Describe the general structural features of glycogen
-has alpha-glucose monomer
-it is a homopolysaccharide
-highly branched chain
-alpha 1-4 glycosidic linkage predominates in straight chain, after 8-10 glycosyl residues branches occur via alpha 1-6 glycosidic linkage
-branches occur more in the center tha
Name the two tissues with the highest concentrations of glycogen
liver and skeletal muscle
Describe the different roles of muscle and liver glycogen
-muscle glycogen serves as a source of energy for itself during strenous exercise
-Liver glycogen is used to buffer and maintain overall blood glucose level
Describe the role of glycogen degradation the in restoring serum glucose during fasting.
during fasting, blood glucose level is low and had to be restored by breaking down stored glycogen in liver via glycogenolysis decreasing liver glycogen
Identify the substrate and product for glycogen synthase and glycogen phosphorylase
primed glycogenin + UDP glucose to growing glycogen chain + UDP/ Glycogen + inorganic P to G1P and remaining glycogen (limit dextrin)
Identify the role of vitamin B6 in glycogen degradation and the role of phosphoglucomutase
-active form of vitamon B6 is PLP which acts as coenzyme for glycogen phosphorylase
-phosphoglucomutase interconverts G6P and G1P
Contrast the roles of liver or muscle glycogen stores contribution to serum glucose
liver glucose contributes to blood glucose level by breaking down stored glycogen in response to low serum glucose, muscle barely contributes to blood glucose due to absence of glucose 6 phosphatase
Indicate the role of glucose 6-phosphatase in serum glucose restoration
present only in the LIVER, it cleaves P from G6P to form free glucose which is released into the blood
Identify the general features (including bond types and which end) of the steps in glycogen synthesis (glycogenesis)
-G6P to G1P via phosphoglucomutase
-G1P + UTP to UDP-Glucose + PPi via UDP-glucose pyrophosphorylase
-PPi + H20 to Pi via pyrophosphate AND
-8 UDP-glucose and glycogenin-OH to primed glycogen + UDP via self glucosylation @ reducing end to act as template
Identify the general features (including bond types and which end) of the steps in glycogen degradation (glycogenolysis)
-Glycogen pyrophosphorylase cleaves a1-4 bonds until 4 glycosyl residues before branch points (limit dextrin) @ nonreducing end using PLP as coenzyme to release G1P
-Glucosyl 4:4 transferase removes 3 of 4 glucoside residues and transfers them to non-redu
Identify the rate-limiting enzymes for both glycogen synthesis and degradation
for glycogen synthesis, the rate limiting enzyme is glycogen synthase and for glycogen degradation, it is glycogen phosphorylase
briefly describe receptor mediated regulation of glycogen phosphorylase and synthase in alpha adrenergic recepto
epinephrine binds to receptor, PLC activated which cleaves PIP2 to DAG and IP3 which stimulates release of Ca from ER, Ca together with DAG activates PKC which phosphorylates synthase and inactivates it
Ca binds to form camoldulin-Ca complex which activat
Discuss the role of cyclic AMP, protein kinase A, AMP, PKC and calmodulin the regulation of glycogen metabolism
-cAMP activates PKA which phosphorylates and activates GP but inactivates GS
-AMP activates GP without phosphorylation
-PKC inactivates GS (presence of epinephrine)
-camoldulin upon Ca binding activates phosphorylase kinase which activates GP
Identify the allosteric regulators of glycogen synthase and phosphorylase in liver and muscle
GS
-Liver= G6P(+)
-Muscle= G6P(+), Ca(-)
GP
-Liver= glucose(-), ATP(-), G6P(-)
-Muscle=AMP(+), Ca(+), G6P(-), ATP(-)
Describe the general mechanism by which insulin activates glycogen synthase and inactivates phosphorylase kinase
stimulates phosphodiesterase which then removes cAMP to 5'AMP and activates phosphoprotein phosphatase which dephosphorylates GS to make it ACTIVE and glycogen phosphorylase kinase which is unable to phosphorylate GP making it INACTIVE or dephosphorylates
Describe the effects of glucagon(liver) and epinephrine(muscle and liver) on glycogen synthesis and degradation.
binds to receptor, activate AC, change ATP to cAMP, activates PKA, phosphorylate glycogen synthase to make it INACTIVE and phosphorylates glycogen phosphorylase kinase which then phosphorylates GP to make it ACTIVE
Identify the enzyme defect associated with Pompe's (type 2) and primary organ
-lysosomal storage disease: lysosomal a1-4 glucosidase/acid maltase
-abnormal vacoules filled with excess glycogen in lysosome
-primarily affects liver and cardiac muscle!
-massive cardiomegaly
Identify the enzyme defect associated with McArdle's (type 5) and primary organ
-skeletal muscle glycogen phosphorylase
-skeletal muscle!
-high glycogen content in muscle
-reduced lactose level after exercise
-weakness and cramps after exercise
-myoglobinemia and myoglobinuria
Identify the enzyme defect associated with Her's (type 6) and primary organ
-liver glycogen phosphorylase
-liver!
-high liver glycogen content
-hepatomegaly
-mild hypoglycemia
Identify the enzyme defect associated with Von Gierke's type 1a and primary organ
-glucose 6 phosphatase
-liver via increase glycogen stores!
-hepatomegaly and renomegaly
-severe hypoglycemia