The metabolism and function of sphingolipids and glycosphingolipids

Abstract

Sphingolipids and glycosphingolipids are emerging as major players in many facets of cell physiology and pathophysiology. We now present an overview of sphingolipid biochemistry and physiology, followed by a brief presentation of recent advances in translational research related to sphingolipids. In discussing sphingolipid biochemistry, we focus on the structure of sphingolipids, and their biosynthetic pathways--the recent identification of most of the enzymes in this pathway has led to significant advances and better characterization of a number of the biosynthetic steps, and the relationship between them. We then discuss some roles of sphingolipids in cell physiology, particularly those of ceramide and sphingosine-1-phosphate, and mention current views about how these lipids act in signal transduction pathways. We end with a discussion of sphingolipids and glycosphingolipids in the etiology and pathology of a number of diseases, such as cancer, immunity, cystic fibrosis, emphysema, diabetes, and sepsis, areas in which sphingolipids are beginning to take a central position, even though many of the details remain to be elucidated.

Host Cell P-glycoprotein Is Essential for Cholesterol Uptake and Replication of Toxoplasma gondii

“…Given the crucial role of ceramide in cell physiology both as a precursor of complex sphingolipids and as a second messenger regulating a variety of cellular processes (reviewed in Ref. 29), we analyzed whether neosynthesis of this lipid was up-regulated in T. gondii grown in DKO host cells. Metabolic labeling of extracellular parasites revealed that ceramide synthesis was higher in T. gondii isolated from DKO host cells after four lysis passages than in WT cells (Fig.…”

Large-scaled human serum sphingolipid profiling by using reversed-phase liquid chromatography coupled with dynamic multiple reaction monitoring of mass spectrometry: Method development and application in hepatocellular carcinoma

“…Beyond serving as structural component of lipid rafts ensuring cellular membrane integrity [3], sphigolipids are emerging as key bioactive molecules, playing pivotal roles in signaling and a plenty of biological events, e.g. growth, proliferation, survival, apoptosis and death [4,5]. Under the normal circumstance, sphigolipid homeostasis is precisely regulated via a complicated metabolic network including de novo biosynthesis, turnover and catabolism [6].…”

Ablation of Ceramide Synthase 2 Causes Chronic Oxidative Stress Due to Disruption of the Mitochondrial Respiratory Chain

“…Ceramide, a key intermediate in the pathway of sphingolipid (SL) 5 metabolism (1)(2)(3)(4), is synthesized by a family of ceramide synthases (CerS), each of which adds acyl chains of defined length to the sphingoid long chain base (5,6). Major advances concerning the biological role of the CerS and of the ceramide species that they generate have been obtained from studies using genetically modified mice in which one of the CerS genes has been ablated.…”