Thematic Review Series: Sphingolipids. Biodiversity of sphingoid bases (“sphingosines”) and related amino alcohols

Abstract

“Sphingosin” was first described by J. L. W. Thudichum in 1884 and structurally characterized as 2S,3R,4E-2-aminooctadec-4-ene-1,3-diol in 1947 by Herb Carter, who also proposed the designation of “lipides derived from sphingosine as sphingolipides.” This category of amino alcohols is now known to encompass hundreds of compounds that are referred to as sphingoid bases and sphingoid base-like compounds, which vary in chain length, number, position, and stereochemistry of double bonds, hydroxyl groups, and other functionalities. Some have especially intriguing features, such as the tail-to-tail combination of two sphingoid bases in the α,ω-sphingoids produced by sponges. Most of these compounds participate in cell structure and regulation, and some (such as the fumonisins) disrupt normal sphingolipid metabolism and cause plant and animal disease. Many of the naturally occurring and synthetic sphingoid bases are cytotoxic for cancer cells and pathogenic microorganisms or have other potentially useful bioactivities; hence, they offer promise as pharmaceutical leads. This thematic review gives an overview of the biodiversity of the backbones of sphingolipids and the broader field of naturally occurring and synthetic sphingoid base-like compounds.

Identification of small subunits of mammalian serine palmitoyltransferase that confer distinct acyl-CoA substrate specificities

“…There are numerous reports of novel LCBs (17), including some with unusual chain lengths that appear to be derived from substrates other than palmitoyl-CoA. The data presented here provide direct evidence for the presence of SPT isozymes with distinct acyl-CoA preferences.…”

“…The profiles shown are for the hLCB1-hLCB2a heterodimer, but a similar result was seen for the hLCB1-hLCB2b heterodimer. This observation, along with the presence of structurally diverse LCBs predicted to be derived from acyl-CoAs other than palmitoyl-CoA in mammalian cells (17), and our previous discovery that a viral fusion SPT prefers myristoyl-CoA as substrate (18), suggested that the different isozymes have different acyl-CoA preferences. This hypothesis was confirmed by assaying each of the SPT isozymes with a panel of acyl-CoA substrates.…”

Stereocontrolled construction of decahydro quinoline ring systems: the case of lepadin alkaloids (Review)

“…The acyclic highly unsaturated crucigasterins 9-12 and obscuraminol A 13 ( Fig. 2) are assumed to be biosynthetically derived from L-or D-alanine and the corresponding unsaturated fatty acids via a pathway similar to that of sphingosine biosynthesis [10][11][12]. It is reasonable to assume that these linear compounds as well as other as yet unisolated and unknown aminoalcohol lipids are engaged in the biosynthetic machinery that produces a set of diverse cyclic C-18 amino alcohols: the tetrahydroindane based amaminols A and B, the decahydroquinoline based lepadins 1-8, the quinolizidine based pictamine (17), and the piperidine based, plant derived prosafrinine (18) [13][14][15].…”

Glycomics meets lipidomics—associations of N-glycans with classical lipids, glycerophospholipids, and sphingolipids in three European populations

“…Sphingolipids also play essential roles as structural components of cell membranes and in cell signaling, and affect health and disease. 29,30 In the following, we present the first comprehensive glycomeand lipidome-wide association study between 46 N-glycan and 183 lipid traits in the human blood of 2041 individuals from Croatia, Sweden, and Great Britain.…”