Abstract
The metabolic O-methylation of endogenous catecholamines and other catechols catalyzed by catechol-O-methyltransferase (COMT EC 2.1.1.6) was first described by Dr. Julix Axelrod and his colleagues almost half a century ago. In the past several years, research interest in this catechol-metabolizing system has been renewed because of its potential pathophysiological and pathogenic significance in estrogen-induced hormonal cancers, in the development of degenerative brain disorders, as well as in the development of cardiovascular diseases. In this review paper, I provide a brief overview of the COMT metabolic system, with particular attentions being paid to the following three areas: (i) the regulation of this catechol-metabolizing system by endogenous regulatory factors (mainly S-adenosyl-L-homocysteine and homocysteine) as well as by exogenous factors such as dietary phytochemicals (ii) decreased metabolic O-methylation of endogenous catecholamines as an important risk factor for the development of ne urodegenerative disorders such as Parkinsons and Alzheimers diseases in the elderly and also as a risk factor for the development of a variety of cardiovascular diseases and (iii) the relative importance of the COMT-catalyzed O-methylation metabolism of endogenous catechol estrogens in the causation and prevention of estrogen-induced hormonal cancers. Some unifying hypotheses are also discussed in this paper with the hope that they may provide useful mechanistic insights into our understanding of the biological functions that are associated with this important metabolic system.
Keywords: heterocyclic amines, hcacdmt, s-comt, mb-comt, endogenous catechol
Current Drug Metabolism
Title: Catechol-O-Methyltransferase (COMT)-Mediated Methylation Metabolism of Endogenous Bioactive Catechols and Modulation by Endobiotics and Xenobiotics: Importance in Pathophysiology and Pathogenesis
Volume: 3 Issue: 3
Author(s): Bao Ting Zhu
Affiliation:
Keywords: heterocyclic amines, hcacdmt, s-comt, mb-comt, endogenous catechol
Abstract: The metabolic O-methylation of endogenous catecholamines and other catechols catalyzed by catechol-O-methyltransferase (COMT EC 2.1.1.6) was first described by Dr. Julix Axelrod and his colleagues almost half a century ago. In the past several years, research interest in this catechol-metabolizing system has been renewed because of its potential pathophysiological and pathogenic significance in estrogen-induced hormonal cancers, in the development of degenerative brain disorders, as well as in the development of cardiovascular diseases. In this review paper, I provide a brief overview of the COMT metabolic system, with particular attentions being paid to the following three areas: (i) the regulation of this catechol-metabolizing system by endogenous regulatory factors (mainly S-adenosyl-L-homocysteine and homocysteine) as well as by exogenous factors such as dietary phytochemicals (ii) decreased metabolic O-methylation of endogenous catecholamines as an important risk factor for the development of ne urodegenerative disorders such as Parkinsons and Alzheimers diseases in the elderly and also as a risk factor for the development of a variety of cardiovascular diseases and (iii) the relative importance of the COMT-catalyzed O-methylation metabolism of endogenous catechol estrogens in the causation and prevention of estrogen-induced hormonal cancers. Some unifying hypotheses are also discussed in this paper with the hope that they may provide useful mechanistic insights into our understanding of the biological functions that are associated with this important metabolic system.
