Cytochrome P450–dependent metabolism of ω-6 and ω-3 long-chain polyunsaturated fatty acids
Abstract
Dietary fish oil omega-3 fatty acids (n-3 PUFAs), such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), protect against arrhythmia and sudden cardiac death using largely unknown mechanisms. EPA and DHA may serve as efficient alternative substrates of arachidonic acid (AA) metabolizing cytochrome P450 (CYP) enzymes. For many of the CYP isoforms, the n-3 PUFAs are the preferred substrates. Moreover, the CYP enzymes oxygenate EPA and DHA with largely different regioselectivities compared to AA. In particular, the omega-3 double bond that distinguishes EPA and DHA from AA is a preferred site of CYP-catalyzed epoxidation reactions. Given the pivotal role of CYP-dependent AA metabolites in the regulation of vascular, renal and cardiac functions, their replacement by unique sets of epoxy- and hydroxy-metabolites derived from EPA and DHA may have far-reaching physiological implications. The currently available data suggest that some of the vasculo- and cardioprotective effects attributed to dietary n-3 PUFAs may be mediated by CYP-dependent metabolites of EPA and DHA.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
EPA and DHA are precursors to bioactive lipid metabolites, including specialized proresolving mediators and cytochrome P450-generated monoepoxides, that could contribute to lower CHD risk.
“Both EPA and DHA are also precursors to bioactive lipid metabolites, including specialized proresolving mediators36 and cytochrome P450–generated monoepoxides,37 that could contribute to lower CHD risk.”
From ω-3 Polyunsaturated Fatty Acid Biomarkers and Coronary Heart Disease: Pooling Project of 19 Cohort Studies (2016) · cites this paper as [37]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Resolving inflammation: dual anti-inflammatory and pro-resolution lipid mediators
Serhan, C. N., Chiang, N., & Van Dyke, T. E. (2008) · Nature Reviews Immunology · doi:10.1038/nri2294 · Cited by 2,932 · see citing works
Marchioli, R., Barzi, F., Bomba, E., Chieffo, C., Di Gregorio, D., Di Mascio, R., Franzosi, M. G., Geraci, E., Levantesi, G., Maggioni, A. P., et al. (2002) · Circulation · doi:10.1161/01.cir.0000014682.14181.f2 · Cited by 1,311 · see citing works
Thies, F., Garry, J. M., Yaqoob, P., Rerkasem, K., Williams, J., Shearman, C. P., Gallagher, P. J., Calder, P. C., & Grimble, R. F. (2003) · The Lancet · doi:10.1016/s0140-6736(03)12468-3 · Cited by 739 · cited 1× · see citing works
“Importantly, n-3 PUFAs also protect against atrial fibrillation in cardiac surgical settings [9] and promote plaque stabilization [90].”
BackgroundLeaf, A., Kang, J. X., Xiao, Y.-F., & Billman, G. E. (2003) · Circulation · doi:10.1161/01.cir.0000069566.78305.33 · Cited by 605 · see citing works
Wada, M., DeLong, C. J., Hong, Y. H., Rieke, C. J., Song, I., Sidhu, R. S., Yuan, C., Warnock, M., Schmaier, A. H., Yokoyama, C., et al. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m703169200 · Cited by 400 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Omega-3 Fatty Acids and Cardiovascular Disease
Mozaffarian, D., & Wu, J. H. Y. (2011) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2011.06.063 · Cited by 1,771 · see citing works
Advances in Our Understanding of Oxylipins Derived from Dietary PUFAs.
Gabbs, M., Leng, S., Devassy, J., Monirujjaman, M., & Aukema, H. (2015) · Advances in Nutrition · doi:10.3945/an.114.007732 · Cited by 734 · see citing works
Dyall, S. C., Balas, L., Bazan, N. G., Brenna, J. T., Chiang, N., Souza, F. D. C., Dalli, J., Durand, T., Galano, J., Lein, P. J., et al. (2022) · Progress in Lipid Research · doi:10.1016/j.plipres.2022.101165 · Cited by 681 · see citing works
“EPA is the preferred substrate for the majority of CYP isoforms, with DHA and ARA metabolized at similar rates [25].”
BackgroundDel Gobbo, L. C., Imamura, F., Aslibekyan, S., Marklund, M., Virtanen, J. K., Wennberg, M., Yakoob, M. Y., Chiuve, S. E., dela Cruz, L., Frazier-Wood, A. C., et al. (2016) · JAMA Internal Medicine · doi:10.1001/jamainternmed.2016.2925 · Cited by 404 · see citing works
(n-3) Fatty Acids and Cardiovascular Health: Are Effects of EPA and DHA Shared or Complementary?
