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[Biochemistry](https://durgical.com/en/biochemistry/) · Enzyme

# AMP-activated protein kinase (AMPK)

The cell's fuel gauge: when ATP falls and AMP rises, it switches off what spends energy and switches on what makes it.

Updated 2026-11-01

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## Key facts

- A heterotrimer: α (catalytic), β (scaffold, binds glycogen) and γ (CBS sites binding AMP, ADP or ATP).
- AMP activates it twice over: allosterically and by protecting threonine 172, phosphorylated by LKB1 (or by CaMKK2 when Ca²⁺ rises).
- It inhibits acetyl-CoA carboxylase (more beta-oxidation, less fat synthesis), HMG-CoA reductase and mTORC1.
- In exercising muscle it moves GLUT4 to the membrane without insulin.
- Structure 4CFE is full-length human AMPK with AMP in the γ-subunit sites; it also shows a synthetic activator bound between α and β.

**Also called**
AMPK, Cellular energy sensor

**EC number**
[2.7.11.31](https://www.enzyme-database.org/query.php?ec=2.7.11.31)

**Genes**
PRKAA1, PRKAA2, PRKAB1, PRKAB2, PRKAG1, PRKAG2, PRKAG3

**Structure (PDB)**
[4CFE](https://www.rcsb.org/structure/4CFE)

## Regulation

- Activation: rising AMP/ATP ratio (exercise, fasting, hypoxia), LKB1, CaMKK2, adiponectin.
- Metformin activates it indirectly by lowering mitochondrial ATP production.
- Plenty of glycogen and high ATP hold it back.

## Inhibitors and toxins

- High ATP (competes with AMP on the γ subunit)
- Compound C (dorsomorphin, experimental use)

## Clinical notes

- Activating PRKAG2 mutations store glycogen in the heart: hypertrophic cardiomyopathy with pre-excitation (Wolff–Parkinson–White).
- Part of metformin's effect (less liver gluconeogenesis) is credited to the AMPK pathway.
- Loss of LKB1 (Peutz–Jeghers syndrome) removes a brake on mTOR and favours polyps and cancers.

## Pathways

- [Fatty acid β-oxidation](https://durgical.com/en/biochemistry/pathways/fatty-acid-oxidation/)
- [Fatty acid synthesis (lipogenesis)](https://durgical.com/en/biochemistry/pathways/fatty-acid-synthesis/)
- [Cholesterol synthesis (mevalonate pathway)](https://durgical.com/en/biochemistry/pathways/cholesterol-synthesis/)

## Related conditions

- [Type 2 diabetes mellitus](https://durgical.com/en/conditions/type-2-diabetes-mellitus/)
- [Metabolic syndrome](https://durgical.com/en/conditions/metabolic-syndrome/)

## Related

- [Acetyl-CoA carboxylase (ACC)](https://durgical.com/en/biochemistry/enzymes/acetyl-coa-carboxylase/)
- [HMG-CoA reductase](https://durgical.com/en/biochemistry/enzymes/hmg-coa-reductase/)
- [mTOR (mechanistic target of rapamycin)](https://durgical.com/en/biochemistry/enzymes/mtor/)
- [Malonyl-CoA](https://durgical.com/en/biochemistry/molecules/malonyl-coa/)
- [Carnitine palmitoyltransferase I (CPT-I)](https://durgical.com/en/biochemistry/enzymes/carnitine-palmitoyltransferase-i/)
- [Exercise metabolism](https://durgical.com/en/biochemistry/topics/exercise-metabolism/)
- [ATP (adenosine triphosphate)](https://durgical.com/en/biochemistry/molecules/atp/)
- [Leptin, appetite and obesity](https://durgical.com/en/biochemistry/topics/leptin-appetite-and-obesity/)
- [Fed, fasting and starvation states](https://durgical.com/en/biochemistry/topics/fed-fasting-and-starvation-states/)

## Test yourself

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

## Which signal activates AMPK?

A rise in AMP (and ADP) relative to ATP, which means energy is short.

## How does AMPK increase beta-oxidation?

It phosphorylates and inhibits acetyl-CoA carboxylase; malonyl-CoA falls and CPT1 lets more fatty acids into the mitochondrion.

## Which heart disease do activating PRKAG2 mutations cause?

A glycogen-storage cardiomyopathy with ventricular pre-excitation.

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

Sources: [PRKAA2: 5'-AMP-activated protein kinase catalytic subunit alpha-2 (human)](https://www.uniprot.org/uniprotkb/P54646/entry) (UniProt, 2026); [PRKAA1: 5'-AMP-activated protein kinase catalytic subunit alpha-1 (human)](https://www.uniprot.org/uniprotkb/Q13131/entry) (UniProt, 2026); [4CFE: Structure of full length human AMPK in complex with a small molecule activator, a benzimidazole derivative (991)](https://www.rcsb.org/structure/4CFE) (RCSB Protein Data Bank, 2026); [PRKAG2 gene: MedlinePlus Genetics](https://medlineplus.gov/genetics/gene/prkag2/) (MedlinePlus, US National Library of Medicine, 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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License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/biochemistry/enzymes/amp-activated-protein-kinase/