GO:0004017 AMP kinase activity: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0004017 AMP kinase activity is a molecular function defined as catalysis of the reaction ATP + AMP = 2 ADP, commonly known as adenylate kinase or myokinase activity.
• This activity maintains cellular adenine nucleotide homeostasis and is distinct from AMP-activated protein kinase (AMPK) signaling, although AMPK is often studied in parallel because it senses AMP/ATP ratios.
• AMP kinase activity is critical in tissues with high energy demand, including skeletal muscle, neurons, and phrenic motor neurons, where it supports plasticity and stress responses.
• Dysregulation of AMP kinase activity has been linked to age-associated sarcopenia, hypoxia responses, post-COVID-19 complications, and cancer-related p53 signaling.
• Key experimental approaches include enzyme-coupled assays, phosphorylation-specific antibodies, and genetic models such as knockout and point-mutation cell lines.
• CRISPR-based knockout, knock-in, and overexpression models enable causal interrogation of AMP kinase activity in disease and metabolic research.
Description
AMP kinase activity (GO:0004017) is a fundamental enzymatic function that catalyzes the reversible conversion of ATP and AMP to two molecules of ADP. This reaction, historically termed myokinase or adenylate kinase activity, is essential for maintaining cellular energy charge and nucleotide balance. Researchers study this activity to understand how cells buffer fluctuations in ATP demand and supply, particularly in excitable tissues such as neurons and muscle. The term is often confused with AMP-activated protein kinase (AMPK), a separate enzyme complex that senses AMP levels; however, GO:0004017 specifically refers to the phosphotransferase activity itself. Accurate annotation of this activity is critical for interpreting metabolic, hypoxia, and disease-related datasets.
AMP kinase activity At A Glance
| GO ID | GO:0004017 |
|---|---|
| GO term | AMP kinase activity |
| Ontology | molecular_function |
| Synonym | Adenylate kinase activity; myokinase activity; ATP:AMP phosphotransferase activity |
| Definition | Catalysis of the reaction: ATP + AMP = 2 ADP |
| Major function | Maintains adenine nucleotide homeostasis by interconverting ATP, ADP, and AMP |
| Related processes | Cellular energy metabolism, hypoxia response, neuronal plasticity, muscle function |
| Common assays | Enzyme-coupled spectrophotometric assays, phosphorylation-specific immunoblotting |
What Is GO:0004017?
According to the Gene Ontology, GO:0004017 AMP kinase activity is defined as the catalysis of the reaction: ATP + AMP = 2 ADP. This activity is synonymous with 5'-AMP-kinase activity, adenylate kinase activity, adenylic kinase activity, adenylokinase activity, ATP:AMP phosphotransferase activity, and myokinase activity. It belongs to the molecular_function ontology aspect and is distinct from AMPK signaling, although both are involved in adenine nucleotide metabolism.
Why Is AMP kinase activity Important in Cell Biology?
AMP kinase activity is central to cellular energy homeostasis because it directly balances ATP, ADP, and AMP pools. In neurons, it regulates phrenic motor plasticity and responses to intermittent hypoxia. In skeletal muscle, it is implicated in age-associated sarcopenia and exercise-induced adaptations. Its dysregulation contributes to post-COVID-19 complications and cancer-related signaling through p53. Thus, precise measurement and manipulation of AMP kinase activity are essential for metabolic, neurobiological, and disease research.
• Maintains cellular energy charge by buffering ATP/ADP/AMP ratios.
• Supports respiratory motor plasticity in phrenic motor neurons.
• Contributes to muscle maintenance and is linked to sarcopenia.
• Mediates hypoxia-induced persulfide formation via cystathionine gamma lyase phosphorylation.
• Involved in post-COVID-19 complications and potential therapeutic targeting.
• Regulates p53 stability through MDMX phosphorylation.
• Activated by resveratrol in neurons, linking diet to neuronal energy sensing.
• Modulated by ghrelin, connecting hormonal signals to AMPK activity.
• Activated by adiponectin signaling components such as β-carotene and lycopene.
• Serves as a biomarker and target in metabolic and neurodegenerative diseases.
What Happens During AMP kinase activity?
Substrate binding and phosphotransfer
In simple terms: The enzyme grabs ATP and AMP and swaps a phosphate group between them.
AMP kinase activity catalyzes the reversible transfer of a phosphate group from ATP to AMP, yielding two ADP molecules. This reaction is essential for maintaining the cellular adenine nucleotide pool and is often measured using enzyme-coupled assays that monitor ADP production.
