title: Reaction of the butter flavorant diacetyl (2,3-butanedione) with N-α-acetylarginine: a model for epitope formation with pulmonary proteins in the etiology of obliterative bronchiolitis.
abstract: The butter flavorant diacetyl (2,3-butanedione) is implicated in causing obliterative bronchiolitis in microwave popcorn plant workers. Because diacetyl modifies arginine residues, an immunological basis for its toxicity is under investigation. Reaction products of diacetyl with N-α-acetylarginine (AcArg) were determined as a model for hapten formation, with characterization by mass spectrometry, NMR, and HPLC with UV detection and radiodetection. Four products were identified by LC-MS, each with a positive ion of m/z 303 (diacetyl + AcArg); one pair displayed an additional ion at m/z 217 (AcArg), the other pair at m/z 285 (- H(2)O). Their (1)H-(13)C NMR correlation spectra were consistent with the addition of one or two of the guanidine nitrogens to form aminols. Open-chain pairs interconverted at pH 2, as did the cyclized, but all four interconverted at neutral pH. This is the first structural characterization of the covalent adducts between diacetyl and an arginine moiety.
authors.affiliation: RTI International, P.O. Box 12194, Research Triangle Park, North Carolina 27709, United States. mathews@rti.org
authors.forename: James M
authors.initials: JM
authors.lastname: Mathews
authors.forename: Scott L
authors.initials: SL
authors.lastname: Watson
authors.forename: Rodney W
authors.initials: RW
authors.lastname: Snyder
authors.forename: Jason P
authors.initials: JP
authors.lastname: Burgess
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Morgan
mesh_terms: D001120:Arginine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000737:chemistry; D001989:Bronchiolitis Obliterans / Q000209:etiology*; D002079:Butter / Q000009:adverse effects / Q000032:analysis*; D003931:Diacetyl / Q000009:adverse effects / Q000737:chemistry*; D005421:Flavoring Agents / Q000009:adverse effects / Q000737:chemistry*; D006801:Humans; D013058:Mass Spectrometry; D008956:Models, Chemical
chemical_list: D005421:Flavoring Agents; D002079:Butter; D001120:Arginine; D003931:Diacetyl; C000015:N-acetyl-L-arginine