glycogen metabolism

Question 1

What happens to excess glucose?

Answer 1

Is stored in the liver and muscles as glycogen

Question 2

glycogen definition

Answer 2

a highly branched polymer of alpha glucose that is soluble and can be broken down rapidly when required, acting as a readily accessible storage form for glucose

Question 3

what is the process of breaking down glycogen called?

Answer 3

glycogenolysis

Question 4

what mediates glycogenolysis?

Answer 4

glycogen phosphorylase

Question 5

what is the mediation in response to?

Answer 5

low energy signals, low blood glucose and during the fight of flight response

Question 6

what is the opposite process of glycogenolysis and what mediates it?

Answer 6

glycogenesis, mediated by glycogen synthase and in response to high blood glucose

Question 7

where is glycogen found?

Answer 7

found in the cytoplasm as granules ranging from 10-40nm

Question 8

brief structure of glycogen

Answer 8

primary glycosidic bond is an alpha 1-4 linkage, and then the branches are alpha 1-6 linkage

every 8-10 residues contain a branch with a 1-6 linkage

Question 9

where is glycogen stored and relative percentages?

Answer 9

liver -10% of liver mass is glycogen

muscle- 2% of muscle mass is glycogen

200g in muscle, 70g in liver

Question 10

what are the different functions of glycogen in each storage location? + how are they regulated

Answer 10

in liver, used to increase blood glucose= liver needs to respond to the blood glucose level

in muscle, used directly to form ATP for muscle contractions- muscle needs to respond to energy demand

Question 11

why is glycogen not used as the sole storage, instead of using fat too?

Answer 11

fat has a higher energy yield than glucose produced from glycogen- 38kj/g compared to 17kj/g

fat is insoluble so doesn’t bind to water, whereas glycogen binds to water, so the resulting body weight would be significantly higher as for every g of glycogen 2g of water is stored

Question 12

why is glycogen present?

Answer 12

maintain a constant blood glucose concentration for red blood cells, the brain and renal medukka

need to be able to produce ATP rapidly in the absence of oxygen

Question 13

benefits of a branched structure

Answer 13

offers multiple end points for rapid degradation

branched structures increase the solubility meaning that it is easier to store close to the site of utilisation, whereas lipids need to be transported by albumins

Question 14

mechanistic definition of glycogenolysis

Answer 14

the catabolism of a polymer of glycogen during sequential removals of glucose monomers via phosphorolysis, catalysed by glycogen phosphorylase

Question 15

glycogen phosphorylase function

Answer 15

glycogen phosphorylase phosphorylates a glucose subunit in the alpha 1-4 linear chain, which results in the production of glucose-1-phosphate, not free glucose

Question 16

what does the formation of G-1-P result in?

Answer 16

glucose is already activated and its trapped in the cell, as the phosphate means that the glucose cannot diffuse out or move through specific GLUT transporters

Question 17

what occurs in the phosphorolysis reaction and how does the structure of the enzyme accommodate for this?

Answer 17

the reaction requires water to be excluded from the active site, which is achieved by having the active site buried in a narrow cleft of the enzyme

Question 18

what happens afterwards to the glucose-1-phosphate molecule?

Answer 18

glucose-1-phosphate is converted to glucose-6-phosphate

catalysed by the enzyme phosphoglucomutase

Question 19

differences in the liver and muscles

Answer 19

the glucose-6-phosphate produced by phosphoglucomutase can be used directly in muscles

in the liver, the glucose 6-phosphate is converted to glucose inside the smooth endoplasmic reticulum, mediated by glucose 6-phosphatase

Question 20

structure of glycogen phosphorylase

Answer 20

a homodimer, where each subunit has a binding site and an active site

binding site connected to the active site by a narrow crevice about 30 amino acids long

Question 21

what is a difficulty for glycogen phosphorylase and how is it overcome?

Answer 21

it can only act on linear 1-4 alpha chains and will immediately come to a halt four residues from a 1-6 chain

a debranching enzyme is used to straighten out the chain

Question 22

what is the debranching enzyme in eukaryotes? + functions

Answer 22

a transferase- transfers three glucose residues from the four residue glycogen branch to a nearby chain

and an alpha 1-6 glucosidase- cleaves the remaining alpha 1-6 bond to release a molecule of glucose and glycogen

Question 23

regulation in the liver explained

Answer 23

most phosphorylase is in the a-relaxed state

phosphorylase A can be transitioned to the T state when there are high concentrations of glucose, thus preventing glycogenolysis

liver only takes up glucose when blood glucose is high, due to GLUT 2

liver phosphorylase is insensitive to AMP/ATP

Question 24

regulation in the muscles explained

Answer 24

in resting skeletal muscle, the majority of phosphorylase is in the inactive b-tense state

it becomes active-R when high concentrations of AMP are detected, encouraging glycogenolysis

high concentrations of ATP and glucose-6-phosphate prevent the change, preventing glycogenolysis

Question 25

Why is AMP a good signalling molecule?

