PHOSPHOG LUCOMUTA SE G-1-P URIDYL TRANSFERAS E GLYCOGEN SYNTHASE
Glycogen Synthase transfers Glucose from UDP-Glucose to the non-reducing end of the Glycogen to form α-1,4 linkages. Branching enzyme :- Amylo α-1,4 1,6 transglucosidase (Glucosyl α-4-6 transferase)
Overall Reaction of Glycogenesis :- (Glucose)n + Glucose + 2 ATP (Glucose)n+1 + 2 ADP + Pi
CHO_met_2_Biochemistry_21-12-2018.pdf
Enzymes of Glycogenolysis :- 1. Glycogen Phosphorylase. 2. Debranching enzyme : α-1 :4 Transferase, α-1,6 and α-1,4 glucosidase 3. Glucose - 6- phosphatase
CHO_met_2_Biochemistry_21-12-2018.pdf
CHO_met_2_Biochemistry_21-12-2018.pdf
 GLUCOSE-6-PHOSPHATASE ABSENT IN MUSCLES  LYSOSOMAL DEGRADATION  Alpha 1,4 glucosidase. (acid maltase)
Regulation of glycogenesis & Glycogenolysis Key enzyme of Glycogenesis- Glycogen Synthase Key enzyme of Glycogenolysis- Glycogen Phosphorylase Three Regulatory Mechanisms 1. Allosteric Regulation. 2. Hormonal Regulation. 3. Influence of Calcium.
Allosteric Regulation of Glycogen Metabolism :- When substrate availability & energy level is high, Glycogen synthesis is increased. When glucose concentration is low & energy level low, Glycogen breakdown is enhanced. In well-fed state, Glucose-6-P allosterically activates Glycogen Synthase. At the same time, allosterically inhibits Glycogen Phosphorylase. Free Glucose in the liver is also a allosteric inhibitor of Glycogen Phosphorylase.
Glycogen Glucose-1- Phosphate Glycogen phosphorylase Glycogen synthase Glucose-6-phosphate + Glucose-6- Phosphate ATP Glucose (liver) Ca 2+ , AMP - + - -
Hormonal Regulation of Glycogen Metabolism :- Hormones control Glycogen synthesis & degradation by covalent modification ie., phosphorylation & Dephosphorylation. cAMP acts as second messenger. cAMP activates Protein Kinase. Protein Kinase causes phosphorylation of enzymes, either activating or deactivating them.
Allosteric Regulation of Glycogen Metabolism :- When substrate availability & energy level is high, Glycogen synthesis is increased. When glucose concentration is low & energy level low, Glycogen breakdown is enhanced. In well-fed state, Glucose-6-P allosterically activates Glycogen Synthase. At the same time, allosterically inhibits Glycogen Phosphorylase. Free Glucose in the liver is also a allosteric inhibitor of Glycogen Phosphorylase.
Glycogen Glucose-1- Phosphate Glycogen phosphorylase Glycogen synthase Glucose-6-phosphate + Glucose-6- Phosphate ATP Glucose (liver) Ca 2+ , AMP - + - -
Hormonal Regulation of Glycogen Metabolism :- Hormones control Glycogen synthesis & degradation by covalent modification ie., phosphorylation & Dephosphorylation. cAMP acts as second messenger. cAMP activates Protein Kinase. Protein Kinase causes phosphorylation of enzymes, either activating or deactivating them.
ATP cAMP Phosphodiesterase 5’AMP Adenylate cyclase Glucagon, Epinephrine + + Insulin + + cAMP dependent Protein Kinase Phosphorylation Inactive Glycogen synthase Active Glycogen Phosphorylase
Effect of Calcium :- Ca 2+ ions released from sarcoplasmic reticulum of muscle muscle contracts Ca 2+ ions bind to calmodulin (calcium binding protein) Calcium calmodulin complex directly activates Protein Kinase without the involvement of cAMP.
