TitleRelative reactivities of N-chloramines and hypochlorous acid with human plasma constituents.
Publication TypeJournal Article
Year of Publication2001
AuthorsCarr AC, Hawkins CL, Thomas SR, Stocker R, Frei B
JournalFree Radic Biol Med
Date Published2001 Mar 01
Keywordsalpha 1-Antitrypsin, Ascorbic Acid, Chloramines, Female, Free Radicals, Humans, Hypochlorous Acid, In Vitro Techniques, Male, Methionine, Oxidants, Serum Albumin, Sulfhydryl Compounds, Taurine

Hypochlorous acid (HOCl), the major strong oxidant produced by the phagocyte enzyme myeloperoxidase, reacts readily with free amino groups to form N-chloramines. Since different N-chloramines have different stabilities and reactivities depending on their structures, we investigated the relative reactivities of three model N-chloramines and HOCl with human plasma constituents. TheN-chloramines studied were N(alpha)-acetyl-lysine chloramine (LysCA, a model of protein-associated N-chloramines), taurine chloramine (TaurCA, the primary N-chloramine produced by activated neutrophils), and monochloramine (MonoCA, a lipophilic N-chloramine). Addition of these chlorine species (100--1000 microM each) to plasma resulted in rapid loss of thiols, with the extent of thiol oxidation decreasing in the order TaurCA = LysCA > MonoCA = HOCl. The single reduced thiol of albumin was the major target. Loss of plasma ascorbate also occurred, with the extent decreasing in the order HOCl > LysCA > TaurCA > MonoCA. Experiments comparing equimolar albumin thiols and ascorbate showed that while HOCl caused equivalent loss of thiols and ascorbate, theN-chloramines reacted preferentially with thiols. The chlorine species also inactivated alpha(1)-antiproteinase, implicating oxidation of methionine residues, and ascorbate provided variable protection depending on the chlorine species involved. Together, our data indicate that in biological fluids N-chloramines react more readily with protein thiols than with methionine residues or ascorbate, and thus may cause biologically relevant, selective loss of thiol groups.

Alternate JournalFree Radic. Biol. Med.
PubMed ID11182523
Grant ListAT-00066 / AT / NCCIH NIH HHS / United States
HL-56170 / HL / NHLBI NIH HHS / United States