Answer 25

very small concentration, around 10 mM, compared to a very large ATP, thus only a small change in ATP causes a large change in AMP

Question 26

covalent modification of phosphorylase + regulation

Answer 26

phosphorylase B in the muscles can be phosphorylated to phosphorylase a by phosphorylase kinase

in muscle cells, phosphorylase kinase is activated by adrenaline

in liver cells, phosphorylase kinase is activated by glucagon,

Question 27

what is the benefit of converting more phosphorylase B into phosphorylase A?

Answer 27

greater concentrated of phosphorylase enzymes will be in the R state, so more will be converting the glycogen into glucose

will all be sensitive to glucose now

Question 28

how is phosphorylase kinase activated ?

Answer 28

1. adrenaline/glucagon bind to the Gs beta adrenergic receptor/glucagon receptor, activationg adenyl cyclase
2. adenyl cyclase then converts ATP to cAMP
3. cAMP activates PKA
4. PKA converts phosphorylase kinase b to phosphorylase kinase a
5. phosphorylase kinase a converts glycogen phosphorylase b to glycogen phosphorylase a which then catalyses glycogenolysis

Question 29

allosteric regulation of phosphorylase kinase explained

Answer 29

phosphorylase kinase can be activated allosterically by calcium

calcium binds to the sigma subunit, calmodulin

Question 30

glycogenesis definition

Answer 30

the process of glycogen synthesis, where glucose monomers are added to existing chains of glycogen for storage

Question 31

stages of glycogenesis

Answer 31

1. glucose- 6-phosphate is converted to glucose 1-phosphate, catalysed by phosphoglucomutase
2. glucose 1-phosphate then converted to UDP-glucose and a PPi using a UTP molecule, catalysed by UDP-glucose pyrphosphorylase
3. UDP-glucose plus an existing glycogen molecule adds an extra glucose molecule to the glycogen, catalysed by glycogen synthase, releasing UDP

Question 32

what drives the forward reaction?

Answer 32

glucose 6 phosphate to 1-phosphate is reversible

driven forward by the cleavage of pPi by pyrophosphatase

Question 33

glycogen synthase energy cost + function

Answer 33

forms 1 1-4 linkages to grow glycogen molecules

cost is 1 molecule of ATP in the form of UTP to UDP

Question 34

What does continued synthesis require + at which point?

Answer 34

when the chain is more than 11 residues long, the branching enzyme takes 7 residues and joins them to an internal site via an alpha 1-6 glycosidic bond

the new bond must be at least 4 residues away from another branching point

Question 35

what happens before glycogen synthase takes over + when?

Answer 35

initially, when there is no starting glycogen molecule glycogenic, a glycosyltransferase, acts as the primer and catalyst for the addition of the first few glucose residues

it is formed of two identical subunits that add glucose units from UDP-glucose to one another

once the chain is 8 residues long, the glycogen synthase takes over

Question 36

what two forms does glycogen phosphorylase exist in?

Answer 36

an active a state

inactive b state

Question 37

regulation of glycogen phosphorylase

Answer 37

becomes inhibited when phosphorylated, activated when dephosphorylated

PKA, signalled by glucagon and adrenaline, phosphorylates phosphorylase kinase which will phosphorylate glycogen phosphorylase activating it increasing glucose production

the PKA will phosphorylate glycogen synthase, so inhibiting it, so less glycogen is unnecessarily synthesised, reducing glucose storage

Question 38

what is this type of regulation called?

Answer 38

reciprocal regulation

Question 39

insulin’s role in reciprocal regulation

Answer 39

activates protein phosphatase 1 which:

• dephosphorylates glycogen synthase, thus activating it- more glycogen formed
• dephosphorylates glycogen phosphorylase, deactivating it

inbits glycogen synthase kinase, which reduces the phosphorylation of glycogen synthase

Question 40

different types of glycogen storage disease explained

Answer 40

type 1- Von Gierke’s Disease-glucose 6-phosphatase deficiency - no glucose 6-phosphatase, so the G6P formed in glycogenolysis cannot be converted to glucose, massive glycogen accumulation , low blood glucose, enlarged liver and kidneys

type III- both liver and muscle glycogen is abnormal, mutation in the debranching enzyme, results in an increased amount of glycogen with short outer branches

type V- deficiency in muscle phosphorylase- painful cramps, increase in pH due to breakdown of phosphocreatine and increase in ADP