Oxygenation of biomembranes by mammalian lipoxygenases: the role of ubiquinone.
15-Lipoxygenase is implicated in the selective breakdown of mitochondria during red cell maturation by virtue of its capability of directly oxygenating phospholipids. To address the reason of the selectivity for mitochondria, we studied the reaction of pure rabbit 15-lipoxygenase with beef heart submitochondrial particles in vitro. This reaction is characterised by a loss of polyenoic fatty acids, the formation of phospholipid-bound hydroperoxy- and keto-polyenoic fatty acids, and oxidative modification of membrane proteins. The total oxygen uptake exceeds the formation of oxygenated polyenoic fatty acids several times. The excessive oxygen uptake was not inhibited by 3,5-di-tert-butyl-4-hydroxytoluene or by respiratory inhibitors, but was partly suppressed by superoxide dismutase plus catalase, salicylate, or mannitol. Pentane-extraction of the submitochondrial particles abolished the excessive oxygen uptake, whereas reconstitution with ubiquinone- 50 restored it. A marked excessive oxygen uptake did not occur during the analogous reaction with erythrocyte ghosts. It is proposed that ubiquinone-50 triggers the formation of hydroxyl radicals from 15-lipoxygenase-derived hydroperoxy-lipids via a Fenton-type reaction driven by ubisemiquinone radicals. A new prooxidative function of ubiquinone in the biologically programmed degradation of mitochondria in certain types of cells is proposed.
Institute of Biochemistry, University Clinics Charite, Humboldt University of Berlin, Germany.
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K
Schnurr
M
M
Hellwing
B
B
Seidemann
P
P
Jungblut
H
H
Kuhn
S M
SM
Rapoport
T
T
Schewe
D000596:Amino Acids / Q000032:analysis; D000818:Animals; D001093:Arachidonate 15-Lipoxygenase / Q000378:metabolism* / Q000494:pharmacology*; D002417:Cattle; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004579:Electron Transport / Q000502:physiology; D015180:Electrophoresis, Gel, Two-Dimensional; D004912:Erythrocytes / Q000201:enzymology; D005231:Fatty Acids, Unsaturated / Q000737:chemistry / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism; D007651:Keto Acids / Q000378:metabolism; D015227:Lipid Peroxidation; D008322:Mammals / Q000378:metabolism; D008929:Mitochondria, Heart / Q000378:metabolism; D008956:Models, Chemical; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors / Q000378:metabolism; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D011817:Rabbits; D013385:Succinate Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism; D014451:Ubiquinone / Q000378:metabolism; D014810:Vitamin E / Q000032:analysis / Q000378:metabolism
D000596:Amino Acids; D005231:Fatty Acids, Unsaturated; D005609:Free Radicals; D007651:Keto Acids; D009097:Multienzyme Complexes; D014451:Ubiquinone; D014810:Vitamin E; D001093:Arachidonate 15-Lipoxygenase; D013385:Succinate Dehydrogenase; C023107:NADH oxidase; D009247:NADH, NADPH Oxidoreductases; D010100:Oxygen