Biosynthesis of <i>N-</i>Docosahexanoylethanolamine from Unesterified Docosahexaenoic Acid and Docosahexaenoyl-Lysophosphatidylcholine in Neuronal Cells
We investigated the synthesis of <i>N-</i>docosahexaenoylethanolamine (synaptamide) in neuronal cells from unesterified docosahexaenoic acid (DHA) or DHA-lysophosphatidylcholine (DHA-lysoPC), the two major lipid forms that deliver DHA to the brain, in order to understand the formation of...
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doaj-59ef67b48063413fba012be792058cb32020-11-25T04:11:55ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-11-01218768876810.3390/ijms21228768Biosynthesis of <i>N-</i>Docosahexanoylethanolamine from Unesterified Docosahexaenoic Acid and Docosahexaenoyl-Lysophosphatidylcholine in Neuronal CellsKarl Kevala0Michel Lagarde1Arthur A. Spector2Hee-Yong Kim3Laboratory of Molecular Signaling, National Institute of Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USACarMeN Laboratory, INSA-Lyon, 69100 Villeurbanne, FranceLaboratory of Molecular Signaling, National Institute of Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USALaboratory of Molecular Signaling, National Institute of Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USAWe investigated the synthesis of <i>N-</i>docosahexaenoylethanolamine (synaptamide) in neuronal cells from unesterified docosahexaenoic acid (DHA) or DHA-lysophosphatidylcholine (DHA-lysoPC), the two major lipid forms that deliver DHA to the brain, in order to understand the formation of this neurotrophic and neuroprotective metabolite of DHA in the brain. Both substrates were taken up in Neuro2A cells and metabolized to <i>N-</i>docosahexaenoylphosphatidylethanolamine (NDoPE) and synaptamide in a time- and concentration-dependent manner, but unesterified DHA was 1.5 to 2.4 times more effective than DHA-lysoPC at equimolar concentrations. The plasmalogen NDoPE (pNDoPE) amounted more than 80% of NDoPE produced from DHA or DHA-lysoPC, with 16-carbon-pNDoPE being the most abundant species. Inhibition of <i>N-</i>acylphosphatidylethanolamine-phospholipase D (NAPE-PLD) by hexachlorophene or bithionol significantly decreased the synaptamide production, indicating that synaptamide synthesis is mediated at least in part via NDoPE hydrolysis. NDoPE formation occurred much more rapidly than synaptamide production, indicating a precursor–product relationship. Although NDoPE is an intermediate for synaptamide biosynthesis, only about 1% of newly synthesized NDoPE was converted to synaptamide, possibly suggesting additional biological function of NDoPE, particularly for pNDoPE, which is the major form of NDoPE produced.https://www.mdpi.com/1422-0067/21/22/8768synaptamidedocosahexaenoic acidlysophosphatidylcholine<i>N-</i>docosahexaenoyl phosphatidylethanolamineplasmalogens<i>N-</i>docosahexaenoyl phosphatidylethanolamine plasmalogen |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Karl Kevala Michel Lagarde Arthur A. Spector Hee-Yong Kim |
spellingShingle |
Karl Kevala Michel Lagarde Arthur A. Spector Hee-Yong Kim Biosynthesis of <i>N-</i>Docosahexanoylethanolamine from Unesterified Docosahexaenoic Acid and Docosahexaenoyl-Lysophosphatidylcholine in Neuronal Cells International Journal of Molecular Sciences synaptamide docosahexaenoic acid lysophosphatidylcholine <i>N-</i>docosahexaenoyl phosphatidylethanolamine plasmalogens <i>N-</i>docosahexaenoyl phosphatidylethanolamine plasmalogen |
author_facet |
Karl Kevala Michel Lagarde Arthur A. Spector Hee-Yong Kim |
author_sort |
Karl Kevala |
title |
Biosynthesis of <i>N-</i>Docosahexanoylethanolamine from Unesterified Docosahexaenoic Acid and Docosahexaenoyl-Lysophosphatidylcholine in Neuronal Cells |
title_short |
Biosynthesis of <i>N-</i>Docosahexanoylethanolamine from Unesterified Docosahexaenoic Acid and Docosahexaenoyl-Lysophosphatidylcholine in Neuronal Cells |
title_full |
Biosynthesis of <i>N-</i>Docosahexanoylethanolamine from Unesterified Docosahexaenoic Acid and Docosahexaenoyl-Lysophosphatidylcholine in Neuronal Cells |
title_fullStr |
Biosynthesis of <i>N-</i>Docosahexanoylethanolamine from Unesterified Docosahexaenoic Acid and Docosahexaenoyl-Lysophosphatidylcholine in Neuronal Cells |
title_full_unstemmed |
Biosynthesis of <i>N-</i>Docosahexanoylethanolamine from Unesterified Docosahexaenoic Acid and Docosahexaenoyl-Lysophosphatidylcholine in Neuronal Cells |
title_sort |
biosynthesis of <i>n-</i>docosahexanoylethanolamine from unesterified docosahexaenoic acid and docosahexaenoyl-lysophosphatidylcholine in neuronal cells |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2020-11-01 |
description |
We investigated the synthesis of <i>N-</i>docosahexaenoylethanolamine (synaptamide) in neuronal cells from unesterified docosahexaenoic acid (DHA) or DHA-lysophosphatidylcholine (DHA-lysoPC), the two major lipid forms that deliver DHA to the brain, in order to understand the formation of this neurotrophic and neuroprotective metabolite of DHA in the brain. Both substrates were taken up in Neuro2A cells and metabolized to <i>N-</i>docosahexaenoylphosphatidylethanolamine (NDoPE) and synaptamide in a time- and concentration-dependent manner, but unesterified DHA was 1.5 to 2.4 times more effective than DHA-lysoPC at equimolar concentrations. The plasmalogen NDoPE (pNDoPE) amounted more than 80% of NDoPE produced from DHA or DHA-lysoPC, with 16-carbon-pNDoPE being the most abundant species. Inhibition of <i>N-</i>acylphosphatidylethanolamine-phospholipase D (NAPE-PLD) by hexachlorophene or bithionol significantly decreased the synaptamide production, indicating that synaptamide synthesis is mediated at least in part via NDoPE hydrolysis. NDoPE formation occurred much more rapidly than synaptamide production, indicating a precursor–product relationship. Although NDoPE is an intermediate for synaptamide biosynthesis, only about 1% of newly synthesized NDoPE was converted to synaptamide, possibly suggesting additional biological function of NDoPE, particularly for pNDoPE, which is the major form of NDoPE produced. |
topic |
synaptamide docosahexaenoic acid lysophosphatidylcholine <i>N-</i>docosahexaenoyl phosphatidylethanolamine plasmalogens <i>N-</i>docosahexaenoyl phosphatidylethanolamine plasmalogen |
url |
https://www.mdpi.com/1422-0067/21/22/8768 |
work_keys_str_mv |
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