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Lorenzo's oil inhibits ELOVL1 and lowers the level of sphingomyelin with a saturated very long-chain fatty acid

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Please use this identifier to cite or link to this item:http://hdl.handle.net/2115/56592

Title: Lorenzo's oil inhibits ELOVL1 and lowers the level of sphingomyelin with a saturated very long-chain fatty acid
Authors: Sassa, Takayuki Browse this author →KAKEN DB
Wakashima, Takeshi Browse this author
Ohno, Yusuke Browse this author
Kihara, Akio Browse this author →KAKEN DB
Keywords: ABCD1
erucic acid
oleic acid
peroxisome
sphingolipids
X-linked adrenoleukodystrophy
elongation of very long-chain fatty acid 1
Issue Date: Mar-2014
Publisher: American Society for Biochemistry and Molecular Biology
Journal Title: Journal of Lipid Research
Volume: 55
Issue: 3
Start Page: 524
End Page: 530
Publisher DOI: 10.1194/jlr.M044586
Abstract: X-linked adrenoleukodystrophy (X-ALD) is a peroxisomal disorder caused by impaired degradation of very long-chain fatty acids (VLCFAs) due to mutations in the ABCD1 gene responsible for VLCFA transport into peroxisomes. Lorenzo's oil, a 4: 1 mixture of glyceryl trioleate and glyceryl trierucate, has been used to reduce the saturated VLCFA level in the plasma of X-ALD patients; however, the mechanism by which this occurs remains elusive. We report the biochemical characterization of Lorenzo's oil activity toward elongation of very long-chain fatty acid (ELOVL) 1, the primary enzyme responsible for the synthesis of saturated and monounsaturated VLCFAs. Oleic and erucic acids inhibited ELOVL1, and, moreover, their 4:1 mixture (the FA composition of Lorenzo's oil) exhibited the most potent inhibitory activity. The kinetics analysis revealed that this was a mixed (not a competitive) inhibition. At the cellular level, treatment with the 4:1 mixture reduced the level of SM with a saturated VLCFA accompanied by an increased level of SM with a monounsaturated VLCFA, probably due to the incorporation of erucic acid into the FA elongation cycle.(jlr) These results suggest that inhibition of ELOVL1 may be an underlying mechanism by which Lorenzo's oil exerts its action.
Rights: This research was originally published in Journal of Lipid Research. Sassa, T., et al. Lorenzo's oil inhibits ELOVL1 and lowers the level of sphingomyelin with a saturated very long-chain fatty acid. Journal of Lipid Research. 2014; 55(3):524-530. (c) 2014 the American Society for Biochemistry and Molecular Biology.
Type: article (author version)
URI: http://hdl.handle.net/2115/56592
Appears in Collections:薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 木原 章雄

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