The effects oftrans fatty acids on fatty acyl Δ5 desaturation by human skin fibroblasts |
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Authors: | Miriam D Rosenthal Mark A Doloresco |
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Affiliation: | (1) Department of Biochemistry, Eastern Virginia Medical School, 23501 Norfolk, VA |
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Abstract: | The effectiveness of different fatty acids as inhibitors of fatty acyl Δ5 desaturation activity in human skin fibroblasts
has been investigated. When incubated with 2.25 μM 14C] eicosatrienoate (20∶3ω6) in otherwise lipid-free medium, these cells rapidly incorporate the radiolabeled fatty acid into
cellular glycerolipids and desaturate it to produce both 14C] arachidonate and 14C] docosatetraenoate. The Δ5 desaturation activity can be enhanced by prior growth of the cells without serum lipids. Elaidate
(9t–18∶1) is a potent inhibitor of Δ5 desaturation whiletrans-vaccenate (11t–18∶1) is virtually without effect. Oleate and linoleate are only mildly inhibitory. Linoelaidate (9t, 12t–18∶2)
is more inhibitory than linoleate but significantly less effective than elaidate. The effects of elaidate can be readily overcome
by increasing the concentration of exogenous eicosatrienoate. Studies with a variety oftrans monounsaturates of differing chain lengths indicate that the ω9trans fatty acids are potent inhibitors of Δ5 desaturation, while ω7trans fatty acids are relatively ineffective. Intact human fibroblasts could thus be important in characterizing novel fatty acids
as selective inhibitors of arachidonate synthesis in vivo. |
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