Regulation by energy status
In simple terms: When energy is low, this activity helps restore balance.
The activity is sensitive to the cellular AMP/ATP ratio, which rises during metabolic stress such as hypoxia or exercise. In phrenic motor neurons, AMP kinase activity differentially regulates plasticity depending on the pattern of stimulation.
Integration with AMPK signaling
In simple terms: AMP kinase activity is not the same as AMPK, but they talk to each other.
Although GO:0004017 refers to the phosphotransferase activity, it is often studied alongside AMP-activated protein kinase (AMPK), which senses AMP and phosphorylates downstream targets such as cystathionine gamma lyase and MDMX. AMPK activity can be measured in response to ghrelin or resveratrol, providing insight into hormonal and dietary regulation.
Role in disease and aging
In simple terms: When this activity goes wrong, it can contribute to muscle loss and other diseases.
Age-associated sarcopenia is linked to altered apelin signaling and AMPK phosphorylation. In post-COVID-19 complications, AMP kinase is considered a promising therapeutic target. Additionally, AMPK induces p53 by phosphorylating MDMX, linking energy stress to tumor suppression.
Key Genes Involved in GO:0004017 AMP kinase activity
The following genes and proteins are directly or indirectly associated with AMP kinase activity and its regulatory network.
| Gene | Major Role | Research Relevance |
|---|---|---|
| AK1 | Cytosolic adenylate kinase | Main enzyme for GO:0004017 in muscle and neurons |
| AK2 | Mitochondrial adenylate kinase | Energy transfer in mitochondria |
| AK3 | Mitochondrial GTP:AMP phosphotransferase | Mitochondrial nucleotide homeostasis |
| AK4 | Mitochondrial adenylate kinase | Stress response and hypoxia |
| AK5 | Brain-specific adenylate kinase | Neuronal energy metabolism |
| AMPK | AMP-activated protein kinase | Senses AMP/ATP ratio; phosphorylates downstream targets |
| CGL | Cystathionine gamma lyase | Phosphorylated by AMPK under hypoxia |
| MDMX | p53 regulator | Phosphorylated by AMPK, leading to p53 activation |
| APLN | Apelin | Exerkine that reverses sarcopenia via AMPK |
| ADIPOR1 | Adiponectin receptor | Activates AMPK signaling |
| GHRL | Ghrelin | Modulates AMPK activity |
| SIRT1 | Sirtuin 1 | Interacts with AMPK in energy sensing |
| PPARGC1A | PGC-1α | Downstream of AMPK in mitochondrial biogenesis |
| MTOR | mTOR kinase | Opposes AMPK in energy signaling |
| TP53 | p53 tumor suppressor | Induced by AMPK via MDMX phosphorylation |
| HIF1A | Hypoxia-inducible factor 1α | Linked to AMPK under hypoxia |
| CBS | Cystathionine beta-synthase | Related to persulfide formation |
| NNT | Nicotinamide nucleotide transhydrogenase | Affects AMPK activity in mitochondria |
How Is AMP kinase activity Regulated?
AMP kinase activity is regulated by the cellular AMP/ATP ratio, which increases during metabolic stress such as hypoxia, exercise, or nutrient deprivation. Hormones like ghrelin and adiponectin can modulate AMPK activity. Resveratrol stimulates AMP kinase activity in neurons, linking dietary polyphenols to energy sensing. Additionally, apelin, an exerkine, reverses age-associated sarcopenia through AMPK-dependent mechanisms. The activity is also integrated with mTOR signaling, which opposes AMPK under nutrient-rich conditions.
AMP kinase activity and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| APLN | Age-associated sarcopenia | Knockout mouse or overexpression cell line |
| MDMX | Cancer (p53 pathway) | Point-mutation knock-in of phosphorylation site |
| CGL | Hypoxia and persulfide formation | Knockout cell line with hypoxia exposure |
| AMPK | Post-COVID-19 complications | Overexpression and knockout models |
| AK1 | Metabolic myopathies | Knockout and point-mutation models |
Metabolic and aging disorders
AMP kinase activity is implicated in age-associated sarcopenia, where apelin signaling and AMPK phosphorylation decline. It also plays a role in post-COVID-19 complications, making it a promising therapeutic target.
Cancer
AMPK induces p53 by phosphorylating MDMX, thereby inhibiting MDMX activity and promoting tumor suppression. This links AMP kinase activity to cancer biology and potential chemotherapeutic strategies.
