RGD Reference Report - Long-chain acyl-CoA synthetase 6 preferentially promotes DHA metabolism. - Rat Genome Database

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Long-chain acyl-CoA synthetase 6 preferentially promotes DHA metabolism.

Authors: Marszalek, JR  Kitidis, C  DiRusso, CC  Lodish, HF 
Citation: Marszalek JR, etal., J Biol Chem. 2005 Mar 18;280(11):10817-26. Epub 2005 Jan 17.
RGD ID: 2312811
Pubmed: PMID:15655248   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M411750200   (Journal Full-text)

Previously we demonstrated that supplementation with the polyunsaturated fatty acids (PUFA) arachidonic acid (AA) or docosahexaenoic acid (DHA) increased neurite outgrowth of PC12 cells during differentiation, and that overexpression of rat acyl-CoA synthetase long-chain family member 6 (Acsl6, formerly ACS2) further increased PUFA-enhanced neurite outgrowth. However, whether Acsl6 overexpression enhanced the amount of PUFA accumulated in the cells or altered the partitioning of any fatty acids into phospholipids (PLs) or triacylglycerides (TAGs) was unknown. Here we show that Acsl6 overexpression specifically promotes DHA internalization, activation to DHA-CoA, and accumulation in differentiating PC12 cells. In contrast, oleic acid (OA) and AA internalization and activation to OA-CoA and AA-CoA were increased only marginally by Acsl6 overexpression. Additionally, the level of total cellular PLs was increased in Acsl6 overexpressing cells when the medium was supplemented with AA and DHA, but not with OA. Acsl6 overexpression increased the incorporation of [(14)C]-labeled OA, AA, or DHA into PLs and TAGs. These results do not support a role for Acsl6 in the specific targeting of fatty acids into PLs or TAGs. Rather, our data support the hypothesis that Acsl6 functions primarily in DHA metabolism, and that its overexpression increases DHA and AA internalization primarily during the first 24 h of neuronal differentiation to stimulate PL synthesis and enhance neurite outgrowth.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
phospholipid biosynthetic process  IMP 2312811 RGD 
positive regulation of long-chain fatty acid import across plasma membrane  IMP 2312811 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Acsl6  (acyl-CoA synthetase long-chain family member 6)


Additional Information