Wu W I, McDonough V M, Nickels J T, Ko J, Fischl A S, Vales T R, Merrill A H, Carman G M
Department of Food Science, Cook College, New Jersey Agricultural Experiment Station, Rutgers University, New Brunswick 08903, USA.
J Biol Chem. 1995 Jun 2;270(22):13171-8. doi: 10.1074/jbc.270.22.13171.
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.
研究了伏马菌素B1对酿酒酵母中脂质生物合成的调控作用。伏马菌素B1抑制酵母细胞的生长。添加伏马菌素B1的细胞以剂量依赖的方式积累游离鞘氨醇和植物鞘氨醇。添加伏马菌素B1的细胞中神经酰胺的细胞浓度降低。在酵母细胞膜中发现了神经酰胺合酶活性，且该活性受到伏马菌素B1的抑制。伏马菌素B1抑制含肌醇鞘脂肌醇磷酸神经酰胺、甘露糖基肌醇磷酸神经酰胺和甘露糖基二肌醇磷酸神经酰胺的合成。伏马菌素B1还导致通过CDP - 二酰甘油依赖性途径合成的主要磷脂的合成以及中性脂质的合成减少。还研究了伏马菌素B1和鞘氨醇碱对鞘脂、磷脂和中性脂质合成途径中酶活性的影响。除了神经酰胺合酶外，伏马菌素B1不影响所检测的任何酶的活性。然而，鞘氨醇和植物鞘氨醇抑制肌醇磷酸神经酰胺合酶、磷脂酰丝氨酸合酶和磷脂酸磷酸酶的活性。这些是酵母中负责脂质合成的关键酶。此处报道的数据表明，伏马菌素B1通过鞘氨醇碱对脂质生物合成酶的调控，协同调节鞘脂、磷脂和中性脂质的生物合成。
