10. Holtzman, M. J., J. Turk, and L. P. Shornick. 1992. Identification of
a pharmacologically distinct prostaglandin H synthase in cultured
epithelial cells. J. Biol. Chem. 267: 21438–21445.
11. Mancini, J. A., G. P. O’Neill, C. Bayly, and P. J. Vickers. 1994.
Mutation of serine-516 in human prostaglandin G/H synthase-2
to methionine or aspirin acetylation of this residue stimulates
15-R-HETE synthesis. FEBS Lett. 342: 33–37.
12. Schneider, C., W. E. Boeglin, H. Yin, D. F. Stec, and M. Voehler.
2006. Convergent oxygenation of arachidonic acid by 5-lipoxyge-
nase and cyclooxygenase-2. J. Am. Chem. Soc. 128: 720–721.
13. Griesser, M., W. E. Boeglin, T. Suzuki, and C. Schneider. 2009.
Convergence of the 5-LOX and COX-2 pathways. Heme-catalyzed
cleavage of the 5S-HETE-derived di-endoperoxide into aldehyde
fragments. J. Lipid Res. 50: 2455–2462.
14. Schneider, C., W. E. Boeglin, and A. R. Brash. 2000. Enantiomeric
separation of hydroxy-eicosanoids by chiral column chromatogra-
phy: effect of the alcohol modifier. Anal. Biochem. 287: 186–189.
15. Rowlinson, S. W., B. C. Crews, D. C. Goodwin, C. Schneider, J. K.
Gierse, and L. J. Marnett. 2000. Spatial requirements for 15-(R)-
hydroxy-5Z,8Z,11Z,13E-eicosatetraenoic acid synthesis within the
cyclooxygenase active site of murine COX-2. Why acetylated COX-1
does not synthesize 15-(R)-HETE. J. Biol. Chem. 275: 6586–6591.
16. Brash, A. R., and W-C. Song. 1996. Detection, assay, and isolation of
allene oxide synthase. Methods Enzymol. 272: 250–259.
17. Zheng, Y., W. E. Boeglin, C. Schneider, and A. R. Brash. 2008. A
49-kDa mini-lipoxygenase from Anabaena sp. PCC 7120 retains
catalytically complete functionality. J. Biol. Chem. 283: 5138–5147.
18. Maas, R. L., J. Turk, J. A. Oates, and A. R. Brash. 1982. Formation
of a novel dihydroxy acid from arachidonic acid by lipoxygenase-
catalyzed double oxygenation in rat mononuclear cells and human
leukocytes. J. Biol. Chem. 257: 7056–7067.
19. Schneider, C., P. Schreier, and H-U. Humpf. 1997. Exciton-coupled
circular dichroism (ECCD) in acyclic hydroxylated dienes: a sensi-
tive method for the direct stereochemical assignment of lipoxyge-
nase products. Chirality. 9: 563–567.
20. Bala, M., C. N. Chin, A. T. Logan, T. Amin, L. J. Marnett, O.
Boutaud, and J. A. Oates. 2008. Acetylation of prostaglandin H2
synthases by aspirin is inhibited by redox cycling of the peroxidase.
Biochem. Pharmacol. 75: 1472–1481.
21. Rector, C. L., D. F. Stec, A. R. Brash, and N. A. Porter. 2007.
Identification of the peroxidation products of 13-hydroxy-gamma-
linolenate and 15-hydroxyarachidonate: mechanistic studies on the
formation of leukotriene-like diols. Chem. Res. Toxicol. 20: 1582–1593.
22. Bild, G. S., C. S. Ramadoss, S. Lim, and B. Axelrod. 1977. Double
dioxygenation of arachidonic acid by soybean lipoxygenase-1.
Biochem. Biophys. Res. Commun. 74: 949–954.
26. Lee, S. H., K. Rangiah, M. V. Williams, A. Y. Wehr, R. N. DuBois,
and I. A. Blair. 2007. Cyclooxygenase-2-mediated metabolism of
arachidonic acid to 15-oxo-eicosatetraenoic acid by rat intestinal
epithelial cells. Chem. Res. Toxicol. 20: 1665–1675.
27. Schneider, C., W. E. Boeglin, and A. R. Brash. 2004. Identification
of two cyclooxygenase active site residues, leucine-384 and glycine-
526, that control carbon ring cyclization in prostaglandin biosyn-
thesis. J. Biol. Chem. 279: 4404–4414.
28. Schneider, C., D. A. Pratt, N. A. Porter, and A. R. Brash. 2007.
Control of oxygenation in lipoxygenase and cyclooxygenase cataly-
sis. Chem. Biol. 14: 473–488.
