Successfully reported this slideshow.
We use your LinkedIn profile and activity data to personalize ads and to show you more relevant ads. You can change your ad preferences anytime.

Glycogen metabolism part-2


Published on

An overview of glycogen degradation

Published in: Education
  • Be the first to comment

Glycogen metabolism part-2

  1. 1. Glycogen metabolism- Part-2 (Glycogen degradation) Namrata Chhabra, M.D., Biochemistry 1/6/2017Namrata Chhabra, M.D., Biochemistry 1
  2. 2. Learning objectives  To understand:  The Purpose  Role of Enzymes and coenzymes, and  The steps involved in the pathway of Glycogenolysis 1/6/2017Namrata Chhabra, M.D., Biochemistry 2
  3. 3. Introduction  Glycogen is a storage form of glucose.  It is a very large, branched polymer of glucose residues that can be broken down to yield glucose molecules when energy is needed.  Most of the glucose residues in glycogen are linked by α-1,4- glycosidic bonds.  Branches at about every tenth residue are created by α-1,6- glycosidic bonds. 1/6/2017Namrata Chhabra, M.D., Biochemistry 3
  4. 4. Glycogen structure 1/6/2017Namrata Chhabra, M.D., Biochemistry 4
  5. 5. Purpose of Glycogenolysis  The controlled breakdown of glycogen and release of glucose increase the amount of glucose that is available between meals. Hence, glycogen serves as a buffer to maintain blood-glucose levels.  Glycogen's role in maintaining blood glucose levels is especially important because glucose is virtually the only fuel used by the brain, except during prolonged starvation. 1/6/2017Namrata Chhabra, M.D., Biochemistry 5
  6. 6. Purpose of Glycogenolysis  The glucose from glycogen is readily mobilized and is therefore a good source of energy for sudden, strenuous activity.  Unlike fatty acids, the released glucose can provide energy in the absence of oxygen and can thus supply energy for anaerobic activity. 1/6/2017Namrata Chhabra, M.D., Biochemistry 6
  7. 7. Enzymes involved in Glycogenolysis  The efficient breakdown of glycogen requires four enzyme activities:  one to degrade glycogen,  two to remodel glycogen so that it remains a substrate for degradation, and  one to convert the product of glycogen breakdown into a form suitable for further metabolism. 1/6/2017Namrata Chhabra, M.D., Biochemistry 7
  8. 8. Enzymes of Glycogenolysis Phosphorylase Bifunctional- Debranching enzyme Phospho- glucomutase Glucose-6- Phosphatase 1/6/2017Namrata Chhabra, M.D., Biochemistry 8
  9. 9. Major coenzyme of Glycogenolysis  Pyridoxal phosphate (PLP), a derivative of vitamin B6, is the major coenzyme involved in the glycogen degradation.  serves as prosthetic group for Glycogen Phosphorylase.  It is held at the active site of Phosphorylase enzyme by a Schiff base linkage, formed by reaction of the aldehyde group of PLP with the ε-amino group of a lysine residue. 1/6/2017Namrata Chhabra, M.D., Biochemistry 9
  10. 10. Glycogen degradation is not just the reverse of glycogenesis Glycogenesis  Glucose-> Glucose-6-P  Glucose-6-P –> Glucose-1-P  Polymerization  Branching  Polymerization  Glycogenolysis  Depolymerization- Removal of glucose as glucose-1-P  Debranching  Depolymerization  Conversion of Glucose-1-P to Glucose-6-P  Conversion of Glucose-6-P to free Glucose 1/6/2017Namrata Chhabra, M.D., Biochemistry 10
  11. 11. Specific steps of Glycogenolysis  Step-1- Depolymerization (Release of Glucose-1-P from Glycogen)  Enzyme- Phosphorylase  Coenzyme– Pyridoxal phosphate  Reaction involved : 1/6/2017Namrata Chhabra, M.D., Biochemistry 11
  12. 12. Step-1- Reaction catalyzed by Phosphorylase  Phosphorylase catalyzes the sequential removal of glucosyl residues from the nonreducing ends of the glycogen molecule (the ends with a free 4-OH group.  Orthophosphate splits the glycosidic linkage between C-1 of the terminal residue and C-4 of the adjacent one. 1/6/2017Namrata Chhabra, M.D., Biochemistry 12
  13. 13. Phosphoroyltic cleavage Why not hydrolytic cleavage ? 1/6/2017Namrata Chhabra, M.D., Biochemistry 13