Type I: VON GIERKE’S DISEASE (G-6-phosphatase) Commonest  Fasting Hypoglycemia.  Adrenaline has no effect.  Lactic Acidosis.  Hyperuricemia.  Liver Enlargement – Cirrhosis. Glycogen Storage Diseases
 TYPE II ( POMPE’S): Lysosomal Maltase (α-1,4 glucosidase).  TYPE III ( CORI’S / LIMIT DEXTRINOSIS): Debranching Enzyme  TYPE IV ( AMYLOPECTINOSIS / ANDERSON’S) : Branching Enzyme.  TYPE V ( McARDLE’S) : Muscle Phosphorylase  TYPE VI ( HER’S) : Liver Phosphorylase  TYPE VII ( TARUI’S) : Phosphofructokinase  TYPE VIII ( PHOSPHORYLASE KINASE )  TYPE IX ( GLYCOGEN SYNTHASE)
QUESTIONS ???? 1) What is Glycogen ? 2) Monosaccharide B) Disaccharide C) Homopolysaccahride D) Heteropolysaccahride 2) It is a Storage form of A) Carbohydrate B) Protein C) Lipid D) All of above 3) Key enzyme of Glycogenesis- A) Hexokinase B) Glucose - 6- phosphatase C) Glycogen Phosphorylase D) Glycogen Synthase 4) Key enzyme of Glycogenolysis A) Glucose - 6- phosphatase B) Glycogen Phosphorylase C) Glycogen Synthase D) None of Above 5) Site of Glycogenesis A) Mitochondria B) Cytosol C) Lysosome D) Nucleus
ANSWERS 1) What is Glycogen ? 2) Monosaccharide B) Disaccharide C) Homopolysaccahride D) Heteropolysaccahride 2) It is a Storage form of A) Carbohydrate B) Protein C) Lipid D) All of above 3) Key enzyme of Glycogenesis- A) Hexokinase B) Glucose - 6- phosphatase C) Glycogen Phosphorylase D) Glycogen Synthase 4) Key enzyme of Glycogenolysis A) Glucose - 6- phosphatase B) Glycogen Phosphorylase C) Glycogen Synthase D) None of Above 5) Site of Glycogenesis A) Mitochondria B) Cytosol C) Lysosome D) Nucleus

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CHO_met_2_Biochemistry_21-12-2018.pdf

  • 2. Glycogen Storage form of glucose in animals. Stored in the liver (6-8%) & muscle (1-2%). Quantity more in the muscle(~250g) than liver(75g) due to higher muscle mass. Stored as granules in the cytosol.
  • 3. Glycogen vs. Fat as source of energy:- Fat cannot be rapidly metabolised like glycogen. Fat cannot generate energy in the absence of oxygen. Brain requires a continuous supply of glucose, which come from glycogen. Fat cannot produce glucose.
  • 5. Glycogenesis :- Synthesis of glycogen from glucose. Site :- Cytosol Activated Glucose –UDP Glucose
  • 8. G Glycogen primer or Glycogenin required to initiate Glycogenesis GLUCOKIN ASE PHOSPHOG LUCOMUTA SE G-1-P URIDYL TRANSFERAS E GLYCOGEN SYNTHASE
  • 9. Glycogen Synthase transfers Glucose from UDP-Glucose to the non-reducing end of the Glycogen to form α-1,4 linkages. Branching enzyme :- Amylo α-1,4 1,6 transglucosidase (Glucosyl α-4-6 transferase)
  • 10. Overall Reaction of Glycogenesis :- (Glucose)n + Glucose + 2 ATP (Glucose)n+1 + 2 ADP + Pi
  • 12. Enzymes of Glycogenolysis :- 1. Glycogen Phosphorylase. 2. Debranching enzyme : α-1 :4 Transferase, α-1,6 and α-1,4 glucosidase 3. Glucose - 6- phosphatase
  • 15.  GLUCOSE-6-PHOSPHATASE ABSENT IN MUSCLES  LYSOSOMAL DEGRADATION  Alpha 1,4 glucosidase. (acid maltase)
  • 16. Regulation of glycogenesis & Glycogenolysis Key enzyme of Glycogenesis- Glycogen Synthase Key enzyme of Glycogenolysis- Glycogen Phosphorylase Three Regulatory Mechanisms 1. Allosteric Regulation. 2. Hormonal Regulation. 3. Influence of Calcium.
  • 17. Allosteric Regulation of Glycogen Metabolism :- When substrate availability & energy level is high, Glycogen synthesis is increased. When glucose concentration is low & energy level low, Glycogen breakdown is enhanced. In well-fed state, Glucose-6-P allosterically activates Glycogen Synthase. At the same time, allosterically inhibits Glycogen Phosphorylase. Free Glucose in the liver is also a allosteric inhibitor of Glycogen Phosphorylase.