Mozaffarian, D., & Wu, J. H. Y. (2012) · The Journal of Nutrition · doi:10.3945/jn.111.149633 · Cited by 368 · see citing works
Involvement of free radicals and oxidative stress in NAFLD/NASH
Sumida, Y., Niki, E., Naito, Y., & Yoshikawa, T. (2013) · Free Radical Research · doi:10.3109/10715762.2013.837577 · Cited by 280 · see citing works
Human Cytochrome P450 1A1 Structure and Utility in Understanding Drug and Xenobiotic Metabolism*
Walsh, A., Szklarz, G., & Scott, E. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.452953 · Cited by 262 · see citing works
Fatty Acid–Regulated Transcription Factors in the Liver
Jump, D. Β., Tripathy, S., & Depner, C. M. (2013) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-071812-161139 · Cited by 228 · see citing works
Omega-3 fatty acid supplementation and cardiovascular disease
Jump, D. Β., Depner, C. M., & Tripathy, S. (2012) · Journal of Lipid Research · doi:10.1194/jlr.r027904 · Cited by 243 · see citing works
Oxidation of polyunsaturated fatty acids to produce lipid mediators
Christie, W. W., & Harwood, J. L. (2020) · Essays in Biochemistry · doi:10.1042/ebc20190082 · Cited by 223 · see citing works
Camelina, an ancient oilseed crop actively contributing to the rural renaissance in Europe. A review
Zanetti, F., Alberghini, B., Jeromela, A. M., Grahovac, N., Rajković, D., Kiprovski, B., & Monti, A. (2021) · Agronomy for Sustainable Development · doi:10.1007/s13593-020-00663-y · Cited by 152 · see citing works
Calder, P. C. (2020) · Essays in Biochemistry · doi:10.1042/ebc20190083 · Cited by 323 · see citing works
Mavangira, V., & Sordillo, L. M. (2017) · Research in Veterinary Science · doi:10.1016/j.rvsc.2017.08.002 · Cited by 131 · see citing works
Eicosanoids in inflammation in the blood and the vessel
Yamaguchi, A. A., Botta, E., & Holinstat, M. A. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.997403 · Cited by 114 · see citing works
“Additionally, members of the CYP4A and CYP4F subfamilies also oxygenate AA to produce 20hydroxyeicosatetraenoic acid (20-HETE) (Arnold et al., 2010) (Figure 1), which undergoes additional oxidation to 20-hydroxyprostaglandin G2 andH2 (Schwartzman et al.”
Backgroundω-3 Fatty Acids and Cardiovascular Diseases: Effects, Mechanisms and Dietary Relevance
Mæhre, H. K., Jensen, I., Elvevoll, E. O., & Eilertsen, K. (2015) · International Journal of Molecular Sciences · doi:10.3390/ijms160922636 · Cited by 92 · see citing works
Rationally Designed Multitarget Agents Against Inflammation and Pain
Hwang, S. H., Wecksler, A. T., Wagner, K. M., & Hammock, B. D. (2013) · Current Medicinal Chemistry · doi:10.2174/0929867311320130013 · Cited by 109 · see citing works
β-oxidation and rapid metabolism, but not uptake regulate brain eicosapentaenoic acid levels
Chen, C. T., & Bazinet, R. P. (2014) · Prostaglandins Leukotrienes and Essential Fatty Acids · doi:10.1016/j.plefa.2014.05.007 · Cited by 110 · see citing works
Toledo, E., Wang, D. D., Ruiz‐Canela, M., Clish, C. B., Razquín, C., Zheng, Y., Guasch‐Ferré, M., Hruby, A., Corella, D., Gómez‐Gracia, E., et al. (2017) · American Journal of Clinical Nutrition · doi:10.3945/ajcn.116.151159 · Cited by 112 · see citing works
Comparison of free serum oxylipin concentrations in hyper- vs. normolipidemic men
Schuchardt, J., Schmidt, S., Kressel, G., Dong, H., Willenberg, I., Hammock, B., Hahn, A., & Schebb, N. (2013) · Prostaglandins, Leukotrienes and Essential Fatty Acids · doi:10.1016/j.plefa.2013.04.001 · Cited by 99 · see citing works
Schebb, N. H., Ostermann, A. I., Yang, J., Hammock, B. D., Hahn, A., & Schuchardt, J. P. (2014) · Prostaglandins & Other Lipid Mediators · doi:10.1016/j.prostaglandins.2014.05.002 · Cited by 93 · see citing works
Epoxyeicosatrienoic Acid Pathway in Human Health and Diseases
Bellien, J., & Joannidés, R. (2013) · Journal of Cardiovascular Pharmacology · doi:10.1097/fjc.0b013e318273b007 · Cited by 92 · see citing works
Dyall, S. C. (2017) · Lipids · doi:10.1007/s11745-017-4292-8 · Cited by 88 · see citing works
The role of long chain fatty acids and their epoxide metabolites in nociceptive signaling
Wagner, K. M., Vito, S., İnceoğlu, B., & Hammock, B. D. (2014) · Prostaglandins & Other Lipid Mediators · doi:10.1016/j.prostaglandins.2014.09.001 · Cited by 78 · see citing works
Role of Soluble Epoxide Hydrolase in Metabolism of PUFAs in Psychiatric and Neurological Disorders
Hashimoto, K. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.00036 · Cited by 95 · see citing works
“…bioactive derivatives by the main enzymes such as cyclooxygenases (COXs), lipoxygenases (LOXs), and cytochrome P450s (CYPs) (Imig and Hammock, 2009; Arnold et al., 2010; Imig, 2012, 2018; Morisseau and Hammock, 2013; Bazinet and Layé, 2014; Urquhart et al., 2015; Westphal et al., 2015; Figure 1).”
