Abstract
Sphingolipids are a specialized group of lipids essential to the composition of the plasma membrane of many cell types; however, they are primarily localized within the nervous system. The amphipathic properties of sphingolipids enable their participation in a variety of intricate metabolic pathways. Sphingoid bases are the building blocks for all sphingolipid derivatives, comprising a complex class of lipids. The biosynthesis and catabolism of these lipids play an integral role in small- and large-scale body functions, including participation in membrane domains and signalling; cell proliferation, death, migration, and invasiveness; inflammation; and central nervous system development. Recently, sphingolipids have become the focus of several fields of research in the medical and biological sciences, as these bioactive lipids have been identified as potent signalling and messenger molecules. Sphingolipids are now being exploited as therapeutic targets for several pathologies. Here we present a comprehensive review of the structure and metabolism of sphingolipids and their many functional roles within the cell. In addition, we highlight the role of sphingolipids in several pathologies, including inflammatory disease, cystic fibrosis, cancer, Alzheimer’s and Parkinson’s disease, and lysosomal storage disorders.
Highlights
Sphingolipids are a set of structurally diverse lipids originally named after the sphinx in the 1870s, due to their enigmatic structure [1]
Phytosphingosine ((2S,3S,4R)-2-aminooctadecane-1,3,4-triol) (PHS) is another mammalian sphingoid base which slightly differs in structure, due to an extra hydroxyl group located at C4, instead of the trans-double bond between C4 and C5 seen in sphingosine
Understanding the mechanisms behind sphingolipid structures, biosynthesis, and catabolism is essential in appreciating the fundamental role they play in small- and largescale functions
Summary
Sphingolipid Metabolism and Implications of Disruption in Sphingolipid Homeostasis. The amphipathic properties of sphingolipids enable their participation in a variety of intricate metabolic pathways. The biosynthesis and catabolism of these lipids play an integral role in small- and large-scale body functions, including participation in membrane domains and signalling; cell proliferation, death, migration, and invasiveness; inflammation; and central nervous system development. We present a comprehensive review of the structure and metabolism of sphingolipids and their many functional roles within the cell. We highlight the role of sphingolipids in several pathologies, including inflammatory disease, cystic fibrosis, cancer, Alzheimer’s and Parkinson’s disease, and lysosomal storage disorders. Comprehensive Review: Sphingolipid Metabolism and Keywords: sphingolipid; sphingosine-1-phosphate; ceramide; glycosphingolipids; neurodegeneration; inflammation; lysosomal storage disorder; biosynthesis; glycosyl hydrolase.
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