Neurodegeneration and hypoxia
In phrenic motor neurons, AMP kinase activity differentially regulates plasticity and responses to intermittent hypoxia. Hypoxia also increases persulfide formation via AMPK-dependent phosphorylation of cystathionine gamma lyase.
From AMP kinase activity-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does loss of AMP kinase activity affect energy homeostasis? | Knockout cell line (e.g., AK1 KO) |
| How does a specific phosphorylation site regulate AMPK function? | Point-mutation knock-in (e.g., MDMX phospho-mutant) |
| Can overexpression of AMPK rescue disease phenotypes? | Overexpression cell model |
| What is the role of AMP kinase activity in hypoxia? | Hypoxia-exposed knockout and wild-type cells |
| How does AMP kinase activity affect neuronal plasticity? | Primary neuron cultures with KO or overexpression |
| Can CRISPR library screening identify modifiers of AMP kinase activity? | Genome-wide CRISPR knockout library |
How to Study the AMP kinase activity Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Enzyme-coupled assay | ADP production or ATP consumption | Quantifying AMP kinase activity in lysates |
| Western blot | Phosphorylation of AMPK or substrates | Monitoring activation in cells |
| CRISPR knockout | Loss of gene function | Testing causality in disease models |
| CRISPR knock-in | Specific mutations or tags | Studying phosphorylation sites |
| Overexpression | Increased protein levels | Rescue or gain-of-function experiments |
| CRISPR library screening | Genome-wide modifiers | Identifying novel regulators |
| Metabolite profiling | Changes in metabolite levels | Linking diet to AMPK activation |
Enzymatic activity assays
AMP kinase activity can be measured using enzyme-coupled spectrophotometric assays that monitor ADP production or ATP consumption. These assays are typically performed in cell lysates or purified protein preparations.
Phosphorylation-specific immunoblotting
Antibodies against phosphorylated AMPK or its substrates (e.g., ACC, MDMX) are used to assess activation status in response to stimuli such as ghrelin or resveratrol.
Genetic manipulation and CRISPR screening
CRISPR knockout, knock-in, and overexpression models allow causal testing of AMP kinase activity in disease models. Library screening can identify novel regulators of the pathway.
Metabolite profiling
Non-target metabolite analysis, such as in tomato extracts, can reveal activation of AMPK signaling by dietary compounds like β-carotene and lycopene.
How CRISPR Can Be Used to Study GO:0004017 AMP kinase activity
Knockout
CRISPR knockout of genes encoding AMP kinase activity (e.g., AK1) can abolish the enzymatic function, allowing researchers to study its role in energy homeostasis and disease.
Point Mutation
Point mutations can be introduced into phosphorylation sites of AMPK substrates (e.g., MDMX) to test their functional significance in p53 signaling.
Knock-in
Knock-in of tagged or mutant versions of AMPK or adenylate kinases enables precise tracking and functional analysis in live cells.
Overexpression
Overexpression of AMPK or adenylate kinases can rescue phenotypes or amplify signaling, useful for studying downstream effects such as sarcopenia reversal.
How EDITGENE Supports AMP kinase activity Research
Researchers studying AMP kinase activity-related genes often need to determine whether a candidate gene is causally involved in a specific metabolic or disease phenotype. EDITGENE provides a comprehensive suite of CRISPR services to enable such investigations.
Contact EDITGENE today to design your custom CRISPR model for AMP kinase activity research.
