scholarly journals Eicosanoid turnover in GtoPdb v.2021.3

2021 ◽  
Vol 2021 (3) ◽  
Author(s):  
Angelo A. Izzo ◽  
Jane A. Mitchell
Keyword(s):  
Oxidative Stress ◽  
Fatty Acids ◽  
Arachidonic Acid ◽  
Cytochrome P450 ◽  
Free Radicals ◽  
Phospholipase A2 ◽  
Oxidative Metabolism ◽  
Molecular Targets ◽  
Structural Analogues ◽  
Biomarkers Of Oxidative Stress

Eicosanoids are 20-carbon fatty acids, where the usual focus is the polyunsaturated analogue arachidonic acid and its metabolites. Arachidonic acid is thought primarily to derive from phospholipase A2 action on membrane phosphatidylcholine, and may be re-cycled to form phospholipid through conjugation with coenzyme A and subsequently glycerol derivatives. Oxidative metabolism of arachidonic acid is conducted through three major enzymatic routes: cyclooxygenases; lipoxygenases and cytochrome P450-like epoxygenases, particularly CYP2J2. Isoprostanes are structural analogues of the prostanoids (hence the nomenclature D-, E-, F-isoprostanes and isothromboxanes), which are produced in the presence of elevated free radicals in a non-enzymatic manner, leading to suggestions for their use as biomarkers of oxidative stress. Molecular targets for their action have yet to be defined.

scholarly journals Eicosanoid turnover (version 2019.5) in the IUPHAR/BPS Guide to Pharmacology Database

2019 ◽  
Vol 2019 (5) ◽  
Author(s):  
Angelo A. Izzo ◽  
Jane A. Mitchell
Keyword(s):  
Oxidative Stress ◽  
Fatty Acids ◽  
Arachidonic Acid ◽  
Cytochrome P450 ◽  
Free Radicals ◽  
Phospholipase A2 ◽  
Oxidative Metabolism ◽  
Molecular Targets ◽  
Structural Analogues ◽  
Biomarkers Of Oxidative Stress

Eicosanoids are 20-carbon fatty acids, where the usual focus is the polyunsaturated analogue arachidonic acid and its metabolites. Arachidonic acid is thought primarily to derive from phospholipase A2 action on membrane phosphatidylcholine, and may be re-cycled to form phospholipid through conjugation with coenzyme A and subsequently glycerol derivatives. Oxidative metabolism of arachidonic acid is conducted through three major enzymatic routes: cyclooxygenases; lipoxygenases and cytochrome P450-like epoxygenases, particularly CYP2J2. Isoprostanes are structural analogues of the prostanoids (hence the nomenclature D-, E-, F-isoprostanes and isothromboxanes), which are produced in the presence of elevated free radicals in a non-enzymatic manner, leading to suggestions for their use as biomarkers of oxidative stress. Molecular targets for their action have yet to be defined.

scholarly journals The dilemma of oxidative stress personified by the diprosopus 8-iso-prostaglandin F2α and prostaglandin F2α

2017 ◽  
Vol 3 (1) ◽  
pp. 11-15 ◽  
Author(s):  
Dimitrios Tsikas
Keyword(s):  
Oxidative Stress ◽  
Arachidonic Acid ◽  
Free Radicals ◽  
Antioxidant Defense ◽  
Prostaglandin F2α ◽  
Enzymatic Reactions ◽  
Biomarkers Of Oxidative Stress

In general, the term “oxidative stress” describes an imbalance between oxidants and antioxidants in favor of the oxidants. While antioxidant defense is widely accepted to involve both enzymatic and non-enzymatic reactions, oxidants are generally assumed to be produced by non-enzymatic processes involving chemically produced free radicals. However, many oxidants are also formed by numerous enzymes and proteins. The F2-isoprostane 8-iso-prostaglandin F2α (8-iso-PGF2α) and malondialdehyde (MDA) are widely used as biomarkers of oxidative stress, although there is evidence that both 8-iso-PGF2α and MDA are also produced enzymatically from arachidonic acid by the action of cyclooxygenase (COX). On the contrary, there is also evidence that PGF2α is produced from arachidonic acid both by the action of COX and non-enzymatically. The duality of oxidative stress, personified by 8-iso-PGF2α and PGF2α, is a serious dilemma and demands new definitions and strategies from the scientists.

