title: Manganese-porphyrin reactions with lipids and lipoproteins.
abstract: 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.
authors.affiliation: Department of Anesthesiology, Biochemistry and Molecular Genetics, Pharmacology and Toxicology, and The Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, AL 35233, USA.
authors.forename: A
authors.initials: A
authors.lastname: Bloodsworth
authors.forename: V B
authors.initials: VB
authors.lastname: O'Donnell
authors.forename: I
authors.initials: I
authors.lastname: Batinic-Haberle
authors.forename: P H
authors.initials: PH
authors.lastname: Chumley
authors.forename: J B
authors.initials: JB
authors.lastname: Hurt
authors.forename: B J
authors.initials: BJ
authors.lastname: Day
authors.forename: J P
authors.initials: JP
authors.lastname: Crow
authors.forename: B A
authors.initials: BA
authors.lastname: Freeman
mesh_terms: D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D002384:Catalysis; D002855:Chromatography, Thin Layer; D016166:Free Radical Scavengers / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D019787:Linoleic Acid / Q000737:chemistry; D008041:Linoleic Acids / Q000737:chemistry; D015227:Lipid Peroxidation; D008054:Lipid Peroxides / Q000737:chemistry; D008055:Lipids / Q000737:chemistry*; D008074:Lipoproteins / Q000737:chemistry*; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D008345:Manganese / Q000737:chemistry*; D013058:Mass Spectrometry; D008665:Metalloporphyrins / Q000737:chemistry* / Q000494:pharmacology; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D016166:Free Radical Scavengers; D008041:Linoleic Acids; D008054:Lipid Peroxides; D008055:Lipids; D008074:Lipoproteins; D008077:Lipoproteins, LDL; D008665:Metalloporphyrins; C038649:13-hydroperoxy-9,11-octadecadienoic acid; D008345:Manganese; C050950:tetrakis(N-methyl-4-pyridiniumyl)porphine manganese(III) complex; D019787:Linoleic Acid