Fig. 1. Major pathway of sphingolipid synthesis in Saccharomyces cerevisiae.

Scheme shows the enzymes of sphingolipid synthesis in S. cerevisiae (Dickson et al, 1998) [63]. The first step is catalyzed by serine-palmitoyl transferase complex (SPT), which catalyzes the condensation of a L-serine and palmitoyl-CoA to 3-ketodihydrosphingosine, CoA and CO₂ (Pinto et al, 1992) [64]. This reaction takes place in the endoplasmic reticulum [63] and its activity is inhibited by myriocin [65]. 3-ketodihydrosphingosine is the precursor of the long chain bases (LCBs) dihydrosphingosine (DHS) and phytosphingosine (PHS). These are N-acylated to form either dihydro- or phytoceramide. The novo pathway is catalyzed by the ceramide synthases Lag1p, Lac1p and Lip1p [66]. Sphingoid bases can also be formed by degradation of ceramides by activation of Ydc1p and Ypc1p ceramidases [63]. These first group of reactions are conserved during evolution among the eukaryotic kingdom [67,68] but the formation of dihydroceramide and phytoceramide is different, as hydroxylation of DHS to form PHS and phytoceramide catalyzed by Sur2p is unique to yeast [69]. In S. cerevisiae, unlike mammalian cells, inositol phosphate and mannose are incorporated to form complex ceramides, inositol phosphoceramides (IPC), mannosylinositolphosphoceramide (MIPC) and mannosyldiinositolphosphoceramide (M(IP)2C). We highlighted in blue boxes the enzymes which were found to be transcriptionally regulated in swi4Δ cells (see Fig. 4) which are Lcb2p (subunit of SPT complex), Tsc10p (3-ketosphinganine reductase), Sur2p (sphinganine C4-hydroxylase), Lac1p (ceramide synthase component), , Ydc1p (alkaline dihydroceramidase), Aur1p (phosphatidylinositol: ceramide phosphoinositol transferase), Scs7p (sphingolipid α-hydroxylase and desaturase), Sur1p (mannosylinositol phosphorylceramide synthase subunit), Csh1p (mannosylinositol phosphorylceramide synthase subunit) and Ipt1p (inositol phosphotransferase).