BackgroundCytochrome P450-generated metabolites derived from ω-3 fatty acids attenuate neovascularization
Yanai, R., Mulki, L., Hasegawa, E., Takeuchi, K., Sweigard, H., Suzuki, J., Gaissert, P., Vavvas, D., Sonoda, K., Rothe, M., et al. (2014) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.1401191111 · Cited by 83 · see citing works
Self-citationProspective for cytochrome P450 epoxygenase cardiovascular and renal therapeutics
Imig, J. D. (2018) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2018.06.015 · Cited by 89 · see citing works
ω-3 and ω-6 long-chain PUFAs and their enzymatic metabolites in neovascular eye diseases
Gong, Y. Q., Fu, Z., Liegl, R. G.-H., Chen, J., Hellström, A., & Smith, L. E. H. (2017) · American Journal of Clinical Nutrition · doi:10.3945/ajcn.117.153825 · Cited by 79 · see citing works
Fatty liver induced by free radicals and lipid peroxidation
Morita, M., Ishida, N., Uchiyama, K., Yamaguchi, K., Itoh, Y., Shichiri, M., Yoshida, Y., Hagihara, Y., Naito, Y., Yoshikawa, T., et al. (2012) · Free radical research · doi:10.3109/10715762.2012.677840 · Cited by 75 · see citing works
Ultraviolet-radiation induced skin inflammation: dissecting the role of bioactive lipids
Nicolaou, A., Pilkington, S. M., & Rhodes, L. E. (2011) · Chemistry and Physics of Lipids · doi:10.1016/j.chemphyslip.2011.04.005 · Cited by 79 · see citing works
Schuchardt, J., Schmidt, S., Kressel, G., Willenberg, I., Hammock, B., Hahn, A., & Schebb, N. (2013) · Prostaglandins, Leukotrienes and Essential Fatty Acids · doi:10.1016/j.plefa.2013.12.008 · Cited by 74 · see citing works
Human Liver Spheroids as a Model to Study Aetiology and Treatment of Hepatic Fibrosis
Hurrell, T., Kastrinou‐Lampou, V., Fardellas, A., Hendriks, D. F. G., Nordling, Å., Johansson, I., Baze, A., Parmentier, C., Richert, L., & Ingelman‐Sundberg, M. (2020) · Cells · doi:10.3390/cells9040964 · Cited by 81 · see citing works
“The FFA effect was anticipated due to the capability of CYP2E1 to oxidize fatty acids [53].”
BackgroundHorakova, O., Medříková, D., van Schothorst, E. M., Bunschoten, A., Flachs, P., Kůs, V., Kuda, O., Bardová, K., Janovská, P., Hensler, M., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0043764 · Cited by 70 · see citing works
Pharmacologic interventions for the prevention and treatment of retinopathy of prematurity
Beharry, K. D. A., Valencia, G. B., Lazzaro, D. R., & Aranda, J. V. (2016) · Seminars in Perinatology · doi:10.1053/j.semperi.2015.12.006 · Cited by 82 · see citing works
Role of the modulation of CYP1A1 expression and activity in chemoprevention
Badal, S., & Delgoda, R. (2014) · Journal of Applied Toxicology · doi:10.1002/jat.2968 · Cited by 63 · see citing works
“Endogenous substrates include the hormones 17β estradiol (Lee et al., 2003) and melatonin (Ma et al., 2005) and inflammatory mediators arachidonic acid and eicosapentoic acid (Arnold et al., 2010; Schwarz et al., 2004).”
