Metabolism of glycogen (glycogenesis & glycogenolysis) Flashcards
What is glycogen ? (7)
- Highly branched homopolysaccharide made of alpha-D glucose units
- Linear portion has a(1-4) linkages, branch points have a(1-6) linkages between glucosyl residues
- Branches 8 glucose residues apart
- Storage form of glucose in animals
- Main stores found in liver & muscle
- Well-fed adult liver contains about 100g glycogen (10% of fresh weight)
- Resting muscle contains 400g glycogen (1-2% of fresh weight)
What is the function of glycogen?
- In the absence of a dietary source of glucose, liver glycogen rapidly degraded to glucose which is released into blood
- Liver glycogen; meant for maintenance of blood glucose level; important during fasting
- Muscle glycogen; meant for providing energy for muscle contraction, does not get converted to free glucose (lacks glucose 6-phosphatase)
- Muscle glycogen extensively degraded during strenuous exercise
What is the definition, site sub cellular site and major enzymes of glycogenesis?
Definition: Synthesis of glycogen
Site: Mainly liver & muscle
Subcellular site: cytosol
Requires energy in the form of ATP & UTP
Major enzymes: glycogen synthase
branching enzymeHow is glycogen metabolized , use diagram to explain ? Use slide # 6 (diagram)
Phosphoglucomutase will change the position of the glucose from carbon 6 to carbon 1. The glucose then reacts with UDP- glucose pyrophosphorylase and forms UDP- glucose ( activated glucose) and then it is attached the the hydroxly group of tyrosine of glycogenin ( protein in the liver that acts as a primer for accepting glucose ). Glycogen synthase will add glucose residues forming a1-4 linkages. Non reducing end is the carbon 4 of glucose. Key: glycogen synthase elongates glucose at the non-reducing end. Branching enzyme breaks the a1-4 linkage and the entire unit of sugars are transferred and a a1-6 linkage is formed. As a result there is a branched glycogen.
Why have a branched glycogen?
So alot of glucose can be stored in a short period of time and so the break down can be done simultaneously
Explain the synthesis of Glycogenesis in detail and include all the enzymes used.
- Glycogen synthase can only elongate an existing chain of glucose, requires a primer
- Primer can be a pre-existing glycogen or a protein called glycogenin
- The –OH group on the side chain of a specific tyrosine residue in glycogenin serves as the site where the initial glucose is attached.
- Glycogenin catalyzes the initial few steps of attachment of glucose residues to itself (autoglucosylation)
- The short glucosyl chain (with (14) linkages) produced serves as a primer which is elongated by glycogen synthase
- Glycogenin forms the core of the glycogen granule
- Glycogen synthase adds glucose (from UDPG) to the nonreducing end of primer (C4), creating a(1-4) linkages
- When the glycogen chain is elongated to about 11-15 residues, branching takes place
- Branching enzyme: amylo-4,6 transferase, removes a set of 6 – 8 glucosyl residues from the nonreducing end of glycogen chain, attaches it to another glucosyl residue by (16) linkage
- Breaks a a(1-4) linkage, creates a new (16) linkage
- The resulting new and the old nonreducing ends are further elongated by glycogen synthase
- Additional branches are created by branching enzyme
- A highly branched tree-like structure is formed
- Branching increases number of nonreducing ends, accelerating the rate of glycogenesis (and its breakdown)
The definition, site sub cellular site and end products and major enzymes of glycogenolysis
Definition: Breakdown of glycogen
Site: Mainly liver & muscle
Subcellular site: cytosol
End products:
Liver: glucose
Muscle: glucose 6-phosphate, which then enters glycolysis producing lactate
Major enzymes: glycogen phosphorylase
debranching enzymeExplain the diagram on slide 10 (glycogenolysis)
one by one the glucose residues are being broken by glycogen phosphorylase and the a1-4 linkage and released as glucose-1-phosphate until the oligosacciride( limit dextrin: 4 carbons) is seen.The debranching enzyme comes into action,The 4:4 transferase breaks the a1-4 linkage of the trisaccride and transfers to a 1-4 linkage as a result the terminal glucose is exposed( green). The terminal glucose( green) is broken down by 1:6 glocosidase as free glucose. The linear chain( red) is then broken down by glycogen phosphorylase until it reach the next branch point.
What is the importance of glycogen phosphorylase ?
