DurgicalDurgical
EN
Open the app

Biochemistry · Metabolic pathway

Glycogen metabolism !

Liver and muscle store glucose as glycogen after a meal and release it when needed, between meals or during exercise.

Updated 2026-11-01

Interactive map

Key facts

  • Synthesis (steps 1–5): glucose is activated as UDP-glucose; glycogen synthase makes α-1,4 bonds and the branching enzyme creates α-1,6 branches every 8–12 residues.
  • Breakdown (steps 6–8): glycogen phosphorylase (with pyridoxal phosphate, B6) cleaves α-1,4 bonds with phosphate and releases glucose 1-phosphate; it stops 4 residues from each branch.
  • The debranching enzyme has two activities: it moves 3 residues to another chain and frees the glucose at the α-1,6 point as free glucose (about 8–10 % of the total).
  • The liver uses its glycogen to keep blood glucose up (it has glucose-6-phosphatase); muscle uses its own only for itself.
  • Glycogenin is the primer protein: it starts each glycogen molecule by binding the first glucose units.
Also called
Glycogenesis and glycogenolysis

Regulation

  • Insulin: activates protein phosphatase 1, which dephosphorylates (activates) glycogen synthase and dephosphorylates (switches off) phosphorylase.
  • Glucagon (liver) and adrenaline (liver and muscle): cAMP → protein kinase A → phosphorylase kinase; phosphorylation activates phosphorylase and inactivates synthase.
  • In muscle, Ca²⁺ from contraction activates phosphorylase kinase and AMP activates phosphorylase directly.
  • Glucose 6-phosphate activates glycogen synthase even when phosphorylated; free glucose inhibits liver phosphorylase.

The steps, one by one

  1. Step 1 · Hexokinase / glucokinase irreversible Glucose + ATP → Glucose 6-phosphate + ADPIt traps glucose in the cell as glucose 6-phosphate (in the liver, glucokinase).
  2. Step 2 · Phosphoglucomutase Glucose 6-phosphate ⇌ Glucose 1-phosphateIt moves the phosphate from carbon 6 to carbon 1.If it fails: Phosphoglucomutase 1 deficiency is a congenital disorder of glycosylation with hypoglycaemia and exercise intolerance.
  3. Step 3 · UDP-glucose pyrophosphorylase irreversible Glucose 1-phosphate + UTP → UDP-glucose + pyrophosphateIt activates glucose by linking it to UDP; hydrolysis of the pyrophosphate makes the step irreversible (costs the equivalent of one ATP).
  4. Step 4 · Glycogen synthase irreversible UDP-glucose + Glycogen → Glycogen with lengthened α-1,4 chains + UDPIt adds the glucose to the end of a chain with an α-1,4 bond: the regulated step of synthesis.If it fails: Liver glycogen synthase deficiency (GSD 0) gives fasting hypoglycaemia with a small liver, and high glucose and lactate after meals.
  5. Step 5 · Branching enzyme irreversible Glycogen with lengthened α-1,4 chains → GlycogenIt cuts a segment of about 7 residues and reattaches it with an α-1,6 bond: more branches, more ends to grow and to break down quickly.If it fails: Its deficiency is GSD IV (Andersen): long-branched glycogen (polyglucosan) that damages the liver. Andersen disease (glycogen storage disease type IV) →
  6. Step 6 · Glycogen phosphorylase irreversible Glycogen + phosphate (Pi) → Glucose 1-phosphate + Limit dextrinIt cleaves α-1,4 bonds with phosphate and releases glucose 1-phosphate; 4 residues from a branch it stops and leaves a limit dextrin for the debranching enzyme to finish.If it fails: Muscle phosphorylase missing: McArdle (GSD V); liver form: Hers (GSD VI). If the debranching enzyme fails: Cori (GSD III). McArdle disease (glycogen storage disease type V) →
  7. Step 7 · Phosphoglucomutase Glucose 1-phosphate ⇌ Glucose 6-phosphateIt moves the phosphate back to carbon 6: muscle feeds this glucose 6-phosphate into glycolysis.
  8. Step 8 · Glucose-6-phosphatase (liver and kidney only) irreversible Glucose 6-phosphate + H₂O → Glucose + phosphate (Pi)In the liver it releases glucose into the blood and holds blood glucose up between meals.If it fails: Its deficiency (von Gierke) traps glucose 6-phosphate: severe hypoglycaemia and a large liver full of glycogen and fat. Von Gierke disease (glycogen storage disease type I) →

Clinical notes

  • Liver glycogen storage diseases (I, III, IV, VI) cause hepatomegaly and hypoglycaemia; muscle forms (V, VII) cause exercise intolerance and cramps; type II (Pompe) is lysosomal and damages heart and muscle.
  • Liver glycogen lasts for about 12–24 h of fasting; after that blood glucose depends on gluconeogenesis.
  • Carbohydrate loading before an endurance event increases muscle glycogen.

Test yourself

Think of the answer, then tap the question to see it.

Which activated form of glucose does glycogen synthase use?

UDP-glucose, made from glucose 1-phosphate and UTP.

Which vitamin does glycogen phosphorylase need?

B6, as pyridoxal phosphate bound to the enzyme.

Why does muscle glycogen not maintain blood glucose?

Muscle has no glucose-6-phosphatase: its glucose 6-phosphate can only go down glycolysis inside the fibre.

How does glucagon affect glycogen synthesis and breakdown?

Through cAMP and PKA it phosphorylates the enzymes: it activates phosphorylase and inactivates glycogen synthase.

What product does the debranching enzyme release at the branch point?

Free (non-phosphorylated) glucose, about 8–10 % of the glucose released from glycogen.

Add to my cards (5)

Educational information, not medical advice. For any symptom, see a health professional.

Sources: Glycogen synthesis (Reactome, 2026); Glycogen breakdown (glycogenolysis) (Reactome, 2026); GYS2: Glycogen [starch] synthase, liver (human) (UniProt, 2026); PYGL: Glycogen phosphorylase, liver form (human) (UniProt, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).

← All of biochemistry

Spotted a mistake?We are always improving for the community. Tell us what is wrong and our team will review it.Report a mistake

Representative model, for educational purposes only.