Mysterious sphingolipids: metabolic interrelationships at the center of pathophysiology

Abstract

Metabolic pathways are complex and intertwined. Deficiencies in one or more enzymes in a given pathway are directly linked with genetic diseases, most of them having devastating manifestations. The metabolic pathways undertaken by sphingolipids are diverse and elaborate with ceramide species serving as the hubs of sphingolipid intermediary metabolism and function. Sphingolipids are bioactive lipids that serve a multitude of cellular functions. Being pleiotropic in function, deficiency or overproduction of certain sphingolipids is associated with many genetic and chronic diseases. In this up-to-date review article, we strive to gather recent scientific evidence about sphingolipid metabolism, its enzymes, and regulation. We shed light on the importance of sphingolipid metabolism in a variety of genetic diseases and in nervous and immune system ailments. This is a comprehensive review of the state of the field of sphingolipid biochemistry.

Diagnostic Value of Menstrual Blood Lipidomics in Endometriosis: A Pilot Study

“…The balance between sphingomyelins and ceramides, which are key components of cell membranes and signaling molecules, is critical for cellular function and homeostasis [101]. Sphingomyelins are synthesized from phosphatidylcholines and ceramides through the action of sphingomyelin synthase, primarily in the plasma and Golgi membranes of cells.…”

Editorial: Sphingolipids in infections, diseases, and disorders

“…S1P is one of the products of sphingolipid metabolic pathways. This de novo synthesis pathway has been extensively reviewed by Jamjoum et al The authors summarized that this pathway occurs on the cytosolic surface of the endoplasmic reticulum and initiates with the condensation of L-serine and palmitoyl-CoA to produce a series of sphingolipids metabolites such as sphinganine, ceramide, and sphingosine (5). S1P biogenesis requires a sphingosine kinase that phosphorylates sphingosine into S1P.…”

Peripheral Upregulation of Parkinson’s Disease-Associated Genes Encoding α-Synuclein, β-Glucocerebrosidase, and Ceramide Glucosyltransferase in Major Depression

“…PD is also intricately connected to sphingolipid metabolism. Abundantly present in the eukaryotic cell membrane, sphingolipids also play a crucial role in diverse cellular processes, including cell differentiation, signal transduction, and apoptosis [ 21 ]. Reduced activity of acid sphingomyelinase, which catalyzes the hydrolysis of sphingomyelin to ceramide, has been linked to an earlier onset of PD [ 22 ].…”