scholarly journals Cytochrome P450/NADPH-dependent biosynthesis of 5,6-trans-epoxyeicosatrienoic acid from 5,6-trans-arachidonic acid

2005 ◽  
Vol 390 (3) ◽  
pp. 719-727 ◽  
Author(s):  
Uzzal Roy ◽  
Robert Joshua ◽  
Russell L. Stark ◽  
Michael Balazy
Keyword(s):  
Arachidonic Acid ◽  
Cytochrome P450 ◽  
Fatty Acid ◽  
Trans Fatty Acid ◽  
Oxidative Metabolism ◽  
Liver Microsomes ◽  
Complex Mixture ◽  
Metabolic Activation ◽  
Lipid Mediator ◽  
Epoxyeicosatrienoic Acid

5,6-trans-AA (5,6-TAA, where TAA stands for trans-arachidonic acid) is a recently identified trans fatty acid that originates from the cis–trans isomerization of AA initiated by the NO2 radical. This trans fatty acid has been detected in blood circulation and we suggested that it functions as a lipid mediator of the toxic effects of NO2. To understand its role as a lipid mediator, we studied the metabolism of 5,6-TAA by liver microsomes stimulated with NADPH. Profiling of metabolites by liquid chromatography/MS revealed a complex mixture of oxidized products among which were four epoxides, their respective hydrolysis products (dihydroxyeicosatrienoic acids), and several HETEs (hydroxyeicosatetraenoic acids) resulting from allylic, bis-allylic and (ω−1)/(ω−2) hydroxylations. We found that the C5–C6 trans bond competed with the three cis bonds for oxidative metabolism mediated by CYP (cytochrome P450) epoxygenase and hydroxylase. This was evidenced by the detection of 5,6-trans-EET (where EET stands for epoxyeicosatrienoic acid), 5,6-erythro-dihydroxyeicosatrienoic acid and an isomer of 5-HETE. A standard of 5,6-trans-EET obtained by iodolactonization of 5,6-TAA was used for the unequivocal identification of the unique microsomal epoxide in which the oxirane ring was of trans configuration. Additional lipid products originated from the metabolism involving the cis bonds and thus these metabolites had the trans C5–C6 bond. The 5,6-trans-isomers of 18- and 19-HETE were likely to be products of the CYP2E1, because a neutralizing antibody partially inhibited their formation without having an effect on the formation of the epoxides. Our study revealed a novel pathway of microsomal oxidative metabolism of a trans fatty acid in which both cis and trans bonds participated. Of particular significance is the detection of the trans-epoxide of AA, which may be involved in the metabolic activation of such trans fatty acids and probably contribute to their biological activity. Unlike its cis-isomer, 5,6-trans-EET was significantly more stable and resisted microsomal hydrolysis and conjugation with glutathione catalysed by hepatic glutathione S-transferase.

scholarly journals Entry of polyunsaturated fatty acids into the brain: evidence that high-density lipoprotein-induced methylation of phosphatidylethanolamine and phospholipase A2 are involved

1996 ◽  
Vol 316 (3) ◽  
pp. 805-811 ◽  
Author(s):  
Valérie MAGRET ◽  
Latifa ELKHALIL ◽  
Françoise NAZIH-SANDERSON ◽  
Françoise MARTIN ◽  
Jean-Marie BOURRE ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Arachidonic Acid ◽  
Polyunsaturated Fatty Acids ◽  
High Density Lipoprotein ◽  
Phospholipase A2 ◽  
Density Lipoprotein ◽  
Bovine Brain ◽  
High Density ◽  
Close Relationship ◽  
The Brain

