glycogen metabolism in muscle & liver Flashcards
1
Q
what are some key facts about glycogen?
A
- polysaccharide: storage form of glucose in the body
- stored as granules predominantly in liver and muscle as an energy reserve
- glycogen is formed from dietary glucose by the process of glycogenesis
- liver glycogen is utilised to maintain plasma glucose levels between meals, whereas muscle glycogen is required to sustain muscle contraction
- glycogen is degraded between meals in the liver by gylcogenolysis pathway to produce glucose-1-phosphate which can be converted to free glucose and exported into the bloodstream to maintain plasma glucose levels or can be broken down in the muscle to provide the energy to support muscle contraction
2
Q
what is the structure of glycogen?
A
- found in the form of granules within cells
- highly branched polysaccharide of glucose consisting of linked glucose molecules with a branch every 8-14 glucose residues
- important to provide large number of ends at which phosphorylase and glycogen synthase can act to ensure rapid breakdown and resynthesis
3
Q
what linkages are used to form glycogen?
A
alpha-1,4 and alpha-1,6 linkages
4
Q
what is mobilisation?
A
when cells switch on the breakdown of stored glycogen very rapidly using a combination of signals
5
Q
what is the mechanism of glycogen breakdown?
A
- the alpha-1,4 linkages are broken down by phosphorolysis, catalysed by glycogen phosphorylase
- it removes single units from non-reducing ends of glycogen to form glucose-1-phosphate
- phosphorolysis is analogous to hydrolysis
- ATP is not involved in this reaction
6
Q
how does glycogen degradation work?
A
- phosphorylase can only bring alpha-1,4 linkages up to within 4 glucose units from a branch point
- transferase activity of the debranching enzyme removes 3 residues from the branch and transfers them to the end of another chain in an alpha-1,4 linkage
- the single glucose unit left at the branch is removed by the action of the alpha-1,6 glycosides activity of the debranching enzymes
- the chain can then be broken down by phosphorylase until it meets the next branch point
7
Q
how does cleaving of the alpha-1,6 linkages at branch points work?
A
- the alpha-1,6 linkages are broken by the alpha-1,6-glucosidase enzyme activity of the debranching enzyme
- it cleaves the bond to form free glucose by hydrolysis and doe not involve phosphate
8
Q
summarise the process of glycogenolysis
A
- occurs in response to low glucose in the plasma or muscle contraction
- major enzyme responsible for controlling the rate of breakdown is glycogen phosphorylase which breaks the bond between the alpha-1,4 linked glucose reduces by the addition of phosphate to produce glucose-1-phosphate
- phosphorylase cannot break alpha-1,6 bonds and therefore breakdown also requires a debranching enzyme to complete the removal of alpha-1,6 glucose links which is a hydrolysis reaction and produces glucose
- in muscle the glucose-1-phosphate enters glycolysis, after conversion to glucose-1-6-phosphate to produce energy to sustain contraction
- it cannot be exported to the blood as mucked lacks glucose-6-phosphatase
- in liver it is converted to glucose and exported into the bloodstream to maintain plasma glucose levels
9
Q
how does glycogen synthesis start?
A
- glycogen synthase can add glucose units only to a pre-existing chain of more than 4 glycosyl residues
- the primary function is carries out by a protein, glycogenin
- UDP-glucose donates the first glycosyl residue and attaches it to the amino acid tyrosine in the glycogenin
- glycogenin extends the glucose chain by up to 7 additional residues from UDP-glucose via alpha-1,4 linkages
10
Q
how doe branches work with glycogen?
A
- glycogen synthase extends the chain in alpha-1,4 linkages by cannot make branches
- branching enzyme transfers a bloc of 6 residues from a growing chain to create a net branch with alpha-1,6 linage
- the new branch does not form with 4 residues of a preexisting brach
11
Q
how is glycogen as an energy store?
A
- glycogen is a good energy store because it can be mobilised very rapidly
- the enzymes phosphorylase and glycogen synthase are very sensitive to regulation by hormones, stress and muscle contraction
- the branched structure provide a large number ends at which the polymer can be added or broken down
- it is a bad store because glucose is hydrophilic and associates with water increasing the overall weight and bulk
12
Q
describe the process of allosteric regulation of phosphorylase
A
- glycogen phosphorylase in muscle is subject to allosteric regulation by AMP, ATP and glucose-6-phosphate
- AMP (present when ATP is depleted during muscle contraction) activates phosphorylase
- ATP and glucose p-6-phosphate which both compete with AMP binding inhibit phosphorylase: they are signs of very high energy levels
- thus, glycogen breakdown is inhibited when ATP and glucose-6-phosphate are plentiful
13
Q
describe the process of allosteric regulation of glycogen synthase
A
- glycogen synthase is allosterically activated by glucose-6-phosphate
- thus, glycogen synthesis is activated when glucose-6-phosphate is plentiful
14
Q
describe the process of covalent modification: regulated glycogen metabolism
A
- mediated by the addition (and removal) of a phosphate group
- addition of a phosphate group is known as phosphorylation and is catalysed by protein kinases
- this is reversible modification; removal of phosphate groups is catalysed by protein phosphates
15
Q
describe how phosphorylase is activated by cAMP-dependent phosphorylation
A
- the cAMP cascade results in phosphorylation of a hydroxyl group in a serine residue of glycogen phosphorylase which promotes transition to the active site
- the phosphorylated enzyme is less sensitive to allosteric inhibitors, thus even if cellular ATP levels and glucose-6-phosphate are high, phosphorylase will be activated
