Manganese-porphyrin reactions with lipids and lipoproteins

Free Radic Biol Med. 2000 Apr 1;28(7):1017-29. doi: 10.1016/s0891-5849(00)00194-5.


Manganese porphyrin complexes serve to catalytically scavenge superoxide, hydrogen peroxide, and peroxynitrite. Herein, reactions of manganese 5,10,15,20-tetrakis(N-ethylpyridinium-2-yl)porphyrin (MnTE-2-PyP(5+)) with lipids and lipid hydroperoxides (LOOH) are examined. In linoleic acid and human low-density lipoprotein (LDL), MnTE-2-PyP(5+) promotes oxidative reactions when biological reductants are not present. By redox cycling between Mn(+3) and Mn(+4) forms, MnTE-2-PyP(5+) initiates lipid peroxidation via decomposition of 13(S)hydroperoxyoctadecadienoic acid [13(S)HPODE], with a second-order rate constant of 8.9 x 10(3) M(-1)s(-1)and k(cat) = 0.32 s(-1). Studies of LDL oxidation demonstrate that: (i) MnTE-2-PyP(5+) can directly oxidize LDL, (ii) MnTE-2-PyP(5+) does not inhibit Cu-induced LDL oxidation, and (iii) MnTE-2-PyP(5+) plus a reductant partially inhibit lipid peroxidation. MnTE-2-PyP(5+) (1-5 microM) also significantly inhibits FeCl(3) plus ascorbate-induced lipid peroxidation of rat brain homogenate. In summary, MnTE-2-PyP(5+) initiates membrane lipid and lipoprotein oxidation in the absence of biological reductants, while MnTE-2-PyP(5+) inhibits lipid oxidation reactions initiated by other oxidants when reductants are present. It is proposed that, as the Mn(+3) resting redox state of MnTE-2-PyP(5+) becomes oxidized to the Mn(+4) redox state, LOOH is decomposed to byproducts that propagate lipid oxidation reactions. When the manganese of MnTE-2-PyP(5+) is reduced to the +2 state by biological reductants, antioxidant reactions of the metalloporphyrin are favored.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Brain Chemistry / drug effects
  • Catalysis
  • Chromatography, Thin Layer
  • Free Radical Scavengers / chemistry
  • Free Radical Scavengers / pharmacology
  • Humans
  • Linoleic Acid / chemistry
  • Linoleic Acids / chemistry
  • Lipid Peroxidation
  • Lipid Peroxides / chemistry
  • Lipids / chemistry*
  • Lipoproteins / chemistry*
  • Lipoproteins, LDL / blood
  • Male
  • Manganese / chemistry*
  • Mass Spectrometry
  • Metalloporphyrins / chemistry*
  • Metalloporphyrins / pharmacology
  • Oxidation-Reduction
  • Rats
  • Rats, Sprague-Dawley


  • Free Radical Scavengers
  • Linoleic Acids
  • Lipid Peroxides
  • Lipids
  • Lipoproteins
  • Lipoproteins, LDL
  • Metalloporphyrins
  • 13-hydroperoxy-9,11-octadecadienoic acid
  • Manganese
  • tetrakis(N-methyl-4-pyridiniumyl)porphine manganese(III) complex
  • Linoleic Acid