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
- Genes
- PRKAA1, PRKAA2, PRKAB1, PRKAB2, PRKAG1, PRKAG2, PRKAG3
- Structure (PDB)
- 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
Related conditions
Related
- Acetyl-CoA carboxylase (ACC)
- HMG-CoA reductase
- mTOR (mechanistic target of rapamycin)
- Malonyl-CoA
- Carnitine palmitoyltransferase I (CPT-I)
- Exercise metabolism
- ATP (adenosine triphosphate)
- Leptin, appetite and obesity
- 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.
Educational information, not medical advice. For any symptom, see a health professional.
Sources: PRKAA2: 5'-AMP-activated protein kinase catalytic subunit alpha-2 (human) (UniProt, 2026); PRKAA1: 5'-AMP-activated protein kinase catalytic subunit alpha-1 (human) (UniProt, 2026); 4CFE: Structure of full length human AMPK in complex with a small molecule activator, a benzimidazole derivative (991) (RCSB Protein Data Bank, 2026); PRKAG2 gene: MedlinePlus Genetics (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.