BackgroundLi, R., Xu, X., Chen, C., Wang, Y., Gruzdev, A., Zeldin, D. C., & Wang, D. W. (2014) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00118.2014 · Cited by 64 · see citing works
Symposium review: Oxylipids and the regulation of bovine mammary inflammatory responses
Sordillo, L. M. (2018) · Journal of Dairy Science · doi:10.3168/jds.2017-13855 · Cited by 60 · see citing works
Jerab, D., Blangero, F., da Costa, P. C. T., Alves, J. L. D. B., Kéfi, R., Jamoussi, H., Morio, B., & Eljaafari, A. (2025) · Nutrients · doi:10.3390/nu17071253 · Cited by 55 · see citing works
“…respiration [69]. n -3 -3 PUFAs are also known to modulate excitability of myocytes, thus reducing arrythmias, but while these effects require the proper functioning of the cytochrome P450 (CYP) enzyme, statins may affect the production of eicosanoids through interactions with CYP [70,71].”
Steinberg, C. (2012) · Springer Netherlands · doi:10.1007/978-94-007-2072-5 · Cited by 57 · see citing works
“The enzyme families of the biotransformation system are not only in charge of metabolizing exogenous and endogenous “wastes”, but also of steroid and fatty acid metabolism (Arnold et al. 2010; Konkel and Schunck 2010).”
BackgroundDas, U. N. (2010) · Journal of Inflammation Research · doi:10.2147/jir.s9425 · Cited by 63 · see citing works
Kurasiak-Popowska, D., Ryńska, B., & Stuper-Szablewska, K. (2019) · Agronomy · doi:10.3390/agronomy9040168 · Cited by 55 · see citing works
Brown, G. T., Cash, B., Blihoghe, D., Johansson, P., Alnabulsi, A., & Murray, G. (2014) · PLoS ONE · doi:10.1371/journal.pone.0090776 · Cited by 53 · see citing works
Shao, Z., Fu, Z., Stahl, A., Joyal, J.-S., Hatton, C. J., Juan, A. M., Hurst, C. G., Evans, L., Cui, Z., Pei, D. T., et al. (2014) · Arteriosclerosis, Thrombosis and Vascular Biology · doi:10.1161/atvbaha.113.302927 · Cited by 53 · see citing works
Ostermann, A. I., Herbers, J., Willenberg, I., Chen, R.-J., Hwang, S., Greite, R., Morisseau, C., Gueler, F., Hammock, B., & Schebb, N. (2015) · Prostaglandins & other lipid mediators · doi:10.1016/j.prostaglandins.2015.06.005 · Cited by 51 · see citing works
Basic aspects of tumor cell fatty acid-regulated signaling and transcription factors
Comba, A., Lin, Y., Eynard, A. R., Valentich, M. A., Fernández-Zapico, M. E., & Pasqualini, M. E. (2011) · Cancer and Metastasis Reviews · doi:10.1007/s10555-011-9308-x · Cited by 50 · see citing works
Lipoxins as biomarkers of lupus and other inflammatory conditions
Das, U. (2011) · Lipids in Health and Disease · doi:10.1186/1476-511x-10-76 · Cited by 50 · see citing works
Gong, Y. Q., Fu, Z., Edin, M. L., Liu, C., Wang, Z., Shao, Z., Fredrick, T. W., Saba, N. J., Morss, P., Burnim, S. B., et al. (2016) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.116.307558 · Cited by 44 · see citing works
Ohashi, H., Nishioka, K., Nakajima, S., Kim, S., Suzuki, R., Aizaki, H., Fukasawa, M., Kamisuki, S., Sugawara, F., Ohtani, N., et al. (2018) · Journal of Biological Chemistry · doi:10.1074/jbc.ra118.005033 · Cited by 47
“CYP1A1 is also reported to metabolize arachidonic acid and produce hydroxyeicosapentaenoic acids (49).”
BackgroundCytokines, angiogenic, and antiangiogenic factors and bioactive lipids in preeclampsia
Das, U. N. (2015) · Nutrition · doi:10.1016/j.nut.2015.03.013 · Cited by 51 · see citing works
Schuchardt, J., Schneider, I., Willenberg, I., Yang, J., Hammock, B., Hahn, A., & Schebb, N. (2014) · Prostaglandins & other lipid mediators · doi:10.1016/j.prostaglandins.2014.03.001 · Cited by 45 · see citing works
Schmidt, S., Stahl, F., Mutz, K., Scheper, T., Hahn, A., & Schuchardt, J. (2012) · Nutrition and Metabolism · doi:10.1186/1743-7075-9-45 · Cited by 45 · see citing works
Beyond VEGF: Targeting Inflammation and Other Pathways for Treatment of Retinal Disease
Muniyandi, A., Hartman, G. D., Song, Y., Mijit, M., Kelley, M., & Corson, T. (2023) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.122.001563 · Cited by 42 · see citing works
“P450 also targets the x -3 double bond of DHA, with a higher catalytic ef fi ciency than arachidonic acid (Arnold et al., 2010a), and produces EDPs (Fer et al., 2008; Arnold et al., 2010b).”
