An important metabolite of ceramide is ceramide 1‑phosphate (C1P). This lipid second messenger was first demonstrated to be mitogenic for fibroblasts and macrophages and later shown to have antiapoptotic properties. C1P is also an important mediator of the inflammatory response, by stimulating the release of arachidonic acid through activation of group IVA cytosolic phospholipase A2, the initial rate‑limiting step of eicosanoid biosynthesis. C1P is formed from ceramide by the action of a specific ceramide kinase (CerK), which is distinct from the sphingosine kinases that synthesize sphingosine‑1‑phosphate. CerK is specific for natural ceramides with the erythro configuration in the base component and esterified to long‑chain fatty acids. CerK can be activated by different agonists, including interleukin 1‑beta, macrophage colony stimulating factor, or calcium ions. Most of the effects of C1P so far described seem to take place in intracellular compartments; however, the recent observation that C1P stimulates cell migration implicates a specific plasma membrane receptor that is coupled to a Gi protein. Therefore, C1P has a dual regulatory capacity acting as an intracellular second messenger to regulate cell survival, or as extracellular receptor ligand to stimulate chemotaxis.
Glucosylceramide has a unique and often ambiguous role in mammalian cells. Activation of glucosylceramide synthase, the enzyme that places a glucosyl moiety onto ceramide, is the first pathway‑committed step to the production of more complex glycosphingolipids such as lactosylceramide and...
Ceramide and sphingosine-1-phosphate are related sphingolipid metabolites that can be generated through a de novo biosynthetic route or derived from the recycling of membrane sphingomyelin. Both these lipids regulate cellular responses to stress, with generally opposing effects....
Ceramide synthases (CerS) are integral membrane proteins of the endoplasmic reticulum. Six mammalian CerS have been described, with each utilizing fatty acyl CoAs of relatively defined chain lengths for N‑acylation of the sphingoid long chain base. In this chapter, we review the main...
The surface of most protozoan parasites relies heavily upon lipid‑anchored molecules, to form protective barriers and play critical functions required for infectivity. Sphingolipids (SLs) play important roles through their abundance and involvement in membrane microdomain formation, as well...
Bioactive sphingolipids play key roles in the regulation of several fundamental biological processes such as proliferation, apoptosis and transformation. The recent development of genetically engineered mouse (GEM) models has enabled the study of functional roles of sphingolipids in normal...
Sphingolipids are a family of ubiquitous membrane components that exhibit multiple functional properties fundamental to cell properties. Sphingolipid transport represents a crucial aspect in the metabolism, signalling and biological role of sphingolipids. Different mechanisms of sphingolipid...
An important metabolite of ceramide is ceramide 1‑phosphate (C1P). This lipid second messenger was first demonstrated to be mitogenic for fibroblasts and macrophages and later shown to have antiapoptotic properties. C1P is also an important mediator of the inflammatory response, by...
Sphingolipid metabolism constitutes a complex pathway system that includes biosynthesis of different types of sphingosines and ceramides, the formation and recycling of complex sphingolipids and the supply of materials for remodeling. Many of the metabolites have several roles, for instance,...
Sphingosine‑1‑phosphate (S1P) is a bioactive lipid mediator with crucial roles in a wide variety of cellular functions across a broad range of organisms. Though a simple molecule in structure, S1P functions are complex. The formation of S1P is catalyzed by one of two sphingosine kinases...
Sphingolipids are well established sources of important signaling molecules. For example, ceramide (Cer) has been described as a potent inhibitor of cell growth and inducer of apoptosis. In contrast, ceramide 1‑phosphate (C1P) has been reported to have mitogenic properties and to inhibit...
Sphingolipid (SPL) metabolism (Fig. 1) serves a key role in the complex mechanisms regulating cellular stress responses to environment. Several SPL metabolites, especially ceramide (Cer), sphingosine (Sph) and sphingosine1‑phosphate (S1P) act as key bioactive molecules governing cell growth...
In the last five years tremendous progress has been made toward the understanding of the mechanisms that govern sphingomyelin (SM) synthesis in animal cells. In line with the complexity of most biological processes, also in the case of SM biosynthesis, the more we learn the more enigmatic and...
Studies using Saccharomyces cerevisiae, the common baker’s or brewer’s yeast, have progressed over the past twenty years from knowing which sphingolipids are present in cells and a basic outline of how they are made to a complete or nearly complete directory of the genes that catalyze...
Gangliosides, characteristic complex lipids present in the external leale of plasma membranes, deeply influence the organization of the membrane as a whole and the function of specific membrane associated proteins due to lipid‑lipid and lipid‑protein lateral interaction. Here we discuss...
Our knowledge of plant sphingolipid metabolism and function has significantly increased over the past years. This applies mainly to the identification and the functional characterization of genes and enzymes involved in sphingolipid biosynthesis. In addition a number of plant mutants have...
Sphingolipids constitute a class of lipids defined by their eighteen carbon amino‑alcohol backbones which are synthesized in the ER from nonsphingolipid precursors. Modification of this basic structure is what gives rise to the vast family of sphingolipids that play significant roles in...
Sphingolipid involvement in infectious disease is a new and exciting branch of research. Various microbial pathogens have been shown to synthesize their own sphingolipids and some have evolved methods to “hijack” host sphingolipids for their own use. For instance, Sphingomonas species are...
Diabetes is a debilitating chronic disease that has no cure and can only be managed by pharmaceutical or nutritional interventions. Worldwide, the incidence of diabetes and diabetic complications is dramatically increasing. This may reflect the incomplete knowledge base underlying the role of...
Evidence has consistently indicated that activation of sphingomyelinases and/or ceramide synthases and the resulting accumulation of ceramide mediate cellular responses to stressors such as Lipopolysaccharide, Interleukin 1β, Tumor Necrosis Factor α, serum deprivation, irradiation and...
Sphingolipids are important components of eukaryotic cells, many of which function as bioactive signaling molecules. As thoroughly discussed elsewhere in this volume, ceramide, central metabolite of the sphingolipid pathway, plays key roles in a variety of cellular responses. Since the...