A Novel Function of Sphingosine Kinase 2 in the Metabolism of Sphinga-4,14-Diene Lipids

Metabolites
Timothy A CouttasAnthony S Don

Abstract

The number, position, and configuration of double bonds in lipids affect membrane fluidity and the recruitment of signaling proteins. Studies on mammalian sphingolipids have focused on those with a saturated sphinganine or mono-unsaturated sphingosine long chain base. Using high-resolution liquid chromatography-tandem mass spectrometry (LC-MS/MS), we observed a marked accumulation of lipids containing a di-unsaturated sphingadiene base in the hippocampus of mice lacking the metabolic enzyme sphingosine kinase 2 (SphK2). The double bonds were localized to positions C4-C5 and C14-C15 of sphingadiene using ultraviolet photodissociation-tandem mass spectrometry (UVPD-MS/MS). Phosphorylation of sphingoid bases by sphingosine kinase 1 (SphK1) or SphK2 forms the penultimate step in the lysosomal catabolism of all sphingolipids. Both SphK1 and SphK2 phosphorylated sphinga-4,14-diene as efficiently as sphingosine, however deuterated tracer experiments in an oligodendrocyte cell line demonstrated that ceramides with a sphingosine base are more rapidly metabolized than those with a sphingadiene base. Since SphK2 is the dominant sphingosine kinase in brain, we propose that the accumulation of sphingadiene-based lipids in SphK2-deficient br...Continue Reading

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Citations

Sep 23, 2020·European Journal of Mass Spectrometry·Edgar White Buenger, Gavin E Reid
Dec 29, 2020·Cellular Signalling·Brenda Wan Shing LamDeron R Herr
Dec 3, 2020·Metabolites·Peeranat JatooratthawichotJames R Ketudat Cairns
Jun 1, 2021·Frontiers in Molecular Biosciences·Rocio Diaz EscarcegaAndrey S Tsvetkov
Oct 27, 2021·Journal of Neurochemistry·Caine C SmithGreg T Sutherland

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Methods Mentioned

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xenograft

Software Mentioned

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BioRad ImageLab

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