Binding of iron to the 5th component of human complement directs oxygen radical-mediated conversion to specific sites and causes nonenzymic activation.
It was earlier found that hydroxyl radicals (OH.) generated in a fluid phase system, convert human C5 to an activated, C5b-like form without cleavage. For the conversion catalytic amounts of divalent iron were necessary; upon their oxidation OH. are generated. In view of the extraordinary reactivity of OH. their specific effect on C5 was surprising. It has now turned out that C5 binds iron, about 13-15 Fe ions per molecule C5. C5 was fully bound to iron-loaded Chelating Sepharose and in this way removed form the medium. Only at the sites where iron is bound, is OH. generation possible. The half-life of OH. is extremely short and hence the radicals can act on C5 only in the immediate environment of the binding sites for iron. In this way the oxidative change of C5, induced by the radicals, is restricted to some sites on the molecule determined by the iron binding. The hydroxyl radical scavenger, dimethylsulfoxide (DMSO), is unable to interfere with the conversion of C5 by OH. generated on iron-Sepharose, it does not reach the site of reaction in that system. In fluid phase systems DMSO does inhibit the conversion of C5 to C5b-like C5.
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Max Planck Institut für experimentelle Medizin, Göttingen, BRD.
Nolte
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Brunahl
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D001665:Binding Sites; D002374:Catalase / Q000494:pharmacology; D003167:Complement Activation / Q000187:drug effects*; D003182:Complement C5 / Q000096:biosynthesis / Q000378:metabolism*; D050776:Complement C5b; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D005296:Ferrous Compounds / Q000494:pharmacology; D006801:Humans; D006878:Hydroxides / Q000494:pharmacology*; D017665:Hydroxyl Radical; D066298:In Vitro Techniques; D007501:Iron / Q000494:pharmacology*; D010084:Oxidation-Reduction; D013858:Thiobarbiturates / Q000494:pharmacology
D003182:Complement C5; D005296:Ferrous Compounds; D006878:Hydroxides; D013858:Thiobarbiturates; D017665:Hydroxyl Radical; C020748:ferrous sulfate; D050776:Complement C5b; D007501:Iron; D002374:Catalase; C029684:thiobarbituric acid; D004121:Dimethyl Sulfoxide