Export Options
About this article
Cite this article as:
Zhu Ting Bao, Catechol-O-Methyltransferase (COMT)-Mediated Methylation Metabolism of Endogenous Bioactive Catechols and Modulation by Endobiotics and Xenobiotics: Importance in Pathophysiology and Pathogenesis, Current Drug Metabolism 2002; 3 (3) . https://dx.doi.org/10.2174/1389200023337586
DOI https://dx.doi.org/10.2174/1389200023337586 |
Print ISSN 1389-2002 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5453 |
Call for Papers in Thematic Issues
Exploring oxidative stress and the anti-oxidant defense system in chronic diseases: therapeutic strategies and future perspective
Ageing is facilitated by oxidative stress (OS), which happens spontaneously. Several studies have demonstrated that OS over an extended period of time has a role in the emergence of several chronic illnesses. Diabetes, cancer, and heart disease are a few examples of these ailments. An imbalance between the body's antioxidants ...read more
Impact of brain tissue binding and plasma protein binding of drugs in DMPK
The impression of brain tissue binding (BTB) or plasma protein binding (PPB) in Drug Metabolism and Pharmacokinetics is critical to understanding the distribution, efficacy, and potential toxicity of drugs that target the central nervous system (CNS). BTB and high PPB influence the distribution of drugs in the body and their ...read more
Interaction between drugs and endocrine diseases
The introduction of highly active antiretroviral therapy accelerated studies and our understanding on the interaction between pharmacological therapies and endocrine diseases. Drugs can precipitate endocrine via different mechanisms, including direct alteration of hormone production and secretion, dysregulation of hormonal axis, effects on hormonal transport, receptor-binding, and cellular signalling. Common drug-induced ...read more
Metabolism-mediated xenobiotic toxicity
Considering the potent modulation of biotransformation enzyme expression and activities by various therapeutic drugs and environmental chemicals, and the commonly combined exposure of humans to both drugs and the ever increasing environmental pollutants simultaneously, knowledge about the combined toxic effects by modulating biotransformation enzymes, such as P450s, UDP- glucuronosyltransferases, and ...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
- Announcements
Related Articles
-
The Expression of the Cold Shock Protein RNA Binding Motif Protein 3 is Transcriptionally Responsive to Organ Temperature in Mice
Protein & Peptide Letters Can Targeting the Incretin Pathway Dampen RAGE-Mediated Events in Diabetic Nephropathy?
Current Drug Targets Potential of Plant-sourced Phenols for Inflammatory Bowel Disease
Current Medicinal Chemistry Emerging Concepts on Inhibitors of Indoleamine 2,3-Dioxygenase in Rheumatic Diseases
Current Medicinal Chemistry Antithrombin, an Important Inhibitor in Blood Clots
Current Topics in Medicinal Chemistry Epicardial Adipocyte-derived TNF-α Modulates Local Inflammation in Patients with Advanced Coronary Artery Disease
Current Vascular Pharmacology Anti-Cancer Activity of 2,4-Disubstituted Thiophene Derivatives: Dual Inhibitors of Lipoxygenase and Cyclooxygenase
Medicinal Chemistry Human Complex Trait Genetics: Lifting the Lid of the Genomics Toolbox - from Pathways to Prediction
Current Genomics Bidirectional Nature of Cardiovascular and Kidney Disease
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Gender, Hormones and the Transmissible Encephalopathies
Current Medicinal Chemistry - Immunology, Endocrine & Metabolic Agents Multimodal Imaging for the Diagnosis of Massive Left Atrial Metastasis from Lung Cancer - A Case Report
Current Medical Imaging Astatine Radiopharmaceuticals: Prospects and Problems
Current Radiopharmaceuticals Prospectives of Antihypertensive Nano-ceuticals as Alternative Therapeutics
Current Drug Targets Advanced Nanomedicines for the Treatment and Diagnosis of Myocardial Infarction and Heart Failure
Current Drug Targets Stem Cells and Congenital Heart Disease: The Future Potential Clinical Therapy Beyond Current Treatment
Current Cardiology Reviews Effect of Aging On Angiogenesis and Arteriogenesis
Current Cardiology Reviews The Bioactive Compounds Obtained from Hawthorn, Chokeberry, Rosehip and Bilberry by Microfiltration
Current Bioactive Compounds The CD4C/HIVNef Transgenic Model of AIDS
Current HIV Research Primary and Secondary Insomnia: Prevalence, Causes and Current Therapeutics
Current Medicinal Chemistry - Central Nervous System Agents Nintedanib as the First Treatment for Group of Progressive Interstitial Lung Diseases: A Review of Patent Literature
Recent Advances in Inflammation & Allergy Drug Discovery