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

1
Centenary Institute, The University of Sydney, Camperdown, NSW 2006, Australia
2
Department of Biochemistry and Molecular Biology, The University of Melbourne, Melbourne, VIC 3010, Australia
3
School of Chemistry, University of Melbourne, Parkville, VIC 3010, Australia
4
Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, VIC 3010, Australia
5
NHMRC Clinical Trials Centre, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2006, Australia
*
Author to whom correspondence should be addressed.
Metabolites 2020, 10(6), 236; https://doi.org/10.3390/metabo10060236
Received: 26 March 2020 / Revised: 27 May 2020 / Accepted: 4 June 2020 / Published: 8 June 2020
(This article belongs to the Section Lipid Metabolism)
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. View Full-Text
Keywords: sphingolipids; sphingadiene; sphingosine; mass spectrometry; sphingosine kinase; brain lipids; ceramide; sphingosine kinase 2; SphK2 sphingolipids; sphingadiene; sphingosine; mass spectrometry; sphingosine kinase; brain lipids; ceramide; sphingosine kinase 2; SphK2
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MDPI and ACS Style

Couttas, T.A.; Rustam, Y.H.; Song, H.; Qi, Y.; Teo, J.D.; Chen, J.; Reid, G.E.; Don, A.S. A Novel Function of Sphingosine Kinase 2 in the Metabolism of Sphinga-4,14-Diene Lipids. Metabolites 2020, 10, 236. https://doi.org/10.3390/metabo10060236

AMA Style

Couttas TA, Rustam YH, Song H, Qi Y, Teo JD, Chen J, Reid GE, Don AS. A Novel Function of Sphingosine Kinase 2 in the Metabolism of Sphinga-4,14-Diene Lipids. Metabolites. 2020; 10(6):236. https://doi.org/10.3390/metabo10060236

Chicago/Turabian Style

Couttas, Timothy A., Yepy H. Rustam, Huitong Song, Yanfei Qi, Jonathan D. Teo, Jinbiao Chen, Gavin E. Reid, and Anthony S. Don. 2020. "A Novel Function of Sphingosine Kinase 2 in the Metabolism of Sphinga-4,14-Diene Lipids" Metabolites 10, no. 6: 236. https://doi.org/10.3390/metabo10060236

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