29. Xiao, G., A. L. Tsai, G. Palmer, W. C. Boyar, P. J. Marshall, and R. J.
Kulmacz. 1997. Analysis of hydroperoxide-induced tyrosyl radicals
and lipoxygenase activity in aspirin-treated human prostaglandin H
synthase-2. Biochemistry. 36: 1836–1845.
30. Schneider, C., and A. R. Brash. 2000. Stereospecificity of hydrogen
abstraction in the conversion of arachidonic acid to 15R-HETE by
aspirin-treated cyclooxygenase-2. J. Biol. Chem. 275: 4743–4746.
31. Tsai, A. L., G. Palmer, G. Wu, S. Peng, N. M. Okeley, W. A. van
der Donk, and R. J. Kulmacz. 2002. Structural characterization of
arachidonyl radicals formed by aspirin-treated prostaglandin H
synthase-2. J. Biol. Chem. 277: 38311–38321.
32. Furse, K. E., D. A. Pratt, C. Schneider, A. R. Brash, N. A. Porter,
and T. P. Lybrand. 2006. Molecular dynamics simulations of ara-
chidonic acid-derived pentadienyl radical intermediate complexes
with COX-1 and COX-2: insights into oxygenation regio- and ste-
reoselectivity. Biochemistry. 45: 3206–3218.
33. Hochgesang, G. P., S. W. Rowlinson, and L. J. Marnett. 2000.
Tyrosine-385 is critical for acetylation of cyclooxygenase-2 by aspi-
rin. J. Am. Chem. Soc. 122: 6514–6515.
34. Setty, B. N., M. J. Stuart, and R. W. Walenga. 1985. Formation of
11-hydroxyeicosatetraenoic acid and 15-hydroxyeicosatetraenoic
acid in human umbilical arteries is catalyzed by cyclooxygenase.
Biochim. Biophys. Acta. 833: 484–494.
35. Setty, B. N., and M. J. Stuart. 1986. 15-Hydroxy-5,8,11,13-eicosatetra-
enoic acid inhibits human vascular cyclooxygenase. Potential role
in diabetic vascular disease. J. Clin. Invest. 77: 202–211.
36. O’Flaherty, J. T., and M. J. Thomas. 1985. Effect of 15-lipoxygenase-
derived arachidonate metabolites on human neutrophil degranu-
lation. Prostaglandins Leukot. Med. 17: 199–212.
37. Morita, E., J. M. Schroder, and E. Christophers. 1990. Identification
of a novel and highly potent eosinophil chemotactic lipid in hu-
man eosinophils treated with arachidonic acid. J. Immunol. 144:
1893–1900.
38. Schwenk, U., E. Morita, R. Engel, and J. M. Schroder. 1992.
Identification of 5-oxo-15-hydroxy-6,8,11,13-eicosatetraenoic acid
as a novel and potent human eosinophil chemotactic eicosanoid. J.
Biol. Chem. 267: 12482–12488.
23. Van Os, C. P. A., G. P. M. Rijke-Schilder, H. Van Halbeek, J.
Verhagen, and J. F. G. Vliegenthart. 1981. Double dioxygenation
of arachidonic acid by soybean lipoxygenase-1. Kinetics and regio-
stereo specificities of the reaction steps. Biochim. Biophys. Acta. 663:
177–193.
39. Claria, J., and C. N. Serhan. 1995. Aspirin triggers previously unde-
scribed bioactive eicosanoids by human endothelial cell-leukocyte
interactions. Proc. Natl. Acad. Sci. USA. 92: 9475–9479.
24. Murphy, R. C., S. Hammarstrom, and B. Samuelsson. 1979.
Leukotriene C: a slow-reacting substance from murine mastocy-
toma cells. Proc. Natl. Acad. Sci. USA. 76: 4275–4279.
25. Rouzer, C. A., T. Matsumoto, and B. Samuelsson. 1986. Single pro-
tein from human leukocytes possesses 5-lipoxygenase and leuko-
triene A4 synthase activities. Proc. Natl. Acad. Sci. USA. 83: 857–861.
40. Serhan, C. N. 2002. Lipoxins and aspirin-triggered 15-epi-lipoxin
biosynthesis: an update and role in anti-inflammation and pro-
resolution. Prostaglandins Other Lipid Mediat. 68–69: 433–455.
41. Gilroy, D. W., T. Lawrence, M. Perretti, and A. G. Rossi. 2004.
Inflammatory resolution: new opportunities for drug discovery.
Nat. Rev. Drug Discov. 3: 401–416.
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