Enzymatic formation of prostamide F2α from anandamide involves a newly identified intermediate metabolite, prostamide H2
Prostaglandin F2α 1-ethanolamide (prostamide F2α) is a potent ocular hypotensive agent in animals and represents a new class of fatty acid amide compounds. Accumulated evidence indicated that anandamide, an endogenous bioactive ligand for cannabinoid receptors, may serve as a common substrate to pro...
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| Format: | Article |
| Language: | English |
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Elsevier
2005-12-01
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| Series: | Journal of Lipid Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520328637 |
| _version_ | 1818715717313232896 |
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| author | Wu Yang Jinsong Ni David F. Woodward Diane D-S. Tang-Liu Kah-Hiing John Ling |
| author_facet | Wu Yang Jinsong Ni David F. Woodward Diane D-S. Tang-Liu Kah-Hiing John Ling |
| author_sort | Wu Yang |
| collection | DOAJ |
| description | Prostaglandin F2α 1-ethanolamide (prostamide F2α) is a potent ocular hypotensive agent in animals and represents a new class of fatty acid amide compounds. Accumulated evidence indicated that anandamide, an endogenous bioactive ligand for cannabinoid receptors, may serve as a common substrate to produce all prostamides, including prostamide F2α. After incubation of anandamide with cyclooxygenase 2 (COX-2), the reaction mixture was profiled by HPLC and an intermediate metabolite was discovered and characterized as a cyclic endoperoxide ethanolamide using HPLC-tandem mass spectrometry. Formation of prostamide F2α was also demonstrated when the intermediate metabolite was isolated and incubated with prostaglandin F synthase (PGF synthase).These results suggest that the biosynthesis of prostamide F2α proceeds in two consecutive steps: oxidation of anandamide to form an endoperoxide intermediate by COX-2, and reduction of the endoperoxide intermediate to form prostamide F2α by PGF synthase. This endoperoxide ethanolamide intermediate has been proposed as prostamide H2. |
| first_indexed | 2024-12-17T19:07:48Z |
| format | Article |
| id | doaj.art-d12733577f7d48708722338bd31fdeec |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-17T19:07:48Z |
| publishDate | 2005-12-01 |
| publisher | Elsevier |
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| series | Journal of Lipid Research |
| spelling | doaj.art-d12733577f7d48708722338bd31fdeec2022-12-21T21:35:57ZengElsevierJournal of Lipid Research0022-22752005-12-01461227452751Enzymatic formation of prostamide F2α from anandamide involves a newly identified intermediate metabolite, prostamide H2Wu Yang0Jinsong Ni1David F. Woodward2Diane D-S. Tang-Liu3Kah-Hiing John Ling4To whom correspondence should be addressed.; Department of Pharmacokinetics and Drug Metabolism, Allergan, Inc., Irvine, CA 92623Department of Pharmacokinetics and Drug Metabolism, Allergan, Inc., Irvine, CA 92623Department of Biological Sciences, Allergan, Inc., Irvine, CA 92623Department of Pharmacokinetics and Drug Metabolism, Allergan, Inc., Irvine, CA 92623Department of Pharmacokinetics and Drug Metabolism, Allergan, Inc., Irvine, CA 92623Prostaglandin F2α 1-ethanolamide (prostamide F2α) is a potent ocular hypotensive agent in animals and represents a new class of fatty acid amide compounds. Accumulated evidence indicated that anandamide, an endogenous bioactive ligand for cannabinoid receptors, may serve as a common substrate to produce all prostamides, including prostamide F2α. After incubation of anandamide with cyclooxygenase 2 (COX-2), the reaction mixture was profiled by HPLC and an intermediate metabolite was discovered and characterized as a cyclic endoperoxide ethanolamide using HPLC-tandem mass spectrometry. Formation of prostamide F2α was also demonstrated when the intermediate metabolite was isolated and incubated with prostaglandin F synthase (PGF synthase).These results suggest that the biosynthesis of prostamide F2α proceeds in two consecutive steps: oxidation of anandamide to form an endoperoxide intermediate by COX-2, and reduction of the endoperoxide intermediate to form prostamide F2α by PGF synthase. This endoperoxide ethanolamide intermediate has been proposed as prostamide H2.http://www.sciencedirect.com/science/article/pii/S0022227520328637cyclooxygenase 2prostaglandin F2α 1-ethanolamideprostaglandin F synthase |
| spellingShingle | Wu Yang Jinsong Ni David F. Woodward Diane D-S. Tang-Liu Kah-Hiing John Ling Enzymatic formation of prostamide F2α from anandamide involves a newly identified intermediate metabolite, prostamide H2 Journal of Lipid Research cyclooxygenase 2 prostaglandin F2α 1-ethanolamide prostaglandin F synthase |
| title | Enzymatic formation of prostamide F2α from anandamide involves a newly identified intermediate metabolite, prostamide H2 |
| title_full | Enzymatic formation of prostamide F2α from anandamide involves a newly identified intermediate metabolite, prostamide H2 |
| title_fullStr | Enzymatic formation of prostamide F2α from anandamide involves a newly identified intermediate metabolite, prostamide H2 |
| title_full_unstemmed | Enzymatic formation of prostamide F2α from anandamide involves a newly identified intermediate metabolite, prostamide H2 |
| title_short | Enzymatic formation of prostamide F2α from anandamide involves a newly identified intermediate metabolite, prostamide H2 |
| title_sort | enzymatic formation of prostamide f2α from anandamide involves a newly identified intermediate metabolite prostamide h2 |
| topic | cyclooxygenase 2 prostaglandin F2α 1-ethanolamide prostaglandin F synthase |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520328637 |
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