Metabolism of 4,7,10,13,16-docosapentaenoic acid by human platelet cyclooxygenase and lipoxygenase

Milks, Michael M.; Sprecher, Howard

doi:10.1016/0005-2760(85)90026-8

Cited by 27 publications

(8 citation statements)

References 13 publications

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“…We reasoned that platelets might generate analogous lipids through metabolizing C22 substrates with three, four, or five double bonds. Indeed, previous studies found exogenous C22 substrate can be metabolized by COX ( Milks and Sprecher, 1985 , Sprecher, 1986 , Sprecher and Careaga, 1986 ); however, their generation from endogenous substrate on agonist activation has never been shown. Analogous lipids from 22:6 were not detected, and ions giving MS/MS fragmentation spectra consistent with resolvins, lipoxins (LXs), or protectins were absent from our dataset.…”

Section: Discussionmentioning

confidence: 96%

Mapping the Human Platelet Lipidome Reveals Cytosolic Phospholipase A2 as a Regulator of Mitochondrial Bioenergetics during Activation

et al. 2016

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SummaryHuman platelets acutely increase mitochondrial energy generation following stimulation. Herein, a lipidomic circuit was uncovered whereby the substrates for this are exclusively provided by cPLA2, including multiple fatty acids and oxidized species that support energy generation via β-oxidation. This indicates that acute lipid membrane remodeling is required to support energetic demands during platelet activation. Phospholipase activity is linked to energy metabolism, revealing cPLA2 as a central regulator of both lipidomics and energy flux. Using a lipidomic approach (LipidArrays), we also estimated the total number of lipids in resting, thrombin-activated, and aspirinized platelets. Significant diversity between genetically unrelated individuals and a wealth of species was revealed. Resting platelets demonstrated ∼5,600 unique species, with only ∼50% being putatively identified. Thrombin elevated ∼900 lipids >2-fold with 86% newly appearing and 45% inhibited by aspirin supplementation, indicating COX-1 is required for major activation-dependent lipidomic fluxes. Many lipids were structurally identified. With ∼50% of the lipids being absent from databases, a major opportunity for mining lipids relevant to human health and disease is presented.

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Section: Discussionmentioning

confidence: 96%

Mapping the Human Platelet Lipidome Reveals Cytosolic Phospholipase A2 as a Regulator of Mitochondrial Bioenergetics during Activation

et al. 2016

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“…They are adrenic acid (7,10,13,16-docosatetraenoic) and 4,7,10,13,16-docosapentaenoic acid. The former has been described as the precursor of dihomo-PGI2 in endothelial cells (Campbell et al, 1985) and of dihomothromboxane in platelets (Van Rollins et al, 1985), and the latter as the precursor of A4-dihomo-prostanoids (Milks & Sprecher, 1985). These studies showed that adrenic acid appears as a potent inhibitor of arachidonic acid cyclo-oxygenation, presumably via a competitive process.…”

Section: Modulation Of Arachidonic Acid Metabolism By Eicosanoidsmentioning

confidence: 96%

Metabolic interactions between eicosanoids in blood and vascular cells

Lagarde

Gualde²,

Rigaud³

1989

Biochemical Journal

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“…DPAn-6 can be a substrate for cyclooxygenases (COX) and lipoxygenases (LOX); bioactive 12-hydroxy-5,8,10,14-eicosatetraenoic acid is a major metabolite [80]. The reaction between DPAn-6 and 15-LOX generated 17(S)-hydroxy-DPAn-6 and 10, 17(S)-hydroxy-DPAn-6 [81], which have anti-inflammatory effects.…”

Section: Discussionmentioning

confidence: 99%

Fifteen weeks of dietary n-3 polyunsaturated fatty acid deprivation increase turnover of n-6 docosapentaenoic acid in rat-brain phospholipids

Igarashi¹,

Kim²,

Gao³

et al. 2012

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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Docosapentaenoic acid (DPAn-6, 22:5n-6) is an n-6 polyunsaturated fatty acid (PUFA) whose brain concentration can be increased in rodents by dietary n-3 PUFA deficiency, which may contribute to their behavioral dysfunction. We used our in vivo intravenous infusion method to see if brain DPAn-6 turnover and metabolism also were altered with deprivation. We studied male rats that had been fed for 15 weeks post-weaning an n-3 PUFA adequate diet containing 4.6% alpha-linolenic acid (α-LNA, 18:3n-3) or a deficient diet (0.2% α-LNA), each lacking docosahexaenoic acid (22:6n-3) and arachidonic acid (AA, 20:4n-6). [1-14C]DPAn-6 was infused intravenously for 5 min in unanesthetized rats, after which the brain underwent high-energy microwaving, and then was analyzed. The n-3 PUFA deficient compared with adequate diet increased DPAn-6 and decreased DHA concentrations in plasma and brain, while minimally changing brain AA concentration. Incorporation rates of unesterified DPAn-6 from plasma into individual brain phospholipids were increased 5.2–7.7 fold, while turnover rates were increased 2.1–4.7 fold. The observations suggest that increased metabolism and brain concentrations of DPAn-6 and its metabolites, together with a reduced brain DHA concentration, contribute to behavioral and functional abnormalities reported with dietary n-3 PUFA deprivation in rodents.

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Metabolism of 4,7,10,13,16-docosapentaenoic acid by human platelet cyclooxygenase and lipoxygenase

Cited by 27 publications

References 13 publications

Mapping the Human Platelet Lipidome Reveals Cytosolic Phospholipase A2 as a Regulator of Mitochondrial Bioenergetics during Activation

Mapping the Human Platelet Lipidome Reveals Cytosolic Phospholipase A2 as a Regulator of Mitochondrial Bioenergetics during Activation

Metabolic interactions between eicosanoids in blood and vascular cells

Fifteen weeks of dietary n-3 polyunsaturated fatty acid deprivation increase turnover of n-6 docosapentaenoic acid in rat-brain phospholipids

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