Flashcards in  Lecture 8: Glycogen Metabolism Deck (87)
whenglycogen reaches 11 residues, a fragment of the chain [about 7 residues long] is broken off at an alpha-1,4 link and reattached elsewhere through an alpha-1,6 link by activity of what enzyme?
Glucosyl (4:6) transferase
The new branching point must be at least ___ residues away from a preexisting branch
What are the 2 reasons for branching of glycogen?
1. Increases solubility
2. Increases number of terminal non-reducing ends
Increases rate at which glycogen can be synthesized and degraded
Key enzyme in glycogen synthesis
2 forms of glycogen synthase
One form in the liver
One form in the muscles and other tissues
Active [non-phosphorylated] form = a form
Inactive [phosphorylated] b form
Interconversion mediated by covalent modifications [fine-tuning role]. What is this regulation?
Regulation of glycogen synthesis
Glycogen synthesis is regulated by what enzyme that phosphorylates?
Glycogen synthase kinase
What hormones affect GSK?
Insulin and PKA
Allosteric: glucose-6-phosphate [powerful activator]- stabilizes the R state
Synthesis and degradation of glycogen pathways are:
Allows for independent regulation.
The 2 key enzymes to glycogen metabolism:
Glycogen phosphorylase (GP)
Both are the rate limiting steps of degradation/synthesis
Both enzymes are regulated by reversible phosphorylation but effects are in opposite directions
How do glucagon and epi control both glycogen breakdown and synthesis?
What is the centerpiece intermediate in glycogen metabolism?
Stimulate glycogen breakdown
Glycogen synthase function:
Stimulate glycogen synthesis.
What is favored in fed state: glycogenolysis or glycogenesis:
B/c BG and insulin elevated and cellular ATP is high- signal of high energy
-when glycogen synthesis is favored, the DEPHOSPHO form of glycogen synthase (active) and glycogen phosphorylase(inactive) are predominant
What is favored in fasting state: glycogenolysis or glycogenesis:
B/c BG levels are low and glucagon levels are high and cellular Ca++ and AMP are elevated -like exercise
-when glycogen degradation is favored PHOSPHORYLATED forms of glycogen synthase (inactive) and glycogen phosphoylase (active) are predominant
Release of _____ by beta cells of pancreas
Binding to its receptor tyrosine kinase
Activation of signaling cascade
Regulation by insulin; insulin
4 key proteins in Regulation by insulin:
-GLUT 4 [glu transporter]
-Protein kinase B [PKB]
-Protein phosphatase 1 [PP1]
-Glycogen synthase kinase 3 [GSK3]
Net result of insulin
Activation of glycogen synthase and inactivation of glycogen phosphorylase
Formation of insulin receptor complex i activated by:
Protein kinase B
This also translocates GLUT to membrane
What phosphorylates PP1 (active) and GSK3 (inactive)
What is function of PP1
Active PP1 dephosphorylates glycogen synthase (activates it)
Dephosphorylates glycogen phosphorylase (GP-deactivating it)
-Reduced sensitivity to insulin
-Called insulin resistance
-Mutations in insulin receptor and/or downstream signaling proteins
-Down-regulation in receptor levels triggered by elevated insulin [leading 2 endocytosis and degradation of the insulin receptor].notreplaced by translation
What type disorder is this?
Type II diabetes
What is the glucose sensor in the liver cells?
Glucose has what effect when bound to liver GP (a)?
Deactivates it and allows glycogen synthase to begin storing energy...b/c it is in fed state or high energy
McArdle syndrome is a disease of:
Limited ability to perform strenuous exercise b/c of painful muscle cramps; otherwise patient is normal.