Abstract
Thioredoxin plays a crucial role in a wide number of physiological processes, which span from reduction of nucleotides to deoxyriboucleotides to the detoxification from xenobiotics, oxidants and radicals. The redox function of Thioredoxin is critically dependent on the enzyme Thioredoxin NADPH Reductase (TrxR). In view of its indirect involvement in the above mentioned physio/pathological processes, inhibition of TrxR is an important clinical goal. As a general rule, the affinities and mechanisms of binding of TrxR inhibitors to the target enzyme are known with scarce precision and conflicting results abound in the literature. A relevant analysis of published results as well as the experimental procedures is therefore needed, also in view of the critical interest of TrxR inhibitors. We review the inhibitors of TrxR and related flavoreductases and the classical treatment of reversible, competitive, non competitive and uncompetitive inhibition with respect to TrxR, and in some cases we are able to reconcile contradictory results generated by oversimplified data analysis.
Keywords: Thioredoxin reductase, mechanism of inhibition, competitive inhibitor, uncompetitive inhibitor, irreversible inhibitor, suicide substrates, pseudo-irreversible inhibition, double-substrate enzyme.
Current Protein & Peptide Science
Title:Thioredoxin Reductase and its Inhibitors
Volume: 15 Issue: 6
Author(s): Fulvio Saccoccia, Francesco Angelucci, Giovanna Boumis, Daniela Carotti, Gianni Desiato, Adriana E. Miele and Andrea Bellelli
Affiliation:
Keywords: Thioredoxin reductase, mechanism of inhibition, competitive inhibitor, uncompetitive inhibitor, irreversible inhibitor, suicide substrates, pseudo-irreversible inhibition, double-substrate enzyme.
Abstract: Thioredoxin plays a crucial role in a wide number of physiological processes, which span from reduction of nucleotides to deoxyriboucleotides to the detoxification from xenobiotics, oxidants and radicals. The redox function of Thioredoxin is critically dependent on the enzyme Thioredoxin NADPH Reductase (TrxR). In view of its indirect involvement in the above mentioned physio/pathological processes, inhibition of TrxR is an important clinical goal. As a general rule, the affinities and mechanisms of binding of TrxR inhibitors to the target enzyme are known with scarce precision and conflicting results abound in the literature. A relevant analysis of published results as well as the experimental procedures is therefore needed, also in view of the critical interest of TrxR inhibitors. We review the inhibitors of TrxR and related flavoreductases and the classical treatment of reversible, competitive, non competitive and uncompetitive inhibition with respect to TrxR, and in some cases we are able to reconcile contradictory results generated by oversimplified data analysis.
Export Options
About this article
Cite this article as:
Saccoccia Fulvio, Angelucci Francesco, Boumis Giovanna, Carotti Daniela, Desiato Gianni, Miele E. Adriana and Bellelli Andrea, Thioredoxin Reductase and its Inhibitors, Current Protein & Peptide Science 2014; 15 (6) . https://dx.doi.org/10.2174/1389203715666140530091910
DOI https://dx.doi.org/10.2174/1389203715666140530091910 |
Print ISSN 1389-2037 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5550 |
Call for Papers in Thematic Issues
Advancements in Proteomic and Peptidomic Approaches in Cancer Immunotherapy: Unveiling the Immune Microenvironment
The scope of this thematic issue centers on the integration of proteomic and peptidomic technologies into the field of cancer immunotherapy, with a particular emphasis on exploring the tumor immune microenvironment. This issue aims to gather contributions that illustrate the application of these advanced methodologies in unveiling the complex interplay ...read more
Artificial Intelligence for Protein Research
Protein research, essential for understanding biological processes and creating therapeutics, faces challenges due to the intricate nature of protein structures and functions. Traditional methods are limited in exploring the vast protein sequence space efficiently. Artificial intelligence (AI) and machine learning (ML) offer promising solutions by improving predictions and speeding up ...read more
Nutrition and Metabolism in Musculoskeletal Diseases
The musculoskeletal system consists mainly of cartilage, bone, muscles, tendons, connective tissue and ligaments. Balanced metabolism is of vital importance for the homeostasis of the musculoskeletal system. A series of musculoskeletal diseases (for example, sarcopenia, osteoporosis) are resulted from the dysregulated metabolism of the musculoskeletal system. Furthermore, metabolic diseases (such ...read more
Protein Folding, Aggregation and Liquid-Liquid Phase Separation
Protein folding, misfolding and aggregation remain one of the main problems of interdisciplinary science not only because many questions are still open, but also because they are important from the point of view of practical application. Protein aggregation and formation of fibrillar structures, for example, is a hallmark of a ...read more
Related Journals
- 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
Related Articles
-
Modulation of Host Cell Nucleocytoplasmic Trafficking During Picornavirus Infection
Infectious Disorders - Drug Targets Tumor-Receptor Imaging in Breast Cancer: A Tool for Patient Selection and Response Monitoring
Current Molecular Medicine Importance and Limitations of Chemotherapy Among the Available Treatments for Gastrointestinal Tumours
Anti-Cancer Agents in Medicinal Chemistry Inhibitory Mechanisms of CME-1, a Novel Polysaccharide from the Mycelia of Cordyceps sinensis, in Platelet Activation
Current Pharmaceutical Biotechnology Cutaneous Melanoma: A Test Field for Immunotherapy and a Medical Challenge
Current Cancer Therapy Reviews Recent Advances in Pretargeted Radioimmunotherapy
Current Medicinal Chemistry Concanavalin A, from an Old Protein to Novel Candidate Anti-Neoplastic Drug
Current Molecular Pharmacology Intracoronary Injection of Glycoprotein IIb/IIIa, Abciximab, as Adjuvant Therapy in Primary Coronary Intervention
Cardiovascular & Hematological Agents in Medicinal Chemistry Highly Organized Nanostructures for Brain Drug Delivery - New Hope or Just a Fad?
CNS & Neurological Disorders - Drug Targets Gold Coordination Complexes as Anticancer Agents
Anti-Cancer Agents in Medicinal Chemistry Chemical and Structural Features Influencing the Biological Activity of Curcumin
Current Pharmaceutical Design Editorial (Thematic Issue: Induced Pluripotent Stem Cells (iPSCs) in the Gastroenterology and Hepatology: from Basic Research to Clinical Applications)
Current Stem Cell Research & Therapy TRP Channels: Emerging Links Between Ca2+, Kidney and Hypertension
Current Hypertension Reviews Bone Seeking Radiopharmaceuticals for Palliation of Pain in Cancer Patients with Osseous Metastases
Anti-Cancer Agents in Medicinal Chemistry Selenium Deficiency in Soils and Crops and its Impact on Animal and Human Health
Current Nutrition & Food Science The Importance of Stereochemistry on the Actions of Vitamin D
Current Topics in Medicinal Chemistry Volatilome Metabolomics and Databases, Recent Advances and Needs
Current Metabolomics HLA Peptide-mediated Strategies for Modulation of Cellular and Humoral Immune Response in Transplantation
Current Pharmacogenomics Wound Healing Effect of an in Situ Forming Hydrogel Loading Curcumin-Phospholipid Complex
Current Drug Delivery Preparation and Antitumor Effect of N-Trimethylchitosan/Fucoidan Ion-Complex Submicron Particles
Current Nanoscience