The Extended Family of Neutral Sphingomyelinases

Abstract

The neutral sphingomyelinases (N-SMases) are considered major candidates for mediating the stress-induced production of ceramide, and N-SMase activity has been identified, characterized, and cloned from bacteria, yeast, and mammalian cells. Although the level of identity between these enzymes is low, a number of key residues thought to be involved in metal binding and catalysis are conserved. This has led to the suggestion of a common catalytic mechanism, and thus, these enzymes are considered to form an extended family of N-SMases. Despite considerable research into N-SMase activity in cell culture and various tissues, the lack, until recently, of molecular identification of specific N-SMase enzymes had precluded specific insights into the regulation, physiological, and pathological roles of these proteins. In this review, we summarize, for the first time, current knowledge of the N-SMase family, focusing on cloned members from bacteria, yeast, and mammalian cells. We also briefly consider the major future directions for N-SMase research which promises highly significant and specific insight into sphingolipid-mediated functions.

Bioactive Sphingolipids in Response to Chemotherapy: A Scope on Leukemias

“…1) [15,16]. Alternatively, ceramides can be synthesized from sphingomyelin by the catalysis of sphingomyelinase (SMase) [17,18]. According to pH optima, SMases are named as acid SMase, neutral SMase, and alkaline SMase.…”

Neutral Sphingomyelinase-3 Is a DNA Damage and Nongenotoxic Stress-Regulated Gene That Is Deregulated in Human Malignancies

“…The former occurs at the cytosolic surface of the endoplasmic reticulum (ER) and is followed by vesicular or CERT-mediated nonvesicular transport of ceramide to the Golgi apparatus (6,7). The generation of ceramide that occurs through the breakdown of sphingomyelin is facilitated by sphingomyelinases, of which there are multiple classes categorized by the pH at which they achieve optimal activity (8).…”

Ceramide-enriched microdomains in planar membranes

“…Sphingomyelinases (SMase) are a group of phospholipases that are responsible for the hydrolysis of SM to give Cer and the water-soluble phosphocholine [4,5]. In common with other phospholipases, they are active at the membrane-water interface and their activity is regulated by membrane properties, including lipid composition, phase separation, membrane curvature and defects, and dipole potential.…”

“…Additional pathways include enzymatic hydrolysis of complex glycosphingolipids or ceramide-1-phosphate and via action of ceramide synthase [2].A significant fraction of cellular ceramide is present as intermediates in the metabolism of more complex sphingolipids. The last decade has seen a major surge in interest in ceramide, largely due to its important role in cell signaling [2][3][4][5]. Ceramides are believed to function as second messengers, thus influencing a diverse range of biological processes, including apoptosis, immune response, bacterial and viral pathogenesis and cell cycle arrest.…”