Abstract
Glucuronidation is an important mechanism used by mammalian systems to clear and eliminate both endogenous and foreign chemicals. Many functional groups are susceptible to conjugation with glucuronic acid, including hydroxyls, phenols, carboxyls, activated carbons, thiols, amines, and selenium. Primary and secondary amines can also react with carbon dioxide (CO2) via a reversible reaction to form a carbamic acid. The carbamic acid is also a substrate for glucuronidation and results in a stable carbamate glucuronide metabolite. The detection and characterization of these products has been facilitated greatly by the advent of soft ionization mass spectrometry techniques and high field NMR instrumentation. The formation of carbamate glucuronide metabolites has been described for numerous pharmaceuticals and they have been identified in all of the species commonly used in drug metabolism studies (rat, dog, mouse, rabbit, guinea pig, and human). There has been no obvious species specificity for their formation and no preference for 1° or 2° amines. Many biological reactions have also been described in the literature that involve the reaction of CO2 with amino groups of biomolecules. For example, CO2 generated from cellular respiration is expired in part through the reversible formation of a carbamate between CO2 and the -amino groups of the α and β-chains of hemoglobin. Also, carbamic acid products of several amines, such as β-N-methylamino-L-alanine (BMAA), ethylenediamine, and L-cysteine have been implicated in toxicity. Studies suggested that a significant portion of amino-compounds in biological samples (that naturally contain CO2/bicarbonate) can be present as a carbamic acid.
Keywords: carbamate, carbamic acid, glucuronide, drug, metabolism, carbon dioxide, amine
Current Drug Metabolism
Title: Reaction of Primary and Secondary Amines to Form Carbamic Acid Glucuronides
Volume: 7 Issue: 8
Author(s): William H. Schaefer
Affiliation:
Keywords: carbamate, carbamic acid, glucuronide, drug, metabolism, carbon dioxide, amine
Abstract: Glucuronidation is an important mechanism used by mammalian systems to clear and eliminate both endogenous and foreign chemicals. Many functional groups are susceptible to conjugation with glucuronic acid, including hydroxyls, phenols, carboxyls, activated carbons, thiols, amines, and selenium. Primary and secondary amines can also react with carbon dioxide (CO2) via a reversible reaction to form a carbamic acid. The carbamic acid is also a substrate for glucuronidation and results in a stable carbamate glucuronide metabolite. The detection and characterization of these products has been facilitated greatly by the advent of soft ionization mass spectrometry techniques and high field NMR instrumentation. The formation of carbamate glucuronide metabolites has been described for numerous pharmaceuticals and they have been identified in all of the species commonly used in drug metabolism studies (rat, dog, mouse, rabbit, guinea pig, and human). There has been no obvious species specificity for their formation and no preference for 1° or 2° amines. Many biological reactions have also been described in the literature that involve the reaction of CO2 with amino groups of biomolecules. For example, CO2 generated from cellular respiration is expired in part through the reversible formation of a carbamate between CO2 and the -amino groups of the α and β-chains of hemoglobin. Also, carbamic acid products of several amines, such as β-N-methylamino-L-alanine (BMAA), ethylenediamine, and L-cysteine have been implicated in toxicity. Studies suggested that a significant portion of amino-compounds in biological samples (that naturally contain CO2/bicarbonate) can be present as a carbamic acid.
Export Options
About this article
Cite this article as:
Schaefer H. William, Reaction of Primary and Secondary Amines to Form Carbamic Acid Glucuronides, Current Drug Metabolism 2006; 7 (8) . https://dx.doi.org/10.2174/138920006779010629
DOI https://dx.doi.org/10.2174/138920006779010629 |
Print ISSN 1389-2002 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5453 |

- Author Guidelines
- Bentham Author Support Services (BASS)
- 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
-
Recent Advances in Designing Substrate-Competitive Protein Kinase Inhibitors
Current Pharmaceutical Design Synthesis, Characterization and Biological Activity of Chemically Modified Insulin Derivative with Alpha Lipoic Acid
Protein & Peptide Letters Micro/Nanoparticle Design and Fabrication for Pharmaceutical Drug Preparation and Delivery Applications
Current Drug Therapy Insight into p95HER2 in Breast Cancer: Molecular Mechanisms and Targeted Therapies
Recent Patents on DNA & Gene Sequences Intracellular Drug Delivery: Mechanisms for Cell Entry
Current Pharmaceutical Design Recent Progress and Related Patents on the Applications of Bone Marrow-Derived Stem/Progenitor Cells in Regenerative Medicine and Cancer Therapies
Recent Patents on Regenerative Medicine Imatinib Mesylate (Gleevec©): Targeted Therapy Against Cancer with Immune Properties
Endocrine, Metabolic & Immune Disorders - Drug Targets Systemic Involvement of IgG4-related Sclerosing Disease
Current Immunology Reviews (Discontinued) The Modern Spectrum of Rhabdomyolysis: Drug Toxicity Revealed by Creatine Kinase Screening
Current Drug Safety Selective Estrogen Receptor Modulators. Current and Future Treatment Options for Osteoporosis
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery (Discontinued) Antioxidant Effects of Glutathione and IGF in a Hyperglycaemic Cell Culture Model of Fibroblasts: Some Actions of Advanced Glycaemic end Products (AGE) and Nicotine
Endocrine, Metabolic & Immune Disorders - Drug Targets Updates on Genome-Wide Association Findings in Eating Disorders and Future Application to Precision Medicine
Current Neuropharmacology Current Perspectives on Anti-Aging Interventions
Letters in Drug Design & Discovery Liposheres as a Novel Carrier for Lipid Based Drug Delivery: Current and Future Directions
Recent Patents on Drug Delivery & Formulation Sperm Quality in Mouse After Exposure to Low Doses of TCDD
Current Topics in Medicinal Chemistry Brachial-Ankle Pulse Wave Velocity as a Novel Measure of Arterial Stiffness: Present Evidences and Perspectives
Current Hypertension Reviews Multicomponent Reactions for the Synthesis of Bioactive Compounds: A Review
Current Organic Synthesis Preface:
Current Topics in Medicinal Chemistry MicroRNAs in Peripheral Artery Disease
Current Topics in Medicinal Chemistry Nitric Oxide-Mediated Endothelial Dysfunction - Is there Need to Treat?
Current Vascular Pharmacology