Glycogen Metabolism Flashcards
Define:
Starch
A polysaccharide made up of straight-chain and branched glucose polymers.
It comes in two key forms, amylose (straight-chain) and amylopectin (branched-chain).
Define:
Glycogen
A stored form of of fuel made up of many branching molecules of glucose.
It is a type of polysaccharide stored in the liver and skeletal muscle.
Define:
Glycogen metabolism
The breakdown or synthesis of stored glucose molecules in their polysaccharide form.
Breakdown is triggered during exercise or periods of fasting by glucagon levels rising.
What kind of linkages are found in starch?
α-linkages
Which kind of starch polymer is straight-chained?
Amylose
What kind of linkages make up amylose?
α-1,4-glycosidic linkages
This gives its straight-chain structure.
Which kind of starch polymer is branch-chained?
Amylopectin
What kind of linkages does amylopectin contain?
Both α-1,4-glycosidic and α-1,6-glycosydic linkages.
The α-1,6-glycosidic linkages occur every ~24-30 glucose units, and give rise to its branched structure.
What is the key difference between α-linkages and β-linkages for humans?
α-linkages are readily digested, whilst β-linkages are not.
What is the main stored form of glucose/carbohydrates in plants?
Starch
For humans, most of our intake of glucose is in the form of starch from our food, such as potatoes.
True or False:
Glycogen is similar to amylopectin of starch, but less branched.
False
Glycogen IS similar to amylopectin, but is MORE branched.
Where is glycogen most concentrated?
In the liver.
(5-6% by mass)
It is also found in the muscles at up to around 1-2% by mass.
What role does α-amylase serve in digestion?
It randomly cleaves α-1,4-linkages (of polysaccharides).
However, it cannot cleave a linkage within four units of each branch point.
What is one major restriction of α-amylase’s cleavage function?
It CANNOT cleave linkages within four units of a branch point and leaves behind highly-branched ‘limit dextrins’.
In plants, ** β-amylase** is able to cut off 2-glucose units.
Where is α-amylase found in animals?
The saliva and pancreatic juice.
How are the ‘limit dextrins’ left behind by α-amylase processed afterwards?
In a two-step reaction carried out by a debranching enzyme.
Describe:
The TWO reactions carried out by the debranching enzyme to further break down ‘limit dextrins’ left behind by α-amylase.
- Transfer of a trisaccharide (taking branch and adding to end of chain).
- Cleavage of the remaining α-1,6-linkage (via α-1,6-glucosidase activity).
After this, α-amylase is able to continue cleaving α-1,4-linkages along the straight chain.
Which enzyme is vital for metabolism of tissue glycogen?
Glycogen phosphorylase
It cleaves and phosphorylates at the non-reducing end (i.e. phosphorolysis).
What is the reaction catalysed by glycogen phosphorylase, and what is the end product formed?
Phosphorolysis of the non-reducing end of a glycogen residue to form α-D-glucose-1-phosphate.
This reaction has a negative ΔG due to the high intracellular concentration of phosphate.
What happens to the α-D-glucose-1-phosphate resulting from the glycogen phosphorylase catalysed reaction after it is formed?
Phosphoglucomutase converts it into glucose-6-phosphate.
Which can be fed into the remaining steps of glycolysis.
How are the two monosaccharides, galactose and mannose related to glucose?
They are epimers.
Thus, after a few extra steps and conversions, they too can be fed into the glycolytic pathway, as seen in the above diagram.
Which enzyme reaction needs to be bypassed for glycogen synthesis to occur?
The reaction carried out by glucose phosphorylase, since it is spontaneous/exergonic.
This is done by activating glucose.
Which enzyme is responsible for activating glucose to bypass glucose phosphorylase in glycogen synthesis?
UDP-glucose pyrophosphorylase
What is the product of the glycogen synthetic reaction catalysed by UDP-glucose pyrophosphorylase?
An activated sugar nucleotide called UDP-glucose.
TWO phosphates are cleaved off UTP during this reaction.
Describe:
Glycogenin, and its association with UDP-glucose.
Glycogenin is a protein dimer whose tyrosine sidechain covalently binds with the first glucose molecule from UDP-glucose.
After the first glucose is bound to glucogenin, how are remaining UDP-glucose molecules added to form glycogen?
Glycogen synthase transfers glucose from UDP-glucose to the C4 hydroxyl at the non-reducing end of the forming glycogen chain.
This forms α-1,4-linkages.
What is the role of the branching enzyme in glycogen synthesis?
It introduces α-1,6-linkages and thus branches to the growing glycogen polysaccharide.
Once it finds a chain of >11 units, it cleaves 6-7 off and transfers it to a C6 hydroxyl of the same/a different chain.
Carbohydrate metabolism is highly regulated by…
…hormones.
When is insulin secreted?
When blood-glucose levels are high.
What does insulin stimulate in regards to hormonal control of glycogen metabolism?
Glycogen synthesis
This is in order to lower blood-glucose levels.
Where is insulin synthesised?
In β cells of the pancreas.
it is then secreted into portal veins.
What transporter is responsible for glucose uptake into muscle, liver, and adipose cells?
GLUT4
How is glycogen synthase activated?
- Inactivation of glycogen synthase kinase 3 (GSK3).
- Allosteric activation via glucose-6-phosphate.
Insulin triggers a cascade that leads to the inactivation of GSK3.
Which TWO hormones have the opposite effects to insulin in regards to carbohydrate metabolism?
Glucagon & adrenaline.
(adrenaline is also known as epiniephrine).
What do glucagon and adrenaline stimulate in regards to hormonal control of glycogen metabolism?
Glucose metabolism / glycogen breakdown.
(i.e. glycolysis).
They simultaneously ‘switch-off’ gluconeogenesis.
Where does glucagon come from, and what kind of molecule is it?
It is a peptide hormone secreted from the pancreas.
Where does adrenaline (epinephrine) come from, and what kind of molecule is it?
It is a catecholamine derived from tyrosine, and released from the adrenal glands.
What cell types does glucagon act on?
Liver & adipose.
What cell types does adrenaline (epinephrine) act on?
Muscle & liver.
What is the second messenger that both glucagon and adrenaline (epinephrine) act via?
cAMP
(cyclic AMP).