- glycogen phosphorylase (PLP dependent-> vitamin B6 derivative and required for glycogen phosphorylase ) sequentially removes the glucosyl residues from the nonreducing ends as glucose 1-P by phosphorolysis
- This will continue until 4 glucose residues remain on each chain before a branch point
- Next, “oligo α-[1→4]→α-[1→4] glucan transferase” activity of debranching enzyme, removes a unit containing the three outer glucose residues & transfers it to the nonreducing end of another chain, exposing the 1→6 branch point
- The α-[1,6] glucosidase activity of debranching enzyme releases the free glucose by cleaving the α-[1,6] linkage
- Glycogen phosphorylase continues to act on remaining glycogen
What is the final product of breakdown of glycogen in the liver and muscle and how is the the final product achieved? explain using a flow chart/diagram
The final product of glycogenolysis in the liver is glucose .The final product of glycongenolysis in the muscle is glucose 6-P why? There is a lack of glucose-6-phosphotase
Ans for the diagram in slide 12
What happens to glycogen in the lysosomes? Deficiency of what enzyme causes lysosomal diseases? and what are the names of the diseases?
A small amount of glycogen (1 – 3%) is continuously degraded by the lysosomal enzyme -glucosidase (acid maltase)
Deficiency of this enzyme causes accumulation of glycogen in lysosomes (Pompe disease or type II glycogen storage disease)
In the liver and muscle, when does glycogenesis happen and when does glycogenolysis occur?
glycogenesis accelerates in well-fed state, glycogenolysis increases in the fasting state
In the skeletal muscle, glycogenolysis occurs during active exercise, glycogenesis begins as soon as muscle is at rest
What are Glycogen synthase & glycogen phosphorylase?
How is the regulation of glycogen metabolism accomplished?(2)
regulatory enzymes
Hormonal regulation (by phosphorylation/ dephosphorylation) to meet the needs of the whole body AND Allosteric (by effector molecules) to meet the needs of a particular tissue
- Explain the hormonal regulation of glycogenolysis ( use diagram on slide 15)
- What does a protein kinase do?
- What is the overall effect of glycogen and insulin?
- What is the role of Ca+?
- What is the role of AMP in muscle?
- Glycagon binds to the glucagon receptors in the liver and epinephrine binds to the b-adrenergic receptor in the muscle and the liver. Both result in these result in the activation of G-coupled receptor to activate adenyly-cyclase to produce cAMP ( second messengar).
cAMP will activate protein kinase A by binding to the regulatory subunits of protein kinase A causing the protein kinase A to release the active catalytic subunit . Protein kinase phosphorylates the glycogen phosphorylates kinase B. When the glycogen phosphorylase kinase is phosphorylated, it is active. The glycogen phosphorylase kinase when active will phosphorylate glycogen phosphorylase B into the active form and as a result the glycogen is degraded. There is a cascade of phosphorylations that are occurring
- It phosphorylates a protein
- If insulin is secreted in well feed state , it will phosphodiesterase which will break down the cAMP ( decrease of cAMP)-> less activation of protein kinase-> less phosphorylation of phosphoylase kinase -> less phosphorylation of glycogen phosphorylase
- Insulin also produces protein phosphotase-1 which acts in two levels . It removes the phosphate from the phosphorylase kinase and glycogen phosphorylase making then inactive.
- Insulin causes the removal and inactivation of the phosphorylase ( dephosphorylation)-> prevents glycogenolysis
- Glycogen and epinephrine will activate the cAMP which will activate the protein kinase-> activate the phosphorylase kinase -> acitvate the glycogen phosphorylase switching it on -> promoting glycogenolysis
4. Ca is released during muscle contraction. The Ca will bind to the calmodium ( calcium modulated protein) subunit of phosphorylase kinase b, activating it without phosphorylation. Phosphorylase kinase can then activate glycogen phosphorylase, causing glycogen degradation. Ca is a allosteric regulator
5. Under extreme condition of anoxia and depletion of ATP, AMP activates glycogen phosphorylase b without it being phosphorylated
Explain the hormonal regulation of glycogenesis and draw it out
During fasting ->Glucagon & epinephrine (receptors in liver) and during exercise -> Epinephrine (receptors in muscle)-> increased cAMP -> phosphorylation of glycogen synthase (less active) -> decreased glycogenesis
In well-fed state, insulin promotes dephosphorylation & activation of glycogen synthase through protein phosphatase; decreased cAMP through phosphodiesterase -> increased glycogenesis
