Metabolic characterization of sciadonic acid (5c,11c,14c-eicosatrienoic acid) as an effective substitute for arachidonate of phosphatidylinositol.
Sciadonic acid (20:3 Delta-5,11,14) is an n-6 series trienoic acid that lacks the Delta8 double bond of arachidonic acid. This fatty acid is not converted to arachidonic acid in higher animals. In this study, we characterized the metabolic behavior of sciadonic acid in the process of acylation to phospholipid of HepG2 cells. One of the characteristics of fatty acid compositions of phospholipids in sciadonic acid-supplemented cells is a higher proportion of sciadonic acid in phosphatidylinositol (PtdIns) (27.4%) than in phosphatidylethanolamine (PtdEtn) (23.2%), phosphatidylcholine (PtdCho) (17.3%) and phosphatidylserine (PtdSer) (20.1%). Similarly, the proportion of arachidonic acid was higher in PtdIns (35.8%) than in PtdEtn (29.1%), PtdSer (18.2%) and PtdCho (20.2%) in arachidonic-acid-supplemented cells. The extensive accumulation of sciadonic acid in PtdIns resulted in the enrichment of newly formed 1-stearoyl-2-sciadonoyl molecular species (38%) in PtdIns and caused the reduction in the level of pre-existing arachidonic-acid-containing molecular species. The kinetics of incorporation of sciadonic acid to PtdEtn, PtdSer and PtdIns of cells were similar to those of arachidonic acid. In contrast to sciadonic acid, neither eicosapentaenoic acid (20:5 Delta-5,8,11,14,17) nor juniperonic acid (20:4 Delta-5,11,14,17) accumulated in the PtdIns fraction. Rather, these n-3 series polyunsaturated fatty acids, once incorporated into PtdIns, tended to be excluded from PtdIns. In addition, the level of arachidonic-acid-containing PtdIns molecular species remained unchanged by eicosapentaenoic-acid-supplementation. These results suggest that sciadonic acid or sciadonic-acid-containing glycerides are metabolized in a similar manner to arachidonic acid or arachidonic-acid-containing glyceride in the biosynthesis of PtdIns and that sciadonic acid can effectively modify the molecular species composition of PtdIns in HepG2 cells. In this regard, sciadonic acid will be an interesting experimental tool to clarify the significance of arachidonic acid-residue of PtdIns-origin bioactive lipids.
Tanaka
T
T
Department of Applied Biological Science, Fukuyama University, Japan.
Morishige
J
J
Takimoto
T
T
Takai
Y
Y
Satouchi
K
K
D000217:Acyltransferases / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D001095:Arachidonic Acids / Q000737:chemistry / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D015118:Eicosapentaenoic Acid / Q000737:chemistry / Q000378:metabolism; D044943:Fatty Acid Desaturases / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D006865:Hydrogenation; D007700:Kinetics; D008246:Lysophospholipids / Q000737:chemistry / Q000378:metabolism; D008862:Microsomes, Liver / Q000737:chemistry / Q000378:metabolism; D010716:Phosphatidylinositols / Q000737:chemistry* / Q000378:metabolism*; D051381:Rats; D013379:Substrate Specificity; D014407:Tumor Cells, Cultured
D001095:Arachidonic Acids; D005231:Fatty Acids, Unsaturated; D008246:Lysophospholipids; D010716:Phosphatidylinositols; C437903:juniperonic acid; D016718:Arachidonic Acid; C045533:eicosa-5,11,14-trienoic acid; D015118:Eicosapentaenoic Acid; D044943:Fatty Acid Desaturases; D000217:Acyltransferases