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]
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]
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.
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.
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]
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
| Glycogenolysis | Glycogenesis |
|---|---|
| Break down of glycogen to glucose | Synthesis 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 insulin | Inhibited 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
| Glycogenolysis | Gluconeogenesis |
|---|---|
| Break down of glycogen to glucose | Synthesis of glucose from non carbohydrate substrates |
| Inhibited by insulin | Inhibited 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 muscle | Occur in liver and kidney |
Animation and Video on Glycogenolysis
Reference:
- Harper’s Illustrated Biochemistry 28/e Metabolism of glycogen
- Lippincott’s Illustrated Reviews Biochemistry 4/e Intermediary metabolism
- Biochemistry notes – usmle step 1
- http://www.dukechildrens.org/services/medical_genetics/glycogen_storage_disease_types
- http://academic.mu.edu/bisc/siebenlistk/3213gluconeogenesis_etal.pdf
- http://www.rpi.edu/dept/bcbp/molbiochem/MBWeb/mb1/part2/gluconeo.htm
- http://aippg.net/threads/which-of-the-following-hormones-stimulates-gluconeogenesis.96376/
- http://en.wikipedia.org/wiki/Glycogenesis
- http://en.wikipedia.org/wiki/Glycogenolysis
- http://www.britannica.com/EBchecked/topic/1540424/glycogenolysis