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Lorenzo's oil inhibits ELOVL1 and lowers the level of sphingomyelin with a saturated very long-chain fatty acid
- Source :
- Journal of Lipid Research, Vol 55, Iss 3, Pp 524-530 (2014)
- Publication Year :
- 2014
- Publisher :
- American Society for Biochemistry and Molecular Biology, 2014.
-
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.
- Subjects :
- Erucic Acids
Fatty Acid Elongases
Very long chain fatty acid
Immunoblotting
Palmitic Acid
QD415-436
Lorenzo's oil
Biology
Biochemistry
Gene Expression Regulation, Enzymologic
Palmitic acid
chemistry.chemical_compound
Endocrinology
Acetyltransferases
medicine
Humans
peroxisome
Triolein
X-linked adrenoleukodystrophy
Research Articles
chemistry.chemical_classification
sphingolipids
Dose-Response Relationship, Drug
Reverse Transcriptase Polymerase Chain Reaction
elongation of very long-chain fatty acid 1
Fatty Acids
ABCD1
Fatty acid
Cell Biology
medicine.disease
Sphingomyelins
Oleic acid
Drug Combinations
Kinetics
erucic acid
HEK293 Cells
chemistry
oleic acid
Erucic acid
Adrenoleukodystrophy
Stearic Acids
HeLa Cells
Subjects
Details
- Language :
- English
- ISSN :
- 00222275
- Volume :
- 55
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Journal of Lipid Research
- Accession number :
- edsair.doi.dedup.....22ced445deb22578043b16e914751dd2