Futerman A H
Department of Membrane Research and Biophysics, Weizmann Institute of Science, Rehovot, Israel.
Biochemistry (Mosc). 1998 Jan;63(1):74-83.
Ceramide can be formed by the activity of two general metabolic pathways, the anabolic pathway, in which ceramide is formed by acylation of a sphingoid long chain base, and the catabolic pathway, in which ceramide is formed by the degradation of either glycosphingolipids or of sphingomyelin (SM). The anabolic reactions take place in the early compartments of the secretory pathway (the endoplasmic reticulum and the Golgi apparatus) and the catabolic reactions take place either in lysosomes or at the plasma membrane. Work from our and other laboratories has shown that neuronal growth and development can be regulated by manipulating ceramide metabolism. Thus, synthesis of glucosylceramide from ceramide is required for axonal growth in cultured hippocampal neurons, but the formation of ceramide from SM, by a sphingomyelinase activity, stimulates the earliest stages of development in these cells, namely the formation of minor neuronal processes and the initial formation of the axon. Thus, ceramide and its metabolites play distinct roles in the same neuron, depending on the intracellular site of generation of ceramide and on the stage of neuronal development.
神经酰胺可通过两种一般代谢途径的活动形成，即合成途径，其中神经酰胺通过鞘氨醇长链碱基的酰化形成；以及分解代谢途径，其中神经酰胺通过糖鞘脂或鞘磷脂（SM）的降解形成。合成反应发生在分泌途径的早期区室（内质网和高尔基体），分解代谢反应发生在溶酶体或质膜。我们实验室和其他实验室的研究表明，通过操纵神经酰胺代谢可以调节神经元的生长和发育。因此，从神经酰胺合成葡糖神经酰胺是培养的海马神经元轴突生长所必需的，但通过鞘磷脂酶活性从SM形成神经酰胺会刺激这些细胞发育的最早阶段，即小神经元突起的形成和轴突的初始形成。因此，神经酰胺及其代谢产物在同一神经元中发挥不同的作用，这取决于神经酰胺产生的细胞内位置和神经元发育阶段。
