Relative reactivities of N-chloramines and hypochlorous acid with human plasma constituents.
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.
Carr
A C
AC
Linus Pauling Institute, Oregon State University, Corvallis, OR 97331-6512, USA. anitra.carr@orst.edu
Hawkins
C L
CL
Thomas
S R
SR
Stocker
R
R
Frei
B
B
D001205:Ascorbic Acid / Q000097:blood / Q000494:pharmacology; D002700:Chloramines / Q000097:blood*; D005260:Female; D005609:Free Radicals / Q000097:blood; D006801:Humans; D006997:Hypochlorous Acid / Q000097:blood*; D066298:In Vitro Techniques; D008297:Male; D008715:Methionine / Q000097:blood; D016877:Oxidants / Q000097:blood; D012709:Serum Albumin / Q000737:chemistry / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000097:blood; D013654:Taurine / Q000031:analogs & derivatives* / Q000097:blood; D000515:alpha 1-Antitrypsin / Q000378:metabolism
D002700:Chloramines; D005609:Free Radicals; D016877:Oxidants; D012709:Serum Albumin; D013438:Sulfhydryl Compounds; D000515:alpha 1-Antitrypsin; D013654:Taurine; C043410:N-chlorotaurine; D006997:Hypochlorous Acid; D008715:Methionine; D001205:Ascorbic Acid