N-acyl-O-phosphocholineserines: Structures of a novel class of lipids that are biomarkers for Niemann-Pick C1 disease

Rohini Sidhu, Yawo Mondjinou, Mingxing Qian, Haowei Song, Arun Babu Kumar, Xinying Hong, Fong Fu Hsu, Dennis J. Dietzen, Nicole M. Yanjanin, Forbes D. Porter, Elizabeth Berry-Kravis, Charles H. Vite, Michael H. Gelb, Jean E. Schaffer, Daniel S. Ory, Xuntian Jiang

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Niemann-Pick disease type C1 (NPC1) is a fatal, neurodegenerative, cholesterol storage disorder. With new therapeutics in clinical trials, there is an urgency to improve diagnostics and monitor therapeutic efficacy with biomarkers. In this study, we sought to define the structure of an unknown lipid biomarker for NPC1 with [M + H]+ ion at m/z 509.3351, previously designated as lysoSM-509. The structure of N-palmitoyl-O-phosphocholineserine (PPCS) was proposed for the lipid biomarker based on the results from mass spectrometric analyses and chemical derivatizations. As no commercial standard is available, authentic PPCS was chemically synthesized, and the structure was confirmed by comparison of endogenous and synthetic compounds as well as their derivatives using liquid chromatographytandem mass spectrometry (LC-MS/MS). PPCS is the most abundant species among N-acyl-O-phosphocholineserines (APCS), a class of lipids that have not been previously detected in biological samples. Further analysis demonstrated that all APCS species with acyl groups ranging from C14 to C24 were elevated in NPC1 plasma. PPCS is also elevated in both central and peripheral tissues of the NPC1 cat model. Identification of APCS structures provide an opportunity for broader exploration of the roles of these novel lipids in NPC1 disease pathology and diagnosis.-Sidhu, R., Y. Mondjinou, M. Qian, H. Song, A. B. Kumar, X. Hong, F-F. Hsu, D. J. Dietzen, N. M. Yanjanin, F. D. Porter, E. Berry- Kravis, C. H. Vite, M. H. Gelb, J. E. Schaffer, D. S. Ory, and X. Jiang. N-acyl-O-phosphocholineserines: structures of a novel class of lipids that are biomarkers for Niemann-Pick C1 disease. J. Lipid Res. 2019. 60: 1410-1424.

Original languageEnglish
Pages (from-to)1410-1424
Number of pages15
JournalJournal of lipid research
Volume60
Issue number8
DOIs
StatePublished - 2019

Keywords

  • LysoSM-509
  • Mass spectrometry
  • Niemann-Pick disease type C
  • Structural identification

Fingerprint

Dive into the research topics of 'N-acyl-O-phosphocholineserines: Structures of a novel class of lipids that are biomarkers for Niemann-Pick C1 disease'. Together they form a unique fingerprint.

Cite this