Flashcards in Lecture 21: Glycogen Coordination & Fuel Metabolism Deck (63)
What is the NTP usually used in glycogen synthesis? Which phosphoanydride bond is attacked?
The α one
Describe the de novo glycogen synthesis pathway.
PRIMER SYNTHESIS catalyzed by glycogenin:
1. Tyr residue attacks C1 of NDP-glucose (NDP released)
2. Glucosyltransferase activity: (-OH) on C4 attacks C1 of another NDP-glucose (NDP released)
--> done until primer has 8-10 glucose
BRANCHING catalyzed by glycogen branching enzyme:
1. Straight-chain series cleaved off
2. Energy released from
α-1,4 bond used to make α-1,6 linkage and heat released
Is glycogen branching enzyme regulated by hormones?
Describe the activation of glycogen phosphorylase.
Phosphorylase kinase phosphorylates glycogen phosphorylase b with 2 ATP = glycogen phosphorylase a + 2 ADP
Describe the deactivation of glycogen phosphorylase.
Phosphoprotein phosphatase-1 (PP1) hydrolyzes the 2 phosphate groups on glycogen phosphorylase a with 2 H2O = glycogen phosphorylase b + 2 Pi
What are the 4 stimulators of phosphorylase kinase in liver and muscle? How does each work?
1. Glucagon (through PKA)
2. Epinephrine (through PKA)
1. Epinephrine (through PKA)
2. Ca2+ (allosteric)
3. AMP (allosteric)
Describe the activation of phosphorylase kinase by glucagon/epi.
Protein kinase A (PKA) phosphorylates phosphorylase kinase b with 2 ATP = phosphorylase kinase a + 2 ADP
Describe the deactivation of phosphorylase kinase.
Phosphoprotein phosphatase-1 (PP1) hydrolyzes the 2 phosphate groups on phosphorylase kinase a with 2 H2O = phosphorylase kinase b + 2 Pi
How is PKA regulated?
Hormonally via cAMP -
Describe the activation of glycogen synthase.
Phosphoprotein phosphatase-1 (PP1) hydrolyzes the 2 phosphate groups on glycogen synthase b with 2 H2O = glycogen synthase a + 2 Pi
Describe the deactivation of glycogen synthase.
Glycogen synthase kinase-3 (GSK-3) using 3 ATP/PKA using 1 ATP/CKII using 1 ATP/phosphorylase kinase using 2 ATP, can ALL phosphorylate glycogen synthase a = phosphorylase kinase a + 2 ADP
What inhibits GSK-3?
What is phosphoprotein phosphatase-1 (PP1) stimulated by? Explain the last 2
2. G6P (from G1P broken down by glycogen phosphorylase)
3. Glucose (from glucose broken down by debranching enzyme)
What is dephosphorylation of glycogen synthase by phosphoprotein phosphatase-1 (PP1) inhibited by?
What are the 3 fuels that skeletal muscle can use?
3. Ketone bodies
Main fuel source of adipose tissue?
Where are FAs mainly synthesized?
At what glucose blood concentration does neural dysfunction occur?
Below 2.5 mM
What fuel does the liver use?
How does the liver avoid using glucose? What other purpose does this serve?
It uses glucokinase (hexokinase 4) instead of hexokinase, which has a high Km and lowe Vmax, so it does not compete with other organs for glucose when glucose is low
Also allows prevention of glucose phosphorylation before it goes through GLUT2
What is necessary to cross the BBB?
What are the 2 places where we find glycogen?
Can muscles break down glycogen for glucose homeostasis?
After how many hours are glycogen stores COMPLETELY depleted?
After how long are the muscle glycogen stores depleted?
Depends on level activity, but after enough starvation hours it's broken down so that the lactate can be converted to alanine for gluconeogenesis
Which phosphate linkage contains more energy: G1P or G6P?
Is the conversion of G1P to G6P reversible? Why?
Yes because the difference in energy between G1P and G6P is small
How much of the muscle glycogen can be RAPIDLY mobilized?
About 50% before branching
Why does debranching enzyme transfer a triose and then hydrolyze the 1,6 bond instead of debranching the whole 4 glucose?
Thermodynamics: alpha 1,4 bonds contain more energy than alpha 1,6 so it would be endothermic to cleave the 1,6 to form a new 1,4 bond