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- Name help_outline 15-oxo-(5S,6R)-dihydroxy-(7E,9E,11Z,13E)-eicosatetraenoate Identifier CHEBI:78311 Charge -1 Formula C20H29O5 InChIKeyhelp_outline KMQGFEBCBYXSPZ-OABWHSJTSA-M SMILEShelp_outline CCCCCC(=O)\C=C\C=C/C=C/C=C/[C@@H](O)[C@@H](O)CCCC([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 2 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline H+ Identifier CHEBI:15378 Charge 1 Formula H InChIKeyhelp_outline GPRLSGONYQIRFK-UHFFFAOYSA-N SMILEShelp_outline [H+] 2D coordinates Mol file for the small molecule Search links Involved in 9,176 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline NADH Identifier CHEBI:57945 (Beilstein: 3869564) help_outline Charge -2 Formula C21H27N7O14P2 InChIKeyhelp_outline BOPGDPNILDQYTO-NNYOXOHSSA-L SMILEShelp_outline NC(=O)C1=CN(C=CC1)[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OC[C@H]2O[C@H]([C@H](O)[C@@H]2O)n2cnc3c(N)ncnc23)[C@@H](O)[C@H]1O 2D coordinates Mol file for the small molecule Search links Involved in 1,073 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline 15-oxo-(5S,6R)-dihydroxy-(7E,9E,11Z)-eicosatrienoate Identifier CHEBI:78325 Charge -1 Formula C20H31O5 InChIKeyhelp_outline FPRPRBFSKMFXRV-JWVNNVTNSA-M SMILEShelp_outline CCCCCC(=O)CC\C=C/C=C/C=C/[C@@H](O)[C@@H](O)CCCC([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 2 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline NAD+ Identifier CHEBI:57540 (Beilstein: 3868403) help_outline Charge -1 Formula C21H26N7O14P2 InChIKeyhelp_outline BAWFJGJZGIEFAR-NNYOXOHSSA-M SMILEShelp_outline NC(=O)c1ccc[n+](c1)[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OC[C@H]2O[C@H]([C@H](O)[C@@H]2O)n2cnc3c(N)ncnc23)[C@@H](O)[C@H]1O 2D coordinates Mol file for the small molecule Search links Involved in 1,142 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
| RHEA:41592 | RHEA:41593 | RHEA:41594 | RHEA:41595 | |
|---|---|---|---|---|
| Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
| UniProtKB help_outline |
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Publications
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Oxidoreductases in lipoxin A4 metabolic inactivation: a novel role for 15-onoprostaglandin 13-reductase/leukotriene B4 12-hydroxydehydrogenase in inflammation.
Clish C.B., Levy B.D., Chiang N., Tai H.-H., Serhan C.N.
The lipoxins (LX) are autacoids that act within a local inflammatory milieu to dampen neutrophil recruitment and promote resolution. 15-Hydroxyprostaglandin dehydrogenase (15-PGDH) and 15-oxoprostaglandin 13-reductase, also termed leukotriene B(4) 12-hydroxydehydrogenase (PGR/LTB(4)DH), are two en ... >> More
The lipoxins (LX) are autacoids that act within a local inflammatory milieu to dampen neutrophil recruitment and promote resolution. 15-Hydroxyprostaglandin dehydrogenase (15-PGDH) and 15-oxoprostaglandin 13-reductase, also termed leukotriene B(4) 12-hydroxydehydrogenase (PGR/LTB(4)DH), are two enzymatic activities appreciated for their roles in the metabolism of prostaglandins and LTB(4). Here, we determined whether these oxidoreductases also catalyze the conversion of lipoxin A(4) (LXA(4)) and assessed the activities of these LXA(4) metabolites. 