ELO2 and ELO3, homologues of the Saccharomyces cerevisiae ELO1 gene, function in fatty acid elongation and are required for sphingolipid formation.
ELO2 and ELO3 were identified from the Saccharomyces cerevisiae genome data base as homologues of ELO1, a gene involved in the elongation of the fatty acid 14:0 to 16:0. Mutations in these genes have previously been shown to produce pleiotropic effects involving a number of membrane functions. The simultaneous disruption of ELO2 and ELO3 has also been shown to produce synthetic lethality, indicating that they have related and/or overlapping functions. Gas chromatography and gas chromatography/mass spectroscopy analyses reveal that null mutations of ELO2 and ELO3 produce defects in the formation of very long chain fatty acids. Analysis of the null mutants indicates that these genes encode components of the membrane-bound fatty acid elongation systems that produce the 26-carbon very long chain fatty acids that are precursors for ceramide and sphingolipids. Elo2p appears to be involved in the elongation of fatty acids up to 24 carbons. It appears to have the highest affinity for substrates with chain lengths less than 22 carbons. Elo3p apparently has a broader substrate specificity and is essential for the conversion of 24-carbon acids to 26-carbon species. Disruption of either gene reduces cellular sphingolipid levels and results in the accumulation of the long chain base, phytosphingosine. Null mutations in ELO3 result in accumulation of labeled precursors into inositol phosphoceramide, with little labeling in the more complex mannosylated sphingolipids, whereas disruption of ELO2 results in reduced levels of all sphingolipids.
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Bureau of Biological Research, Rutgers University, Nelson Laboratories, Piscataway, New Jersey 08855-1059, USA.
Toke
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Mandala
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Martin
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D000123:Acetyltransferases; D000595:Amino Acid Sequence; D001345:Autoradiography; D002855:Chromatography, Thin Layer; D005227:Fatty Acids / Q000378:metabolism*; D005656:Fungal Proteins / Q000235:genetics* / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D016415:Sequence Alignment; D013107:Sphingolipids / Q000096:biosynthesis*; D013110:Sphingosine / Q000031:analogs & derivatives / Q000378:metabolism
D005227:Fatty Acids; D005656:Fungal Proteins; D008565:Membrane Proteins; D029701:Saccharomyces cerevisiae Proteins; D013107:Sphingolipids; D000123:Acetyltransferases; C107117:ELO1 protein, S cerevisiae; C107118:ELO2 protein, S cerevisiae; C107119:SUR4 protein, S cerevisiae; D013110:Sphingosine; C005682:safingol