Maekawa, M;
Jinnoh, I;
Matsumoto, Y;
Narita, A;
Mashima, R;
Takahashi, H;
Iwahori, A;
... Mano, N; + view all
(2019)
Structural Determination of Lysosphingomyelin-509 and Discovery of Novel Class Lipids from Patients with Niemann–Pick Disease Type C.
International Journal of Molecular Sciences
, 20
(20)
, Article 5018. 10.3390/ijms20205018.
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Abstract
Niemann–Pick disease type C (NPC) is an autosomal recessive disorder caused by the mutation of cholesterol-transporting proteins. In addition, early treatment is important for good prognosis of this disease because of the progressive neurodegeneration. However, the diagnosis of this disease is difficult due to a variety of clinical spectrum. Lysosphingomyelin-509, which is one of the most useful biomarkers for NPC, was applied for the rapid and easy detection of NPC. The fact that its chemical structure was unknown until recently implicates the unrevealed pathophysiology and molecular mechanisms of NPC. In this study, we aimed to elucidate the structure of lysosphingomyelin-509 by various mass spectrometric techniques. As our identification strategy, we adopted analytical and organic chemistry approaches to the serum of patients with NPC. Chemical derivatization and hydrogen abstraction dissociation–tandem mass spectrometry were used for the determination of function groups and partial structure, respectively. As a result, we revealed the exact structure of lysosphingomyelin-509 as N-acylated and O-phosphocholine adducted serine. Additionally, we found that a group of metabolites with N-acyl groups were increased considerably in the serum/plasma of patients with NPC as compared to that of other groups using targeted lipidomics analysis. Our techniques were useful for the identification of lysosphingomyelin-509.
| Type: | Article |
|---|---|
| Title: | Structural Determination of Lysosphingomyelin-509 and Discovery of Novel Class Lipids from Patients with Niemann–Pick Disease Type C |
| Location: | Switzerland |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3390/ijms20205018 |
| Publisher version: | https://doi.org/10.3390/ijms20205018 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| Keywords: | HAD–MS/MS, LC–MS/MS, N-acyl-phospholipids, Niemann–Pick disease type C, biomarkers, chemical derivatization, chemical diagnosis, identification, lysosphingomyelin-509, structural determination |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Genetics and Genomic Medicine Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10085736 |
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