Abstract
Adenosine- and uridine-cytidine kinases, purine-nucleoside phosphorylase, hypoxanthine-guanine phosphoribosyl transferase, and several related enzymes, are components of the salvage pathways which reduce the loss of intracellular purine and pyrimidine rings. Although this could explain the role of these enzymes, it poses a problem of the role of the cytosolic 5'-nucleotidase. Why are nucleosides produced from nucleoside-monophosphates, only to be converted back to the same compounds? To date, it is well established that a cross talk exists between the extracellular and intracellular nucleoside metabolism. In districts, such as brain, which are dependent on salvage nucleotide synthesis, nucleosides are produced through the action of the ecto-5'-nucleotidase, the last component of a series of plasma-membrane bound enzyme proteins, catalyzing the successive dephosphorylation of released nucleoside-triphosphates. Both nucleosidetriphosphates (mainly ATP and UTP) and nucleosides (mainly adenosine), act as extracellular signals. Once transported into cell cytosol, all nucleosides are salvaged back to nucleoside-triphosphates, with the exception of inosine, whose salvage is limited to IMP. Intracellular balance of nucleosides is maintained by the action of several enzymes, such as adenosine deaminase, uridine phosphorylase and cytidine deaminase, and by at least three 5'-nucleotidases, the ADP activated AMP preferring cN-IA, the ATP-ADP activated IMP-GMP preferring cN-II, and the UMP-CMP preferring cN-III. Here we are reviewing the mechanisms whereby cytosolic 5'-nucleotidases control changes in nucleoside and nucleotide concentration, with the aim to provide a common basis for the study of the relationship between biochemistry and other related disciplines, such as physiology and pharmacology.
Keywords: 5'-nucleotidases, cN-IA, cN-II, cN-III, nucleoside utilization, nucleoside recycling.
Current Medicinal Chemistry
Title:The Functional Logic of Cytosolic 5’-Nucleotidases.
Volume: 20 Issue: 34
Author(s): P. L. Ipata and F. Balestri
Affiliation:
Keywords: 5'-nucleotidases, cN-IA, cN-II, cN-III, nucleoside utilization, nucleoside recycling.
Abstract: Adenosine- and uridine-cytidine kinases, purine-nucleoside phosphorylase, hypoxanthine-guanine phosphoribosyl transferase, and several related enzymes, are components of the salvage pathways which reduce the loss of intracellular purine and pyrimidine rings. Although this could explain the role of these enzymes, it poses a problem of the role of the cytosolic 5'-nucleotidase. Why are nucleosides produced from nucleoside-monophosphates, only to be converted back to the same compounds? To date, it is well established that a cross talk exists between the extracellular and intracellular nucleoside metabolism. In districts, such as brain, which are dependent on salvage nucleotide synthesis, nucleosides are produced through the action of the ecto-5'-nucleotidase, the last component of a series of plasma-membrane bound enzyme proteins, catalyzing the successive dephosphorylation of released nucleoside-triphosphates. Both nucleosidetriphosphates (mainly ATP and UTP) and nucleosides (mainly adenosine), act as extracellular signals. Once transported into cell cytosol, all nucleosides are salvaged back to nucleoside-triphosphates, with the exception of inosine, whose salvage is limited to IMP. Intracellular balance of nucleosides is maintained by the action of several enzymes, such as adenosine deaminase, uridine phosphorylase and cytidine deaminase, and by at least three 5'-nucleotidases, the ADP activated AMP preferring cN-IA, the ATP-ADP activated IMP-GMP preferring cN-II, and the UMP-CMP preferring cN-III. Here we are reviewing the mechanisms whereby cytosolic 5'-nucleotidases control changes in nucleoside and nucleotide concentration, with the aim to provide a common basis for the study of the relationship between biochemistry and other related disciplines, such as physiology and pharmacology.
Export Options
About this article
Cite this article as:
Ipata L. P. and Balestri F., The Functional Logic of Cytosolic 5’-Nucleotidases., Current Medicinal Chemistry 2013; 20 (34) . https://dx.doi.org/10.2174/0929867311320340002
DOI https://dx.doi.org/10.2174/0929867311320340002 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
ABAD: A Potential Therapeutic Target for Aβ-Induced Mitochondrial Dysfunction in Alzheimers Disease
Mini-Reviews in Medicinal Chemistry Oxidative and Nitrosative Stress and Immune-inflammatory Pathways in Patients with Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS)
Current Neuropharmacology Control and Role of Plateau Potential Properties in the Spinal Cord
Current Pharmaceutical Design Recent Patents on Ophthalmic Nanoformulations and Therapeutic Implications
Recent Patents on Drug Delivery & Formulation Regulation of the Protein C Anticoagulant and Antiinflammatory Pathways
Current Medicinal Chemistry Nanoparticles for Cancer Targeting: Current and Future Directions
Current Drug Delivery Lung Defence Mechanisms and Their Potential Role in the Prevention of Ventilator Associated Pneumonia
Current Respiratory Medicine Reviews GluVII:06 - A Highly Conserved and Selective Anchor Point for Non-Peptide Ligands in Chemokine Receptors
Current Topics in Medicinal Chemistry Lentiviral Vectors: A Versatile Tool to Fight Cancer
Current Molecular Medicine Chronopharmaceutics Based Modern Colon Specific Drug Delivery Systems
Current Drug Discovery Technologies Targeting Epigenetics in Nervous System Disease
CNS & Neurological Disorders - Drug Targets Leptin in Joint and Bone Diseases: New Insights
Current Medicinal Chemistry Crosstalk Signalling Role in Modulation of Drugs Side Effects
Current Molecular Pharmacology Targeting Drugs Against Fibroblast Growth Factor(s)-Induced Cell Signaling
Current Drug Targets Thyroid Hormone Treatment for Differentiated Thyroid Carcinoma: What Drug, How Long, What Dose?
Current Cancer Therapy Reviews The Bioartificial Kidney in the Treatment of Acute Kidney Injury
Current Drug Targets A Comprehensive Review on Exosomes and Microvesicles as Epigenetic Factors
Current Stem Cell Research & Therapy Antiphospholipid Antibody-Mediated Thrombotic Mechanisms in Antiphospholipid Syndrome: Towards Pathophysiology-Based Treatment
Current Pharmaceutical Design Cellular Energetical Actions of “Chemical” and “Surgical” Vagotomy in Gastrointestinal Mucosal Damage and Protection: Similarities, Differences and Significance for Brain-Gut Function
Current Neuropharmacology Induced Pluripotent Stem Cells as a Model for Therapy Personalization of Pediatric Patients: Disease Modeling and Drug Adverse Effects Prevention
Current Medicinal Chemistry