Abstract
Nicotinamide mononucleotide adenylyltransferease (NMNAT), a rate-limiting enzyme present in all organisms, reversibly catalyzes the important step in the biosynthesis of NAD from ATP and NMN. NAD and NADP are used reversibly in anabolic and catabolic reactions. NAD is necessary for cell survival in oxidative stress and DNA damage. Based on their localization, three different NMNATs have been recognized, NMNAT-1 (homohexamer) in the nucleus (chromosome 1 p32-35), NMNAT-2 (homodimer) in the cytoplasm (chromosome 1q25) and NMNAT-3 (homotetramer) in the mitochondria. NMNAT also catalyzes the metabolic conversion of potent antitumor prodrugs like tiazofurin and benzamide riboside to their active forms which are analogs of NAD. NAD synthase- NMNAT acts as a chaperone to protect against neurodegeneration, injury-induced axonal degeneration and also correlates with DNA synthesis during cell cycle. Since its activity is rather low in tumor cells it can be exploited as a source for therapeutic targeting. Steps involved in NAD synthesis are being utilized as targets for chemoprevention, radiosensitization and therapy of wide range of diseases, such as cancer, multiple sclerosis, neurodegeneration and Huntingtons disease.
Keywords: Nicotinamide 5'-monucleotide adenylyltransferase, nicotinamide adenine dinucleotide, targeted therapy, tiazofurin, benzamide riboside, homohexamer, radiosensitization, neurodegeneration, Huntington's disease
Current Medicinal Chemistry
Title: NMNAT Expression and its Relation to NAD Metabolism
Volume: 18 Issue: 13
Author(s): H. N. Jayaram, P. Kusumanchi and J. A. Yalowitz
Affiliation:
Keywords: Nicotinamide 5'-monucleotide adenylyltransferase, nicotinamide adenine dinucleotide, targeted therapy, tiazofurin, benzamide riboside, homohexamer, radiosensitization, neurodegeneration, Huntington's disease
Abstract: Nicotinamide mononucleotide adenylyltransferease (NMNAT), a rate-limiting enzyme present in all organisms, reversibly catalyzes the important step in the biosynthesis of NAD from ATP and NMN. NAD and NADP are used reversibly in anabolic and catabolic reactions. NAD is necessary for cell survival in oxidative stress and DNA damage. Based on their localization, three different NMNATs have been recognized, NMNAT-1 (homohexamer) in the nucleus (chromosome 1 p32-35), NMNAT-2 (homodimer) in the cytoplasm (chromosome 1q25) and NMNAT-3 (homotetramer) in the mitochondria. NMNAT also catalyzes the metabolic conversion of potent antitumor prodrugs like tiazofurin and benzamide riboside to their active forms which are analogs of NAD. NAD synthase- NMNAT acts as a chaperone to protect against neurodegeneration, injury-induced axonal degeneration and also correlates with DNA synthesis during cell cycle. Since its activity is rather low in tumor cells it can be exploited as a source for therapeutic targeting. Steps involved in NAD synthesis are being utilized as targets for chemoprevention, radiosensitization and therapy of wide range of diseases, such as cancer, multiple sclerosis, neurodegeneration and Huntingtons disease.
Export Options
About this article
Cite this article as:
N. Jayaram H., Kusumanchi P. and A. Yalowitz J., NMNAT Expression and its Relation to NAD Metabolism, Current Medicinal Chemistry 2011; 18 (13) . https://dx.doi.org/10.2174/092986711795590138
DOI https://dx.doi.org/10.2174/092986711795590138 |
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
-
1, 2-Benzisoxazole: A Privileged Structure with a Potential for Polypharmacology
Current Pharmaceutical Design The Guanylyl Cyclase Inhibition by MB as Vasoplegic Circulatory Shock Therapeutical Target
Current Drug Targets The Potential Role of Sirtuins Regarding the Effects of Exercise on Aging- Related Diseases
Current Aging Science Roles of Arterial Baroreceptor Reflex During Bezold-Jarisch Reflex
Current Cardiology Reviews Endothelial Effects of Drugs Designed to Treat Erectile Dysfunction
Current Pharmaceutical Design Glycine/NMDA Receptor Antagonists as Potential CNS Therapeutic Agents: ACEA-1021 and Related Compounds
Current Topics in Medicinal Chemistry Overview of Systems Biology and Omics Technologies
Current Medicinal Chemistry Lipid Rafts and Redox Regulation of Cellular Signaling in Cholesterol Induced Atherosclerosis
Current Cardiology Reviews Lipoprotein Like Nanoparticles Used in Drug and Gene Delivery
Current Pharmaceutical Design Interactive Effect of Cigarette Smoking and Gene Variants for Predisposing to Cardiovascular Disease
Current Pharmaceutical Design Characterization of Adipose-Derived Stem Cells: An Update
Current Stem Cell Research & Therapy Inflammation and Inflammatory Cell Recruitment in Acute Cerebrovascular Diseases
Current Immunology Reviews (Discontinued) Role of Dietary Fiber in Formation and Prevention of Small Intestinal Ulcers Induced by Nonsteroidal Anti-Inflammatory Drug
Current Pharmaceutical Design MicroRNAs as Diagnostic, Prognostic and Predictive Biomarkers of Cardiac Disease
Recent Patents on Biomarkers Pulmonary Hypertension in the Critically Ill
Current Hypertension Reviews Therapeutic Indications and Action Mechanisms of Bilirubin: Suggestions from Natural Calculus Bovis
Current Signal Transduction Therapy Recombinant Tissue-Type Plasminogen Activator (Alteplase) in the Management of Acute Ischemic Stroke: A Review of its Pharmacological Properties, Efficacy, Safety and Pharmacoeconomic Aspects
Current Drug Therapy Stem Cells and Translational Medicine: From Research to Clinical Procedures
Current Tissue Engineering (Discontinued) The Plasma and Tissue Kininogen-kallikrein-kinin System: Role in the Cardiovascular System
Current Medicinal Chemistry - Cardiovascular & Hematological Agents Benefits of L-Arginine on Cardiovascular System
Mini-Reviews in Medicinal Chemistry