title: Carbamoylated free amino acids in uremia: HOCl generates volatile protein modifying and cytotoxic oxidant species from N-carbamoyl-threonine but not threonine.
abstract: N-carbamoylation is the non-enzymatic reaction of cyanate with amino groups. Due to urea-formed cyanate in uremic patients beside carbamoylated proteins also free amino acid carbamoylation has been detected, a modification which has been linked to disturbed protein synthesis as NH(2)-derivatisation interferes with peptide bond formation. HOCl the product of the activated MPO/H(2)O(2)/Cl(-) system is known to react with the NH(2)-group of free amino acids to form chloramines which could exert some protective effect against protein modification and cytotoxicity induced by HOCl. As N-carbamoylation may inhibit formation of chloramines we have used N-carbamoyl-threonine as a model amino acid to study its ability to limit the reactivity of HOCl with proteins (LDL and human serum albumin) and cells (THP-1 monocytes and coronary artery endothelial cells). The data indicate that N-carbamoylation completely abolished the protein- and cell-protective effect of threonine against HOCl attack. In contrast to threonine the reaction of HOCl with carbamoyl-threonine resulted in the formation of volatile oxidant species with protein modifying and cytotoxic potential. The volatile lipophilic inorganic monochloramine (NH(2)Cl) was identified as a breakdown product of this reaction.
authors: Center of Pathobiochemistry and Genetics, Department of Medical Chemistry and Pathobiochemistry, Medical University of Vienna, Waehringerstr. 10, A-1090 Vienna, Austria.
authors: Sabine M
authors: SM
authors: Schreier
authors: Marianne
authors: M
authors: Hollaus
authors: Marcela
authors: M
authors: Hermann
authors: Leopold
authors: L
authors: Jirovetz
authors: Markus
authors: M
authors: Exner
authors: Stylianos
authors: S
authors: Kapiotis
authors: Bernhard M K
authors: BM
authors: Gmeiner
authors: Hilde
authors: H
authors: Laggner
mesh_terms: D000447:Aldehydes / Q000378:metabolism; D002219:Carbamates / Q000378:metabolism*; D002460:Cell Line; D003603:Cytotoxins / Q000633:toxicity*; D006801:Humans; D006997:Hypochlorous Acid / Q000633:toxicity*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D016877:Oxidants / Q000633:toxicity*; D012709:Serum Albumin / Q000378:metabolism*; D013912:Threonine / Q000031:analogs & derivatives* / Q000378:metabolism*; D014511:Uremia / Q000378:metabolism*; D014835:Volatilization
chemical_list: D000447:Aldehydes; D002219:Carbamates; D003603:Cytotoxins; D008077:Lipoproteins, LDL; D016877:Oxidants; D012709:Serum Albumin; D013912:Threonine; D006997:Hypochlorous Acid