Glycogen metabolism Flashcards
What is glycogen?
Polysaccharide storage of glucose in the body.
Where is glycogen stored?
Predominantly in the liver.
In muscles.
A little in the brain.
When glucose is dissolved in water are the molecules homogenous?
No: some will be in a linear form others in one of the two variations of the cyclic form (a or b D glucopyranose). At equilibrium ~ 36% a , 64% b and 0.02 linear.
Which isomer of glucose is capable of forming glycogen?
a - D - glucose
What are the steps of glycogen catabolism / glycogenolysis?
Glycogen -> glycogen(n-1) + glucose 1-phosphate by glycogen phosphorylase
Glucose 1-phosphate -> glucose 6-phosphate by phosphoglucomutase (6’ carbon phosphorylated then 1’ carbon has phosphate rmoved)
Glucose 6-phosphate can enter glycolysis.
How does glycogen form?
α 1’ - 4’ linkages between α-D-glucoses form linear sequences. α 1’-6’ linkages to form a branch.
How is glycogenolysis regulated?
Glucagon (liver) and adrenaline (muscle) trigger cAMP cascades.
Ligand arrives at receptor and activates G protein. the alpha subunit has its bound GDP phosphorylated to GTP to make in its active form and allow the alpha subunit to dissociate from the G protein complex. The active alpha subunit will then bind to adenylate cyclase (another membrane protein) activating it. Once active adenylate cyclase catalyses the formation of cAMP from ATP. cAMP activates protein kinase A (PKA) which in turn activates glycogen phosphorylase.
How does cAMP cascade activate glycogen phosphorylase?
Phosphorylation of the serine hydroxyl residue in glycogen phosphorylase.
What two enzymes digest glycogen and were?
Glucose phosphorylase digest 1 - 4 linkages
Glucosidases digests the 1 - 6 linkages at the branches via hydrolysis.
How does the liver increase blood glucose levels?
glucose 6-phosphate cannot be circulated in the CVS only glucose can so it must be dephosphorylated by glucose 6-phosphatase
What happens to the products of glycogenolysis when produced 1. in the liver 2. in muscles/brain.
- -> glucose -> CVS
- -> Glycolysis pathway
How is glucose added to glycogen.
The enzyme UDP-glucose phosphorylase gives UDP-glucose from glucose 1-phosphate and UTP. UDP glucoses are the units of glucose that are able to be added to glycogen. UDP-glucose is added to glycogen via glycogen synthase, UDP is released as glucose joins the chain. For a UDP glucose to be added in this way the glycogen has to already have a chain of 4 glucosyl residues.
How does a glycogen molecule initially form?
Glycogenin (a homo dimer) receives the first glucosyl residue from UDP-glucose. The 1’ carbon of the glucose bonds covalently to the OH group of a tyrosine residue in glycogenin. The first few glucoses are added by autocatalysis.
How do the branches of glycogen form?
Glycosyl 4,6 transferase is the branching enzyme and it transfers a block of 7 residues to the chain forming a new alpha 1-6 linkage.
Why is glycogen a good energy store? Why is it bad?
It can be mobilised very rapidly by only 2 reactions/enzymes.
The catabolic enzymes are very sensitive to regulation by hormones, stress and muscle contraction. The branched structure creates a large reactive surface area allowing many enzymes to bind at once.
The bad:
Glucose is hydrophilic and therefore water associates with glycogen granules increasing the overall weight and bulk of glycogen.