15-Oxo-LXA(4) was generated by incubating LXA(4) with 15-PGDH and NAD(+) for studies of its further conversion. PGR/LTB(4)DH catalyzed the NADH-dependent reduction of 15-oxo-LXA(4) to yield 13,14-dihydro-15-oxo-LXA(4). With NADH as a cofactor, 15-PGDH acted as a 15-carbonyl reductase and catalyzed the conversion of 13,14-dihydro-15-oxo-LXA(4) to 13, 14-dihydro-LXA(4). Human polymorphonuclear leukocytes (PMN) exposed to native LXA(4), 15-oxo-LXA(4), or 13,14-dihydro-LXA(4) did not produce superoxide anions. At concentrations where LXA(4) and a metabolically stable LXA(4) analog potently inhibited leukotriene B(4)-induced superoxide anion generation, the further metabolites were devoid of activity. Neither 15-oxo-LXA(4) nor 13, 14-dihydro-LXA(4) effectively competed with (3)H-labeled LXA(4) for specific binding to recombinant LXA(4) receptor (ALXR). In addition, introducing recombinant PGR/LTB(4)DH into a murine exudative model of inflammation increased PMN number by approximately 2-fold, suggesting that this enzyme participates in the regulation of PMN trafficking. These results establish the structures of LXA(4) further metabolites and indicate that conversion of LXA(4) to oxo- and dihydro-products represents a mode of LXA(4) inactivation in inflammation. Moreover, they suggest that these eicosanoid oxidoreductases have multifaceted roles controlling the levels of specific eicosanoids involved in the regulation of inflammation. << Less
J. Biol. Chem. 275:25372-25380(2000) [PubMed] [EuropePMC]
This publication is cited by 2 other entries.
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Identification of dual cyclooxygenase-eicosanoid oxidoreductase inhibitors: NSAIDs that inhibit PG-LX reductase/LTB(4) dehydrogenase.
Clish C.B., Sun Y.P., Serhan C.N.
Eicosanoids play key roles in many physiologic and disease processes, and their regulation by nonsteroidal anti-inflammatory drugs (NSAIDs) is critical to many therapeutic approaches. These autacoids are rapidly inactivated by specific enzymes such as 15-hydroxyprostaglandin dehydrogenase (15-PGDH ... >> More
Eicosanoids play key roles in many physiologic and disease processes, and their regulation by nonsteroidal anti-inflammatory drugs (NSAIDs) is critical to many therapeutic approaches. These autacoids are rapidly inactivated by specific enzymes such as 15-hydroxyprostaglandin dehydrogenase (15-PGDH) and 15-oxoprostaglandin 13-reductase/leukotriene B(4) 12-hydroxydehydrogenase (PGR/LTB(4)DH) that act on main series of eicosanoids (i.e., leukotrienes, prostaglandins), and recently found to act in lipoxin inactivation. Here, a panel of NSAIDs was assessed to determine each compound's ability to inhibit eicosanoid-directed activities of either the recombinant 15-PGDH or the PG-LXR/LTB(4)DH. The recombinant 15-PGDH that acts on both prostaglandin E(2) (PGE(2)) and lipoxin A(4) (LXA(4)) was not significantly inhibited by the NSAIDs tested. In contrast, several of the widely used NSAIDs were potent inhibitors of the PG-LXR/LTB(4)DH that metabolizes 15-oxo-PGE(2), and LTB(4) as well as 15-oxo-LXA(4). Diclofenac and indomethacin each inhibited PG-LXR/LTB(4)DH-catalyzed conversion of 15-oxo-PGE(2) to 13,14-dihydro-15-oxo-PGE(2) by 70 and 95%, respectively. Also, a COX-2 inhibitor, niflumic acid, inhibited the PG-LXR/LTB(4)DH eicosanoid oxidoreductase (EOR) by 80% while other COX-2 inhibitors such as nimesulide and NS-398 did not inhibit this enzyme. These results indicate that certain clinically useful NSAIDs such as diclofenac and indomethacin, in addition to inhibiting cyclooxygenases (1 and 2), also interfere with eicosanoid degradation by blocking PG-LXR/LTB(4)DH (EOR) and are members of a new class of dual cyclooxygenase (COX)-EOR inhibitors. Moreover, they suggest that the impact of NSAIDs on PG-LXR/LTB(4)DH activities as targets in the local tissue regulation of eicosanoid-mediated processes should be taken into account. << Less
Biochem. Biophys. Res. Commun. 288:868-874(2001) [PubMed] [EuropePMC]
This publication is cited by 2 other entries.