On the oxidation of cytochrome c by hypohalous acids.
Oxidation of cytochrome c, a key protein in mitochondrial electron transport and a mediator of apoptotic cell death, by reactive halogen species (HOX, X2), i.e., metabolites of activated neutrophils, was investigated by stopped-flow. The fast initial reactions between FeIIIcytc and HOX species, with rate constants (at pH 7.6) of k > 3 x 10(6) M(-1) s(-1) for HOBr, k > 3 x 10(5) M(-1) s(-1) for HOCl, and k = (6.1+/-0.3) x 10(2) M(-1) s(-1) for HOI, are followed by slower intramolecular processes. All HOX species lead to a blue shift of the Soret absorption band and loss of the 695-nm absorption band, which is an indicator for the intact iron to Met-80 bond, and of the reducibility of FeIIIcytc. All HOX species do, in fact, persistently impair the ability of FeIIIcytc to act as electron acceptor, e.g., in reaction with ascorbate or O2*-. I2 selectively oxidizes the iron center of FeIIcytc, with a stoichiometry of 2 per I2, and with k(FeIIcytc + I2) approximately 4.6 x 10(4) M(-1) s(-1) and k(FeIIcytc + I2*-) = (2.9+/-0.4) x 10(8) M(-1) s(-1). Oxidation of FeIIcytc by HOX species is not selectively directed toward the iron center; HOBr and HOCl are considered to react primarily by N-halogenation of side chain amino groups, and HOI mainly by sulfoxidation. There is some evidence for the generation of HO* radicals upon reaction of HOCl with FeIIcytc. Chloramines (e.g., NH2Cl), bromamine (NH2Br), and cyclo-Gly2 chloramide oxidize FeIIcytc slowly and unselectively, but iodide efficiently catalyzes reactions of these N-halogens to yield fast selective oxidation of the iron center; this is due to generation of I2 by reaction of I- with the N-halogen and recycling of I- by reaction of I2 with FeIIcytc. Iodide also catalyzes methionine sulfoxidation and thiol oxidation by NH2Cl. The possible biological relevance of these findings is discussed.
Prütz
W A
WA
Institut für Molekulare Medizin und Zellforschung, Universität Freiburg, Germany. pruetz@ruf.uni-freiburg.de
Kissner
R
R
Nauser
T
T
Koppenol
W H
WH
D001959:Bromates / Q000737:chemistry* / Q000494:pharmacology; D002384:Catalysis / Q000187:drug effects; D003574:Cytochrome c Group / Q000737:chemistry* / Q000187:drug effects; D004579:Electron Transport / Q000187:drug effects; D017022:Flow Injection Analysis / Q000379:methods; D006997:Hypochlorous Acid / Q000737:chemistry* / Q000494:pharmacology; D007454:Iodides / Q000737:chemistry; D017613:Iodine Compounds / Q000737:chemistry* / Q000494:pharmacology; D007501:Iron / Q000737:chemistry; D010084:Oxidation-Reduction / Q000187:drug effects; D013053:Spectrophotometry
D001959:Bromates; D003574:Cytochrome c Group; D007454:Iodides; D017613:Iodine Compounds; C081961:hypoiodous acid; D006997:Hypochlorous Acid; D007501:Iron; C027664:hypobromous acid