Manganese-porphyrin reactions with lipids and lipoproteins

Manganese porphyrin complexes serve to catalytically scavenge superoxide, h ydrogen peroxide, and peroxynitrite. Herein, reactions of manganese 5,10,15 ,20-tetrakis(N-ethylpyridinium-2-yl)porphyrin (MnTE-2-PyP5+) with lipids an d lipid hydroperoxides (LOOH) are examined. In linoleic acid and human low- density lipoprotein (LDL), MnTE-2-PyP5+ promotes oxidative reactions when b iological reductants are not present. By redox cycling between Mn+3 and Mn4 forms, MnTE-2-PyP5+ initiates lipid peroxidation via decomposition of 13( S)hydroperoxyoctadecadienoic acid [13(S)HPODE], with a second-order rate co nstant of 8.9 x 10(3) M(-1)s(-1)and k(cat) = 0.32 s(-1). Studies of LDL oxi dation demonstrate that: (i) MnTE-2-PyP5+ can directly oxidize LDL, (ii) Mn TE-2-PyP5+ does not inhibit Cu-induced LDL oxidation, and (iii) MnTE-2-PyP5 + plus a reductant partially inhibit lipid peroxidation. MnTE-2-PyP5+ (1-5 mu M) also significantly inhibits FeCl3 plus ascorbate-induced lipid peroxi dation of rat brain homogenate. In summary, MnTE-2-PyP5+ initiates membrane lipid and lipoprotein oxidation in the absence of biological reductants, w hile MnTE-2-PyP5+ inhibits lipid oxidation reactions initiated by other oxi dants when reductants are present. It is proposed that, as the Mn+3 resting redox state of MnTE-2-PyP5+ becomes oxidized to the Mn+4 redox state, LOOH is decomposed to byproducts that propagate lipid oxidation reactions. When the manganese of MnTE-2-PyP5+ is reduced to the +2 state by biological red uctants, antioxidant reactions of the metalloporphyrin are favored. (C) 200 0 Elsevier Science Inc.