Cytochromes P450 from family 4 are the main omega hydroxylating enzymes in humans: CYP4F3B is the prominent player in PUFA metabolism1
Human CYP450 ω-hydroxylases of the CYP4 family are known to convert arachidonic acid (AA) to its metabolite 20-hydroxyeicosatetraenoic acid (20-HETE). This study deals with hydroxylations of four PUFAs, eicosatrienoic acid (ETA), AA, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) by eit...
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| Format: | Article |
| Language: | English |
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Elsevier
2008-11-01
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| Series: | Journal of Lipid Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520346150 |
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| author | Maude Fer Laurent Corcos Yvonne Dréano Emmanuelle Plée-Gautier Jean-Pierre Salaün François Berthou Yolande Amet |
| author_facet | Maude Fer Laurent Corcos Yvonne Dréano Emmanuelle Plée-Gautier Jean-Pierre Salaün François Berthou Yolande Amet |
| author_sort | Maude Fer |
| collection | DOAJ |
| description | Human CYP450 ω-hydroxylases of the CYP4 family are known to convert arachidonic acid (AA) to its metabolite 20-hydroxyeicosatetraenoic acid (20-HETE). This study deals with hydroxylations of four PUFAs, eicosatrienoic acid (ETA), AA, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) by either human recombinant CYP4s enzymes or human liver microsomal preparations. CYP4F3A and CYP4F3B were the most efficient ω-hydroxylases of these PUFAs. Moreover, the differences in the number of unsaturations of ETA, AA, and EPA allowed us to demonstrate a rise in the metabolic rate of hydroxylation when the double bond in 14-15 or 17-18 was missing. With the CYP4F enzymes, the main pathway was always the ω-hydroxylation of PUFAs, whereas it was the (ω-1)-hydroxylation with CYP1A1, CYP2C19, and CYP2E1. Finally, we demonstrated that the ω9 and ω3 PUFAs (ETA, EPA, and DHA) could all be used as alternative substrates in AA metabolism by human CYP4F2 and -4F3B. Thus, they decreased the ability of these enzymes to convert AA to 20-HETE. However, although ETA was the most hydroxylated substrate, EPA and DHA were the most potent inhibitors of the conversion of AA to 20-HETE. These findings suggest that some physiological effects of ω3 FAs could partly result from a shift in the generation of active hydroxylated metabolites of AA through a CYP-mediated catalysis. |
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| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-20T04:17:09Z |
| publishDate | 2008-11-01 |
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| series | Journal of Lipid Research |
| spelling | doaj.art-fa55e3eea7af4ddfb8962da1d94924aa2022-12-21T19:53:44ZengElsevierJournal of Lipid Research0022-22752008-11-01491123792389Cytochromes P450 from family 4 are the main omega hydroxylating enzymes in humans: CYP4F3B is the prominent player in PUFA metabolism1Maude Fer0Laurent Corcos1Yvonne Dréano2Emmanuelle Plée-Gautier3Jean-Pierre Salaün4François Berthou5Yolande Amet6Laboratoire de Biochimie EA 948, Faculté de Médecine, Université de Bretagne Occidentale, Brest, FranceLaboratoire de Biochimie EA 948, Faculté de Médecine, Université de Bretagne Occidentale, Brest, France; Institut National de la Santé et de la Recherche Médicale U613, Faculté de Médecine, Université de Bretagne Occidentale, Brest, FranceLaboratoire de Biochimie EA 948, Faculté de Médecine, Université de Bretagne Occidentale, Brest, FranceLaboratoire de Biochimie EA 948, Faculté de Médecine, Université de Bretagne Occidentale, Brest, FranceLaboratoire de Biochimie EA 948, Faculté de Médecine, Université de Bretagne Occidentale, Brest, France; Centre National de la Recherche Scientifique UMR 7139, Station Biologique, Roscoff, FranceLaboratoire de Biochimie EA 948, Faculté de Médecine, Université de Bretagne Occidentale, Brest, FranceLaboratoire de Biochimie EA 948, Faculté de Médecine, Université de Bretagne Occidentale, Brest, FranceHuman CYP450 ω-hydroxylases of the CYP4 family are known to convert arachidonic acid (AA) to its metabolite 20-hydroxyeicosatetraenoic acid (20-HETE). This study deals with hydroxylations of four PUFAs, eicosatrienoic acid (ETA), AA, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) by either human recombinant CYP4s enzymes or human liver microsomal preparations. CYP4F3A and CYP4F3B were the most efficient ω-hydroxylases of these PUFAs. Moreover, the differences in the number of unsaturations of ETA, AA, and EPA allowed us to demonstrate a rise in the metabolic rate of hydroxylation when the double bond in 14-15 or 17-18 was missing. With the CYP4F enzymes, the main pathway was always the ω-hydroxylation of PUFAs, whereas it was the (ω-1)-hydroxylation with CYP1A1, CYP2C19, and CYP2E1. Finally, we demonstrated that the ω9 and ω3 PUFAs (ETA, EPA, and DHA) could all be used as alternative substrates in AA metabolism by human CYP4F2 and -4F3B. Thus, they decreased the ability of these enzymes to convert AA to 20-HETE. However, although ETA was the most hydroxylated substrate, EPA and DHA were the most potent inhibitors of the conversion of AA to 20-HETE. These findings suggest that some physiological effects of ω3 FAs could partly result from a shift in the generation of active hydroxylated metabolites of AA through a CYP-mediated catalysis.http://www.sciencedirect.com/science/article/pii/S0022227520346150ω-hydroxylation(ω-1)-hydroxylationinhibition |
| spellingShingle | Maude Fer Laurent Corcos Yvonne Dréano Emmanuelle Plée-Gautier Jean-Pierre Salaün François Berthou Yolande Amet Cytochromes P450 from family 4 are the main omega hydroxylating enzymes in humans: CYP4F3B is the prominent player in PUFA metabolism1 Journal of Lipid Research ω-hydroxylation (ω-1)-hydroxylation inhibition |
| title | Cytochromes P450 from family 4 are the main omega hydroxylating enzymes in humans: CYP4F3B is the prominent player in PUFA metabolism1 |
| title_full | Cytochromes P450 from family 4 are the main omega hydroxylating enzymes in humans: CYP4F3B is the prominent player in PUFA metabolism1 |
| title_fullStr | Cytochromes P450 from family 4 are the main omega hydroxylating enzymes in humans: CYP4F3B is the prominent player in PUFA metabolism1 |
| title_full_unstemmed | Cytochromes P450 from family 4 are the main omega hydroxylating enzymes in humans: CYP4F3B is the prominent player in PUFA metabolism1 |
| title_short | Cytochromes P450 from family 4 are the main omega hydroxylating enzymes in humans: CYP4F3B is the prominent player in PUFA metabolism1 |
| title_sort | cytochromes p450 from family 4 are the main omega hydroxylating enzymes in humans cyp4f3b is the prominent player in pufa metabolism1 |
| topic | ω-hydroxylation (ω-1)-hydroxylation inhibition |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520346150 |
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