  • 18. Glycogen Glucose-1- Phosphate Glycogen phosphorylase Glycogen synthase Glucose-6-phosphate + Glucose-6- Phosphate ATP Glucose (liver) Ca 2+ , AMP - + - -
  • 19. Hormonal Regulation of Glycogen Metabolism :- Hormones control Glycogen synthesis & degradation by covalent modification ie., phosphorylation & Dephosphorylation. cAMP acts as second messenger. cAMP activates Protein Kinase. Protein Kinase causes phosphorylation of enzymes, either activating or deactivating them.
  • 20. Allosteric Regulation of Glycogen Metabolism :- When substrate availability & energy level is high, Glycogen synthesis is increased. When glucose concentration is low & energy level low, Glycogen breakdown is enhanced. In well-fed state, Glucose-6-P allosterically activates Glycogen Synthase. At the same time, allosterically inhibits Glycogen Phosphorylase. Free Glucose in the liver is also a allosteric inhibitor of Glycogen Phosphorylase.
  • 21. Glycogen Glucose-1- Phosphate Glycogen phosphorylase Glycogen synthase Glucose-6-phosphate + Glucose-6- Phosphate ATP Glucose (liver) Ca 2+ , AMP - + - -
  • 22. Hormonal Regulation of Glycogen Metabolism :- Hormones control Glycogen synthesis & degradation by covalent modification ie., phosphorylation & Dephosphorylation. cAMP acts as second messenger. cAMP activates Protein Kinase. Protein Kinase causes phosphorylation of enzymes, either activating or deactivating them.
  • 23. ATP cAMP Phosphodiesterase 5’AMP Adenylate cyclase Glucagon, Epinephrine + + Insulin + + cAMP dependent Protein Kinase Phosphorylation Inactive Glycogen synthase Active Glycogen Phosphorylase
  • 24. Effect of Calcium :- Ca 2+ ions released from sarcoplasmic reticulum of muscle muscle contracts Ca 2+ ions bind to calmodulin (calcium binding protein) Calcium calmodulin complex directly activates Protein Kinase without the involvement of cAMP.
  • 25. Type I: VON GIERKE’S DISEASE (G-6-phosphatase) Commonest  Fasting Hypoglycemia.  Adrenaline has no effect.  Lactic Acidosis.  Hyperuricemia.  Liver Enlargement – Cirrhosis. Glycogen Storage Diseases
  • 26.  TYPE II ( POMPE’S): Lysosomal Maltase (α-1,4 glucosidase).  TYPE III ( CORI’S / LIMIT DEXTRINOSIS): Debranching Enzyme  TYPE IV ( AMYLOPECTINOSIS / ANDERSON’S) : Branching Enzyme.  TYPE V ( McARDLE’S) : Muscle Phosphorylase  TYPE VI ( HER’S) : Liver Phosphorylase  TYPE VII ( TARUI’S) : Phosphofructokinase  TYPE VIII ( PHOSPHORYLASE KINASE )  TYPE IX ( GLYCOGEN SYNTHASE)
  • 27. QUESTIONS ???? 1) What is Glycogen ? 2) Monosaccharide B) Disaccharide C) Homopolysaccahride D) Heteropolysaccahride 2) It is a Storage form of A) Carbohydrate B) Protein C) Lipid D) All of above 3) Key enzyme of Glycogenesis- A) Hexokinase B) Glucose - 6- phosphatase C) Glycogen Phosphorylase D) Glycogen Synthase 4) Key enzyme of Glycogenolysis A) Glucose - 6- phosphatase B) Glycogen Phosphorylase C) Glycogen Synthase D) None of Above 5) Site of Glycogenesis A) Mitochondria B) Cytosol C) Lysosome D) Nucleus
  • 28. ANSWERS 1) What is Glycogen ? 2) Monosaccharide B) Disaccharide C) Homopolysaccahride D) Heteropolysaccahride 2) It is a Storage form of A) Carbohydrate B) Protein C) Lipid D) All of above 3) Key enzyme of Glycogenesis- A) Hexokinase B) Glucose - 6- phosphatase C) Glycogen Phosphorylase D) Glycogen Synthase 4) Key enzyme of Glycogenolysis A) Glucose - 6- phosphatase B) Glycogen Phosphorylase C) Glycogen Synthase D) None of Above 5) Site of Glycogenesis A) Mitochondria B) Cytosol C) Lysosome D) Nucleus