Glycogen Metabolism Flashcards
What is the blood glucose regulation of glycogen release and what does it lead to?
1) Decreased blood glucose levels
2) Release of glucagon
3) Increased cAMP
4) Increased PKA
5) Decreased Fructose 2,6-bisphosphate
6) Decreased pyruvate kinase
7) Decreased conversion of phosphoenolpyruvate to pyruvate
8) Increased amounts of phosphoenolpyruvate is diverted to the synthesis of glucose
What are the three main sources of blood glucose?
Diet
Degredation of glycogen
Gluconeogenesis
What are the main sources of glycogen?
Skeletal muscle
Liver
What is the function of muscle glycogen?
Muscle glycogen provides a ready source of glucose for the synthesis of ATP during muscle contraction
What is the function of liver glycogen?
Liver glycogen maintains blood glucose levels during fasting
Liver glycogen can maintain blood glucose levels for 10 to 18 hours
Describe the structure of glycogen.
Glycogen is a branched-chain polysaccharide that is made up of alpha-D-glucose monomers
The primary glycosidic bond is an alpha 1-4 linkage
After 8 to 10 residues, there is a branch that contains an alpha 1-6 linkage
How is glycogen synthesized?
Glycogen synthesis is endergonic and requires the input of energy.
Energy for glycogen synthesis comes from ATP and UTP, which reacts with glucose-1-phosphate, forming UDP-glucose, in a reaction catalysed by UDP-glucose pyrophosphorylase.
Glycogen is synthesized from monomers of UDP-glucose by the enzyme glycogen synthase, which progressively lengthens the glycogen chain with (α1→4) bonded glucose.
As glycogen synthase can lengthen only an existing chain, the protein glycogenin is needed to initiate the synthesis of glycogen.
The glycogen-branching enzyme, amylo (α1→4) to (α1→6) transglycosylase, catalyzes the transfer of a terminal fragment of 6-7 glucose residues from a nonreducing end to the C-6 hydroxyl group of a glucose residue deeper into the interior of the glycogen molecule.
The branching enzyme can act upon only a branch having at least 11 residues, and the enzyme may transfer to the same glucose chain or adjacent glucose chains.
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What is glycogenin?
Glycogenin is an enzyme that catalyzes the transfer of glucose from UDP-glucose
How is glycogen broken down?
Glycogen is cleaved from the nonreducing ends of the chain by the enzyme glycogen phosphorylase to produce monomers of glucose-1-phosphate, which is then converted to glucose 6-phosphate by phosphoglucomutase.
A special debranching enzyme is needed to remove the alpha(1-6) branches in branched glycogen and reshape the chain into linear polymer. The G6P monomers produced have three possible fates:
- G6P can continue on the glycolysis pathway and be used as fuel.
- G6P can enter the pentose phosphate pathway via the enzyme glucose-6-phosphate dehydrogenase to produce NADPH and 5-carbon sugars.
- In the liver and kidney, G6P can be dephosphorylated back to glucose by the enzyme glucose 6-phosphatase. This is the final step in the gluconeogenesis pathway.
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Picture of the hormonal regulation of glycogen break down.
What is glycogenolysis?
Glycogenolysis is the breakdown of glycogen(n) to glucose-1-phosphate and glycogen(n-1). Glycogen branches are catabolized by the sequential removal of glucose monomers via phosphorolysis, by the enzyme glycogen phosphorylase
How is glycogenolysis regulated?
Glycogenolysis is regulated hormonally in response to blood sugar levels by glucagon and insulin, and stimulated by epinephrine during the fight-or-flight response.
In myocytes, glycogen degradation may also be stimulated by neural signals.
What is glycogenesis?
Glycogenesis is the process of glycogen synthesis, in which glucose molecules are added to chains of glycogen for storage.
This process is activated during rest periods following the Cori cycle, in the liver, and also activated by insulin in response to high glucose levels, for example after a carbohydrate-containing meal.
What are the steps of glycogenesis?
- Glucose is converted into glucose-6-phosphate by the action of glucokinase or Hexokinase
- Glucose-6-phosphate is converted into glucose-1-phosphate by the action of Phosphoglucomutase, passing through an obligatory intermediate step of glucose-1,6-bisphosphate.
- Glucose-1-phosphate is converted into UDP-glucose by the action of Uridyl Transferase (also called UDP-glucose pyrophosphorylase) and pyrophosphate is formed, which is hydrolysed by pyrophosphatase into 2 molecules of Pi.
- Glucose molecules are assembled in a chain by glycogen synthase, which must act on a pre-existing glycogen primer or glycogenin (small protein that forms the primer). The mechanism for joining glucose units is that glycogen synthase binds to UDPG, causing it to break down into an oxonium ion, also formed in glycogenolysis. This oxonium ion can readily add to the 4-hydroxyl group of a glucosyl residue on the 4 end of the glycogen chain.
- Branches are made by branching enzyme (also known as amylo-α(1:4)→α(1:6)transglycosylase), which transfers the end of the chain onto an earlier part via α-1:6 glycosidic bond, forming branches, which further grow by addition of more α-1:4 glycosidic units.
