{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T11:44:01Z","timestamp":1770723841612,"version":"3.49.0"},"reference-count":39,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2014,7,8]],"date-time":"2014-07-08T00:00:00Z","timestamp":1404777600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Bipolar Disorders"],"published-print":{"date-parts":[[2014,12]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Valproic acid (VPA), a mood stabilizer used for treating bipolar disorder (BD), uncompetitively inhibits acylation of arachidonic acid (AA) by recombinant AA\u2010selective acyl\u2010CoA synthetase 4 (Acsl4) at an enzyme inhibition constant (<jats:italic>K<\/jats:italic><jats:sub>i<\/jats:sub>) of 25\u00a0mM. Inhibition may account for VPA's ability to reduce AA turnover in brain phospholipids of unanesthetized rats and to be therapeutic in BD. However, VPA is teratogenic. We tested whether valnoctamide (VCD), a non\u2010teratogenic amide derivative of a VPA chiral isomer, which had antimanic potency in a phase III BD trial, also inhibits recombinant Acsl4.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Rat Acsl4\u2010flag protein was expressed in<jats:italic><jats:styled-content style=\"fixed-case\">E<\/jats:styled-content>scherichia coli<\/jats:italic>. We used Michaelis\u2013Menten kinetics to characterize and quantify the ability of VCD to inhibit conversion of AA to AA\u2010CoA by recombinant Acsl4<jats:italic>in vitro<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Acsl4\u2010mediated activation of AA to AA\u2010CoA by Acsl4 was inhibited uncompetitively by VCD, with a<jats:italic>K<\/jats:italic><jats:sub>i<\/jats:sub>of 6.38\u00a0mM.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>VCD's ability to uncompetitively inhibit AA activation to AA\u2010CoA by Acsl4, at a lower<jats:italic>K<\/jats:italic><jats:sub>i<\/jats:sub>than VPA, suggests that, like VPA, VCD may reduce AA turnover in rat brain phospholipids. If so, VCD and other non\u2010teratogenic Acsl4 inhibitors might be considered further for treating BD.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bdi.12220","type":"journal-article","created":{"date-parts":[[2014,7,8]],"date-time":"2014-07-08T07:18:48Z","timestamp":1404803928000},"page":"875-880","source":"Crossref","is-referenced-by-count":11,"title":["Valnoctamide, a non\u2010teratogenic amide derivative of valproic acid, inhibits arachidonic acid activation<i>in vitro<\/i>by recombinant acyl\u2010CoA synthetase\u20104"],"prefix":"10.1111","volume":"16","author":[{"given":"Hiren R","family":"Modi","sequence":"first","affiliation":[{"name":"Brain Physiology and Metabolism Section Laboratory of Neurosciences National Institute on Aging National Institutes of Health Bethesda MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mireille","family":"Basselin","sequence":"additional","affiliation":[{"name":"Brain Physiology and Metabolism Section Laboratory of Neurosciences 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