Glycogen Synthesis Flashcards
*• Know the roles of glycogen synthase and the branching enzyme in the construction of
glycogen (i.e. figure 25.2)
Glycogen synthase is the key REGULATORY enzyme in glycogen synthesis. It will transfer a glucose moiety from UDP-glucose to the C-4 TERMINAL residue of a glycogen chain to form an alpha-1,4 glycosidic bond.
*Understand how glycogen synthesis and glycogen breakdown are reciprocally regulated
The phosphorylation of both processes have an opposite effect.
In glycogen synthesis: synthase is active in unphosphorylated form and inactive in the phosphorylated form.
Whereas in glycogen degradation: glycogen phosphorylase is activated when PHOSPHORYLATED and inactivated when unphosphorylated.
*Be aware of the differences in glycogen metabolism between the liver and muscle
In liver -high blood glucose levels stimulate glycogen synthesis, inhibit glycogen breakdown. Glucose will bind to phosphorylase to inhbit it and allow PP1 to dephosphorylate glycogen phosphorylase and synthase (activate synthesis)
In muscle- protein kinase A will phosphorylate gM, remove it and phosphorylate inhbitor which will bind and inactivate PP1 (converts glycogen degradation to synthesis).
if pp1 inactivated, it will allow degradation to still be active.
*Understand the metabolic fates of individuals suffering from type I and type II diabetes.
Type I diabetes- Insulin not produced at all, no way for insulin to initiate cascade to activate glycogen synthesis (constant degradation, leading to excess sugar)
Type II diabetes- Inuslin resistance; signaling pathway not responsive (failure to inactivate GSK, leading to degradation still active- excess sugar) can be lethal
What is the purpose of UDP-glucose in glycogen synthesis? What enzymes synthesizes it? Is this reaction irreversible or reversible?
UDP-glucose (Uridine Diphosphate Glucose) is the glucose donor in glycogen synthesis.
UDP-glucose is synthesized by UDP-glucose pyrophosphorylase, which converts Glucose 1-phosphate and UTP to make UDP-glucose.
This reaction is subsequently deemed irreversible by hydrolysis of pyrophoshpate (PPi and H20 > 2 Pi)
What makes UTP a special molecule?
UTP is a high energy phosphoryl transfer. In the reaction to make UDP glucose, once, pyrophosphate is cleaved by water, it will shift the reaction to the RIGHT.
Reaction: Glucose-1-phosphate and UTP > UDP-glucose and PPi
PPi and H20 > 2 Pi
What structures does Glycogen synthase require to extend glucose chains and how are these structures made?
Glycogen synthase requires an oligosaccharide of glucose residues as a primer.
The primer is synthesized by GLYCOGENIN, which is a dimer of two identical subunits.
Each subunit of glycogenin generates an oligosaccharide of glucose residues 10-20 molecules long.
Glycogen synthase will then extend this primer.
What enzyme only cleaves alpha 1, 4 linkages in glycogen synthesis? What enzyme cleaves 1,6 linkages? How does this help?
Glycogen synthase can ONLY cleave alpha-1,4 linkages.
A branching enzyme generates branches by cleaving alpha-1,4 linkage and taking a block of about 7 glucoses and synthesizing and alpha, 1-6 linkage. Synthase will then extend both non-reducing ends followed by more branching.
What is the purpose of branching in glycogen synthesis?
Branching increases solubility, and increases the ends for synthesis and degradation.
When is glycogen synthase active versus in inactive? What must occur for the enzyme to be in active state?
What is the key regulatory process for glycogen synthase?
Glycogen synthase is usually INACTIVE in the PHOSPHORYLATED b form, and is usually ACTIVE when in the UNPHOSPHORYLATED a form.
Key regulatory process for glycogen synthase:
conversion of the b form in the T state to the ACTIVE R state of the b form by BINDING GLUCOSE 6-PHOSPHATE.
What two factors inhibit glycogen synthesis? Compare these factors to glycogen breakdown. Also mention the purpose of Protein kinase A in glycogen synthesis.
What two enzymes phosphorylate glycogen synthase?
Epinephrine and Glucagon signaling pathways INHIBIT glycogen SYNTHESIS.
However, epinephrine and glucagon STIMULATE glycogen BREAKDOWN.
Protein kinase A (PKA) phosphorylates Glycogen synthase to form glycogen synthase b and INHIBIT glycogen synthesis.
Glycogen Synthase kinase (GSK) also phosphorylates and INHIBITS glycogen synthase
When levels of glucagon and epinephrine GO UP, do you want to turn on synthesis of glycogen or turn it off?
TURN OFF. Increase in glucagon and epinephrine will want to inhibit glycogen synthesis, so they can be able to gain glucose form glycogen breakdown. Glucagon- is when glucose levels drop, hence it will like to activate glycogenolysis or glycogen breakdown to release glucose (that is stored in glycogen)
compare and contrast what occurs in glycogen synthesis or glycogen breakdown in scenarios after eating a meal or Resting; or Exercise, or glucose needed.
After a meal, or resting, glucose and Insulin levels will be high, so you will want to store glucose into glycogen storage form by stimulating glycogen synthesis (unphosphorylating glycogen synthase).
activating Protein kinase A (phosphorylate/inactivate synthase) will inhibit glycogen synthesis.
Exercise/or fasting state: glucose is needed so glycogen breakdown will be activated in order to release glucose from storage form glycogen. If you phosphorylate glycogen phosphorylase, it will activate glycogen breakdown. if protein phosphatase dephosphorylates phosphorylase, it will inhibit breakdown.
How is protein phosphatase 1 regulated in Muscle?
Regulation of protein phosphatase 1 in muscle occurs in two steps:
1. Protein kinase A will phosphorylate GM, which which will dissociate the GM catalytic subunit from its substrates (PP1 and inhibitor) in glycogen particle.
2. Protein kinase A will then phosphorylate inhibitor subunit and INACTIVATE catalytic unit PP1.
This describes the breakdown of glycogen in muscle which is induced by exercise or fasting.
what is the function of Protein phosphatase 1 in glycogen metabolism?
Protein phosphatase 1 shifts glycogen metabolism from degradation mode to SYNTHESIS mode.
PP1 removes phosphoryl groups from glycogen synthase b, converting it into more active a form.
PP1 also removes phosphoryl groups from phosphorylase kinase and glycogen phosphorylase, inhibiting glycogen DEGRADATION.
