title: Ceramides and other bioactive sphingolipid backbones in health and disease: lipidomic analysis, metabolism and roles in membrane structure, dynamics, signaling and autophagy.
abstract: Sphingolipids are comprised of a backbone sphingoid base that may be phosphorylated, acylated, glycosylated, bridged to various headgroups through phosphodiester linkages, or otherwise modified. Organisms usually contain large numbers of sphingolipid subspecies and knowledge about the types and amounts is imperative because they influence membrane structure, interactions with the extracellular matrix and neighboring cells, vesicular traffic and the formation of specialized structures such as phagosomes and autophagosomes, as well as participate in intracellular and extracellular signaling. Fortunately, "sphingolipidomic" analysis is becoming feasible (at least for important subsets such as all of the backbone "signaling" subspecies: ceramides, ceramide 1-phosphates, sphingoid bases, sphingoid base 1-phosphates, inter alia) using mass spectrometry, and these profiles are revealing many surprises, such as that under certain conditions cells contain significant amounts of "unusual" species: N-mono-, di-, and tri-methyl-sphingoid bases (including N,N-dimethylsphingosine); 3-ketodihydroceramides; N-acetyl-sphingoid bases (C2-ceramides); and dihydroceramides, in the latter case, in very high proportions when cells are treated with the anticancer drug fenretinide (4-hydroxyphenylretinamide). The elevation of DHceramides by fenretinide is befuddling because the 4,5-trans-double bond of ceramide has been thought to be required for biological activity; however, DHceramides induce autophagy and may be important in the regulation of this important cellular process. The complexity of the sphingolipidome is hard to imagine, but one hopes that, when partnered with other systems biology approaches, the causes and consequences of the complexity will explain how these intriguing compounds are involved in almost every aspect of cell behavior and the malfunctions of many diseases.
authors.affiliation: School of Biology, Chemistry and Biochemistry, Petit Institute of Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332-0230, USA.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Zheng
authors.forename: Jessica
authors.initials: J
authors.lastname: Kollmeyer
authors.forename: Holly
authors.initials: H
authors.lastname: Symolon
authors.forename: Amin
authors.initials: A
authors.lastname: Momin
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Munter
authors.forename: Elaine
authors.initials: E
authors.lastname: Wang
authors.forename: Samuel
authors.initials: S
authors.lastname: Kelly
authors.forename: Jeremy C
authors.initials: JC
authors.lastname: Allegood
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Qiong
authors.initials: Q
authors.lastname: Peng
authors.forename: Harsha
authors.initials: H
authors.lastname: Ramaraju
authors.forename: M Cameron
authors.initials: MC
authors.lastname: Sullards
authors.forename: Myles
authors.initials: M
authors.lastname: Cabot
authors.forename: Alfred H
authors.initials: AH
authors.lastname: Merrill
mesh_terms: D001343:Autophagy; D002518:Ceramides / Q000502:physiology*; D004194:Disease; D006801:Humans; D006868:Hydrolysis; D015394:Molecular Structure; D015398:Signal Transduction; D013107:Sphingolipids / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D013347:Subcellular Fractions / Q000378:metabolism
chemical_list: D002518:Ceramides; D013107:Sphingolipids