title: Determination of the alpha-tocopherol inhibition rate constant for peroxidation in low-density lipoprotein.
abstract: This work reports an estimate of the inhibition rate constant (k(inh)) for alpha-tocopherol (alpha-TOH) in low-density lipoproteins (LDL) based on cholesteryl linoleate hydroperoxide products formed during autoxidation of intact lipoproteins. The ratio of cis,trans/trans,trans product hydroperoxides was determined during the consumption of the antioxidant. For a reasonable determination of k(inh) in LDL, the pro-oxidant behavior of alpha-TOH was minimized by oxidizing LDL with an unsymmetrical amphiphilic azo initiator which significantly reduces phase-transfer mediated pro-oxidant effects of alpha-TOH. This initiator delivers a more constant flux of initiator radicals into LDL lipid regions and permits determination of alpha-TOH k(inh) in LDL. Development of a tocopherol-mediated peroxidation (TMP) model and analysis of cholesteryl linoleate hydroperoxide cis,trans/trans,trans product ratios provided an estimated value for the inhibition rate constant of alpha-TOH in a lipoprotein of k(inh) = 5.9 +/- 0.5 x 10(5) M(-)(1) s(-)(1)
authors.affiliation: Department of Chemistry, Vanderbilt University, Nashville, Tennessee 37235, USA.
authors.forename: Sean M
authors.initials: SM
authors.lastname: Culbertson
authors.forename: Fernando
authors.initials: F
authors.lastname: Antunes
authors.forename: Christine M
authors.initials: CM
authors.lastname: Havrilla
authors.forename: Ginger L
authors.initials: GL
authors.lastname: Milne
authors.forename: Ned A
authors.initials: NA
authors.lastname: Porter
mesh_terms: D000975:Antioxidants / Q000493:pharmacokinetics / Q000494:pharmacology*; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D019787:Linoleic Acid / Q000737:chemistry / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008054:Lipid Peroxides / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000097:blood / Q000378:metabolism*; D008081:Liposomes / Q000378:metabolism; D008956:Models, Chemical; D010084:Oxidation-Reduction; D012044:Regression Analysis; D013237:Stereoisomerism; D013816:Thermodynamics; D024502:alpha-Tocopherol / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D005609:Free Radicals; D008054:Lipid Peroxides; D008077:Lipoproteins, LDL; D008081:Liposomes; D019787:Linoleic Acid; D024502:alpha-Tocopherol