期刊
JOURNAL OF LIPID RESEARCH
卷 57, 期 7, 页码 1194-1203出版社
ELSEVIER
DOI: 10.1194/jlr.M067033
关键词
deoxysphingolipids; double bond position; dimethyl disulfide adducts; mass spectrometry; differential-mobility spectrometry; ozone-induced dissociation; structural isomers
资金
- European Commission [305707]
- Swiss National Science Foundation (SNF) [31003A_153390/1]
- Hurka Foundation
- Novartis Foundation
- Rare Disease Initiative Zurich (radiz, Clinical Research Priority Program for Rare Diseases, University of Zurich)
- Australian Research Council [DP150101715, LP110200648]
- Australian Research Council [LP110200648] Funding Source: Australian Research Council
The 1-deoxysphingolipids (1-deoxySLs) are formed by an alternate substrate usage of the enzyme, serine-palmitoyltransferase, and are devoid of the C1-OH-group present in canonical sphingolipids. Pathologically elevated 1-deoxySL levels are associated with the rare inherited neuropathy, HSAN1, and diabetes type 2 and might contribute to. cell failure and the diabetic sensory neuropathy. In analogy to canonical sphingolipids, it was assumed that 1-deoxySLs also bear a (4E) double bond, which is normally introduced by sphingolipid delta(4)-desaturase 1. This, however, was never confirmed. We therefore supplemented HEK293 cells with isotope-labeled D-3-1-deoxysphinganine and compared the downstream formed D-3-1-deoxysphingosine (1-deoxySO) to a commercial synthetic SPH m18:1(4E)(3OH) standard. Both compounds showed the same m/z, but differed in their RPLC retention time and atmospheric pressure chemical ionization in-source fragmentation, suggesting that the two compounds are structural isomers. Using dimethyl disulfide derivatization followed by MS2 as well as differential-mobility spectrometry combined with ozone-induced dissociation MS, we identified the carbon-carbon double bond in native 1-deoxySO to be located at the (Delta 14) position. Comparing the chromatographic behavior of native 1-deoxySO to chemically synthesized SPH m18: 1(14Z) and (14E) stereoisomers assigned the native compound to be SPH m18: 1(14Z). This indicates that 1-deoxySLs are metabolized differently than canonical sphingolipids.-Steiner, R., E. M. Saied, A. Othman, C. Arenz, A. T. Maccarone, B. L. J. Poad, S. J. Blanksby, A. von Eckardstein, and T. Hornemann. Elucidating the chemical structure of native 1-deoxysphingosine.
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