Enzymes and Receptors of Prostaglandin Pathways with Arachidonic Acid-derived Versus Eicosapentaenoic Acid-derived Substrates and Products*♦

@article{Wada2007EnzymesAR,
  title={Enzymes and Receptors of Prostaglandin Pathways with Arachidonic Acid-derived Versus Eicosapentaenoic Acid-derived Substrates and Products*♦},
  author={Masayuki Wada and Cynthia J. DeLong and Yu H. Hong and Caroline Jill Rieke and Inseok Song and Ranjinder S. Sidhu and Chong Yuan and Mark Warnock and Alvin H. Schmaier and Chieko Yokoyama and Emer M. Smyth and Stephen J. Wilson and Garret A. FitzGerald and R. Michael Garavito and Dexin Sui and John W. Regan and William L. Smith},
  journal={Journal of Biological Chemistry},
  year={2007},
  volume={282},
  pages={22254 - 22266}
}
Dietary fish oil containing ω3 highly unsaturated fatty acids has cardioprotective and anti-inflammatory effects. Prostaglandins (PGs) and thromboxanes are produced in vivo both from the ω6 fatty acid arachidonic acid (AA) and the ω3 fatty acid eicosapentaenoic acid (EPA). Certain beneficial effects of fish oil may result from altered PG metabolism resulting from increases in the EPA/AA ratios of precursor phospholipids. Here we report in vitro specificities of prostanoid enzymes and receptors… 

Arachidonic Acid-metabolizing Cytochrome P450 Enzymes Are Targets of ω-3 Fatty Acids*

It is found that these ω-3 epoxides are highly active as antiarrhythmic agents, suppressing the Ca2+-induced increased rate of spontaneous beating of neonatal rat cardiomyocytes, at low nanomolar concentrations.

Different Fatty Acids Compete with Arachidonic Acid for Binding to the Allosteric or Catalytic Subunits of Cyclooxygenases to Regulate Prostanoid Synthesis*

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.

Dietary omega-3 fatty acids modulate the eicosanoid profile in man primarily via the CYP-epoxygenase pathway[S]

It is proposed that CYP-dependent epoxy-metabolites of EPA and DHA may function as mediators of the vasodilatory and cardioprotective effects of omega-3 fatty acids and could serve as biomarkers in clinical studies investigating the cardiovascular effects of EPA/DHA supplementation.

Cytochrome P 450-dependent metabolism of-6 and-3 long-chain polyunsaturated fatty acids

The currently available data suggest that some of the vasculoand cardioprotective effects attributed to dietary n-3 PUFAs may be mediated by CYP-dependent metabolites of EPA and DHA.

Formation of Highly Reactive Cyclopentenone Isoprostane Compounds (A3/J3-Isoprostanes) in Vivo from Eicosapentaenoic Acid*

These studies have, for the first time, definitively characterized novel, highly reactive A/J-ring IsoP compounds that form in abundance from the oxidation of EPA in vivo.

The factor in EDHF: Cytochrome P450 derived lipid mediators and vascular signaling.

Effect of eicosapentaenoic acid on E-type prostaglandin synthesis and EP4 receptor signaling in human colorectal cancer cells.

It is concluded that EPA-FFA drives a COX-2-dependent "PGE (2)-to-PGE(3) switch" in human CRC cells and that PGE (3) acts as a partial agonist at the PGE(2) EP4 receptor.

Omega-3 fatty acids cause dramatic changes in TLR4 and purinergic eicosanoid signaling

In resident peritoneal macrophages, docosapentaenoic acid (DPA) was responsible for cyclooxygenase inhibition after EPA supplementation, offering fresh insights into how EPA exerts anti-inflammatory effects indirectly through elongation to 22-carbon DPA.
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