title: Formation of leukotoxin (9,10-epoxy-12-octadecenoic acid) during the autoxidation of phospholipids promoted by hemoproteins.
abstract: Myoglobin (Mb) and cytochrome c (Cyt c) are known to promote lipid peroxidation when mixed with certain types of phospholipids. In the presence of phospholipids such as cardiolipin (CL), ferrous Mb and Cyt c were converted to ferric hemoproteins, and autoxidation of the phospholipids and the oxidation of free linoleic acid (LA) added to the reaction mixture were observed. When the reaction mixture comprising 0.01 mM Cyt c, 0.2 mM CL and 0.1 mM LA was incubated, 92.7% of LA was consumed, and the LA products included 2.49 microM 9,10-epoxy-12-octadecenoic acid (leukotoxin) and its isomer which are potent inhibitors of mitochondrial respiration and have toxic effects on cardiac function. Hemoglobin (Hb) could promote almost no lipid peroxidation in the presence of any kinds of phospholipids. The experiments using some scavengers of active oxygen species revealed that tocopherol and ascorbic acid could strongly reduced LA oxidation caused by Cyt c or Mb. As LTx production was also observed when LA was mixed with Fe2+, LTx may be a common product where non-enzymatic lipid peroxidation occurs.
authors.affiliation: Department of Forensic Medicine, Faculty of Medicine, University of Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Iwase
authors.forename: T
authors.initials: T
authors.lastname: Takatori
authors.forename: H
authors.initials: H
authors.lastname: Niijima
authors.forename: M
authors.initials: M
authors.lastname: Nagao
authors.forename: T
authors.initials: T
authors.lastname: Amano
authors.forename: K
authors.initials: K
authors.lastname: Iwadate
authors.forename: Y
authors.initials: Y
authors.lastname: Matsuda
authors.forename: M
authors.initials: M
authors.lastname: Nakajima
authors.forename: M
authors.initials: M
authors.lastname: Kobayashi
mesh_terms: D002308:Cardiolipins / Q000737:chemistry*; D003574:Cytochrome c Group / Q000737:chemistry; D005609:Free Radicals; D006861:Hydrogen Peroxide; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000138:chemical synthesis* / Q000737:chemistry; D015227:Lipid Peroxidation; D009211:Myoglobin / Q000737:chemistry*; D010084:Oxidation-Reduction
chemical_list: D002308:Cardiolipins; D003574:Cytochrome c Group; D005609:Free Radicals; D008041:Linoleic Acids; D009211:Myoglobin; C051208:9,10-epoxy-12-octadecenoic acid; D019787:Linoleic Acid; D006861:Hydrogen Peroxide