ArticleBiochimica et biophysica acta2011
Valproate uncompetitively inhibits arachidonic acid acylation by rat acyl-CoA synthetase 4: relevance to valproate's efficacy against bipolar disorder.
Article in Biochimica et biophysica acta, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02272010 (Targeted Alterations in n-3 and n-6 Fatty Acids for the Management of Mood Variability in the Maintenance Phase of Bipolar Disorder), which is not on this map. Cited by 18 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Targeted Alterations in n-3 and n-6 Fatty Acids for the Management of Mood Variability in the Maintenance Phase of Bipolar Disorder
Who cites it
18 citing papers in PubMed, 25 citations in OpenAlex.
- Adjunctive dietary intervention for bipolar disorder: a randomized, controlled, parallel-group, modified double-blinded trial of a high n-3 plus low n-6 diet.Bipolar disorders · 2022Trial
- Aqueous-Phase Polycondensation of Hydroxy Fatty Acids via a Whole-Cell CoA Activation-Acyltransferase Cascade.JACS Au · 2026Article
- Untargeted LC-MS/MS Metabolomics Study of HO-AAVPA and VPA on Breast Cancer Cell Lines.International journal of molecular sciences · 2023Article
- Acyl-CoA synthetases as regulators of brain phospholipid acyl-chain diversity.Prostaglandins, leukotrienes, and essential fatty acids · 2020Review
- Valnoctamide, which reduces rat brain arachidonic acid turnover, is a potential non-teratogenic valproate substitute to treat bipolar disorder.Psychiatry research · 2017Article
- Comparative teratogenicity analysis of valnoctamide, risperidone, and olanzapine in mice.Bipolar disorders · 2015Article
- Pathways of polyunsaturated fatty acid utilization: implications for brain function in neuropsychiatric health and disease.Brain research · 2015Review
- Valnoctamide, a non-teratogenic amide derivative of valproic acid, inhibits arachidonic acid activation in vitro by recombinant acyl-CoA synthetase-4.Bipolar disorders · 2014Article
- Lithium and the other mood stabilizers effective in bipolar disorder target the rat brain arachidonic acid cascade.ACS chemical neuroscience · 2014Review
- The low levels of eicosapentaenoic acid in rat brain phospholipids are maintained via multiple redundant mechanisms.Journal of lipid research · 2013Article
- Propylisopropylacetic acid (PIA), a constitutional isomer of valproic acid, uncompetitively inhibits arachidonic acid acylation by rat acyl-CoA synthetase 4: a potential drug for bipolar disorder.Biochimica et biophysica acta · 2013Article
- Chronic clozapine reduces rat brain arachidonic acid metabolism by reducing plasma arachidonic acid availability.Journal of neurochemistry · 2013Article
- A novel aromatic carboxylic acid inactivates luciferase by acylation of an enzymatically active regulatory lysine residue.PloS one · 2013Article
- The synthesis and in vivo pharmacokinetics of fluorinated arachidonic acid: implications for imaging neuroinflammation.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2012Article
- Imaging brain signal transduction and metabolism via arachidonic and docosahexaenoic acid in animals and humans.Brain research bulletin · 2012Review
- Chronic valproate treatment blocks D2-like receptor-mediated brain signaling via arachidonic acid in rats.Neuropharmacology · 2011Article
- Chronic olanzapine treatment decreases arachidonic acid turnover and prostaglandin E₂ concentration in rat brain.Journal of neurochemistry · 2011Article
- Kinetics of eicosapentaenoic acid in brain, heart and liver of conscious rats fed a high n-3 PUFA containing diet.Prostaglandins, leukotrienes, and essential fatty acidsArticle
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundThe ability of chronic valproate (VPA) to reduce arachidonic acid (AA) turnover in brain phospholipids of unanesthetized rats has been ascribed to its inhibition of acyl-CoA synthetase (Acsl)-mediated activation of AA to AA-CoA. Our aim was to identify a rat Acsl isoenzyme that could be inhibited by VPA in vitro.
methodsRat Acsl3-, Acsl6v1- and Acsl6v2-, and Acsl4-flag proteins were expressed in E. coli, and the ability of VPA to inhibit their activation of long-chain fatty acids to acyl-CoA was estimated using Michaelis-Menten kinetics.
resultsVPA uncompetitively inhibited Acsl4-mediated conversion of AA and of docosahexaenoic (DHA) but not of palmitic acid to acyl-CoA, but did not affect AA conversion by Acsl3, Acsl6v1 or Acsl6v2. Acsl4-mediated conversion of AA to AA-CoA showed substrate inhibition and had a 10-times higher catalytic efficiency than did conversion of DHA to DHA-CoA. Butyrate, octanoate, or lithium did not inhibit AA activation by Acsl4.
conclusionsVPA's ability to inhibit Acsl4 activation of AA and of DHA to their respective acyl-CoAs, when related to the higher catalytic efficiency of AA than DHA conversion, may account for VPA's selective reduction of AA turnover in rat brain phospholipids, and contribute to VPA's efficacy against bipolar disorder.
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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.