ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2012
Metabolism of circulating ADP in the bloodstream is mediated via integrated actions of soluble adenylate kinase-1 and NTPDase1/CD39 activities.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 60 citations in OpenAlex.
- Trial
- Soluble ecto-5'-nucleotidase (5'-NT), alkaline phosphatase, and adenosine deaminase (ADA1) activities in neonatal blood favor elevated extracellular adenosine.The Journal of biological chemistry · 2013Trial
- Emerging Roles of Adenosine Metabolism in Astrocytes During Brain Injury.CNS neuroscience & therapeutics · 2026Review
- Methodological guidelines for P2X receptor assays and data interpretation.Cell death & disease · 2026Review
- Extracellular Purine Metabolism-Potential Target in Multiple Sclerosis.Molecular neurobiology · 2024Review
- Circulating Ectonucleotidases Signal Impaired Myocardial Perfusion at Rest and Stress.Journal of the American Heart Association · 2023Article
- Regulation of Adenine Nucleotide Metabolism by Adenylate Kinase Isozymes: Physiological Roles and Diseases.International journal of molecular sciences · 2023Review
- The Role of Cluster of Differentiation 39 (CD39) and Purinergic Signaling Pathway in Viral Infections.Pathogens (Basel, Switzerland) · 2023Review
- Inflammatory biomarkers after an exercise intervention in childhood acute lymphoblastic leukemia survivors.EJHaem · 2022Article
- ATP and Adenosine Metabolism in Cancer: Exploitation for Therapeutic Gain.Pharmacological reviews · 2022Review
- Optimized HPLC method to elucidate the complex purinergic signaling dynamics that regulate ATP, ADP, AMP, and adenosine levels in human blood.Purinergic signalling · 2022Article
- Role of CD39 in COVID-19 Severity: Dysregulation of Purinergic Signaling and Thromboinflammation.Frontiers in immunology · 2022Article
- Assessing the Interactions of Statins with Human Adenylate Kinase Isoenzyme 1: Fluorescence and Enzyme Kinetic Studies.International journal of molecular sciences · 2021Article
- Conversion of extracellular ATP into adenosine: a master switch in renal health and disease.Nature reviews. Nephrology · 2020Review
- Nucleotide ecto-enzyme metabolic pattern and spatial distribution in calcific aortic valve disease; its relation to pathological changes and clinical presentation.Clinical research in cardiology : official journal of the German Cardiac Society · 2020Article
- Review
- Soluble and membrane-bound adenylate kinase and nucleotidases augment ATP-mediated inflammation in diabetic retinopathy eyes with vitreous hemorrhage.Journal of molecular medicine (Berlin, Germany) · 2019Article
- Generation and Function of Non-cell-bound CD73 in Inflammation.Frontiers in immunology · 2019Review
- Alteration of Extracellular Nucleotide Metabolism in Pseudoxanthoma Elasticum.The Journal of investigative dermatology · 2018Article
- Erythrocytes retain hypoxic adenosine response for faster acclimatization upon re-ascent.Nature communications · 2017Article
Corrections and comments
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Authors and funding
4 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Extracellular ATP and ADP trigger inflammatory, vasodilatatory, and prothrombotic signaling events in the vasculature, and their turnover is governed by networks of membrane-associated enzymes. The contribution of soluble activities to intravascular nucleotide homeostasis remains controversial. By using thin-layer chromatographic assays, we revealed transphosphorylation of [γ-(32)P]ATP and AMP by human and murine sera, which was progressively inhibited by specific adenylate kinase (AK) inhibitor Ap(5)A. This phosphotransfer reaction was diminished markedly in serum from knockout mice lacking the major AK isoform, AK1, and in human serum immunodepleted of AK1. We also showed that ∼75% ADP in cell-free serum is metabolized via reversible AK1 reaction 2ADP ↔ ATP + AMP. The generated ATP and AMP are then metabolized through the coupled nucleotide pyrophosphatase/phosphodiesterase and 5'-nucleotidase/CD73 reactions, respectively. Constitutive presence of another nucleotide-converting enzyme, nucleoside triphosphate diphosphohydrolase-1 (NTPDase1, known as CD39), was ascertained by the relative deficiency of serum from CD39-null mice to dephosphorylate [(3)H]ADP and [γ-(32)P]ATP, and also by diminished [(3)H]ADP hydrolysis by human serum pretreated with NTPDase1 inhibitors, POM-1 and ARL-67156. In summary, we have identified hitherto unrecognized soluble forms of AK1 and NTPDase1/CD39 that contribute in the active cycling between the principal platelet-recruiting agent ADP and other circulating nucleotides.
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Registered trials
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