BackgroundHennebelle, M., Otoki, Y., Yang, J., Hammock, B. D., LEVITT, A. J., Taha, A. Y., & Swardfager, W. (2017) · Psychiatry Research · doi:10.1016/j.psychres.2017.02.056 · Cited by 47 · see citing works
“For total oxylipins, 50–100 µL of plasma were mixed with 10 µL surrogate standard solution (500 nM), 10 µL of antioxidant solution and 100 µL of extraction buffer (0.1% acetic acid and 0.1% BHT in methanol) and kept in −80 °C overnight (Arnold et al., 2010b).”
BackgroundMethodResultInfluentialSerum and Fecal Oxylipins in Patients with Alcohol-Related Liver Disease
Gao, B., Lang, S., Duan, Y., Wang, Y., Shawcross, D. L., Louvet, A., Mathurin, P., Ho, S. B., Stärkel, P., & Schnabl, B. (2019) · Digestive Diseases and Sciences · doi:10.1007/s10620-019-05638-y · Cited by 43 · see citing works
Limbu, R., Cottrell, G., & McNeish, A. (2018) · PLoS ONE · doi:10.1371/journal.pone.0192484 · Cited by 41 · see citing works
Igarashi, M., Kim, H., Chang, L., Ma, K., & Rapoport, S. I. (2011) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2011.07597.x · Cited by 44 · see citing works
“…conversion to bioactive docosanoids such as resolvins, docosatrienes, and neuroprotectins by enzymes such as 15-LOX, and by other metabolic pathways (Gavino and Gavino 1991; Robinson et al. 1992; Hong et al. 2003; Gleissman et al. 2010; Arnold et al. 2010; Bazan et al. 2010; Groeger et al. 2010).”
Rasquel-Oliveira, F. S., da Silva, M. D. V., Martelossi-Cebinelli, G., Fattori, V., Casagrande, R., & Verri, W. A., Jr. (2023) · Molecules · doi:10.3390/molecules28135032 · Cited by 42 · see citing works
“The first double bond on C3, present in omega-3 but not omega-6, is a preferred site of epoxidation catalyzed by CYP450 [76].”
BackgroundHasegawa, E., Inafuku, S., Mulki, L., Okunuki, Y., Yanai, R., Smith, K. E., Kim, C. B., Klokman, G., Bielenberg, D. R., Narender, P., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1620898114 · Cited by 39 · see citing works
Self-citationBonafini, S., Antoniazzi, F., Maffeis, C., Minuz, P., & Fava, C. (2015) · Prostaglandins & Other Lipid Mediators · doi:10.1016/j.prostaglandins.2015.03.006 · Cited by 41 · see citing works
Monk, J. M., Turk, H. F., Liddle, D. M., Boer, A. D., Power, K. A., David, W. L., & Robinson, L. E. (2014) · Nutrients · doi:10.3390/nu6114760 · Cited by 45 · see citing works
Exploring the role of LC-PUFA metabolism in pregnancy complications
Godhamgaonkar, A. A., Wadhwani, N. S., & Joshi, S. (2020) · Prostaglandins Leukotrienes and Essential Fatty Acids · doi:10.1016/j.plefa.2020.102203 · Cited by 41 · see citing works
Webster, C. M., Deline, M. L., & Watts, J. L. (2012) · Developmental Biology · doi:10.1016/j.ydbio.2012.10.002 · Cited by 37 · see citing works
“The adverse health effects of excess dietary omega-6 PUFAs may be mediated by eicosanoids, which are powerful shortlived signaling molecules produced from 20-carbon polyunsaturated fatty acids (PUFAs) through a series of oxidation reactions.”
