Glycogen metabolism Flashcards
How much glycogen is stored in the body ?
200 - 300 grams
Why do animals store energy as glycogen ?
- the controlled breakdown and synthesis of glucose helps to maintain blood glucose levels in the body
- it is important because glucose is the main fuel for the brain
- glucose from glycogen is readily mobilised
- glycogen can provide energy under anaerobic conditions
What is the normal level of blood glucose ?
5 mM
What are the 2 main sites of glycogen storage ?
- liver
- skeletal muscle
it can also be stored as insoluble granules in the cytosol but this is not good
Describe the structure of glycogen
- it is an alpha 1,4 linked polymer
- it is coiled with an alpha 1,6 linkage every 10 residues
Describe the pathway of glycogen synthesis
1) glucose is taken up from the blood by facilitated diffusion using transport proteins
2) hexokinase will phosphorylate glucose into glucose 6 - phosphate in order to trap it in the cell
- in the liver this process is carried out by glucokinase because it is not inhibited by glucose 6 - phosphate
3) glucose 6 - phosphate is then converted to glucose 1 - phosphate by the enzyme phosphoglucomutase
4) the glucose 1 - phosphate is activated by the enzyme UDP - glucose pyrophosphorylase which produces UDP - glucose
5) glycosyl units are added to the non reducing end of the glycogen molecule to form an alpha 1,4 glycosidic bond using using the enzyme glycogen synthase
- a primer is required for this to happen and this is controlled by the enzyme glycogenin
6) a branching enzyme will break an alpha 1,4 linkage and reattach it with an alpha 1,6 linkage
What are the transport proteins used to take up glucose in the glycogen synthesis pathway ?
- GLUT 2 is present in the liver and beta cells of the pancreas
- it is a low affinity transporter and so glucose will only be taken up when there is a high concentration of it
- GLUT 4 is present in skeletal muscle and fat cells
- this transporter is mostly present in the cytosol and so insulin will send signals and allow for the presentation of GLUT 4 on the surface
What is the technical term for glycogen synthesis ?
glycogenesis
Describe the enzyme glycogen synthase
- key regulatory enzyme of glycogen synthesis
- regulated by covalent modification
- phosphorylation by protein kinase A will convert the active form of the enzyme into the inactive form
- insulin will activate a phosphatase enzyme which will dephosphorylate the enzyme to activate it
- glucose 6 - phosphate will bind allosterically to the inactive form of the enzyme and make it more active
Describe the pathway for the breakdown of glycogen
1) glycogen is converted into glucose 1 - phosphate by glycogen phosphorylase
- it removes glucose residues at the non reducing end and a debranching enzyme is required
2) glucose 1 - phosphate is converted into glucose 6 - phosphate by phosphoglucomutase
3) the fate of glucose 6 - phosphate is dependent on the tissue
What is the technical term for glycogen breakdown ?
glycogenolysis
Describe the enzyme glycogen phosphorylase
- key regulatory enzyme of glycogen breakdown
- responds to hormones such as insulin, adrenaline and glucagon
- it is controlled by covalent modification
- also controlled by allosteric regulation but this is different for different tissues :
- in muscle : AMP acts a positive allosteric effector increasing activity of this enzyme but if lots of ATP then negative allosteric effector and decreases activity of the enzyme
- in liver : glucose controls the activity of this enzyme - glucose is a negative allosteric effector because if glucose levels are high we don’t want glycogen breakdown so decreases the activity of this enzyme
How is glycogenesis and glycogenolysis regulated ?
- regulated by hormone triggered cAMP cascade which acts through protein kinase A
Describe the role of protein phosphatase 1
- activated by a signal cascade brought about by high levels of insulin
- reverses the effect of protein kinase A and so dephosphorylates glycogen synthase activating it
What are glycogen storage diseases ?
inherited genetic defects which means that enzymes needed to degrade stored glycogen are defective
