Oxidative modification of protein structures under the action of myeloperoxidase and the hydrogen peroxide and chloride system.

Myeloperoxidase of neutrophilic leukocytes (MPO) at pH 4.0 to 6.5 mediated oxidation of Cl- ions, yielding hypochloride (OCl-) which then reacted with amino acids and polypeptides. Thiol and thioether groups may be oxidized to disulfide or to sulphoxides and sulphonic acids respectively. Tryptophanyl residues yielded 2-oxoindole. Epsilon amino groups of lysine produced chloramine which, however, decomposed, yielding aldehyde residues. Bovine serum albumin treated with MPO-Cl-H2O2 system yielded derivatives with a decreased affinity to antialbumin antibodies and increased electrophoretic mobility. Albumin aldehyde derivatives were also obtained. At H2O2 molar ratio with albumin 20:1, a precipitation of albumin occurred, due to the formation of new polymeric albumin derivatives. The lysozyme (LZM) lost its enzyme activity when 1.4 to 1.8 mol of H2O2 per 1 mol of LZM was used. Addition of H2O2 above molar ratio 5:1 produced LZM polymerization to di-, tri-, tetra and pentameric derivatives. IgA exposed to the MPO-Cl-H2O2-Cl- system split into light chains (molecular weight: 25.8 kDa), heavy chains (molecular weight: 81.8 kDa) and a third polypeptide which size was half the light chain size (molecular weight: 13.9 kDa). The IgA exceeding the HOCl ratio 1:350 (mg/mumol) produced both precipitation and degradation of the IgA polypeptide structure. The treatment of IgG with HOCl released a fragment corresponding to half the light chain size, the light chain, and the heavy chain, whereas HOCl treatment of IgM released only a fragment which size was smaller than the heavy chain and another fragment which size was the same as the light chain. The MPO-Cl-H2O2 system produced many specific changes in protein structures.(ABSTRACT TRUNCATED AT 250 WORDS)