ELO2 AND ELO3, HOMOLOGS 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 membr ane functions, The simultaneous disruption of ELO2 and ELO3 has also b een shown to produce synthetic lethality, indicating that they have re lated and/or overlapping functions, Gas chromatography and gas chromat ography/mass spectroscopy analyses reveal that mull mutations of ELO2 and ELO3 produce defects in the formation of very long chain fatty aci ds, Analysis of the null mutants indicates that these genes encode com ponents of the membrane-bound fatty acid elongation systems that produ ce the 26-carbon very long chain fatty acids that are precursors for c eramide and sphingolipids, Elo2p appears to be involved in the elongat ion of fatty acids up to 24 carbons, it appears to have the highest af finity for substrates with chain lengths less than 22 carbons. Elo3p a pparently has a broader substrate specificity and is essential for the conversion of 24-carbon acids to as carbon species. Disruption of eit her gene reduces cellular sphingolipid levels and results in the accum ulation of the long chain base, phytosphingosine. Null mutations In EL O3 result in accumulation of labeled precursors into inositol phosphoc eramide, with little labeling in the more complex mannosylated sphingo lipids, whereas disruption of ELO2 results in reduced levels of all sp hingolipids.