Abstract
In mammals, cellular 5'-nucleotidase (5'-NT) activity (EC 3.1.3.5) encompasses a number of genetically and structurally distinct enzyme forms, either membrane-bound or soluble, mainly cytosolic, that are characterized by broad specificity towards nucleoside 5'-monophosphate substrates differing in base (purine/pyrimidine) and/or sugar (oxy/deoxy-ribose) moieties. In particular, among the cytosolic 5'-NTs active towards pyrimidine nucleotides are cN-III and cdN, ubiquitously distributed in mammalian tissues and treated as a single entity in the early days. cN-III was first linked to a genetic defect, hereditary pyrimidine nucleotidase deficiency, associated to a nonspherocytic hemolytic anemia disorder of still unclear mechanism but metabolically characterized by abnormally high levels of pyrimidine compounds and ribonucleoproteins in erythrocytes, as evidenced by occurrence of basophilic stippling on blood smearings. Since the first review on pyrimidine-specific nucleotidases (Amici, A.; Magni, G., Arch. Biochem. Biophys., 2002, 397(2), 184- 190), excellent overviews on the topic appeared in the literature. In the present contribution, the major findings on these two enzymatic proteins, cN-III and cdN, will be described with particular emphasis on the relationships between their structure and function, as well as on their roles in normal and pathological conditions. The catalytic mechanism of both specific hydrolytic and phosphotransferase activities, possessed by both enzymes, will be discussed also in the light of recent solution of both cN-III and cdN three-dimensional structures. This review also focuses on possible therapeutic approaches involving cellular 5'-NTs in detoxifying common antiviral and antineoplastic drugs.
Keywords: (Deoxy)pyrimidine 5'(3')-nucleotidase cdN, Nonspherocytic hemolytic anemia, Pyrimidine 5'-nucleotidase cN-III, Pyrimidine drug analogues, Pyrimidine homeostasis, Pyrimidine nucleotidase deficiency, Pyrimidine salvaging.
Current Medicinal Chemistry
Title:The Enzymology of Cytosolic Pyrimidine 5’-Nucleotidases: Functional Analysis and Physiopathological Implications.
Volume: 20 Issue: 34
Author(s): Giulio Magni, Adolfo Amici and Giuseppe Orsomando
Affiliation:
Keywords: (Deoxy)pyrimidine 5'(3')-nucleotidase cdN, Nonspherocytic hemolytic anemia, Pyrimidine 5'-nucleotidase cN-III, Pyrimidine drug analogues, Pyrimidine homeostasis, Pyrimidine nucleotidase deficiency, Pyrimidine salvaging.
Abstract: In mammals, cellular 5'-nucleotidase (5'-NT) activity (EC 3.1.3.5) encompasses a number of genetically and structurally distinct enzyme forms, either membrane-bound or soluble, mainly cytosolic, that are characterized by broad specificity towards nucleoside 5'-monophosphate substrates differing in base (purine/pyrimidine) and/or sugar (oxy/deoxy-ribose) moieties. In particular, among the cytosolic 5'-NTs active towards pyrimidine nucleotides are cN-III and cdN, ubiquitously distributed in mammalian tissues and treated as a single entity in the early days. cN-III was first linked to a genetic defect, hereditary pyrimidine nucleotidase deficiency, associated to a nonspherocytic hemolytic anemia disorder of still unclear mechanism but metabolically characterized by abnormally high levels of pyrimidine compounds and ribonucleoproteins in erythrocytes, as evidenced by occurrence of basophilic stippling on blood smearings. Since the first review on pyrimidine-specific nucleotidases (Amici, A.; Magni, G., Arch. Biochem. Biophys., 2002, 397(2), 184- 190), excellent overviews on the topic appeared in the literature. In the present contribution, the major findings on these two enzymatic proteins, cN-III and cdN, will be described with particular emphasis on the relationships between their structure and function, as well as on their roles in normal and pathological conditions. The catalytic mechanism of both specific hydrolytic and phosphotransferase activities, possessed by both enzymes, will be discussed also in the light of recent solution of both cN-III and cdN three-dimensional structures. This review also focuses on possible therapeutic approaches involving cellular 5'-NTs in detoxifying common antiviral and antineoplastic drugs.
Export Options
About this article
Cite this article as:
Magni Giulio, Amici Adolfo and Orsomando Giuseppe, The Enzymology of Cytosolic Pyrimidine 5’-Nucleotidases: Functional Analysis and Physiopathological Implications., Current Medicinal Chemistry 2013; 20 (34) . https://dx.doi.org/10.2174/0929867311320340009
DOI https://dx.doi.org/10.2174/0929867311320340009 |
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
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
Current advances in inherited cardiomyopathy
Describe in detail all novel advances in multimodality imaging related to inherited cardiomyopathy diagnosis and prognosis. Shed light to deeper phenotypic characterization. Acknowledge recent advances in genetics, genomics and precision medicineread 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
-
Angiogenesis in Chronic Lymphocytic Leukemia
Current Angiogenesis (Discontinued) Immune Mechanism, Aging, Season and Diseases: Modulatory Role of Melatonin
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) c-Myc and Downstream Targets in the Pathogenesis and Treatment of Cancer
Recent Patents on Anti-Cancer Drug Discovery Structure, Substrate Complexation and Reaction Mechanism of Bacterial Asparaginases
Current Chemical Biology Recent Advance in the Research of Flavonoids as Anticancer Agents
Mini-Reviews in Medicinal Chemistry Flavonoids in Cancer Prevention
Anti-Cancer Agents in Medicinal Chemistry Neuronal Generation from Somatic Stem Cells: Current Knowledge and Perspectives on the Treatment of Acquired and Degenerative Central Nervous System Disorders
Current Gene Therapy Thymidylate Synthase Gene in Pharmacogenetics
Current Pharmacogenomics Tyrosine Kinase Inhibitor as a new Therapy for Ischemic Stroke and other Neurologic Diseases: is there any Hope for a Better Outcome?
Current Neuropharmacology Dietary Phytochemicals in Chemoprevention of Cancer: An Update
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Proteolytic Cleavage of Notch: “HIT and RUN”
Current Molecular Medicine Innovations and Opportunities to Improve Conventional (Deoxy)Nucleoside and Fluoropyrimidine Analogs in Cancer
Current Medicinal Chemistry The Aging of the Adaptive Immune System
Current Immunology Reviews (Discontinued) MicroRNA Dysregulation in the Myelodysplastic Syndromes
MicroRNA Retroviral Gene Therapy: Safety Issues and Possible Solutions
Current Gene Therapy TNF-Related Apoptosis-Inducing Ligand (TRAIL): A Potential Candidate for Combined Treatment of Hematological Malignancies
Current Pharmaceutical Design Bypass Mechanisms of Resistance to Tyrosine Kinase Inhibition in Chronic Myelogenous Leukaemia
Current Drug Discovery Technologies Clinical Pharmacogenetics of Methotrexate
Current Drug Metabolism Therapeutic Use of Molecules that Mimic Pathogen Danger Signals
Endocrine, Metabolic & Immune Disorders - Drug Targets The Chemistry and Bio-Medicinal Significance of Pyrimidines & Condensed Pyrimidines
Current Topics in Medicinal Chemistry