  14. 14. Advantages of Phosphoroyltic cleavage  The phosphoroylytic cleavage of glycogen is energetically advantageous because the released sugar is already phosphorylated.  In contrast, a hydrolytic cleavage would yield glucose, which would then have to be phosphorylated at the expense of the hydrolysis of a molecule of ATP to enter the glycolytic pathway.  An additional advantage of phosphoroylytic cleavage for muscle cells is that glucose 1-phosphate, negatively charged under physiological conditions, cannot diffuse out of the cell. 1/6/2017Namrata Chhabra, M.D., Biochemistry 14
  15. 15. Problem with Phosphorylase  The α-1,6-glycosidic bonds at the branch points are not susceptible to cleavage by phosphorylase.  Glycogen phosphorylase stops cleaving α -1,4 linkages when it reaches a terminal residue four residues away from a branch point.  Because about 1 in 10 residues is branched, glycogen degradation by the phosphorylase alone would come to a halt after the release of six glucose molecules per branch. 1/6/2017Namrata Chhabra, M.D., Biochemistry 15
  16. 16. Step-2- Remodeling and Debranching  Special Bifunctional enzyme with two enzyme activities  Transferase and Debranching (α-1,6- glucosidase)  Both these enzymes remodel the glycogen for continued degradation by the phosphorylase. 1/6/2017Namrata Chhabra, M.D., Biochemistry 16
  17. 17. Role of Transferase  Transferase shifts a block of three glucosyl residues from one outer branch to the other.  This transfer exposes a single glucose residue joined by an α-1,6-glycosidic linkage.  Debranching enzyme, hydrolyzes the α -1, 6- glycosidic bond, resulting in the release of a free glucose molecule.  The transferase and α-1,6-glucosidase convert the branched structure into a linear one, which paves the way for further cleavage by phosphorylase. 1/6/2017Namrata Chhabra, M.D., Biochemistry 17
  18. 18. Phosphorylase versus debranching enzyme- Outcomes  Glucose-1-P is released as an outcome of reaction catalyzed by Phosphorylase  Free glucose is released by the action of debranching enzyme 1/6/2017Namrata Chhabra, M.D., Biochemistry 18
  19. 19. Step-3- Conversion of Glucose-1-P to Glucose-6-P  Phosphoglucomutase converts glucose 1-phosphate into glucose 6- phosphate in a reversible reaction.  The catalytic site of an active mutase molecule contains a phosphorylated serine residue.  The phosphoryl group is transferred from the serine residue to the C-6 hydroxyl group of glucose 1-phosphate to form glucose 1,6- bisphosphate.  The C-1 phosphoryl group of this intermediate is then shuttled to the same serine residue, resulting in the formation of glucose 6- phosphate and the regeneration of the phosphoenzyme. 1/6/2017Namrata Chhabra, M.D., Biochemistry 19
  20. 20. Reaction catalyzed by Phosphoglucomutase 1/6/2017Namrata Chhabra, M.D., Biochemistry 20
  21. 21. Step-4- Fate of Glucose-6-P  Glucose 6-phosphate derived from glycogen can  (1) be used as a fuel for anaerobic or aerobic metabolism as in, for instance, muscle;  (2) be converted into free glucose in the liver and subsequently released into the blood;  (3) be processed by the pentose phosphate pathway to generate NADPH or ribose in a variety of tissues. 1/6/2017Namrata Chhabra, M.D., Biochemistry 21
  22. 22. The fate is different in liver and muscle  The liver contains a hydrolytic enzyme, glucose 6-phosphatase, which cleaves the phosphoryl group to form free glucose and orthophosphate.  Glucose 6-phosphatase is absent from most other tissues. Consequently, glucose 6-phosphate is retained for the generation of ATP.  In contrast, glucose is not a major fuel for the liver. The liver releases glucose into the blood during muscular activity and between meals to be taken up primarily by the brain and skeletal muscle. 1/6/2017Namrata Chhabra, M.D., Biochemistry 22
  23. 23. Reaction catalyzed by Glucose-6- Phosphatase 1/6/2017Namrata Chhabra, M.D., Biochemistry 23
  24. 24. Glycogenesis versus Glycogenolysis • Glycogenolysis and Glycogenesis are not the just the reverse of each other. • The reaction pathways, enzymes and coenzymes are all different and, • both the ways are reciprocally regulated. 1/6/2017Namrata Chhabra, M.D., Biochemistry 24
  25. 25. Regulation of glycogen metabolism  To be continued in the next section… 1/6/2017Namrata Chhabra, M.D., Biochemistry 25
  26. 26. Thank you 1/6/2017Namrata Chhabra, M.D., Biochemistry 26