20 - Glycogen Metabolism & Hormonal Control of Glucose Metabolism Flashcards
What is glycogen?
Reversible storage of glucose, can be made into glucose-1-phosphate by glycogenolysis
Glucose-1-phosphate can be made into glycogen by glycogen synthesis
Glycogen is a highly branched polymer of glucose with various non-reducing ends, branch points and reducing ends
What is glycogen synthesized from?
glucose-1-phosphate, which is from glucose-6-phosphate
What type of bonds in glycogen are straight chain? Branch points?
Straight chain: alpha 1-4 glycosidic bonds
Branch point: alpha 1-6 glycosidic bonds
What enzyme converts glucose-6-phosphate to glucose-1-phosphate? (so that G1P can be converted to glycogen)
phosphoglucomutase
What are the steps in the synthesis of glycogen?
- Activation of glucose by linkage to UTP. Glucose-1-phosphate reacts with UTP to form UDP-glucose (this costs energy when pyrophosphate is released)
- Formation of alpha 1-4 glycosidic bonds as the chain is lengthened by glycogen synthase (regulatory step of glycogen synthesis)
- Generation of branch points by glycogen branching enzyme. Whole chunks of glycogen chain are added onto another chain forming alpha 1-6 glycosidic bonds
What is the regulatory step of glycogen synthesis?
The lengthening of the chain by glycogen synthase forming alpha 1-4 glycosidic bonds
What are the steps of glycogen degradation?
- Glycogen phosphorylase cleaves alpha 1-4 bonds by substitution of a phosphate group (phosphorolysis). Breakdown until 4 linked glucose units are left on branch
- Transferase/debranching enzyme transfers remaining 3 glucose units to another terminal of glycogen (alpha 1-4 bond)
- alpha 1-6 glucosidase removes the final glucose
- Phosphoglucomutase converts glucose-1-phosphate form the glycogen phosphorylase reaction to glucose-6-phosphate
- Glucose-6-phosphatase dephosphorylates G6P to glucose (nearly exclusively in the liver, not in muscle!)
Why does glycogen not get broken down in muscles?
Because muscles don’t have glucose-6-phosphatase to convert it to glucose. G6P couldn’t be transported to the liver anyways because it is phosphorylated (and therefore can’t leave the cell)
Glycogen-derived glucose, however, is only used for muscle activity, it is not distributed throughout the body.
What is glycogenesis?
Energy/glucose storage as glycogen
What is glycogenolysis?
Mobilizing energy/glucose from glycogen when needed in muscles (though the process happens in the liver)
How is glycogen metabolism regulated?
Phosphorylation activated glycogen phosphorylase but inactivates glycogen synthase, making sure that the same signal stimualtes one direction and inhibits the other so that reactions are reciprocally controlled and futile cycles don’t occur
Control of this phosphorylase activity happens with allosteric regulation, where glycogen breakdown is stimulated by AMP (low energy) and inhibited by ATP (high energy) and the product (G6P)
But in the liver we need a second level of regulation for integration with the needs of the rest of the body, regulation by external signals is used.
The external signal is phosphorylase kinase, which is only inhibited by glucose. It phosphorylates the phosphorylase to inhibit its ability to stimulate breakdown of glycogen (so that more glycogen can be made form the excess glucose)
Because phosphorylase kinase is only regulated by glucose, glycogen can be broken down to glucose even if the cell has sufficient energy (allowing it to provide glucose for muscles)
Does phosphorylase activity increase or decease when blood glucose increases?
decreases, phosphorylase activity acts to stimulate breakdown of glycogen
Glycogen synthase on the other hand becomes more active when blood glucose increases
What is the hormonal response to low blood glucose?
- Glucagon secreted from pancreas
- Glucagon stimulates cAMP formation which activates protein kinase A
- PKA initiates a phosphorylation cascade to activate glycogen phosphorylase and inhibit glycogen synthase
- Breakdown of glycogen to glucose to supply glucose to the rest of the body
Only the liver, not the muscle reacts to glucagon. Muscle keeps glycogen for activity, no coordination with blood glucose levels.
What is the hormonal response to high blood glucose?
- Insulin secretion from pancreas
- Insulin activates phosphoprotein phosphatase in muscle and liver
- Dephosphorylation and activation of glycogen synthase
- Dephosphorylation and inhibition of glycogen phosphorylase
- Storage of glucose as glycogen in muscle and liver
In muscle, allosteric regulation of glycogen phosphorylase is important. In the liver, most regulation is through phosphorylation.
Insulin does not directly inhibit adenylate cyclase and its activation of PKA, it inhibits secretion of glucagon and epinephrine.
How does glucagon and epinephrine stimulate breakdown of glycogen?
Glucagon and epinephrine activate adenylate cyclase to synthesize cyclic AMP (cAMP). cAMP triggers a phosphorylation cascade to activate glycogen phosphorylase (which will then cause the breakdown of glycogen)