BackgroundInfluentialSoluble Epoxide Hydrolase Regulation of Lipid Mediators Limits Pain
Wagner, K. M., Gomes, A. V., McReynolds, C. B., & Hammock, B. D. (2020) · Neurotherapeutics · doi:10.1007/s13311-020-00916-4 · Cited by 40 · see citing works
Astarita, G., McKenzie, J. H., Wang, B., Strassburg, K., Doneanu, A., Johnson, J. S., Baker, A., Hankemeier, T., Murphy, J., Vreeken, R. J., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0096221 · Cited by 37 · see citing works
Polyunsaturated fatty acids and their metabolites in the pathobiology of schizophrenia
Das, U. N. (2012) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2012.06.010 · Cited by 37 · see citing works
Eicosanoid formation by a cytochrome P450 isoform expressed in the pharynx of Caenorhabditis elegans
Kosel, M., Wild, W., Bell, A., Rothe, M., Lindschau, C., Steinberg, C. E. W., Schunck, W., & Menzel, R. (2011) · Biochemical Journal · doi:10.1042/bj20101942 · Cited by 39 · see citing works
Self-citationMorin, C., Fortin, S., & Rousseau, É. (2011) · American Journal of Physiology. Heart and Circulatory Physiology · doi:10.1152/ajpheart.00380.2011 · Cited by 32
“The CYP450-dependent DHA metabolites include the epoxydocosapentaenoic acid (EpDPE) regioisomers 4,5-, 7,8-, 10,11-, 13,14-, 16,17-, and 19,20-EpDPE (4, 6, 22).”
BackgroundLi, M., Li, Z., & Fan, Y. (2025) · Frontiers in Nutrition · doi:10.3389/fnut.2025.1598588 · Cited by 23 · see citing works
“The cytochrome P450 pathway refers to the cardioprotective effects of EPA and DHA as effective replacement substrates for the metabolism of cytochrome P450 (CYP) enzymes in arachidonic acid (AA) (54), which simultaneously regulates vasodilation and cerebral blood flow (55).”
Angiogenesis and vascular stability in eicosanoids and cancer
Hu, J., Frömel, T., & Fleming, I. (2018) · Cancer and Metastasis Reviews · doi:10.1007/s10555-018-9732-2 · Cited by 30 · see citing works
Opgenorth, J., Sordillo, L. M., & VandeHaar, M. J. (2020) · Journal of Dairy Science · doi:10.3168/jds.2019-17380 · Cited by 28 · see citing works
“Cytochrome enzymes, for example, use both n-3 and n-6 FA as substrates but, with increasing concentrations of n-3 FA, will sometimes favor EPA over ARA as a substrate (Arnold et al., 2010).”
BackgroundIgarashi, M., Chang, L., Ma, K., & Rapoport, S. (2013) · Prostaglandins, Leukotrienes and Essential Fatty Acids · doi:10.1016/j.plefa.2013.09.004 · Cited by 28 · see citing works
Is multiple sclerosis a proresolution deficiency disorder?
Das, U. (2012) · Nutrition (Burbank, Los Angeles County, Calif.) · doi:10.1016/j.nut.2011.12.016 · Cited by 27 · see citing works
Aarnio, V., Lehtonen, M., Storvik, M., Callaway, J., Lakso, M., & Wong, G. (2011) · Frontiers in Pharmacology · doi:10.3389/fphar.2011.00012 · Cited by 27
“…cyp-35 family), similarly as in fish and insects (Nelson, 2003; Feyereisen, 2006), indicating an evolutionally old distinction between the major CYP clades, probably due to their early separated endogenous functions, which in human include metabolism of fatty acid derivatives (Arnold et al., 2010).”
BackgroundGatto, F., Schulze, A., & Nielsen, J. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.06.038 · Cited by 30 · see citing works
Simeone, T., Matthews, S., & Simeone, K. (2017) · Epilepsia · doi:10.1111/epi.13809 · Cited by 24 · see citing works
Lepionka, T., Białek, A., Białek, M., Czauderna, M., Stawarska, A., Wrzesień, R., Bielecki, W., Paśko, P., Galanty, A., & Bobrowska-Korczak, B. (2019) · Prostaglandins & other lipid mediators · doi:10.1016/j.prostaglandins.2019.03.005 · Cited by 23 · see citing works
Alnabulsi, A., Swan, R., Cash, B., Alnabulsi, A., & Murray, G. (2017) · British Journal of Cancer · doi:10.1038/bjc.2017.135 · Cited by 23 · see citing works
“The CYP4 and higher numbered families are involved in the metabolism of a diverse range of endogenous compounds including eicosanoids, fatty acids, steroids and vitamins (Spector, 2009; Arnold et al, 2010; Panigrahy et al, 2010; Fleming, 2011; Guengerich and Cheng, 2011; Niwa et al, 2011).”
BackgroundMak, S., Yu, C.-M., Sun, W.-T., He, G., Liu, X.-C., & Yang, Q. (2017) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2017.10.016 · Cited by 22 · see citing works
“Epoxy fatty acids (EpFAs), such as epoxyeicosatrienoic acids (EETs) derived from arachidonic acid, are important lipid mediators that have pathophysiological significance in the cardiovascular system (Arnold et al., 2010).”
