InChI=1S/C20H32O4/c21-18-14-10-6-5-8-12-16-19(22)15-11-7-3-1-2-4-9-13-17-20(23)24/h2-4,7-8,11-12,15,19,21-22H,1,5-6,9-10,13-14,16-18H2,(H,23,24)/b4-2-,7-3-,12-8-,15-11+ |
NUPDGIJXOAHJRW-LNESKJDXSA-N |
C(=C\C(C/C=C\CCCCCO)O)/C=C\C/C=C\CCCC(=O)O |
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Bronsted acid
A molecular entity capable of donating a hydron to an acceptor (Bronsted base).
(via oxoacid )
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human xenobiotic metabolite
Any human metabolite produced by metabolism of a xenobiotic compound in humans.
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View more via ChEBI Ontology
Outgoing
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12,20-DiHETE
(CHEBI:90990)
has functional parent
(5Z,8Z,10E,14Z)-12-hydroxyicosatetraenoic acid
(CHEBI:84447)
12,20-DiHETE
(CHEBI:90990)
has role
human xenobiotic metabolite
(CHEBI:76967)
12,20-DiHETE
(CHEBI:90990)
is a
ω-hydroxy-long-chain fatty acid
(CHEBI:140997)
12,20-DiHETE
(CHEBI:90990)
is a
dihydroxyicosatetraenoic acid
(CHEBI:72868)
12,20-DiHETE
(CHEBI:90990)
is conjugate acid of
12,20-DiHETE(1−)
(CHEBI:90719)
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Incoming
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12,20-DiHETE(1−)
(CHEBI:90719)
is conjugate base of
12,20-DiHETE
(CHEBI:90990)
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(5Z,8Z,10E,14Z)-12,20-dihydroxyicosa-5,8,10,14-tetraenoic acid
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(5Z,8Z,10E,14Z)-12,20-dihydroxyicosatetraenoic acid
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ChEBI
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12,20-dihydroxy-(5Z,8Z,10E,14Z)-icosatetraenoic acid
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ChEBI
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24406269
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Reaxys Registry Number
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Reaxys
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Kalsotra A, Turman CM, Kikuta Y, Strobel HW (2004) Expression and characterization of human cytochrome P450 4F11: Putative role in the metabolism of therapeutic drugs and eicosanoids. Toxicology and applied pharmacology 199, 295-304 [PubMed:15364545] [show Abstract] We previously reported the cDNA cloning of a new CYP4F isoform, CYP4F11. In the present study, we have expressed CYP4F11 in Saccharomyces cerevisiae and examined its catalytic properties towards endogenous eicosanoids as well as some clinically relevant drugs. CYP4F3A, also known as a leukotriene B4 omega-hydroxylase, was expressed in parallel for comparative purposes. Our results show that CYP4F11 has a very different substrate profile than CYP4F3A. CYP4F3A metabolized leukotriene B4, lipoxins A4 and B4, and hydroxyeicosatetraenoic acids (HETEs) much more efficiently than CYP4F11. On the other hand, CYP4F11 was a better catalyst than CYP4F3A for many drugs such as erythromycin, benzphetamine, ethylmorphine, chlorpromazine, and imipramine. Erythromycin was the most efficient substrate for CYP4F11, with a Km of 125 microM and Vmax of 830 pmol min(-1) nmol(-1) P450. Structural homology modeling of the two proteins revealed some interesting differences in the substrate access channel including substrate recognition site 2 (SRS2). The model of CYP4F11 presents a more open access channel that may explain the ability to metabolize large molecules like erythromycin. Also, some wide variations in residue size, charge, and hydrophobicity in the FG loop region may contribute to differences in substrate specificity and activity between CYP4F3A and CYP4F11. | Kikuta Y, Kusunose E, Sumimoto H, Mizukami Y, Takeshige K, Sakaki T, Yabusaki Y, Kusunose M (1998) Purification and characterization of recombinant human neutrophil leukotriene B4 omega-hydroxylase (cytochrome P450 4F3). Archives of biochemistry and biophysics 355, 201-205 [PubMed:9675028] [show Abstract] Recombinant human neutrophil leukotriene B4 (LTB4) omega-hydroxylase (cytochrome P450 4F3) has been purified to a specific content of 14. 