Glycogenesis

Not to be confused withGlycolysis,Glycogenolysis,orGluconeogenesis.

Glycogenesisis the process ofglycogensynthesis, in whichglucosemolecules are added to chains of glycogen for storage. This process is activated during rest periods following theCori cycle,in theliver,and also activated byinsulinin response to highglucose levels.

Steps

• Glucoseis converted intoglucose 6-phosphateby the action ofglucokinaseorhexokinasewith conversion of ATP to ADP.
• Glucose-6-phosphate is converted intoglucose-1-phosphateby the action ofphosphoglucomutase,passing through the obligatory intermediateglucose-1,6-bisphosphate.
• Glucose-1-phosphate is converted intoUDP-glucoseby the action of the enzymeUDP-glucose pyrophosphorylase.Pyrophosphateis formed, which is later hydrolysed bypyrophosphataseinto two phosphate molecules.
• The enzymeglycogeninis needed to create initial short glycogen chains, which are then lengthened and branched by the other enzymes of glycogenesis.Glycogenin,a homodimer, has atyrosineresidue on each subunit that serves as the anchor for the reducing end of glycogen. Initially, about seven UDP-glucose molecules are added to each tyrosine residue by glycogenin, forming α(1→4) bonds.
• Once a chain of seven glucose monomers is formed,glycogen synthasebinds 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 byglycogen 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.

Metabolism of commonmonosaccharides,includingglycolysis,gluconeogenesis,glycogenesis andglycogenolysis

Control and regulations

Glycogenesis responds to hormonal control.

One of the main forms of control is the varied phosphorylation of glycogen synthase and glycogen phosphorylase. This is regulated by enzymes under the control of hormonal activity, which is in turn regulated by many factors. As such, there are many different possible effectors when compared to allosteric systems of regulation.

Epinephrine (adrenaline)

See also:Epinephrine

Glycogen phosphorylase is activated by phosphorylation, whereas glycogen synthase is inhibited.

Glycogen phosphorylase is converted from its less active "b" form to an active "a" form by the enzyme phosphorylase kinase. This latter enzyme is itself activated by protein kinase A and deactivated by phosphoprotein phosphatase-1.

Protein kinase A itself is activated by thehormoneadrenaline.Epinephrinebinds to a receptor protein that activates adenylate cyclase. The latter enzyme causes the formation ofcyclic AMPfromATP;two molecules ofcyclic AMPbind to the regulatory subunit of protein kinase A, which activates it allowing the catalytic subunit of protein kinase A to dissociate from the assembly and to phosphorylate other proteins.

Returning to glycogen phosphorylase, the less active "b" form can itself be activated without the conformational change. 5'AMP acts as an allosteric activator, whereas ATP is an inhibitor, as already seen withphosphofructokinasecontrol, helping to change the rate of flux in response to energy demand.

Epinephrinenot only activatesglycogen phosphorylasebut also inhibits glycogen synthase. This amplifies the effect of activating glycogen phosphorylase. This inhibition is achieved by a similar mechanism, as protein kinase A acts to phosphorylate the enzyme, which lowers activity. This is known as co-ordinate reciprocal control. Refer toglycolysisfor further information of the regulation of glycogenesis.

Calcium ions

Calcium ions orcyclic AMP(cAMP) act as secondary messengers. This is an example of negative control. The calcium ions activate phosphorylase kinase. This activates glycogen phosphorylase and inhibits glycogen synthase.

See also

• Glycogenolysis
• Glycogen synthase
• Glycogen storage disease