title: Reaction of primary and secondary amines to form carbamic acid glucuronides.
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 (CO(2)) 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 degrees or 2 degrees amines. Many biological reactions have also been described in the literature that involve the reaction of CO(2) with amino groups of biomolecules. For example, CO(2) generated from cellular respiration is expired in part through the reversible formation of a carbamate between CO(2) and the alpha-amino groups of the alpha- and beta-chains of hemoglobin. Also, carbamic acid products of several amines, such as beta-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 CO(2)/bicarbonate) can be present as a carbamic acid.
authors.affiliation: Department of Safety Assessment, Merck Research Laboratories, West Point, PA 19486, USA. william_schaefer@merck.com
authors.forename: William H
authors.initials: WH
authors.lastname: Schaefer
mesh_terms: D000588:Amines / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D002219:Carbamates / Q000737:chemistry / Q000378:metabolism*; D002245:Carbon Dioxide / Q000737:chemistry / Q000378:metabolism; D020719:Glucuronides / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry
chemical_list: D000588:Amines; D002219:Carbamates; D020719:Glucuronides; D002245:Carbon Dioxide; C070766:carbamic acid