Glycogen Metabolism Flashcards
describe the location of glycogen in the body
- the largest amount of glycogen is found in skeletal muscle (400g)
- the highest concentration of glycogen is found in the liver (100g)
- glycogen storage diseases can affect both
what activates glycogen synthesis?
- insulin activates glycogen synthesis in both liver and muscle
- glycogen synthase is the regulated enzyme and is active when it is dephosphorylated
- insulin activates protein phosphatase 1 which cleaves phosphates that were added by PKA
what inhibits glycogen synthesis in the liver and muscle?
- glucagon and epinephrine activate PKA which phosphorylates key regulatory enzymes
- glycogen synthase is inhibited when it is phosphorylated
describe the molecules involved in glycogen synthesis
describe the enzyme involved in converting glucose 6-P and glucose 1-P
- phosphoglucomutase catalyzes the change in position of the phosphate; the direction of the reversible rxn is dependent on the concentrations
describe UDP glucose
- UDP glucose is the highly activated form of glucose which is used for synthesis of glycogen as well as other glycosylations
- UDP-glucose is synthesized from G1P and UTP (UDP-glucose pyrophosphorylase)
explain why glycogen synthase needs a primer
-
glycogen synthase cannot link UDP-glucose to each other without a primer
- in most cases the primer is in the form of branched glycogen chains that have not been degraded
- the protein glycogenin is needed for de-novo synthesis after all glycogen chains are degraded and will form a primer that can be used by glycogen synthase
- glycogenin stays inside the newly formed glycogen granule
describe the steps of glycogen synthesis
- glycogenin is a self-glucosylating enzyme that uses UDP-glucose and adds approx. 8 glucose units in tandem to its own tyrosine residue
- glycogen synthase recognizes the precursor and is able to form a1,4 bonds at the nonreducing ends
- the branching enzyme (4:6 transferase) removes a chain of 6-8 glucosyl residues from the nonreducing end by cleavage of an a1-4 bond and attaches it to a non-terminal glucosyl residue by an a1-6 linkage
contrast glycogen degradation in liver vs muscle
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liver:
- glycogen degradation in hepatocytes needs hormonal activation by glucagon and epinephrine which occurs only during fasting and stress
- the main purpose is to increase blood glucose
-
muscle:
- glycogen degradation in skeletal muscle and is activated by Ca during contraction
- in flight and fight situations: epinephrine accelerates muscle glycogen degradation
- the main purpose is to produce ATP
describe the steps of glycogen degradation
describe the regulation of phosphorylation
summarize the covalent modifications of enzymes and activation
- glycogen synthase is activated by dephosphorylation
- protein kinase 1, insulin
- glycogen phosphorylase is activated by phosphorylation
- glycogen phosphorylase kinase
- glycogen phosphorylase kinase is activated by phosphorylation
- PKA, epinephrine
- glucagon only in liver
describe the allosteric regulation of glycogen metabolism in liver and muscle
- Glucose 6-P activates glycogen synthase and inhibits glycogen phosphorylase in liver and muscle
- ATP inhibits phosphorylase in liver and muscle
- glucose inhibits hepatic glycogen phosphorylase
- AMP activates muscle glycogen phosphorylase
describe the steps of glycogen degredation and the coenzyme needed
- glycogen phosphorylase performs phosphorolytical cleavage of glycogen to G1P
- inorganic phosphate is used instead of water
-
PLP is needed for this reaction
- PLP is a coenzyme which is formed from vit. B6
describe the function of the debranching enzyme
- the 4:4 transferase activity forms longer branches
- the 1:6 glucosidase activity cleaves the a(1,6) bond and forms 1 molecule of free glucose
- longer branches with only a(1,4) linkages are again available for glycogen phosphorylase
summarize the function of PKA
glucagon and epinephrine initiate PKA activity
