Glycogenesis 4.2/5 (5)

Glycogenesis


Glycogenesis

  • Glycogen is the major storage form of carbohydrate in animals similar to starch in plants.
  • It  is a homopolymer made up of repeated units of α- D glucose and each molecule is linked to another by 1→4 glycosidic bond which is a link connecting the 1st C atom of the active glucose residue to the 6th C atom of the approaching glucose molecule.
  • Once there is a chain consisting of 8 to 10 glycosidic residues in the glycogen fragment, branching begins by 1→6 linkages.
  • Glycogenesis is the process of glycogen synthesis, in which glucose molecules are added to chains of glycogen for storage.

Glycogenesis



Location

Glycogenesis takes place in the cytoplasm of cells in muscle, liver, and adipose tissue.

  • Substrate: UDP-glucose.
  • Result : Changes glucose to glycogen

Steps Involved

  • Glucose is converted into glucose-6-phosphate by the action of glucokinase or hexokinase  with conversion of ATP to ADP.
  • Glucose-6-phosphate is converted into glucose-1-phosphate by the action of phosphoglucomutase, passing through the obligatory intermediate glucose-1,6-bisphosphate.
  • Glucose-1-phosphate is converted into UDP-glucose by the action of the enzyme UDP-glucose pyrophosphorylase. Pyrophosphate is formed, which is later hydrolysed by pyrophosphatase into two phosphate molecules.
  • The enzyme glycogenin is needed to create initial short glycogen chains, which are then lengthened and branched by the other enzymes of glycogenesis.
  • Glycogenin, a homodimer, has a tyrosine residue on each subunit that serves as the anchor for the reducing end of glycogen. Initially, about eight UDP-glucose molecules are added to each tyrosine residue by glycogenin, forming α (1→4) bonds.
  • Once a chain of eight glucose monomers is formed, glycogen synthase binds to the growing glycogen chain and adds UDP-glucose to the 4-hydroxyl group of the glucosyl residue on the non-reducing end of the glycogen chain, forming more α(1→4) bonds in the process.
  • Branches are made by glycogen branching enzyme (also known as amylo α(1:4)→α(1:6)transglycosylase), which transfers the end of the chain onto an earlier part via α-1:6 glycosidic bond, forming branches, which further grow by addition of more α-1:4 glycosidic units.
  • Energy requirement: In the synthesis of glycogen, one ATP is required per glucose incorporated into the polymeric branched structure of glycogen. 

 Important Enzymes

  • Glycogen synthase: Adds glucose units to the nonreducing ends of existing chains in α-1,4 linkages.
  • Glucosyl (4:6) transferase : Transfers seven-glucose-residue-long pieces from the nonreducing ends of the chains to create internal branches with α-1,6 linkages.

 Stimulation


Insulin stimulates glycogenesis via dephosphorylation and thus activation of glycogen synthase.

The process is also activated during rest periods following the Cori cycle.

Inhibition

Glucagon (liver) and epinephrine (liver and muscle) inhibit glycogenesis via the cAMP protein kinase A  phosphorylation cascade, which results in phosphorylation and thus deactivation of glycogen synthase.

Significance

Glucose and its precursors are obtained through food. However under certain conditions they might not a reliable and continuous source of energy.

The glycogenesis process is therefore a built in mechanism of the body which stores the excess carbohydrates we consume, in the form of glycogen which could be broken down to glucose when needed.



References

  1. David Hames and Nigel Hooper (2005). Biochemistry. Third ed. Taylor & Francis Group: New York.
  2. Lehninger, A. L., Nelson, D. L., & Cox, M. M. (2000). Lehninger principles of biochemistry. New York: Worth Publishers.
  3. https://www.checkdiabetes.org/glycogenesis/
  4. https://en.wikipedia.org/wiki/Glycogenesis

Glycogenesis

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