Abstract
The regulation of lipid biosynthesis in the yeast Saccharomyces cerevisiae by fumonisin B1 was examined. Fumonisin B1 inhibited the growth of yeast cells. Cells supplemented with fumonisin B1 accumulated free sphinganine and phytosphingosine in a dose-dependent manner. The cellular concentration of ceramide was reduced in fumonisin B1-supplemented cells. Ceramide synthase activity was found in yeast cell membranes and was inhibited by fumonisin B1. Fumonisin B1 inhibited the synthesis of the inositol-containing sphingolipids inositol phosphorylceramide, mannosylinositol phosphorylceramide, and mannosyldiinositol phosphorylceramide. Fumonisin B1 also caused a decrease in the synthesis of the major phospholipids synthesized via the CDP-diacylglycerol-dependent pathway and the synthesis of neutral lipids. The effects of fumonisin B1 and sphingoid bases on the activities of enzymes in the pathways leading to the synthesis of sphingolipids, phospholipids, and neutral lipids were also examined. Other than ceramide synthase, fumonisin B1 did not affect the activities of any of the enzymes examined. However, sphinganine and phytosphingosine inhibited the activities of inositol phosphorylceramide synthase, phosphatidylserine synthase, and phosphatidate phosphatase. These are key enzymes responsible for the synthesis of lipids in yeast. The data reported here indicated that the biosynthesis of sphingolipids, phospholipids and neutral lipids was coordinately regulated by fumonisin B1 through the regulation of lipid biosynthetic enzymes by sphingoid bases.
Highlights
Role as structural components of membranes, lipids function as cofactors and activators of membrane-associated enzymes [3] and playa major role in cell signaling mechanisms [4,5,6]
Much attention has been paid to the role sphingoid bases play in lipid metabolism and cell signaling in mammalian cells [6, 25]
Effect of Fumonisin B I on Cellular Concentrations of Sphingoid Bases-We previously demonstrated that free sphinganine and phytosphingosine exist in S. cerevisiae [24]
Summary
Role as structural components of membranes, lipids function as cofactors and activators of membrane-associated enzymes [3] and playa major role in cell signaling mechanisms [4,5,6]. The biochemical mechanisms affecting the activity of phospholipid biosynthetic enzymes include regulation by inositol [14], nucleotides [15, 16], phosphorylation [17,18,19], lipids [20,21,22,23], and sphingoid bases [24]. The data reported here were consistent with the conclusion that the synthesis of the major lipid classes was coordinately regulated by sphingoid bases. The mechanism of this regulation was due in part to the inhibition of key lipid biosynthetic enzymes including IPC synthase, PS synthase, and PA phosphatase by sphingoid bases
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