5C- Formation/Degradation of Glycogen Flashcards
What is the structure of glycogen in the liver and muscle?
A branched glucose polysaccharide composed of chain of glucosyl units linked by a-1,4 bonds with a-1,6 branches every 8-10 residue
What is the function of glycogen in the liver?
First and immediate source to maintain blood glucose during fasting or exercise
What is the function of glycogen in the muscle?
Used to generate ATP for muscle contraction
What is the role of glucose-6-phosphatase?
ONLY IN THE LIVER. It hydrolyzes G6P to glucose.
Give the steps of glycogen synthesis from glucose.
Glucose –hexokinase–> G6P G1P –> reacts with UTP –UDPglucose phosphorylase–> UDP-glucose –> glycogen synthase transfers glucose residues from UDP glucose to the non-reducing ends of the glycogen primer
How does the glycogen form branches?
Basically, you lengthen the polysaccharide chains of a preexisting glycogen molecule at an alpha-1,4-glucose. When the chain reaches 11 residues in length, a transferease cleaves 6-8 residues and glucose synthase attaches it to a glycosyl unit by an alpha1,6 bond.
Why do we branch glycogen?
Increase sites for synthesis & degradation
Enhance the solubility of the molecule
Why is glucose-6-phophatase important in the liver?
Glucose 6-phosphatase is important because it is turns Glucose 6 phosphate into glucose to maintain the blood glucose in our body
What is the role of glycogen phosphorylase in glycogen breakdown?
Removes glucose residues, one at a time from the nonreducing ends of glycogen molecule
It add phosphate to the anomeric carbon of the terminal glycosidic bond to cleave a-1,4 bonds, producing glucose 1 phosphate
It can continue to hydrolyze a-1,4 linkages until it reaches a point four glucose residue from an a-1,6branch
What is glycogen phosphorylase activated by?
It is activated by covalent modification (opposite of glycogen synthase)and is referred to as glycogen phosphorylase A and when it is inactive, it is referred to as glycogen phosphorylase B
What is the role of the debrancher enzyme in glycogen breakdown?
The last glucose unit at the branch point, which is linked a-1,6 bond, is hydrolyzed by a-1,6-glucosidase forming free glucose
Name the enzyme, organ, and clinical manifestations of Type Ib (Von Gierkes) disease.
E- glucose 6-phoshatase. O-liver. M-hepatomegaly, grwoth failure, fasting hypoglycemia.
Name the enzyme, organ, and clinical manifestations of type II (Pompe) disease.
E-lysosomal alpha-glucosidase. O-all organs with lysosomes. M-muscle hypotonia, cardiac failure, death, myopathy, muscular dystrophy.
Name the enzyme, organ, and clinical manifestations of type III disease.
E-debrancer enzyme (amylo 1,6-glucosidase). O- liver, SkM, heart. M- fasting hypoglycemia, hepatomegaly, myopathic features.
Name the enzyme, organ, and clinical manifestations of type IV (Anderson) disease.
You enter get stuck in the matrix, Neo. E-branching enzyme (amylo 4,6 glucosidase). O- liver. M- hepatosplenomegaly, death.
Name the enzyme, organ, and clinical manifestations of type V (McArdles) disease.
E- muscle glycogen phosphorylase. O- SkM. M- excercise induced muscular pain, cramps, and progressive weakness, someitmes with myoglobinuria.
How does epinephrine regulate glycogen metabolism in the liver and SkM?
Degradation of liver glycogen is activated by epinephrine as well as blood glucose level(glucagon). Epinephrine is released in response to exercise, hypoglycemia or other stress situations in which there is an immediate demand for blood glucose. Epinephrine will also activate skeletal muscle glycogenolysis.
How do changes in insulin and glucagon during the fasting states regulate metabolism of glycogen in the liver?
An increase in glucagon and decrease in insulin during fasting state initiates a cAMP-directed phosphorylation cascade
phosphorylation of glycogen phosphorylase to an active enzyme (degradation stimulated)
phosphorylation of glycogen synthase to an inactive enzyme (synthesis inhibited)
How does the change in 2nd messengers in the glucagon pathway activate glycogenolysis?
Protein kinase A phosphorylates phosphorylase kinase making it active (using ATP)
Then phosphorylated phosophorylase kinse phosphorylates glycogen phosphorylase B making it active to glycogen phosphorylase A. (Using ATP and phosphate from ATP is transferred onto the activated glycogen phosphorylase A) & glycogenolysis is stimulated
Inhibition of glycogen synthase and activation of glycogen phosphorylase, glycogen is degraded to glucose 1-phosphate
What is the mechanism of epinephrine when it acts through β-agonist receptors?
Epinephrine acting at the β receptors, transmits a signal through G-protein to adenylate cylcase
Adenylate cyclase will increase cAMP and activate protein kinase A (similar to glucagon)
What is the mechanism of epinephrine when it acts through α-agonist receptors?
Gq pathway to activate Ca:CAM complex, which activates both phosphorylase kinase (activates glycogen phosphorylase) and CAM-dependent protein kinase (inactivates glycogen synthase)
What pathway does insulin activate in the liver?
Insulin will activate hepatic PP-1 through the insulin receptor tyrosine kinase phosphorylation cascade
Hepatic PP1: major protein phosphatases involved in glycogen metabolism.
It removes phosphate groups from phosphorylase kinase, glycogen phosporylase and glycogen synthase.
Insulin also may activate the phosphodiesterase that coverts cAMP to AMP
Decreasing cAMP and inactivating protein kinase A
What is the role of Ca++ in muscle and liver glycogen metabolism?
- Sarcoplasmic reticulum release Ca2+
- Ca2+ comes together with calmodulin= Ca2+Calmodulin
- Ca2+Calmodulin activates phosphorylase kinase
