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

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

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Item Type: Article
Status: Published
Official URL: https://doi.org/10.3390/metabo10060236
Journal or Publication Title: Metabolites
Volume: 10
Number: 6
Page Range: p. 236
Date: 2020
Divisions: Lipid Cell Biology
Depositing User: General Admin
Identification Number: 10.3390/metabo10060236
ISSN: 2218-1989
Date Deposited: 04 Jan 2021 00:05

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 brains results from the slower catabolism of these lipids, combined with a bottleneck in the catabolic pathway created by the absence of SphK2. We have therefore uncovered a previously unappreciated role for SphK2 in lipid quality control.

Couttas, Timothy Andrew
Rustam, Yepy Hardi
Song, Huitong
Qi, Yanfei
Teo, Jonathan David
Chen, Jinbiao
Reid, Gavin Edmund
Don, Anthony Simon
Last Modified: 08 Apr 2021 05:23
URI: https://eprints.centenary.org.au/id/eprint/820

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