Glycogenesis

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Glycogenesis is the conversion of glucose monomers to glycogen, a highly branched homopolysaccharide consisting of α-1,4 and α-1,6-glycosidic bonds using energy from the hydrolysis of UTP and ATP. This occurs when there is excess glucose present in the blood. As blood passes through the pancreas, the excess glucose stimulates the production of the hormone insulin which in turn stimulates the conversion of glucose to glycogen for storage in liver cells and muscle cells.

This is vital to prevent hyperglycaemia, which is excess glucose in the blood plasma, as well as renal loss of glucose. Hyperglycaemia causes an increase in the osmotic pressure and causes cells to shrivel.

There are many enzymes involved in the synthesis of glycogen. An example of this is glycogen synthase which is a key enzyme involved in the process. This enzyme is controlled by glycogen in that acts as a primer for the synthesis. This specific molecule is what limits the size of the glycogen that is made.

Pathway

  1. Hexokinase is used to phosphorylate a glucose molecule. This uses the hydrolysis of ATP for the addition of the phosphate group.
  2. The phosphate group is moved from the 6’ C to the 1’C by phosphoglucomutase.
  3. UTP is used to convert glucose-1-phosphate to UDP-glucose. Pyrophosphate detaches from UTP and then the phosphate of UMP bonds to the 1’ phosphate of glucose. Carried out by UPD-glucose pyrophosphorylase.4) The glucose molecule is cleaved from the rest of the molecule and is then bonded (alpha 1,4) to another glucose molecule. This is carried out by glycogen synthase.
  4. When the initial chain is around 10 monomers in length, part of the chain is cleaved. This smaller fragment is then bonded (alpha 1,6) to a monomer in the original chain to result in the branching. Carried out by Amylo(1,4 to 1,6) transglycosylase.
  5. Steps 3 and 4 are then repeated to form a larger glycogen molecule[1].

Glycogen disorders

Type 0- lack of glycogen synthase.Type I- Von Gurke’s disease, lack of glucose-6-phosphatase.Type III- Cori’s disease, lack of amylo-1,6- glucosidase.Type IV- Andersen’s disease, amylo-(1,4 to 1,6)-glucosidase[2].

The multistep process involves a series of enzymes and intermediate products to ensure the addition of glucose molecules to glycogen chains which can then be stored[3].

Also see: Gluconeogenesis and Glycolysis.

References

  1. Adair W. Carbohydrates. xPharm: The Comprehensive Pharmacology Reference. 2007;:1-12
  2. Anderson S. Glycogen synthesis and breakdown. [Lecture] Newcastle University. 5th December 2018
  3. http://themedicalbiochemistrypage.org/glycogen.php
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