BackgroundLeineweber, C. G., Pietzner, A., Zhang, I., Blessin, U., Rothe, M., Schott, E., Schebb, N., & Weylandt, K. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21051875 · Cited by 21
Bonafini, S., Tagetti, A., Gaudino, R., Cavarzere, P., Montagnana, M., Danese, E., Benati, M., Ramaroli, D. A., Raimondi, S., Giontella, A., et al. (2018) · European Journal of Nutrition · doi:10.1007/s00394-018-1677-2 · Cited by 29 · see citing works
New Therapies of Neovascular AMD—Beyond Anti-VEGFs
Yerramothu, P. (2018) · Vision · doi:10.3390/vision2030031 · Cited by 21 · see citing works
High fat diet induced obesity is mitigated in Cyp3a-null female mice
Kumar, R., Litoff, E. J., Boswell, W. T., & Baldwin, W. S. (2018) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2018.05.001 · Cited by 21 · see citing works
Tagetti, A., Ericson, U., Montagnana, M., Danese, E., Almgren, P., Nilsson, P., Engström, G., Hedblad, B., Minuz, P., Orho-Melander, M., et al. (2015) · Prostaglandins & other lipid mediators · doi:10.1016/j.prostaglandins.2015.05.003 · Cited by 21
Rijjal, D. A., Liu, Y., Lai, M., Song, Y., Danaei, Z., Wu, A., Mohan, H., Li, W., Schopfer, F. J., Dai, F. F., et al. (2021) · iScience · doi:10.1016/j.isci.2021.102909 · Cited by 19 · see citing works
“The CYP enzymes metabolize polyunsaturated fatty acids including AA, EPA, and DHA (Arnold et al., 2010).”
BackgroundImanikia, S., Hylands, P., & Stürzenbaum, S. (2015) · Biochemistry and Biophysics Reports · doi:10.1016/j.bbrep.2015.06.007 · Cited by 20
Braeckman, R., Stirtan, W., & Soni, P. N. (2014) · Clinical drug investigation · doi:10.1007/s40261-014-0194-1 · Cited by 19 · see citing works
Meital, L. T., Windsor, M. T., Jewell, R. M. L. R., Young, P., Schulze, K., Magee, R., O’Donnell, J., Jha, P. K., Perissiou, M., Golledge, J., et al. (2019) · Journal of Lipid Research · doi:10.1194/jlr.p093013 · Cited by 18 · see citing works
Eicosanoids via CYP450 and cardiovascular disease: Hints from genetic and nutrition studies.
Fava, C., & Bonafini, S. (2018) · Prostaglandins & other lipid mediators · doi:10.1016/j.prostaglandins.2018.10.001 · Cited by 18 · see citing works
Shysh, A., Nagibin, V., Kaplinskii, S. P., & Dosenko, V. (2016) · Pharmacological Reports · doi:10.1016/j.pharep.2016.06.013 · Cited by 18 · see citing works
Synthesis and function of fatty acids and oxylipins, with a focus on Caenorhabditis elegans
Mokoena, N., Sebolai, O. M., Albertyn, J., & Pohl, C. H. (2020) · Prostaglandins & Other Lipid Mediators · doi:10.1016/j.prostaglandins.2020.106426 · Cited by 24 · see citing works
Wiest, E. F., Walsh-Wilcox, M. T., Rothe, M., Schunck, W., & Walker, M. K. (2016) · Toxicological Sciences · doi:10.1093/toxsci/kfw145 · Cited by 16 · see citing works
“This shift in PUFA membrane composition subsequently shifts the P450-mediated omega-hydroxylase metabolic profile (Agbor et al., 2014; Arnold et al., 2010b; Fischer et al., 2014).”
BackgroundMethodResultInfluentialSelf-citationOmega-3 Fatty Acids and Vitamin D in Cardiology
Güttler, N., Zheleva, K., Parahuleva, M. S., Chasan, R., Bilgin, M., Neuhof, C., Burgazli, K. M., Niemann, B., Erdogan, A. R., & Böning, A. (2012) · Cardiology Research and Practice · doi:10.1155/2012/729670 · Cited by 20 · see citing works
Rahim, M. A., Uzma, M., Al‐Asmari, F., Koraqi, H., Ramadan, M. F., Castro-Muñoz, R., & Zongo, E. (2025) · Food Science & Nutrition · doi:10.1002/fsn3.71008 · Cited by 16 · see citing works
Chiarella, G., Marcianò, G., Viola, P., Palleria, C., Pisani, D., Rania, V., Casarella, A., Astorina, A., Scarpa, A., Esposito, M., et al. (2021) · Nutrients · doi:10.3390/nu13103646 · Cited by 16 · see citing works
“Omega-3 fatty acids Omega-3 and omega-6 can be metabolized by CYP1A1, CYP2E1, CYP2C, CYP2J2, CYP4A, CYP4F, and other isoforms as efficient alternative substrates of arachidonic acid metabolizing CYP enzymes [111].”
