Abstract
The cyclooxygenase isoenzymes, COX-1 and COX-2, catalyze the formation of prostaglandins, thromboxane, and levuloglandins. The prostaglandins are autocoid mediators that affect virtually all known physiological and pathological processes via their reversible interaction with G-protein coupled membrane receptors. The levuloglandins are a newer class of products that appear to act via irreversible, covalent attachment to numerous proteins. COX enzymes are clinically important because they are inhibited by aspirin and numerous other non-steroidal anti-inflammatory drugs. This inhibition of COX confers relief from inflammatory, pyretic, thrombotic, neurodegenerative and oncological maladies. About one hundred years have elapsed since Hoffman designed and synthesized acetylsalicylic (aspirin) as an agent intended to lessen the gastrointestinal irritation of salicylates while maintaining their efficacy. During the past forty years systematic advances in our understanding of the structure, regulation and function of COX isoenzymes have enabled the design and synthesis of COX-2 selective inhibitors as agents intended to lessen the gastrointestinal irritation of aspirin and non-selective NSAIDs. This review discusses: 1) how two separate catalytic processes in COX - peroxidase and prostaglandin synthase - act in an integrated fashion manner to generate prostaglandins; 2) why irreversible inactivation of COX is important constitutively and pharmacologically; 3) how cells have managed to use two closely related, almost identical enzymes in ways that discriminate their physiological versus pathological roles; 4) how investigators have used these advances to formulate and test medically important uses for old drugs (i.e. aspirin) and create new ones that still seek to achieve Hoffmans original goal.
Keywords: Cyclooxygenase Enzymes, COX-1 and COX-2, isoenzymes, anti-inflammatory drugs
Current Pharmaceutical Design
Title: Cyclooxygenase Enzymes: Regulation and Function
Volume: 10 Issue: 6
Author(s): F. A. Fitzpatrick
Affiliation:
Keywords: Cyclooxygenase Enzymes, COX-1 and COX-2, isoenzymes, anti-inflammatory drugs
Abstract: The cyclooxygenase isoenzymes, COX-1 and COX-2, catalyze the formation of prostaglandins, thromboxane, and levuloglandins. The prostaglandins are autocoid mediators that affect virtually all known physiological and pathological processes via their reversible interaction with G-protein coupled membrane receptors. The levuloglandins are a newer class of products that appear to act via irreversible, covalent attachment to numerous proteins. COX enzymes are clinically important because they are inhibited by aspirin and numerous other non-steroidal anti-inflammatory drugs. This inhibition of COX confers relief from inflammatory, pyretic, thrombotic, neurodegenerative and oncological maladies. About one hundred years have elapsed since Hoffman designed and synthesized acetylsalicylic (aspirin) as an agent intended to lessen the gastrointestinal irritation of salicylates while maintaining their efficacy. During the past forty years systematic advances in our understanding of the structure, regulation and function of COX isoenzymes have enabled the design and synthesis of COX-2 selective inhibitors as agents intended to lessen the gastrointestinal irritation of aspirin and non-selective NSAIDs. This review discusses: 1) how two separate catalytic processes in COX - peroxidase and prostaglandin synthase - act in an integrated fashion manner to generate prostaglandins; 2) why irreversible inactivation of COX is important constitutively and pharmacologically; 3) how cells have managed to use two closely related, almost identical enzymes in ways that discriminate their physiological versus pathological roles; 4) how investigators have used these advances to formulate and test medically important uses for old drugs (i.e. aspirin) and create new ones that still seek to achieve Hoffmans original goal.
Export Options
About this article
Cite this article as:
Fitzpatrick A. F., Cyclooxygenase Enzymes: Regulation and Function, Current Pharmaceutical Design 2004; 10 (6) . https://dx.doi.org/10.2174/1381612043453144
DOI https://dx.doi.org/10.2174/1381612043453144 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...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
-
Molecular Targeting of Cell Death Signal Transduction Pathways in Cancer
Current Signal Transduction Therapy Eicosanoids in Prevention and Management of Diseases
Current Molecular Medicine Monoclonal Antibodies in the Management of Solid Tumors
Current Topics in Medicinal Chemistry Tumor Cell Hypoxia and the Hypoxia-Response Signaling System as a Target for Prostate Cancer Therapy
Current Drug Targets Anesthesia Issues in Central Nervous System Disorders
Current Aging Science <i>In-silico</i> Studies and Wet-Lab Validation of Camptothecin Derivatives for Anti-Cancer Activity Against Liver (HepG2) and Lung (A549) Cancer Cell Lines
Current Topics in Medicinal Chemistry Cytochrome P450-Activated Prodrugs: Targeted Drug Delivery
Current Medicinal Chemistry CD47 Functionalization of Nanoparticles as a Poly(ethylene glycol) Alternative: A Novel Approach to Improve Drug Delivery
Current Drug Targets Gene Transfer and Drug Delivery with Electric Pulse Generators
Current Drug Metabolism Perfusion Computed Tomography and its Application in Oncologic Practice
Current Molecular Imaging (Discontinued) Strategies for Development of Antimalarials Based on Encapsulated Porphyrin Derivatives
Mini-Reviews in Medicinal Chemistry The Role and Therapeutic Potential of Ser/Thr Phosphatase PP2A in Apoptotic Signalling Networks in Human Cancer Cells
Current Molecular Medicine Design, Synthesis and Biological Evaluation of Quinoxalin-2(1H)-one Derivatives as EGFR Tyrosine Kinase Inhibitors
Anti-Cancer Agents in Medicinal Chemistry Evaluation of the Ability of an Organic Derivative of Ruthenium(II) to Reinforce the Cytotoxicity of Fast Neutron Against Malignant Cells in Culture
Letters in Drug Design & Discovery Oxidative Stress and Opioids' Toxicity: An Update
Mini-Reviews in Organic Chemistry Anti-Inflammatory Effects of Triterpenoids; Naturally Occurring and Synthetic Agents
Mini-Reviews in Organic Chemistry Cancer Stem Cells – Are Surface Markers Alone Sufficient?
Current Stem Cell Research & Therapy Prognostic and Predictive Value of Epithelial to Mesenchymal Transitionassociated Markers in Oral Squamous Cell Carcinoma
Current Proteomics Meet Our Editorial Board Member
Current Stem Cell Research & Therapy Lymphatic Targeting of Nanosystems for Anticancer Drug Therapy
Current Pharmaceutical Design