Glycogen Synthesis Test II Flashcards
Three key steps of Glycogenesis?
- Trapping and activation of Glucose by Hexo/Glucokinase which catalyzes to G6P.
- Elongation of Glycogen with Glycogen Synthase
- Branching with Glucosyl transferase
When is glycogenesis favored?
Favored in the fed state with an increase in Blood glucose levels, increased insulin, increased ATP
In glycogenesis what form is glycogen synthase and glycogen phosphorylase in?
Synthase is dephosphorylated and active
GP is dephosphorylated and inactive
What type of bond links glucose molecules linearly?
a-1,4-glycosidic linkages
What type of bond creates branches in glycogenesis?
a-1,6-glycosidic linkages
How does glucose get to the UDP- Glucose stage in glycogenesis?
Glucose is phosphorylated by hexokinase/gluco into G6P.
G6P is reversibly isomerized to Glucose-1-p by Phosphoglucomutase (PGM)
G1P is transfered to UTP by Uridine diphosphage-glucose pyrophosphorylase which generates UDP Glucose
What two substrates make UDP-Glucose?
G1P + UTP
How does elongation of a glycogen primer occur?
Glycogen synthase the rate limiting enzyme catalyzes transfer of glucose from UDP-Glucose to non reducing end of glycogen chain.
How does branching of glycogen chains occur?
When the chain reaches about 11 long 7 residues are broken off at the a-1,4 link and re attached by an a-1,6 link by Glucosyl(4:6) transferase
What is the rate limiting enzyme of glycogenesis?
Glycogen Synthase
What does branching do to the glycogen?
Increases its solubility and increases the rate it can be made and broke down
Describe steps of glycogenolysis.
Glycogen –>G1P –> G6P–> can go to Glycolysis, broke further into glucose by liver, or into the Pentose phosphate pathway
What stimulates Glycogenolysis?
Low blood glucose levels, high glucagon
What is the RLS of glycogenolysis?
Glycogen being broke to Glucose-1-phosphate by glycogen phosphorylase
What occurs during glycogenolysis?
Glycogen broke to G1P by Glycogen Phosphorylase
G1P converted to G6P using phosphoglucomutase
How does the phosphoglucomutase enzyme work? Glycogenolysis
A phosphoryl group is transferred from the enzyme to substrate at position 6, there is already one at position 1. Next the phosphate at position one is removed and G6P is left.
How does the branch transfer and release of glucose occur? Glycogenolysis
Transferase moves 3 of the four remaining glucose to the non reducing end of chain forming a14 bond. Then Debranching enzyme (a-1,6-glucosidase) cleaves the a16 bond to release the remaining glucose. Glucose is then phosphorylated by hexokinase.
What is G6P’s fate in the liver and muscle in glycogenolysis?
Muscle cells don’t have glucose-6-phosphatase so G6P cannot leave the cell. Liver does have this enzyme though, so it converts G6P to glucose for release into the blood stream.
If acid maltase, found in lysosomal glycogenolysis, is defective what disease results?
Pompe disease (GSDII) Can give IV of recombinant human a-glucosidase
If there is a deficiency in a-1,6-glucosidase (debranching) enzyme what occurs and what disease?
GSD III/Cori
Glycogen molecules with large number of short branches
Deficiency in glucosyl (4:6) transferase (branching) what disease results?
Anderson Disease/ GSD IV
long chain glycogen few branches death by 5, cirrhosis
Deficiency in muscle glycogen phosphorylase?
GSD V/ McArdle Disease
Rate limiting step of glycogen breakdown, un able to supply muscles with enough glucose, muscle cramps weakness, myoglobinuria
Deficiency in liver glycogen phosphorylase?
GSD VI/Hers Disease
Prevents glycogen breakdown in liver-hepatomegaly and low blood glucose levels
