Glycogenolysis (Tissue glycogen catabolism)

Question 1

Tissue Glycogenolysis Step 1

Answer 1

1) O-glycosidic (α1->4) bonds are broken by phosphorolysis from the nonreducing ends.
-Phosphorolysis is catalyzed by the glycogen phosphorylase (same enzyme in liver and muscles).
-The reaction stops 4 glucose units before a (α1->6) branch.
2) Generating Glucose-1-phosphate

Question 2

Tissue glycogenolysis (catabolism) Step 2

Answer 2

Transfer of 3 glucose molecules (trisaccharide) of the lateral chain to the nonreducing end of another chain by glycogen debranching enzyme ((α1,4->1,4) glycosyltransferase activity)

**In image: the trisaccharide was added to an adjacent branch (blue) but it could have been added to the nonreducing end of the main chain.

Question 3

Tissue glycogenolysis reaction 3

Answer 3

Hydrolysis of the (α1->6) bond by Glycogen debranching enzyme ((α1Ò6) glucosidase activity) which Produces one molecule of glucose per (α1->6) bond

Question 4

Tissue glycogenolysis reaction 4

Answer 4

Phosphorolysis of the remaining (α1->4) bonds by Glycogen phosphorylase Producing multiple molecules of glucose-1-phosphate.

Question 5

Tissue glycogenolysis reaction 5

Answer 5

Isomerisation of glucose-1-phosphate into glucose-6-phosphate by phosphoglucomutase
which in the muscle, glucose-6-phosphate (intermediate of glycolysis) directly enters glycolysis.

Question 6

Tissue glycogenolysis reaction 6 (ONLY OCCURS IN THE LIVER)

Answer 6

Hydrolysis of glucose-6-phosphate in glucose by Glucose-6-phosphatase where glucose is then exported into the blood circulation

**Glucose-6-phosphatase is absent from the muscle.

Question 7

Glycogenolysis steps in the muscle

Answer 7

Note: Hexokinase has low km so forms glucose 6-phosphate which is then put directly into glycolysis

Question 8

Glycogenolysis steps in the liver

Answer 8

Glucose now instead goes straight into the bloodstream

Question 9

Name a congenital defect of glycogen metabolism in humans and can you explain why?
What other pathway(s) will be affected?
Can you suggest a treatment?

Answer 9

The von Gierke’s disease, which is also called Glycogen storage disease type I (GSD I), is characterized by a deficiency in glucose 6-phosphatase activity. Abnormal accumulation of glycogen is observed in affected individuals

Can you explain why? Will have an accumulation of glucose-6-pjosphate so it will return back to glycogen synthesis

Will this occur in the muscle? There is no glucose-6-phosphatase so it wont affect the muscle

What other pathway is affected? Gluconeogenesis (liver cannot release glucose when needed, and when you need to produce glucose in between meals, it will not work because glucose-6- phosphatase is deficient) wont occur

Why build of lactic acid? Will produce lactate, but when it reaches the liver it needs to be converted back to glucose, but it wont be able to because of lack of glucose-6-phosphatase causing acidic blood

Question 10

What 2 other effects can occur from glycogen storage disease type I (von Gierke’s disease)

Answer 10

1) Hypoglycemia: No breakdown of glycogen to maintain blood glucose level
2) Lactic acidosis: Impairment in gluconeogenesis
and causes an accumulation of G6P blocks the conversion of lactate to pyruvate

As a result: Need to take specific sugars that are encapsulated, need to take complex sugars frequently (wake up in the middle of the night and such) because you need a constant glucose supply
In photo have enlarged liver causing bulging stomach because of glycogen build up
-You can develop cirrhosis from an enlarged liver