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[Biochemistry](https://durgical.com/en/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

- **Step 1 · [Hexokinase / glucokinase](https://durgical.com/en/biochemistry/enzymes/hexokinase/)** irreversible [Glucose](https://durgical.com/en/biochemistry/molecules/glucose/) + [ATP](https://durgical.com/en/biochemistry/molecules/atp/) → [Glucose 6-phosphate](https://durgical.com/en/biochemistry/molecules/glucose-6-phosphate/) + ADP It traps glucose in the cell as glucose 6-phosphate (in the liver, glucokinase).
- **Step 2 · Phosphoglucomutase** [Glucose 6-phosphate](https://durgical.com/en/biochemistry/molecules/glucose-6-phosphate/) ⇌ Glucose 1-phosphate It 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.
- **Step 3 · UDP-glucose pyrophosphorylase** irreversible Glucose 1-phosphate + UTP → [UDP-glucose](https://durgical.com/en/biochemistry/molecules/udp-glucose/) + pyrophosphate It activates glucose by linking it to UDP; hydrolysis of the pyrophosphate makes the step irreversible (costs the equivalent of one ATP).
- **Step 4 · [Glycogen synthase](https://durgical.com/en/biochemistry/enzymes/glycogen-synthase/)** irreversible [UDP-glucose](https://durgical.com/en/biochemistry/molecules/udp-glucose/) + [Glycogen](https://durgical.com/en/biochemistry/molecules/glycogen/) → Glycogen with lengthened α-1,4 chains + UDP It 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.
- **Step 5 · Branching enzyme** irreversible Glycogen with lengthened α-1,4 chains → [Glycogen](https://durgical.com/en/biochemistry/molecules/glycogen/) It 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) →](https://durgical.com/en/conditions/andersen-disease/)
- **Step 6 · [Glycogen phosphorylase](https://durgical.com/en/biochemistry/enzymes/glycogen-phosphorylase/)** irreversible [Glycogen](https://durgical.com/en/biochemistry/molecules/glycogen/) + phosphate (Pi) → Glucose 1-phosphate + Limit dextrin It 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) →](https://durgical.com/en/conditions/mcardle-disease/)
- **Step 7 · Phosphoglucomutase** Glucose 1-phosphate ⇌ [Glucose 6-phosphate](https://durgical.com/en/biochemistry/molecules/glucose-6-phosphate/) It moves the phosphate back to carbon 6: muscle feeds this glucose 6-phosphate into glycolysis.
- **Step 8 · [Glucose-6-phosphatase (liver and kidney only)](https://durgical.com/en/biochemistry/enzymes/glucose-6-phosphatase/)** irreversible [Glucose 6-phosphate](https://durgical.com/en/biochemistry/molecules/glucose-6-phosphate/) + H₂O → [Glucose](https://durgical.com/en/biochemistry/molecules/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) →](https://durgical.com/en/conditions/von-gierke-disease/)

## 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.

## Related conditions

- [Von Gierke disease (glycogen storage disease type I)](https://durgical.com/en/conditions/von-gierke-disease/)
- [Pompe disease (glycogen storage disease type II)](https://durgical.com/en/conditions/pompe-disease/)
- [Cori disease (glycogen storage disease type III)](https://durgical.com/en/conditions/cori-disease/)
- [Andersen disease (glycogen storage disease type IV)](https://durgical.com/en/conditions/andersen-disease/)
- [McArdle disease (glycogen storage disease type V)](https://durgical.com/en/conditions/mcardle-disease/)
- [Hers disease (glycogen storage disease type VI)](https://durgical.com/en/conditions/hers-disease/)
- [Tarui disease (muscle phosphofructokinase deficiency)](https://durgical.com/en/conditions/tarui-disease/)

## Related

- [Glycogen](https://durgical.com/en/biochemistry/molecules/glycogen/)
- [UDP-glucose](https://durgical.com/en/biochemistry/molecules/udp-glucose/)
- [Glucose](https://durgical.com/en/biochemistry/molecules/glucose/)
- [Glucose 6-phosphate](https://durgical.com/en/biochemistry/molecules/glucose-6-phosphate/)
- [Hexokinase](https://durgical.com/en/biochemistry/enzymes/hexokinase/)
- [Glycogen synthase](https://durgical.com/en/biochemistry/enzymes/glycogen-synthase/)
- [Glycogen phosphorylase](https://durgical.com/en/biochemistry/enzymes/glycogen-phosphorylase/)
- [Glycogen debranching enzyme](https://durgical.com/en/biochemistry/enzymes/glycogen-debranching-enzyme/)
- [Glucose-6-phosphatase](https://durgical.com/en/biochemistry/enzymes/glucose-6-phosphatase/)
- [Glycolysis](https://durgical.com/en/biochemistry/pathways/glycolysis/)
- [Gluconeogenesis](https://durgical.com/en/biochemistry/pathways/gluconeogenesis/)

## 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.

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

Sources: [Glycogen synthesis](https://reactome.org/PathwayBrowser/#/R-HSA-3322077) (Reactome, 2026); [Glycogen breakdown (glycogenolysis)](https://reactome.org/PathwayBrowser/#/R-HSA-70221) (Reactome, 2026); [GYS2: Glycogen [starch] synthase, liver (human)](https://www.uniprot.org/uniprotkb/P54840/entry) (UniProt, 2026); [PYGL: Glycogen phosphorylase, liver form (human)](https://www.uniprot.org/uniprotkb/P06737/entry) (UniProt, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).

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Representative model, for educational purposes only.

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