BackgroundMaksymchuk, O., & Chashchyn, M. (2012) · Pathophysiology · doi:10.1016/j.pathophys.2012.07.002 · Cited by 16
Genic-intergenic polymorphisms of CYP1A genes and their clinical impact.
Kukal, S., Thakran, S., Kanojia, N., Yadav, S., Mishra, M. K., Guin, D., Singh, P., & Kukreti, R. (2023) · Gene · doi:10.1016/j.gene.2023.147171 · Cited by 15 · see citing works
Bonafini, S., & Fava, C. (2017) · Prostaglandins & other lipid mediators · doi:10.1016/j.prostaglandins.2017.01.004 · Cited by 15 · see citing works
Shen, Q., Otoki, Y., Sobel, R., Nagra, R., & Taha, A. Y. (2022) · Multiple Sclerosis and Related Disorders · doi:10.1016/j.msard.2022.104236 · Cited by 14 · see citing works
Icosapent Ethyl: A Review of Its Use in Severe Hypertriglyceridemia
Kim, E. S., & McCormack, P. L. (2014) · American Journal of Cardiovascular Drugs · doi:10.1007/s40256-014-0099-7 · Cited by 14 · see citing works
Fuller, H., Race, A., Fenton, H., Burke, L., Downing, A., Williams, E. A., Rees, C. J., Brown, L. C., Loadman, P., & Hull, M. (2023) · Prostaglandins, Leukotrienes and Essential Fatty Acids · doi:10.1016/j.plefa.2023.102570 · Cited by 13
Expression of arachidonic acid-metabolizing cytochrome P450s in human megakaryocytic Dami cells
Jarrar, Y., Shin, J.-G., & Lee, S.-J. (2013) · In vitro Cellular & Developmental Biology-Animal · doi:10.1007/s11626-013-9633-1 · Cited by 13
“CYP4A and 4F subfamilies have been identified as the main P450s for 20-HETE production (Lasker et al. 2000; Pearson et al. 2009), although multiple studies showed that CYP1A1 hydroxylases ARA to 20-HETE Retention Time (min) (Aboutabl et al. 2009; Arnold et al. 2010).”
- Authors
- Arnold, C., Konkel, A., Fischer, R., & Schunck, W.-H.
- Affiliations
- Max Delbrück Center (DE)
- Corresponding author
- Schunck, Wolf-Hagen
- Venue
- Pharmacological Reports
- Published
- 2010-05
- Volume
- 62
- Issue
- 3
- Pages
- 536-547
- ISSN
- 1734-1140 (ISSN-L)
- OpenAlex
- W1998719368
- Cited by
- 174
- References
- 111
- Citations by year
- 2026: 2 · 2025: 10 · 2024: 6 · 2023: 13 · 2022: 9 · 2021: 8 · 2020: 10 · 2019: 10 · 2018: 12 · 2017: 13 · 2016: 10 · 2015: 11 · 2014: 19 · 2013: 12 · 2012: 15
- FWCI
- 1.47
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Pharmacological Reports (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Eicosanoids and Hypertension Pharmacology
- Health Sciences › Medicine › Pharmacology › Inflammatory mediators and NSAID effects
- Keywords
- cytochrome P450, omega-3 fatty acids, omega-6 fatty acids, eicosapentaenoic acid, docosahexaenoic acid, arachidonic acid metabolism, fatty acid epoxidation, regioselectivity, epoxy fatty acids, hydroxy fatty acids, fish oil, cardioprotection, vascular protection, sudden cardiac death, cardiac arrhythmias
- MeSH terms
- Cytochrome P-450 CYP2J2, Animals, Cardiotonic Agents, Cardiovascular Diseases, Cytochrome P-450 Enzyme System, Docosahexaenoic Acids, Epoxide Hydrolases, Humans, Hydroxyeicosatetraenoic Acids, Eicosapentaenoic Acid, Fatty Acids, Omega-3, Arachidonic Acid, Death, Sudden, Cardiac, Cytochrome P-450 CYP1A1, Cytochrome P-450 CYP2E1, Fatty Acids, Omega-6
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
