Glycogenolysis

Glycogenolysis Definition

Glycogenolysis is the process of degradation of glycogen to glucose 1 phosphate and glucose in liver and muscle. [9] Glycogen serves as the storage form of carbohydrate in our body corresponding to starch in plants.

When there is more supply of glucose to our body, immediately after meals, it gets stored in the form of glycogen in liver and muscles.  The stored Glycogen comes to rescue when the blood glucose drops down, a situation which prevails between our daily meals. [1, 2, 3]

Branched structure of glycogen picture
Picture 1: Branched structure of glycogen

Image Source: static.newworldencyclopedia.org

Structure of Glycogen

Glycogen is a homopolymer made up of repeated units of α D glucose and has an appearance of an extensively branched tree.

Each glucose molecule is linked to each other by α 1→4 glycosidic bond along the length of the chain which is formed between the 1st carbon atom of one glucose residue and the 4th carbon atom of the next glucose residue in the chain and by α 1→6 linkage at the branch points.  [1, 2, 3]

Chemical structure of glycogen image
Picture 2: Chemical structure of glycogen

Image Source: tutorvista.com

Glycogenolysis Pathway

Glycogenolysis happens in the major storage organs of glycogen – liver and muscle, when the body is need of more energy or when the blood glucose is low. Glycogenolysis is not the reversal of Glycogenesis.

It is catalyzed by different set of enzymes. In this process, the linkages between the glucose residues are broken down, forming glucose 6 phosphate or free glucose so that it could be used for producing energy.

Glycogenolysis Steps

Action of glycogen phosphorylase

The key enzyme of glycogenolysis is glycogen phosphorylase which is aided by another molecule called pyridoxal phosphate. This enzyme cleaves the glucose residues sequentially and yield glucose 1 phosphate.

This cleavage is known as phosphorolysis [9] which continues until 4 residues are present on either side of a branching point. The resultant smaller and less branched glycogen molecule , Limit Dextrin. It cannot be broken down further by Glycogen phosphorylase.

Glycogen phosphorylase photo
Picture 3: Glycogen phosphorylase stereoisomers

Image Source: wikimedia.org

What does the Debranching enzyme do?

Debranching enzyme is a single molecule consisting of 2 enzyme activities – α – [1→4]→α-[1→4] glucan transferase and glucosidase. The first enzyme activity removes the glycogen fragment containing 3 or 4 residues in a branch and move them to a nearby chain.

This involves breaking up of 1→ 4 glycosidic link in one point and the formation of the same at another point on the molecule.

The second enzyme activity breaks the 1→ 6 glycosidic link at the branching point and release free glucose. Once the branching is lost, remaining linear fragment of glycogen is available for the action of phosphorylase and the process continues.

 

Action of Debranching enzyme picture
Picture 4: Action of Debranching enzyme

Image Source: themedicalbiochemistrypage.org

Formation of end products

The glycogen in the liver is used to increase the blood glucose level when needed. The glycogen in muscle is used to supply energy during muscle contraction as in physical exercise and not to increase blood glucose.

The end products – glucose and glucose 1 phosphate are formed by the combined action of the two enzymes -debranching enzyme and gllycogen phosphorylase.

The glucose 1 phosphate gets converted to glucose 6 phosphate by an enzyme Phosphoglucomutase. The glucose 6 phosphate gets cleaved to glucose by glucose 6 phosphatase which is present in liver, kidney and intestine.

As muscle lacks this enzyme, the glucose 6 phosphate is diverted to glycolysis, which is a process that provides energy to the cells.[1,2]

Defect in any one of the steps in glycogenolysis results in accumulation of glycogen in the cells resulting in a group of disorders called Glycogen Storage disorders causing damage to liver and muscle. This occurs mainly due to deficiency of the enzymes. [4]

Steps of glycogenolysis image
Picture 3: Steps of glycogenolysis

Image Source: tuscany-diet.net

Regulation of Glycogenolysis

Stimulation of glycogenolysis

A tight regulation of glycogenolysis is needed to keep the blood sugar under check. When the blood sugar and the energy levels are low, glycogenolysis comes into play. Glucagon and epinephrine are the hormones which are secreted in low blood sugar and when the body is in distress. [10]

These hormones act through an intermediate molecule called cAMP which is necessary for the activation of Glycogen phosphorylase. This mechanism is commonly found in liver.

In muscles, only epinephrine causes effective glycogenolysis and in muscles, there is increased calcium inside the cells during muscle contraction .

This also results in activation of glycogen phosphorylase through a series of complicated reactions which does not involve cAMP. Epinephrine is the hormone of fight, fright and  flight. [9]

Inhibition of glycogenolysis

When there is excessive glucose or intermediates of glycolysis like glucose 6 phosphate or ATP, the energy currency, glycogenolysis is inhibited and the metabolism is shifted towards glycolysis and Glycogenesis.

Insulin, the anti diabetogenic hormone inhibits glycogenolysis and prevents increase in blood sugar level.

 

Difference between Glycogenolysis and  Glycogenesis

GlycogenolysisGlycogenesis
Break down of glycogen to glucoseSynthesis of glycogen from glucose
Stimulated by fasting, between meals physical
exercise, glucagon, epinephrine
Stimulated by increased blood glucose level as in
well fed state, insulin
Inhibited by insulinInhibited by glucagon, epinephrine
Glycogen phosphorylase is the key enzyme which
is phosphorylated in its active form.
Glycogen synthase is the key enzyme which is
dephosphorylated in active form

 

Difference between Glycogenolysis and Gluconeogenesis

GlycogenolysisGluconeogenesis
Break down of glycogen to glucoseSynthesis of glucose from non carbohydrate
substrates
Inhibited by insulinInhibited by insulin
Glycogen phosphorylase is the key enzyme which
is phosphorylated in its active form.
There are 4 key enzymes – Pyruvate carboxylase,

Phosphoenol pyruvate carboxykinase, Fructose 1,
6 bisphosphatase and Glucose 6 phosphatase
Occur in liver and muscleOccur in liver and kidney

 

Animation and Video on Glycogenolysis

Link

Reference:

  1. Harper’s Illustrated Biochemistry 28/e Metabolism of glycogen
  2. Lippincott’s Illustrated Reviews Biochemistry 4/e Intermediary metabolism
  3. Biochemistry notes – usmle step 1
  4. http://www.dukechildrens.org/services/medical_genetics/glycogen_storage_disease_types
  5. http://academic.mu.edu/bisc/siebenlistk/3213gluconeogenesis_etal.pdf
  6. http://www.rpi.edu/dept/bcbp/molbiochem/MBWeb/mb1/part2/gluconeo.htm
  7. http://aippg.net/threads/which-of-the-following-hormones-stimulates-gluconeogenesis.96376/
  8. http://en.wikipedia.org/wiki/Glycogenesis
  9. http://en.wikipedia.org/wiki/Glycogenolysis
  10. http://www.britannica.com/EBchecked/topic/1540424/glycogenolysis

Published by Dr. Rajesh MD under Diabetes Information.
Article was last reviewed on January 8th, 2022.

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