Oxygenation of phosphatidylcholine by human polymorphonuclear leukocyte 15-lipoxygenase

Jung, Geralyn; Yang, Daichang; Nakao, Akira

doi:10.1016/0006-291x(85)90453-x

Cited by 57 publications

(25 citation statements)

References 12 publications

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“…On chiral analysis the 9-HANA product chromatographed as one main peak with no definite minor enantiomer, so it was not possible to determine order of elution and infer chirality. We also tested 1-palmitoyl-2-linoleoylphosphatidycholine as a potential substrate for AtLOX1 using the bile salt deoxycholate as detergent, a condition that achieves reaction with plant 13-LOX [26], coral 8R-LOX [9], as well as several mammalian arachidonate 12-LOX and 15-LOX [27][28][29][30]. However, we could detect no reaction with the recombinant 9-LOX, in agreement with a result reported for a purified tomato 9-LOX [20].…”

Section: Catalytic Activity With Other Substratessupporting

confidence: 88%

“…While caution is warranted in interpretation of negative results, this lack of reaction classifies the linoleate 9-LOX along with other LOX enzymes that are predicted to exhibit carboxyl end-first binding and that show no reaction with very large phospholipid esters (arachidonate 8S-LOX and 5S-LOX) [9,28]. (By contrast, all the LOX enzymes that have predicted tail-first substrate binding do react specifically with phospholipid ester substrates [5,9,[26][27][28][29][30]). Again, our interpretation is that the 9S-LOX active site can accommodate substrates with C-1 appendages of the size of ethanolamide or glycerol, and that overall, the carboxyl end-first binding is the most satisfactory model for oxygenations by linoleate 9S-LOX enzymes.…”

Section: Discussionmentioning

confidence: 99%

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Investigation of Substrate Binding and Product Stereochemistry Issues in Two Linoleate 9‐Lipoxygenases

Boeglin

Itoh

Zheng

et al. 2008

Lipids

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Herein we characterize the Arabidopsis thaliana AtLOX1 and tomato (Solanum lycopersicum) LOXA proteins as linoleate 9S-lipoxygenases (9-LOX), and use the enzymes to test a model that predicts a relationship between substrate binding orientation and product stereochemistry. The cDNAs were heterologously expressed in E. coli and the proteins partially purified by nickel affinity chromatography using a N-terminal (His)6-tag. Both enzymes oxygenated linoleic acid almost exclusively to the 9S-hydroperoxide with turnover numbers of 300–400/s. AtLOX1 showed a broad range of activity over the range pH 5–9 (optimal at pH 6); tomato LOXA also showed optimal activity around pH 5–7 dropping off more sharply at pH 9. Site-directed mutagenesis of a conserved active site Ala (Ala562 in AtLOX1, Ala 564 in tomato LOXA, and typically conserved as Ala in S-LOX and Gly in R-LOX), revealed that substitution with Gly led to the production of a mixture of 9S- and 13R-hydroperoxyoctadecadienoic acids from linoleic acid. To follow up on earlier reports of 9-LOX metabolism of anandamide (van Zadelhoff et al., 1998, Biochem. Biophys. Res. Commun. 248, 33), we also tested this substrate with the mutants, which produced predictable shifts in product profile, including a shift from the prominent 11S-hydroperoxy derivative of wild-type to include the 15R-hydroperoxide. These results conform to a model that predicts a head-first substrate binding orientation for 9S-LOX. We also found that linoleoyl-phosphatidylcholine is not a 9S-LOX substrate, which is consistent with this conclusion.

