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C1-64 Glycogen Metabolism I
Reno SMASH!
13
Biochemistry
Professional
10/24/2010

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Term

 

 

 

Glycogen

Definition

Glycogen serves as storage carbohydrate in animals, insects and fungi
Glc residues in a-1,4 linkage- tens of thousands per molecule (up to 100 million Da molecular weight)
Heavily branched (a-1,6 branchpoints 8-12 residues apart) to allow rapid mobilization of Glc by sequential removal of monomers from many non-reducing ends
In animals, glycogen accumulates in most tissues but major accumulation in liver and muscle- 1-2% wet weight resting muscle, 6-8% wet weight “fed” liver

Term

 

 

 

Why store fuel as a glucose polymer rather than fat?

Definition

-Muscle cannot mobilize fat as rapidly as glycogen.

-Fat cannot be metabolized anaerobically.

-Animals cannot use carbons from most fatty acids for Glc synthesis, so fat metabolism alone is not adequate to maintain blood Glc levels.

Term




Why store glucose as a polymer?

Definition

1.  Reserve in [glycogen]intracellular is only ~ 0.01 uM; same amount of reserve if stored as Glc monomers would require 0.4 M Glc in cytosol, which would cause a significant osmotic pressure problem

2.  Retaining Glc in cells requires phosphorylation to Glc-6-P; if stored as Glc monomers would cause serious ionic strength problem

 

Term




UDP-Glc formation is catalyzed by ?

Definition

Glc-1-P uridylyl transferase

 

Reaction requires 1 UTP

UTP is energetically equivalent to ATP due to nucleoside diphosphate kinase reaction:

UDP  +  ATP <-> UTP  +  ADP

=> 1 ATP is required for each Glc residue added to glycogen

Term




Glycogen synthase

Definition

-catalyzes addition of Glc from UDP-Glc to growing chain


-can form a-1->4 but not 1->6 (branch) linkages 


-cannot catalyze de novo glycogen synthesis

Term




Glycogenin

Definition

-a self glucosylating enzyme that generates a glycogen “primer”

Glycogenin catalyzes covalent linkage of Glc to its own Tyr194
Up to seven additional Glc residues are linked to the first.

Glycogenin-Glc
8 primes glycogen synthesis

Term

 

 

 

Glycogenin and glycogen synthase act together to form the main chain

Definition

1.1st Glc is transferred to glycogenin
2.Glycogen synthase joins the complex
3.Linear polymer (n~8 Glc) elongated on glycogenin
4.Glycogen synthase extends and dissociates from glycogenin
5.Branching occurs; glycogen synthase may dissociate and act elsewhere on the molecule, glycogenin remains covalently bound

Term




How does branching occur?

Definition

Glycosyl-(1,4->1,6)-transferase, or branching enzyme, moves a terminal segment of ~ 7 residues to a branch position

Energy of a-1,4 bond hydrolysis drives a-1,6 bond formation

Branching: Pros

  Increases number of non-reducing ends for digestion

  Increases density of polymer

  Increases hydration/solubility of polymer

Term




Liver glycogen 

Definition

stores allow maintenance of blood Glc


Glycogen is stored in the fed state, and Glc from glycogen is exported in fasting state to maintain blood Glc

Term




Muscle glycogen 

Definition

-are used to fuel activity


-Glycogen is stored after meals and during inactivity


-Glycogen is used as a major source of Glc during activity


Remember, fasting state does NOT deplete muscle glycogen for weeks, whereas exercise depletes it in hours 

Term

 

 

 

Glucose-6-Phosphate

Definition

-is an allosteric activator of glycogen synthase

 

-Activates glycogen synthase ONLY in the phosphorylated (less active) state

Term

 

 

 

Hormonal signals determine phosphorylation state of glycogen synthase.....

Definition

-Insulin and glucagon are peptide hormones secreted by pancreatic b and a cells, respectively, in response to blood Glc levels
-When blood Glc is high, pancreatic cells secrete insulin, whereas secretion of glucagon is inhibited
-When blood Glc falls, pancreatic cells no longer release insulin, and secretion of glucagon increases
-Liver cells have cell surface receptors for insulin and glucagon that have different signaling mechanisms to provoke opposite responses

Term

 

 

 

Phospoglucomutase

Definition

-turns glucose-6-phosphate to glucose-1-phosphate

 

 

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