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| AK1 Knockout HEK293 Cell Line | EDJ-KQ2633 | Human | 203 | Details Get a Quote |
| AK2 Knockout HEK293 Cell Line | EDJ-KQ2830 | Human | 204 | Details Get a Quote |
| AK3 Knockout HEK293 Cell Line | EDJ-KQ3401 | Human | 50808 | Details Get a Quote |
| AK7 Knockout HEK293 Cell Line | EDJ-KQ8151 | Human | 122481 | Details Get a Quote |
| AK5 Knockout HEK293 Cell Line | EDJ-KQ8508 | Human | 26289 | Details Get a Quote |
| AK9 Knockout HEK293 Cell Line | EDJ-KQ8808 | Human | 221264 | Details Get a Quote |
| AK8 Knockout HEK293 Cell Line | EDJ-KQ11569 | Human | 158067 | Details Get a Quote |
| AK3 Knockout A-549 Cell Line | EDJ-KQ25100 | Human | 50808 | Details Get a Quote |
| AK3 Knockout HCT 116 Cell Line | EDJ-KQ25101 | Human | 50808 | Details Get a Quote |
| AK3 Knockout HeLa Cell Line | EDJ-KQ25102 | Human | 50808 | Details Get a Quote |
| AK7 Knockout A-549 Cell Line | EDJ-KQ34056 | Human | 122481 | Details Get a Quote |
| AK7 Knockout HeLa Cell Line | EDJ-KQ34057 | Human | 122481 | Details Get a Quote |
| AK9 Knockout A-549 Cell Line | EDJ-KQ35107 | Human | 221264 | Details Get a Quote |
| AK9 Knockout HCT 116 Cell Line | EDJ-KQ35108 | Human | 221264 | Details Get a Quote |
| AK9 Knockout HeLa Cell Line | EDJ-KQ35109 | Human | 221264 | Details Get a Quote |
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Frequently Asked Questions About AMP kinase activity
What is AMP kinase activity?
AMP kinase activity (GO:0004017) is the catalysis of the reaction ATP + AMP = 2 ADP, also known as adenylate kinase or myokinase activity.
What genes are involved in AMP kinase activity?
Genes include AK1, AK2, AK3, AK4, AK5, and AMPK, which encode enzymes with this activity or related regulatory functions.
How is AMP kinase activity measured?
It is measured using enzyme-coupled assays, phosphorylation-specific immunoblotting, or metabolite profiling.
What is the difference between AMP kinase activity and AMPK?
AMP kinase activity refers to the phosphotransferase reaction (GO:0004017), while AMPK is a protein kinase complex that senses AMP and phosphorylates downstream targets.
What diseases are associated with AMP kinase activity?
It is linked to sarcopenia, post-COVID-19 complications, cancer, and hypoxia-related disorders.
Can CRISPR be used to study AMP kinase activity?
Yes, CRISPR knockout, knock-in, point mutation, and overexpression models are widely used to study this activity.
What is the role of AMP kinase activity in neurons?
It regulates phrenic motor plasticity and responses to intermittent hypoxia.
How does resveratrol affect AMP kinase activity?
Resveratrol stimulates AMP kinase activity in neurons, linking diet to energy sensing.
What is the relationship between AMP kinase activity and p53?
AMPK induces p53 by phosphorylating MDMX, thereby inhibiting its activity.
What model systems are used to study AMP kinase activity?
Common models include knockout cell lines, primary neurons, and hypoxia-exposed cells.
Conclusion
AMP kinase activity (GO:0004017) is a core molecular function that maintains cellular energy balance and is implicated in diverse physiological and pathological processes. Its study requires precise enzymatic assays and genetic models, which CRISPR technology now makes readily accessible. Understanding this activity offers insights into metabolism, aging, and disease, with potential therapeutic applications.
References
- 1. Perim RR et al.. 2020. Spinal AMP kinase activity differentially regulates phrenic motor plasticity.. J Appl Physiol (1985) 128(3):523-533 PMID: 31971473
- 2. Vinel C et al.. 2018. The exerkine apelin reverses age-associated sarcopenia.. Nat Med 24(9):1360-1371 PMID: 30061698
- 3. Mohri S et al.. 2022. Integration of bioassay and non-target metabolite analysis of tomato reveals that β-carotene and lycopene activate the adiponectin signaling pathway, including AMPK phosphorylation.. PLoS One 17(7):e0267248 PMID: 35776737
- 4. Alam S et al.. 2023. Hypoxia increases persulfide and polysulfide formation by AMP kinase dependent cystathionine gamma lyase phosphorylation.. Redox Biol 68:102949 PMID: 37922764
- 5. Lim CT et al.. 2012. Measurement of AMP-activated protein kinase activity and expression in response to ghrelin.. Methods Enzymol 514:271-87 PMID: 22975059
- 6. Ashraf MS et al.. 2024. AMP kinase: A promising therapeutic drug target for post-COVID-19 complications.. Life Sci 359:123202 PMID: 39489398
- 7. Dasgupta B et al.. 2007. Resveratrol stimulates AMP kinase activity in neurons.. Proc Natl Acad Sci U S A 104(17):7217-22 PMID: 17438283
- 8. He G et al.. 2014. AMP-activated protein kinase induces p53 by phosphorylating MDMX and inhibiting its activity.. Mol Cell Biol 34(2):148-57 PMID: 24190973
