TY - JOUR
T1 - N-acyl-O-phosphocholineserines
T2 - Structures of a novel class of lipids that are biomarkers for Niemann-Pick C1 disease
AU - Sidhu, Rohini
AU - Mondjinou, Yawo
AU - Qian, Mingxing
AU - Song, Haowei
AU - Kumar, Arun Babu
AU - Hong, Xinying
AU - Hsu, Fong Fu
AU - Dietzen, Dennis J.
AU - Yanjanin, Nicole M.
AU - Porter, Forbes D.
AU - Berry-Kravis, Elizabeth
AU - Vite, Charles H.
AU - Gelb, Michael H.
AU - Schaffer, Jean E.
AU - Ory, Daniel S.
AU - Jiang, Xuntian
N1 - Publisher Copyright:
Copyright © 2019 Sidhu et al.
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
KW - LysoSM-509
KW - Mass spectrometry
KW - Niemann-Pick disease type C
KW - Structural identification
UR - http://www.scopus.com/inward/record.url?scp=85071055471&partnerID=8YFLogxK
U2 - 10.1194/jlr.RA119000157
DO - 10.1194/jlr.RA119000157
M3 - Article
C2 - 31201291
AN - SCOPUS:85071055471
SN - 0022-2275
VL - 60
SP - 1410
EP - 1424
JO - Journal of lipid research
JF - Journal of lipid research
IS - 8
ER -