ArticleThe Journal of biological chemistry2016
Different Fatty Acids Compete with Arachidonic Acid for Binding to the Allosteric or Catalytic Subunits of Cyclooxygenases to Regulate Prostanoid Synthesis.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 76 citations in OpenAlex.
- An Adaptive Bayesian Design for Personalized Dosing in a Cancer Prevention Trial.American journal of preventive medicine · 2020Trial
- Fatty Acid and Oxylipin Metabolism Differentiate Isolated Postcapillary From Combined Pre- and Postcapillary Pulmonary Hypertension.Circulation. Heart failure · 2026Article
- Plasma fatty acid composition modifies the cardiovascular risk of long-term PMLipids in health and disease · 2026Article
- Allosteric regulation of prostaglandin endoperoxide HThe Journal of biological chemistry · 2025Review
- Alpha-linolenic acid reshapes the gastrointestinal ecology to enhance immune function in dairy cows: insights from microbiome and metabolome profiling.Frontiers in microbiology · 2025Article
- Activity-dependent COX-2 proteolysis modulates aerobic respiration and proliferation in a prostaglandin-independent manner.iScience · 2024Article
- Oxylipins Derived from PUFAs in Cardiometabolic Diseases: Mechanism of Actions and Possible Nutritional Interactions.Nutrients · 2024Review
- "A Time to Tear Down and a Time to Mend": The Role of Eicosanoids in Atherosclerosis.Arteriosclerosis, thrombosis, and vascular biology · 2024Article
- Mexican Native Black Bean Anthocyanin-Rich Extracts Modulate Biological Markers Associated with Inflammation.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Omega-3 fatty acids in the treatment of spinal cord injury: untapped potential for therapeutic intervention?Molecular biology reports · 2022Review
- Changes in Serum, Red Blood Cell, and Colonic Fatty Acids in a Personalized Omega-3 Fatty Acid Supplementation Trial.Nutrition and cancer · 2022Article
- Article
- Emerging Role of Phospholipase-Derived Cleavage Products in Regulating Eosinophil Activity: Focus on Lysophospholipids, Polyunsaturated Fatty Acids and Eicosanoids.International journal of molecular sciences · 2021Review
- DHA 12-LOX-derived oxylipins regulate platelet activation and thrombus formation through a PKA-dependent signaling pathway.Journal of thrombosis and haemostasis : JTH · 2021Article
- Article
- Do Eicosapentaenoic Acid and Docosahexaenoic Acid Have the Potential to Compete against Each Other?Nutrients · 2020Review
- A high fat diet with a high C18:0/C16:0 ratio induced worse metabolic and transcriptomic profiles in C57BL/6 mice.Lipids in health and disease · 2020Article
- Lipid mechanisms in hallmarks of cancer.Molecular omics · 2020Review
- An Activity-Based Sensing Approach for the Detection of Cyclooxygenase-2 in Live Cells.Angewandte Chemie (International ed. in English) · 2020Article
- The Biosynthesis of Enzymatically Oxidized Lipids.Frontiers in endocrinology · 2020Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Prostaglandin endoperoxide H synthases (PGHSs), also called cyclooxygenases (COXs), convert arachidonic acid (AA) to PGH2. PGHS-1 and PGHS-2 are conformational heterodimers, each composed of an (Eallo) and a catalytic (Ecat) monomer. Previous studies suggested that the binding to Eallo of saturated or monounsaturated fatty acids (FAs) that are not COX substrates differentially regulate PGHS-1 versus PGHS-2. Here, we substantiate and expand this concept to include polyunsaturated FAs known to modulate COX activities. Non-substrate FAs like palmitic acid bind Eallo of PGHSs stimulating human (hu) PGHS-2 but inhibiting huPGHS-1. We find the maximal effects of non-substrate FAs on both huPGHSs occurring at the same physiologically relevant FA/AA ratio of ∼20. This inverse allosteric regulation likely underlies the ability of PGHS-2 to operate at low AA concentrations, when PGHS-1 is effectively latent. Unlike FAs tested previously, we observe that C-22 FAs, including ω-3 fish oil FAs, have higher affinities for Ecat than Eallo subunits of PGHSs. Curiously, C-20 ω-3 eicosapentaenoate preferentially binds Ecat of huPGHS-1 but Eallo of huPGHS-2. PGE2 production decreases 50% when fish oil consumption produces tissue EPA/AA ratios of ≥0.2. However, 50% inhibition of huPGHS-1 itself is only seen with ω-3 FA/AA ratios of ≥5.0. This suggests that fish oil-enriched diets disfavor AA oxygenation by altering the composition of the FA pool in which PGHS-1 functions. The distinctive binding specificities of PGHS subunits permit different combinations of non-esterified FAs, which can be manipulated dietarily, to regulate AA binding to Eallo and/or Ecat thereby controlling COX activities.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.