The conversion of phosphatidylethanolamine (PE) into phosphatidylcholine (PC) by a sequence of three transmethylation reactions is shown to be stimulated by the apolipoprotein E-free subclass of high-density lipoprotein (HDL3) in isolated bovine brain capillary (BBC) membranes. HDL3-induced stimulation of BBC membranes pulsed with [methyl-14C]methionine causes a transient increase in each methylated phospholipid, i.e. phosphatidyl-N-monomethylethanolamine (PMME), phosphatidyl-NN-dimethylethanolamine (PDME) and PC. PC substrate arising from the activation of PE N-methyltransferase (PEMT) is hydrolysed by a phospholipase A2 (PLA2), as demonstrated by the accumulation of lysophosphatidylcholine (lyso-PC). When PE containing [14C]arachidonic acid in the sn-2 position ([14C]PAPE) is incorporated into BBC membranes, HDL3 stimulation induces the formation of PMME, PDME, PC and lyso-PC and the release of [14C]arachidonic acid, which correlates with the previous production of lyso-PC, suggesting that HDL3 stimulates a PLA2 that can release polyunsaturated fatty acids (PUFA). Both PEMT and PLA2 activities depend on a HDL3 concentration in the range 0–50 μg/ml and are strictly dependent on HDL3 binding, because HDL3 modified by tetranitromethane is no longer able to bind to specific receptors and to trigger PEMT and PLA2 activation. Moreover, HDL3 prelabelled with [14C]PAPE can stimulate PDME and lyso-PC synthesis in BBC membranes in the presence of S-adenosylmethionine, suggesting that HDL3 can supply BBC membranes in polyunsaturated PE and can activate enzymes involved in PE N-methylation and PUFA release. The results support the hypothesis of a close relationship between HDL3 binding, PE methylation and PUFA release, and suggest that the PC pool arising from PE could be used as a pathway for the supply of PUFA to the brain.

scholarly journals Calcium entry in Trypanosoma brucei is regulated by phospholipase A2 and arachidonic acid

1998 ◽  
Vol 336 (3) ◽  
pp. 659-666 ◽  
Author(s):  
Jason EINTRACHT ◽  
Ronald MAATHAI ◽  
Alan MELLORS ◽  
Larry RUBEN
Keyword(s):  
Fatty Acids ◽  
Arachidonic Acid ◽  
Phospholipase A2 ◽  
Trypanosoma Brucei ◽  
Mammalian Cells ◽  
Pla2 Activity ◽  
Kinase Activation ◽  
Phospholipid Hydrolysis ◽  
Protein Kinase Activation ◽  
Chain Lengths

In contrast with mammalian cells, little is known about the control of Ca2+ entry into primitive protozoans. Here we report that Ca2+ influx in pathogenic Trypanosoma brucei can be regulated by phospholipase A2 (PLA2) and the subsequent release of arachidonic acid (AA). Several PLA2 inhibitors blocked Ca2+ entry; 3-(4-octadecyl)-benzoylacrylic acid (OBAA; IC50 0.4±0.1 µM) was the most potent. We identified in live trypanosomes PLA2 activity that was sensitive to OBAA and could be stimulated by Ca2+, suggesting the presence of positive feedback control. The cell-associated PLA2 activity was able to release [14C]AA from labelled phospholipid substrates. Exogenous AA (5–50 µM) also initiated Ca2+ entry in a manner that was inhibited by the Ca2+ antagonist La3+ (100 µM). Ca2+ entry did not depend on AA metabolism or protein kinase activation. The cell response was specific for AA, and fatty acids with greater saturation than tetraeicosanoic acid (AA) or with chain lengths less than C20 exhibited greatly diminished ability to initiate Ca2+ influx. Myristate and palmitate inhibited PLA2 activity and also inhibited Ca2+ influx. Overall, these results demonstrate that Ca2+ entry into T. bruceican result from phospholipid hydrolysis and the release of eicosanoic acids.

scholarly journals Effect of 5-trans isomer of arachidonic acid on model liposomal membranes studied by a combined simulation and experimental approach

2018 ◽  
Author(s):  
Ioanna Tremi ◽  
Dimitrios Anagnostopoulos ◽  
Ellas Spyratou ◽  
Paraskevi Gkeka ◽  
Alexandros G. Georgakilas ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Arachidonic Acid ◽  
Free Radicals ◽  
Lipid Bilayers ◽  
Unsaturated Fatty Acids ◽  
Md Simulations ◽  
Γ Irradiation ◽  
Physiological Concentration ◽  
Increased Risk ◽  
Average Size

