Green - Glycogen Metabolism Flashcards
How is glycogen stored?
Large cytostolic granules
Complex contains enzymes that synthesize, degrade, and regulate
What major enzymes or hormones control glycogen metabolism?
Insulin and Glucagon
What type of linkages are found in glycogen?
Structure
1-4 linked glucose with 1-6 branches
Structure:
Reducing and Non-Reducing Ends
Where does addition/remobal occur in glycogen?
Addition/Removal of glucose residues occur at non-reducing ends
What are three major enzymes of synthesis and breakdown of glycogen?
- Glycogen Phosphorylase
- Glycogen Debranching Enzyme
- Phosphoglucomutase
Glycogen Phosphorylase
Removes glucose from non-reducing ends
Requires pyridoxal phosphate as co-factor
Enzyme stops when reaches four glucose molecules from (α1-6) branch point
Further degradation requires glycogen debranching enzyme
Glycogen Debranching Enzyme
Removes branches–two major functions
- Transferase activity moves 3 glucose molecules from branch to non-reducing end
- Glucosidase activity removes remaining glucose molecule
Phosphoglucomutase
Converts G1P to G6P
Glucose 6-phosphatase
Where is it expressed?
Conversion of G6P to Glucose
Expressed in liver/kidney, NOT muscle and adipose tissue
Where does glycogen synthesis and breakdown occur?
Liver and skeletal muscle
What is the starting point for glycogen synthesis?
Starts w/glucose 6-phosphate; converted to glucose 1-phosphate by phosphoglucomutase
UDP-glucose Pyrophosphorylase
G1P converted to UDP-glucose
Glycogen Synthase
Adds glucose residues to non-reducing end of glycogen
Glycogen Branching Enzyme
Adds (α1-6) branches (opposite of debranching enzyme)
What does initiation require?
Requires primer
- usually preformed (α1-4) polyglucose chain or branch having at least 8 glucose residues
- Glycogenin Protein acts as both primer and enzyme
Glycogenin Protein
Acts as primer and enzyme in glycogen synthesis initiation
Regulation of Glycogen Phosphorylase?
Two subunits
a = catalytically active
b = less active
Regulated by phosphorylation
active = phosphorylated
inactive = not phosphorylated
Phosphorylase B Kinase
Phosphoprotein Phosphatase 1 (PP1)
Phosphorylase B Kinase: Phosphorylates glycogen phosphorylase to ACTIVATE
PP1: Dephosphorylates glycogen phosphorylase to INACTIVATE
Activators of Glycogen Phosphorylase
Inhibitors of Glycogen Phosphorylase
Activators: Epinephrine, Ca2+, AMP, Glucagon
Inhibitors: ATP, G6P, Insulin
What can act as glucose sensor in liver?
Glycogen Phosphorylase
Glucose Levels Low = Glycogen Phosphorylase A
Glucose Levels High = Glycogen Phosphorylase B
Glycogen Synthase
Two forms:
a = active
b = inactive
Regulation by phosphorylation
active = unphosphorylated
inactive = phosphorylated
Glycogen Synthase regulation
Activators: Glucose, G6P, Insulin
Inhibitors: Epinephrine, Glucagon
High and Low blood glucose:
Glycogen Breakdown / Glycogen Synthesis / Glycolysis
High Blood Glucose:
Decrease Glycogen Breakdown, Increase Glycogen Synthesis, Increase Glycolysis
Low Blood Glucose:
Increase Glycogen Breakdown, Decrease Glycogen Synthesis, Decrease Glycolysis
How is carbohydrate metabolism regulated in muscle?
Muscle uses glycogen only for own use
When active, requires ATP generated by glycolysis–muscle lacks enzymatic machinery for gluconeogenesis
What type of receptors do muscle cells lack?
Muscle cells lack glucagon receptors
Muscle isozyme of pyruvate kinase NOT phosphorylated by PKA
Muscle cells not inhibited by high cAMP
Hypoglycemia
No glycogen
Hyperglycemia
Too much glycogen, builds up in tissues