Glycogen Synthesis Pathway

Karthika.P

General Introduction
The anabolic pathway Glycogen is a molecule that serves as the secondary long-term energy storage in animal and fungal cells. In Cyanobacteria, Glycogen Synthesis occurs during unfavorable conditions like salt stress and oxidative stress. In essence, this pathway must activate glucose units for transfer to glycogen chains.

STEP1
Phosphorylation of Glucose from G6P and isomerization to form G1P. Conversion of G1P and UTP into Uridine Disphospho Glucose, The first reaction, catalyzed by UDP-Glucose Pyrophosphorylase (UGPP) In contrast ADP-Glucose Pyrophosphorylase is involved in Cyanobacteria.

contd

Conversion of G1P & UTP to UDP-Glucose- Step1

The UDP-glucose pyrophosphorylase reaction is a phosphoanhydride exchange, with a phosphoryl oxygen of glucose-1-P attacking the aphosphorus of UTP to form UDPglucose and pyrophosphate.
Glucose-1-P + UTP UDP-glucose + pyrophosphate

STEP 1
The high energy phosphate bonds of UTP make the formation of UDPG energetically favorable. The pyrophosphate formed along with UDPG can readily be broken down to Pi + Pi by the enzyme pyrophosphatase. This helps to pull the reaction even further to the right.

STEP 2
Catalyzed by the enzyme Glycogen Synthase. Combines carbon 1 of the UDPG-derived glucose onto the carbon 4 of the non-reducing end of a glycogen chain to form the familiar alpha(1,4) glycogen links and produces UDP. The UDPG "side step" in glycogen synthesis thus uses the energy of UTP and UDP to make the reaction energetically favorable and the cell manages to overcome a significant energy barrier. contd...

Formation of alpha(1-4) Linkage

The mechanism proceeds by cleavage of the C-O bond between the glucose moiety and the Gr-beta-phosphate of UDP-glucose, leaving an oxonium ion intermediate, which is rapidly attacked by the C-4 hydroxyl oxygen of a terminal glucose unit on glycogen

STEP 2
Glycogen Synthase will only add glucose units from UDPG onto a pre existing glycogen chain that has at least four glucose residues. Linkage of the first few glucose units to form the minimal "primer" needed for glycogen synthase recognition is catalyzed by a protein called Glycogenin. This attaches to the 1st glucose and catalyzes linkage of the first 8 glucoses by alpha(1,4) bonds.

STEP 3
Catalyzed by Amylo-(1,4 to 1,6)-transglycosylase (OR) Branching Enzyme. Glycogen is a branched polymer of glucose units. Branching Enzyme breaks alpha(1,4) chains and carries the broken chain to the carbon #6 and forms an alpha(1,6) linkage. For each branching reaction, the resulting polymer has gained a new terminus at which growth can occur. contd...

Branching Reaction

The reaction involves the transfer of a 6 or 7-residue segment from the non reducing end of a linear chain (a branch) at least 11 residues in length to the C-6 hydroxyl of a glucose residue of the same chain or another chain.

Glycogen Synthase
Dimer in animals and plants, but in Cyanobacteria it is Homotetramer 2 Domains Size- Bacterial & Plant Synthase- ~50 kDa Mammalian & Yeast- ~80 kDa

ADP-Glucose Phosphorylase
ADP-glucose pyrophosphorylase indicate a regulation of glycogen synthesis by 3phosphoglycerate and orthophosphate in cyanobacteria. This would allow photosynthesis to influence glycogen synthesis directly.

Branching Enzyme