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Glycogen Metabolism
Lecture on Sept 30,2011- joined with glycogenesis
28
Biochemistry
Professional
10/21/2011

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Term

What is UDP- Glucose?

 

How is it synthesized?

Definition

Source of all glucosyl residues that add to the glycogen molecule

 

UDP-Glucose is synthesized from G1P and UTP by UDP-glucose pyrophosphorylase

Term
Why is glycogen necessary if gluconeogenesis can occur in liver and kidney?
Definition
Gluconeogenesis is a slow process, and glycogen can be metabolized quickly
Term
Glycogen Synthesis
Definition

Starts with Glycogenin, which accepts glucose residues from UDP-Glucose. This starts to build a chain.

 

The chain elongates and every 6 or 8 links will lead to a branch.

The use UDP is converted back to UTP

Term
What is the benefit of branching in a glycogen molecule?
Definition
more branches mean more reducing ends to add on, quicker mobilization and quicker sytnehsis because there are more starting sites.
Term
2 main places glycogen is synthesized and stored
Definition
Liver and skeletal muscle
Term
Primary product of glycogenolysis
Definition
G1P, done by breaking 1-4 or 1-6 bonds (shortening of the chains)
Term
How are glycogen chains shortened?
Definition
Glycogen phosphorylase cleaves bonds down to 4 residues on each chain before a branch point. This is as far as it can degrade
Term
Glycogen phosphorylase
Definition
rate-limiting enzyme in glycogenolysis
Term
Oligo gucatransferase
Definition

de-branching enzyme

 

removes outer 3 or 4 residues at a branch

Term
Where do we see G6Pase?
Definition

In the last step on gluconeogenesis

 

It converts G6Pase to glucose. Glucose is then transported by GLUT 7 to the cytosol, then out to blood to maintain blood glucose levels

Term
What happens to G6P in muscle?
Definition
There is no G6Pase in the muscle, so G6P enters glycolysis to provide ATP
Term
alpha (1-4) glucosidase
Definition

lysosomal enzyme that degrades about 1-3% of all glycogen

 

Mechanism of action is unknown

 

Deficiency of this enzyme can cause glycogen accumulation in lysosome vacuoles

Term
Pompe Disease
Definition

abnormal storage of glycogen. Glycogen builds up in the lysosomal vacuoles which alter the lysosome function.

 

Disease like this can range from mild disorders to fatality (fatality usually in infants)

Term
Regulatory Pathways of Glycogen Synthesis and Degradation
Definition

1. glycogen synthase and glycogen phosphorylase are allosterically controlled

 

2.  hormonal regulation (epinephrine)

Term
2 paths for glycogenolysis
Definition
Cytoplasm and lysosomes
Term
How is glycogen degraded in the muscle
Definition

Muscle contraction releases Ca++ in S, which binds calmodulin, which activates phosphorylase kinase

 

(occurs in anorexia or ATP depletion)

Term
Definition
Glucose binds & inhibits glycogen phosphorylase a, becomes a better substrate for protein phosphatase 1.
 
In muscle, insulin increases uptake of glucose so­ G6P increases, (a potent glycogen phosphorylase inhibitor)
Term
Lysosomal degrading of glycogen
Definition

by alph(1>4)glucosidase, deficiency will make glycogen accumulate in vacuoles (Pompe disease)

 

Term
Glycogen Storage Disease
Definition

defect in enzyme for glycogen synthesis/degrading

 

accumulate in tissues or have abnormal structure, can be fatal to mild

Term
Glycogen Synthesis/Degrading tightly regulated by...
Definition

1. glycogen synthae/glycogen phosphorylase allosterically controlled

 

2. paths of synthesis, degrading hormonally regulated

Term
Allosteric regulation of glycogen synthesis/degrading
Definition

well fed state: glycog synthase activated by high G6P, glycog phosphorylase inhibited by high G6P & ATP

 

degrading in muscle by calcium binding calmodulin, activate phosphorylase kinase.

glycog phosphorylase active in muscle increases AMP (anorexia and ATP depletion events)

Term
Hormonal regulation
Definition

Ep signals needed for glucose/energy

Gs > AC > cAMP > PKA, phosphorylates inactive b form of phosphorylase kinase

 

 

Term
cAMP directed glycogen inhibition
Definition

Gs leads to AC then cAMP then PKA, phosphorylates and inactivates glycogen synthase.

 

Term
4 things to promote glycogen synthesis in liver
Definition

G6P, Insulin (+synthase)

 

Glucose, ATP (- phosphorylase)

Term
3 things to promote glycogenolysis in liver
Definition

Glucagon

Epinephrine

Caffeine

(+ phosphorylase) > phosphorylation of phosphorylase= activation

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