Abstract
Ornithine transcarbamylase (OTC; EC 2.1.3.3) is a one-carbon-unit transferring enzyme that synthesizes citrulline using ornithine and carbamoylphosphate as substrates. It is involved in the metabolic transformation of arginine and proline, and it participates in the urea cycle in vertebrates and in the formation of putrescine in plants. Its enzymatic reaction is consistent with a ping-pong mechanism. OTC is expressed in a large variety of organisms from bacteria to mammals. Its gene can be regulated by glucocorticoids and other transcriptional factors such as C/EBP and HNF-4. The functional enzyme exists mostly as a trimer with an approximate molecular weight of 38 kDa. Inborn errors associated with a deficiency of OTC activity cause mainly urea cycle-related disorders, and lead to hyperammonemic states that may become lethal. In humans and experimental animals, OTC is localized in the mitochondrial matrix, mainly in the liver, but it is also in the intestinal epithelial cells. Some states of hepatotoxicity are associated with hepatocyte disruption and release of OTC into the bloodstream. However, recent evidence suggests that during active cell proliferation (e.g., during liver regeneration), OTC is also released from the hepatic tissue but without apparent damage. In this situation, extracellular and circulating hepatic OTC could be playing a different role, possibly functioning as a signaling molecule.
Keywords: Liver, mitochondria, circulating OTC, protein structure, enzymatic reaction, signaling molecule
Current Medicinal Chemistry
Title: Molecular and Biochemical Features of the Mitochondrial Enzyme Ornithine Transcarbamylase: A Possible New Role as a Signaling Factor
Volume: 17 Issue: 21
Author(s): Mauricio Diaz-Munoz and Rolando Hernandez-Munoz
Affiliation:
Keywords: Liver, mitochondria, circulating OTC, protein structure, enzymatic reaction, signaling molecule
Abstract: Ornithine transcarbamylase (OTC; EC 2.1.3.3) is a one-carbon-unit transferring enzyme that synthesizes citrulline using ornithine and carbamoylphosphate as substrates. It is involved in the metabolic transformation of arginine and proline, and it participates in the urea cycle in vertebrates and in the formation of putrescine in plants. Its enzymatic reaction is consistent with a ping-pong mechanism. OTC is expressed in a large variety of organisms from bacteria to mammals. Its gene can be regulated by glucocorticoids and other transcriptional factors such as C/EBP and HNF-4. The functional enzyme exists mostly as a trimer with an approximate molecular weight of 38 kDa. Inborn errors associated with a deficiency of OTC activity cause mainly urea cycle-related disorders, and lead to hyperammonemic states that may become lethal. In humans and experimental animals, OTC is localized in the mitochondrial matrix, mainly in the liver, but it is also in the intestinal epithelial cells. Some states of hepatotoxicity are associated with hepatocyte disruption and release of OTC into the bloodstream. However, recent evidence suggests that during active cell proliferation (e.g., during liver regeneration), OTC is also released from the hepatic tissue but without apparent damage. In this situation, extracellular and circulating hepatic OTC could be playing a different role, possibly functioning as a signaling molecule.
Export Options
About this article
Cite this article as:
Diaz-Munoz Mauricio and Hernandez-Munoz Rolando, Molecular and Biochemical Features of the Mitochondrial Enzyme Ornithine Transcarbamylase: A Possible New Role as a Signaling Factor, Current Medicinal Chemistry 2010; 17 (21) . https://dx.doi.org/10.2174/092986710791331031
DOI https://dx.doi.org/10.2174/092986710791331031 |
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
-
A New Glucocorticoid Hypothesis of Brain Aging: Implications for Alzheimers Disease
Current Alzheimer Research Recent Advances in Targeting Viral Proteases for the Discovery of Novel Antivirals
Current Topics in Medicinal Chemistry Preclinical Evaluation of Efficacy and Safety of an Improved Lentiviral Vector for the Treatment of β-Thalassemia and Sickle Cell Disease
Current Gene Therapy Patents of Pentoxifylline Administration on Some Diseases and Chronic Wounds
Recent Patents on Regenerative Medicine Cardiac Stem Cell Regeneration in Metabolic Syndrome
Current Pharmaceutical Design Heat Shock Proteins: Mediators of Atherosclerotic Development
Current Drug Targets Viral Myocarditis and Dilated Cardiomyopathy: Etiology and Pathogenesis
Current Pharmaceutical Design Neuronal Ceroid Lipofuscinosis: The Increasing Spectrum of an Old Disease
Current Molecular Medicine Effect of Alpha-1-Acid Glycoprotein Binding on Pharmacokinetics and Pharmacodynamics
Current Drug Metabolism Lipodystrophy, Insulin Resistance, and Adiponectin Concentration in HIV-Infected Children and Adolescents
Current HIV Research Subject index to volume 3
Current Molecular Medicine Extracellular Vesicles as Novel Delivery Tools for Cancer Treatment
Current Cancer Drug Targets The Role of Neopterin in Atherogenesis and Cardiovascular Risk Assessment
Current Medicinal Chemistry Stem Cells in Cardiovascular Regeneration: From Preservation of Endogenous Repair to Future Cardiovascular Therapies
Current Pharmaceutical Design RNA Interference as a Tool for Alzheimers Disease Therapy
Mini-Reviews in Medicinal Chemistry Tumor-Targeting Peptides and Small Molecules as Anti-Cancer Agents to Overcome Drug Resistance
Current Medicinal Chemistry TRPV1 Function in Health and Disease
Current Pharmaceutical Biotechnology Biomedical Applications of Natural Polymers for Drug Delivery
Current Organic Chemistry Recently Patented Viral Nucleotide Sequences and Generation of Virus-Derived Vaccines
Recent Patents on Anti-Infective Drug Discovery Reactive Oxygen Species in Myocardial Reperfusion Injury: From Physiopathology to Therapeutic Approaches
Current Pharmaceutical Biotechnology