Repair of amino acid radicals of apolipoprotein B100 of low-density lipoproteins by flavonoids. A pulse radiolysis study with quercetin and rutin.
Selective oxidative damage to apolipoprotein B in LDL can be effected radiolytically by (*)Br(2)(-) radicals. Twenty-seven Trp residues constitute major primary sites of oxidation, but two-thirds of oxidized Trps ((*)Trp) that are formed are repaired by intramolecular electron transfer from Tyr residues with formation of phenoxyl radicals (TyrO(*)). Analysis of (*)Trp and TyrO(*) transient absorbance changes suggests that other apolipoprotein B residues, probably Cys, are oxidized. LDL-bound quercetin can efficiently repair this damage. Absorption studies show that a LDL particle has the capacity to bind approximately 10 quercetin molecules through interaction with apolipoprotein B. The repair occurs by intramolecular electron transfer characterized by a rate constant of 2 x 10(3) s(-)(1). In contrast, rutin, a related flavonoid which does not bind to LDL, cannot repair oxidized apolipoprotein B. Urate is a hydrophilic plasma antioxidant which displays synergistic antioxidant properties with flavonoids. Urate radicals produced by (*)Br(2)(-) can also be repaired by LDL-bound quercetin. This repair occurs with a reaction rate constant of 6.8 x 10(7) M(-)(1) s(-)(1). Comparison with previous studies conducted with human serum albumin-bound quercetin suggests that quercetin analogues tailored to be carried preferentially by lipoproteins might be more powerful plasma antioxidants than natural quercetin carried by serum albumin.
Centro de Metabolismo e Endocrinologia da Faculdade de Medicina de Lisboa, 1649-028 Lisboa, Portugal.
Paulo
P
Filipe
Patrice
P
Morlière
Larry K
LK
Patterson
Gordon L
GL
Hug
Jean-Claude
JC
Mazière
Cécile
C
Mazière
João P
JP
Freitas
Afonso
A
Fernandes
René
R
Santus
D000596:Amino Acids / Q000737:chemistry* / Q000378:metabolism; D000975:Antioxidants / Q000737:chemistry* / Q000378:metabolism; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B / Q000737:chemistry* / Q000378:metabolism; D001965:Bromides / Q000378:metabolism; D004579:Electron Transport; D005609:Free Radicals / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008077:Lipoproteins, LDL / Q000737:chemistry* / Q000378:metabolism; D008956:Models, Chemical; D010084:Oxidation-Reduction; D010100:Oxygen / Q000633:toxicity; D011675:Pulse Radiolysis / Q000379:methods; D011794:Quercetin / Q000737:chemistry* / Q000378:metabolism; D012431:Rutin / Q000737:chemistry* / Q000378:metabolism; D014364:Tryptophan / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism; D014527:Uric Acid / Q000378:metabolism
D000596:Amino Acids; D000975:Antioxidants; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B; D001965:Bromides; D005609:Free Radicals; D008077:Lipoproteins, LDL; C408694:tyrosine radical; D014527:Uric Acid; D014443:Tyrosine; D012431:Rutin; D014364:Tryptophan; D011794:Quercetin; D010100:Oxygen