Sphingolipids as Signaling and Regulatory Molecules

Abstract 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 membrane biology and provide many bioactive metabolites that regulate cell function. Despite […]

An Overview of Sphingolipid Metabolism: From Synthesis to Breakdown Part 2

Ceramide Kinase and Ceramide-1-Phosphate Although ceramide is primarily converted into more complex sphingolipids in the Golgi, ceramide can also be phosphorylated to produce ceramide-1-phosphate (C1P). C1P is produced in the trans-Golgi and potentially the plasma membrane, by ceramide kinase (CERK). CERK, a member of the DAG kinase family, was originally identified based on its homology […]

Sphingolipid Transport Part 1

Abstract 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, signaling and biological role of sphingolipids. Different mechanisms of sphingolipid movements contribute to their selective localization in different membranes but also in different portions and sides of the […]

Sphingolipid Transport Part 2

Intermembrane Sphingolipid Transport Sphingolipids are unevenly distributed in different subcellular membranes and, as described above, in the single membrane as well. The heterogeneous distribution of complex sphingolipids in the different subcellular membranes, varying from 3-4% of total membrane lipids in the ER to about 20 mol % in the PM and lysosomes,84 strongly reflects the […]

Sphingolipid Analysis by High Performance Liquid Chromatography-Tandem Mass Spectrometry (HPLC-MS/MS) Part 1

Abstract 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 and programmed cell death (Fig. 2). Perturbations in sphingolipids of one type may enhance or interfere […]

Sphingolipid Analysis by High Performance Liquid Chromatography-Tandem Mass Spectrometry (HPLC-MS/MS) Part 2

Analysis of Intact Sphingolipids by Mass Spectrometry Mass spectrometry is a powerful detection technique that enables separation and characterization ofcompounds according to their mass-to-charge ratio (m/z). Its essential components include a sample inlet, ion source, mass analyzer, detector and data handling system. The combination of sensitivity, selectivity, speed and ability to provide invaluable structural information […]

Ceramide Synthases: Roles in Cell Physiology and Signaling (Sphingolipids)

Abstract 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 ^-acylation of the sphingoid long chain base. In this topic, we review the main functional features of the CerS proteins, discuss their fatty acid specificity, […]

Tales and Mysteries of the Enigmatic Sphingomyelin Synthase Family (Sphingolipids)

Abstract 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 finely tuned the system appears. Therefore […]

Ceramide in Stress Response (Sphingolipids) Part 1

Abstract 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 1P, tumor necrosis factor a, serum deprivation, irradiation and various antitumor treatments. Recent studies had identified the genes encoding most of the enzymes responsible for the generation of […]

Ceramide in Stress Response (Sphingolipids) Part 2

Mechanisms for Ceramide Generation during Stress Ceramide does not move spontaneously between cellular membranes and is transported either during normal membrane biogenesis, or with the aid of CERT, a protein that transfers ceramides synthesized at the endoplasmic reticulum to the Golgi apparatus. This insolubility of ceramide suggests that once generated, ceramide is likely to remain […]