AbstractUnsaturated fatty acids are found in humans predominantly in the cis configuration. Fatty acids in the trans configuration are primarily the result of human processing (trans fats), but can also be formed endogenously by radical stress. The cis-trans isomerization of fatty acids by free radicals could be connected to several pathologies. Trans fats have been linked to an increased risk of coronary artery disease; however, the reasons for the resulting pathogenesis remain unclear. Here, we investigate the effect of a mono trans isomer of arachidonic acid (C20:4-5trans,8cis,11cis,14cis) produced by free radicals in physiological concentration on a model erythrocyte membrane using a combined experimental and theoretical approach. Molecular Dynamics (MD) simulations of two model lipid bilayers containing arachidonic acid and its 5-trans isomer in 3% mol. were carried out for this purpose. The 5-trans isomer formation in the phospholipids was catalyzed by HOCH2CH2S• radicals, generated from the corresponding thiol by γ-irradiation, in multilamellar vesicles (MLVs) of SAPC. Large unilamellar vesicles were made by the extrusion method (LUVET) as a biomimetic model for cis-trans isomerization. Atomic Force Microscopy and Dynamic Light Scattering were used to measure the average size, morphology, and the z-potential of the liposomes. Both results from MD simulations and experiments are in agreement and indicate that the two model membranes display different physicochemical properties in that the bilayers containing the trans fatty acids were more ordered and more rigid than those containing solely the cis arachidonic acid. Correspondingly, the average size of the liposomes containing trans isomers was smaller than the ones without.

Glycine protection against hypoxic but not phospholipase A2-induced injury in rat proximal tubules

1993 ◽  
Vol 264 (1) ◽  
pp. F94-F99 ◽  
Author(s):  
J. F. Wetzels ◽  
X. Wang ◽  
P. E. Gengaro ◽  
R. A. Nemenoff ◽  
T. J. Burke ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Arachidonic Acid ◽  
Lactate Dehydrogenase ◽  
Phospholipase A2 ◽  
Cell Injury ◽  
Proximal Tubules ◽  
Exogenous Arachidonic Acid ◽  
Induced Changes ◽  
Phospholipid Degradation ◽  
Isolated Rat

We studied the effects of glycine (2 mM) on hypoxia-induced changes in phospholipids and fatty acids in isolated rat proximal tubules. In this preparation, 25 min of hypoxia caused cell injury, as reflected by the release of lactate dehydrogenase (LDH) (13.1 +/- 0.8 vs. 43.5 +/- 3.2%; P < 0.01). Hypoxia caused increases in fatty acids and in lysophospholipids. Glycine prevented the hypoxia-induced cell injury (LDH 13.1 +/- 0.8 vs. 11 +/- 0.7%; not significant) but did not attenuate the increases in fatty acids or lysophospholipids. In additional experiments, the effects of glycine on phospholipid changes and cell injury induced by exogenous phospholipase A2 (PLA2) were studied. PLA2 caused dramatic increases in fatty acids and lysophospholipids and mild cell injury; these effects were not influenced by glycine. In contrast, glycine attenuated increases in LDH release induced by exposing the tubules to exogenous arachidonic acid. In conclusion, glycine does not prevent the phospholipid degradation induced by either exogenous PLA2 or hypoxia in isolated proximal tubules and yet affords protection against hypoxia and exogenous arachidonic acid.

scholarly journals Oxidative Stress in Dog with Heart Failure: The Role of Dietary Fatty Acids and Antioxidants

2011 ◽  
Vol 2011 ◽  
pp. 1-5 ◽  
Author(s):  
Emmanuelle Sagols ◽  
Nathalie Priymenko
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Fatty Acids ◽  
Free Radicals ◽  
Vitamin E ◽  
Essential Fatty Acids ◽  
Dietary Fatty Acids ◽  
The Other ◽  
The One

In dogs with heart failure, cell oxygenation and cellular metabolism do not work properly, leading to the production of a large amount of free radicals. In the organism, these free radicals are responsible of major cellular damages: this is oxidative stress. However, a suitable food intake plays an important role in limiting this phenomenon: on the one hand, the presence of essential fatty acids in the composition of membranes decreases sensitivity of cells to free radicals and constitutes a first protection against the oxidative stress; on the other hand, coenzyme Q10, vitamin E, and polyphenols are antioxidant molecules which can help cells to neutralize these free radicals.

Tobacco Smoke Free Radicals and Related Biomarkers of Oxidative Stress

2017 ◽  
Vol 112 ◽  
pp. 130-131 ◽  
Author(s):  
Reema Goel ◽  
Zachary Bitzer ◽  
Samantha Reilly ◽  
Neil Trushin ◽  
Lisa Reinhart ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Free Radicals ◽  
Tobacco Smoke ◽  
Biomarkers Of Oxidative Stress
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