Week 6: Glycogen Flashcards
What is glucose energy for?
- Brain
- Cells lacking mitochondria
- Cells with few mitochondria
- Exercising muscles
- Sudden and strenuous activity
How is blood glucose obtained?
- Diet
- Gluconeogenesis
- Degradation of glycogen
Where is glycogen stored?
Liver
Where would glycogen degradation and synthesis occur?
Cytosol of the cell
What is glycogen made from?
- Excess blood glucose
2. Recycling glucogenic metabolites
What occurs when glycogen is degraded?
Energy is produced
Describe the functions of glycogen storage in the muscle?
- Serves as a fuel reserve for ATP synthesis
- Store are replenished after depletion from exercise
- When glycogen is used up, proteins degrade into amino acids enter gluconeogenesis
Describe the functions of glycogen storage in the liver?
- Storage increases during the well-fed state and depletes during a fast
- Used to maintain blood glucose concentration
- Maintains glood glucose for 10-18hrs
Describe the structure of glycogen
- Granules within the cytoplasm
- The more branch points the more terminal residues become available
- It’s a branched chain polysaccharide (homopolymer)
- Each a-D-glucose is joined by a-1,4 glycosidic bonds
- Branch points occur every 8-10 glycosyl residue by a-1,0 glycosidic bond
What is the purpose for glycogen to be highly branched?
Makes it possible for several glucose residues to be released at once to meet energy needs
What are the 3 steps of glycogen metabolism?
- Release of glucose-1-phosphate from glycogen
- Remodeling of glycogen for continued degradation
- Conversion of glucose 1-phosphate into glucose 6-phosphate
What occurs during the 1st reaction of glycogen breakdown?
Glycogen is phosphorolyzed by glycogen phosphorylase cleaving a glucose 1-phosphate molecule and a shortened glycogen molecule
Does the 1st reaction of glycogen breakdown require ATP?
No
Explain the process of debranching glycogen?
- Glycogen phosphorylase works on noreducing ends to reach 4 residues from branch point
- Branch point is removed by 2 enzymatic activities
- Debranching enzyme transfers a block of 3 residues to the nonbranching end of the chain
- Debranching enzyme cleaves the single remaining glucose which is becomes a free glucose unit
- Glycogen phosphorylase continues
What occurs during the 2nd reaction of glycogen breakdown?
Glucose-1-phosphate is isomerized by phosophoglucomutase to form glucose-6-phosphate
Describe glycogen breakdown in the liver
- Liver glycogen phosphorylase breaks down glycogen to glucose-1-phosphate
- Through glucose-6-phosphotase, glucose-1-phosphate is converted to glucose-6-phosphate
- Glucose and Pi are shuttled back to cytoplasm by transporters
- Glucose is released from cell by transporter, GLUT2
Describe glycogen breakdown in the muscle
- Muscle glycogen phosphorylase breaks down glycogen to glucose-1-phosphate
- Glucose-1-phosphate is converted to glucose-6-phosphate without glucose-6-phosphotase
- Glucose-6-phosphotate enters the glycolytic pathway directly
- Saves 1 ATP
What are the fates of glucose-6-phosphate?
- Processing by the glycolytic pathway
- Conversion into free glucose for the release into the blood (liver)
- Processing by the pentose phosphate pathway
What is glycogen synthesis?
Synthesis of glycogen requiring more enzymes and metabolic intermediates than glycogen degradation
Blood glucose must meet what criteria to initiate glycogen synthesis?
- Phosphorylated
- Attached to UDP
- Added to glycogen
What instigates Glucose-6-P to Glucose-1-P?
Phosphoglucomutase
What occurs during stage 1 of glycogen synthesis?
- Glucose-1-P is catalyzed by UDP-glucose pyrophosphorylase with UTP to produces UDP-glucose and PPi
- PPi is hydrolyzed to Pi and Pi by pyrophosphatase
What occurs during stage 2 of glycogen synthesis?
- UDPG is added onto a growing glycogen chain by glycogen synthase
- UTP is released once glycosidic bond is formed
- UTP must be regenerated from UDP and ATP by nucleoside diphosphate kinase
What is the general structure of a glycogen particle?
Glycogenin primer to initiate glycogen synthase
How are glycogenin primers synthesized?
Glycogenin enzymes
What is a branching enzyme?
Catalyzes the reactions needed to introduce a branch point during the synthesis of glycogen
Describe the mode of action of the branching enzyme in glycogen synthesis
- Transfers a segment (7 residues long) from the end of a growing chain to the branch point where it catalyzes the formation of the required
- α-1,6 glycosidic linkage α-1,6 glycosidic linkage occurs at least 4 residues away from previous branch point
- Glycogen synthase can then extend the branches
What would be the major controlling factor in the synthesis and breakdown of glycogen?
Glycogen phosphorylase
What are the regulatory steps to glycogen degradation?
- Enzyme is subject to allosteric control and covalent modification
- Phosphorylation leads to activation of glycogen phosphorylase
- Dephosphorylation leads to inhibition of glycogen phosphorylase
- Phosphorylation is controlled by the hormones epinephrine and glucagon (activates breakdown of glycogen)
What are the regulatory steps to glycogen synthesis?
- Inactive form is the phosphorylated form, and the active form is unphosphorylated
- Phosphorylation is stimulated by hormonal signals (glucagon or epinephrine) via the enzyme cAMP-dependent protein kinase
- Becomes inactive after phosphorylation at the same time the hormonal signal is activating phosphorylase
Describe the allosteric control of glycogen metabolism in the liver
- Glycogen synthase is allosterically activated by elevated glucose-6-phosphate
- Glycogen phosphorylase is allosterically inhibited by glucose 6-phosphate and ATP.
- Glucose inhibits glycogen phosphorylase in the liver only.
Describe the allosteric control of glycogen metabolism in the muscle
- Glycogen synthase is allosterically activated by elevated glucose-6-phosphate
- Glycogen phosphorylase is allosterically inhibited by glucose 6-phosphate and ATP
- Ca2+ release into the cytoplasm activates muscle glycogen phosphorylase to release glucose 1-phosphate to convert into glucose 6-phosphate to enter glycolysis and produce ATP.
- In a low energy state, increased AMP levels activate glycogen phosphorylase.
Describe the hormonal control using the insulin-signaling pathway
- At high blood glucose levels, insulin would bind to the insulin receptor producing a net dephosphorylation
- Protein phosphatase 1 inactivates glycogen phosphorylase
- Protein phosphatase 1 activates glycogen synthase increasing glycogen synthesis
- Increasing glucose import into the liver
Describe the hormonal control using the glucagon-signaling pathway
- At low blood glucose levels, glucagon would bind to the glucagon receptor producing net phosphorylation
- Protein kinase A inactivates glycogen synthase
- Protein kinase A activates phosphorylase kinase which activates glycogen phosphorylase
- Glycogen degradation increase as well as glucose export from liver