8 nmol of P450/mg of protein from yeast cells. The purified enzyme was homogenous as judged from the SDS-PAGE, with an apparent molecular weight of 55 kDa. The enzyme catalyzed the omega-hydroxylation of LTB4 with a Km of 0.64 microM and Vmax of 34 nmol/min/nmol of P450 in the presence of rabbit hepatic NADPH-P450 reductase and cytochrome b5. Furthermore, various eicosanoids such as 20-hydroxy-LTB4, 6-trans-LTB4, lipoxin A4, lipoxin B4, 5-HETE and 12-HETE, and 12-hydroxy-stearate and 12-hydroxy-oleate were efficiently omega-hydroxylated, although their Km values were much higher than that of LTB4. In contrast, no activity was detected toward laurate, palmitate, arachidonate, 15-HETE, prostaglandin A1, and prostaglandin E1, all of which are excellent substrates for the CYP4A fatty acid omega-hydroxylases. This is the first time human neutrophil LTB4 omega-hydroxylase has been isolated in a highly purified state and characterized especially with respect to its substrate specificity. | Rosolowsky M, Falck JR, Campbell WB (1996) Metabolism of arachidonic acid by canine polymorphonuclear leukocytes synthesis of lipoxygenase and omega-oxidized metabolites. Biochimica et biophysica acta 1300, 143-150 [PubMed:8652640] [show Abstract] Both polymorphonuclear (PMN) leukocytes and metabolites of arachidonic acid, especially lipoxygenase products, have been reported to contribute to myocardial damage after coronary artery occlusion and reperfusion. While canine models of myocardial ischemia were used in many of these studies, very little is known about arachidonic acid metabolism by canine PMNs. Moreover, it is unclear whether arachidonic acid metabolites released by canine PMNs affect vascular tone. Therefore, we characterized arachidonic acid metabolism by canine PMNs and determined the effect of these metabolites on vascular tone of isolated canine coronary arteries. Suspensions of canine PMNs were incubated with [14C]arachidonic acid and the calcium ionophore A23187. The incubation media was extracted, and the metabolites resolved by HPLC. 20-Hydroxy-leukotriene B4 (LTB4), 12,20-dihydroxyeicosatetraenoic acid (diHETE), LTB4, 12-hydroxyheptadeclatrienoic acid (HHT), and 12-(S)-hydroxyeicosatetraenoic acid (HETE) were isolated, and their structures confirmed by gas chromatography/mass spectrometry. There was also evidence for the formation of 20-HETE, thromboxane B2 (TXB2), 5-HETE, and several isomers of LTB4. None of the arachidonic acid metabolites that were isolated from incubates of canine PMNs augmented vascular tone, but material migrating with 12,20-diHETE relaxed canine coronary arteries. Authentic 12(S),20-diHETE also produced a concentration-related relaxation of canine coronary artery. 12(R), 20-diHETE was inactive. 20-HETE inhibited A23187-induced PMN aggregation. Thus, arachidonic acid is metabolized in canine PMNs through the cyclooxygenase, lipoxygenases and cytochrome P-450 pathways. Whether these metabolites contribute to myocardial injury remains to be determined. | Hajjar DP, Pomerantz KB (1989) Eicosanoids and their role in atherosclerosis. Archives des maladies du coeur et des vaisseaux 82 Spec No 4, 21-26 [PubMed:2514663] [show Abstract] Our laboratory has been actively investigating the role of endogenously synthesized eicosanoids in the control of vascular cholesterol metabolism. Using an in vivo rabbit model, cholesteryl esters (CE) accumulated under the regenerating edge of the endothelium due to reductions in CE hydrolytic activity and the accumulation of LDL. In addition, the aortic neointima immediately formed after de- endothelialization synthesized little PGI2, but regained its capacity to synthesize PGI2 over time of endothelial cell regeneration. Importantly, hypercholesterolemia inhibited the recovery of PGI2-synthetic capacity by the vessel wall using this model. Using cultured arterial smooth muscle cells, PGI2 and its derivatives (but not PGE2 and PGE1) stimulated lysosomal (acid) and cytoplasmic (neutral) CE hydrolase activities and reduced cellular cholesterol content. CE-synthetic activity was unaffected by PGI2 or its stable metabolites, but was inhibited by PGE2. Eicosanoids generated from platelet-neutrophil-smooth muscle cell interactions (including platelet-generated arachidonic acid, 12-HETE, 12,20-diHETE) may be important in the role of eicosanoids in mediating vascular cholesterol metabolism. We also observed that CE-enriched arterial smooth muscle cells have reduced capacity to synthesize PGI2 and PGE2. Collectively, our data suggest that eicosanoids derived from blood-borne cells and the vascular endothelium may regulate cholesterol metabolism in smooth muscle cells, and that eicosanoid regulation of vascular CE content may be impaired during hypercholesterolemia owing to an inability of arterial tissue to generate PGI2 and related eicosanoids. |
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