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Section: Catalytic Activity With Other Substratessupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Investigation of Substrate Binding and Product Stereochemistry Issues in Two Linoleate 9‐Lipoxygenases

Boeglin

Itoh

Zheng

et al. 2008

Lipids

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“…Docosahexaenoic acid, an ω-3 PUFA is also oxidized by 15-lipoxygenase as part of the synthesis of resolvins and protectins [13, 15]. In keeping with their broadened substrate scope the 12- and 15-lipoxygenases are known to be reactive towards intact phospholipids, and do not require their hydrolysis for peroxidation [17, 18]. …”

Section: Biological Synthesis Of Lipid Peroxidesmentioning

confidence: 99%

Lipid peroxidation in cell death

Gaschler

Stockwell

2017

Biochemical and Biophysical Research Communications

1,244

881

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Disruption of redox homeostasis is a key phenotype of many pathological conditions. Though multiple oxidizing compounds such as hydrogen peroxide are widely recognized as mediators and inducers of oxidative stress, increasingly, attention is focused on the role of lipid hydroperoxides as critical mediators of death and disease. As the main component of cellular membranes, lipids have an indispensible role in maintaining the structural integrity of cells. Excessive oxidation of lipids alters the physical properties of cellular membranes and can cause covalent modification of proteins and nucleic acids. This review discusses the synthesis, toxicity, degradation, and detection of lipid peroxides in biological systems. Additionally, the role of lipid peroxidation is highlighted in disease and death, and strategies to control the accumulation of lipid peroxides are discussed.

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“…Generally, free polyunsaturated fatty acids are preferred as substrates for LOXs [1,[2][3][4]. Nonetheless, there have been reports [5][6][7][8][9][10][11][12][13][14] that certain plant LOXs can oxidize phospholipids [5][6][7] or triglycerides [8]. Additionally, mammalian LOXs such as reticulocyte LOX or leukocyte-type LOX (12-LOX) oxygenate complex substrates such as phospholipids or biomembranes [9][10][11][12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Oxygenation of 1‐Docosahexaenoyl Lysophosphatidylcholine by Lipoxygenases; Conjugated Hydroperoxydiene and Dihydroxytriene Derivatives

Huang

Kim

Sok

2007

Lipids

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Oxygenation of 1-docosahexaenoyl lysophosphatidylcholine (docosahexaenoyl-lysoPC) by soybean lipoxygenase-1 (LOX-1) or porcine leukocyte LOX was examined. The oxidized products were identified to be hydroperoxydocosahexaenoyl-lysoPC by UV and LC/MS spectrometric analyses. In SP-HPLC and chiral phase-HPLC analyses, the products from the oxygenation of docosahexaenoyl-lysoPC by soybean LOX-1 and porcine leukocyte LOX were found to contain hydroperoxide group mainly at C-17 and C-14, respectively with the S form as a major enantiomer. Next, the sequential exposure of docosahexaenoyl-lysoPC to soybean LOX-1 and porcine leukocyte LOX led to the formation of conjugated triene derivatives possessing a maximal absorption at 271 nm with shoulders at 262 and 281 nm. Based on MS-MS analysis, the conjugated triene derivatives were identified to be 10,17- or 16,17-dihydroxydocosahexaenoyl-lysoPC analogues, suggesting that the diols were produced mainly from hydrolysis of 16,17(S)-epoxide intermediate. In kinetic studies, docosahexaenoyl-lysoPC was more favorable than docosahexaenoic acid as substrate for soybean LOX-1 or leukocyte LOX. Taken together, it is proposed that docosahexaenoyl-lysoPC can be oxygenated as substrates for some lipoxygenases to form conjugated diene and/or triene derivatives.

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Oxygenation of phosphatidylcholine by human polymorphonuclear leukocyte 15-lipoxygenase

Cited by 57 publications

References 12 publications

Investigation of Substrate Binding and Product Stereochemistry Issues in Two Linoleate 9‐Lipoxygenases

Investigation of Substrate Binding and Product Stereochemistry Issues in Two Linoleate 9‐Lipoxygenases

Lipid peroxidation in cell death

Oxygenation of 1‐Docosahexaenoyl Lysophosphatidylcholine by Lipoxygenases; Conjugated Hydroperoxydiene and Dihydroxytriene Derivatives

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