Glycogen synthesis and breakdown template

Glucose 6-phosphate → α-D-glucose 1-phosphate (phosphoglucomutase) → UDP-glucose (UTP, pyrophosphorylase) → glycogen (n + 1) (glycogen synthase), branching enzyme; glycogen phosphorylase (Pᵢ, PLP) releases glucose 1-phosphate, and the debranching enzyme removes the branches.

What the template shows

• Glucose is stored as α-1,4 chains with α-1,6 branches: built from UDP-glucose, released as glucose 1-phosphate
• Synthesis: glucose is activated as UDP-glucose
• R = 5′-uridyl (UDP-glucose); R′ = rest of the chain. Glycogen synthase adds the glucose to the 4-OH of a non-reducing end
• glucose 6-phosphate
• α-D-glucose 1-phosphate
• UDP-glucose
• Breakdown: phosphorolysis, not hydrolysis
• Glycogen phosphorylase (PLP) splits the terminal α-1,4 bond with Pᵢ; R = rest of the chain
• glucose 1-phosphate
• Branches: made by the branching enzyme, removed by the debranching enzyme
• Branching enzyme (amylo-(1,4→1,6)-transglycosylase)
• cuts off a block of ≈ 7 residues from a chain of ≥ 11 and joins it α-1,6 at least 4 residues from the next branch
• reducing end
• Debranching enzyme
• phosphorylase stops 4 residues from a branch; the transferase moves 3 of them, then α-1,6-glucosidase frees the last as glucose
• free glucose
• glucose residue (α-1,4 chain)
• residues moved by the enzyme
• residue joined α-1,6 (freed as glucose)
• Each glucose stored costs one UTP (= one ATP); PPᵢ hydrolysis by pyrophosphatase pulls UDP-glucose formation forward. Glycogenin primes a new particle.
• Phosphorolysis gives glucose 1-phosphate that needs no ATP to enter glycolysis; phosphoglucomutase turns it into glucose 6-phosphate.
• Glucagon and adrenaline → cAMP → PKA → phosphorylase kinase → phosphorylase a (active) while glycogen synthase is phosphorylated and turned off; insulin does the reverse.
• Liver releases free glucose (glucose-6-phosphatase) for the blood; muscle keeps glucose 6-phosphate for its own glycolysis (McArdle disease: no muscle phosphorylase).

Drawn with 135 atoms, 4 arrows, 111 shapes – every one editable in MolDraw.

Sources

• Nelson & Cox, Lehninger Principles of Biochemistry, 8th ed., 2021, ch. 15 Textbook
• Berg, Tymoczko, Gatto & Stryer, Biochemistry, 9th ed., 2019 Textbook
• Voet & Voet, Biochemistry, 4th ed., Wiley 2011 Textbook
• Caputto, Leloir, Cardini & Paladini, J. Biol. Chem. 1950, 184, 333 Original paper
• Leloir, Olavarría, Goldemberg & Carminatti, Arch. Biochem. Biophys. 1959, 81, 508 Original paper
• Cori, Schmidt & Cori, Science 1939, 89, 464 Original paper