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Abnormal liver phosphatidylcholine synthesis revealed in patients with acute respiratory distress syndrome

Abnormal liver phosphatidylcholine synthesis revealed in patients with acute respiratory distress syndrome
Abnormal liver phosphatidylcholine synthesis revealed in patients with acute respiratory distress syndrome
Acute respiratory distress syndrome (ARDS) is associated with a severe pro-inflammatory response; although decreased plasma cholesterol concentration has been linked to systemic inflammation, any association of phospholipid metabolic pathways with ARDS has not been characterized. Plasma phosphatidylcholine (PC), the major phospholipid of circulating lipoproteins, is synthesized in human liver by two biologically diverse pathways: the CDP:choline and phosphatidylethanolamine-N-methyltransferase (PEMT) pathways. Here, we used electrospray ionization–MS/MS both to characterize plasma PC compositions and to quantify metabolic fluxes of both pathways using stable isotopes in patients with severe ARDS and in healthy controls. Direct incorporation of methyl-D9-choline estimated CDP:choline pathway flux, while PEMT flux was determined from incorporations of one and two methyl-D3 groups derived from methyl-D9-choline. Results of MS/MS analysis showed significant alterations in plasma PC composition in patients with ARDS versus healthy controls. In particular, the increased overall methyl-D9-PC enrichment and—most important—the much lower methyl-D3-PC and methyl-D6-PC enrichments—suggest increased flux through the CDP:choline pathway and reduced flux through the PEMT pathway in ARDS. To our knowledge, this study is the first to demonstrate significant plasma PC molecular compositional changes combined with associated alterations in the dynamics of PC synthetic pathways in patients with ARDS.
mrthyl-D9-choline, Stable isotope
0022-2275
Postle, Anthony
0fa17988-b4a0-4cdc-819a-9ae15c5dad66
Dushianthan, Ahilanandan
013692a2-cf26-4278-80bd-9d8fcdb17751
Cusack, Rebecca
dfb1595f-2792-4f76-ac6d-da027cf40146
Grocott, Michael
1e87b741-513e-4a22-be13-0f7bb344e8c2
Postle, Anthony
0fa17988-b4a0-4cdc-819a-9ae15c5dad66
Dushianthan, Ahilanandan
013692a2-cf26-4278-80bd-9d8fcdb17751
Cusack, Rebecca
dfb1595f-2792-4f76-ac6d-da027cf40146
Grocott, Michael
1e87b741-513e-4a22-be13-0f7bb344e8c2

Postle, Anthony, Dushianthan, Ahilanandan, Cusack, Rebecca and Grocott, Michael (2018) Abnormal liver phosphatidylcholine synthesis revealed in patients with acute respiratory distress syndrome. Journal of Lipid Research, [JLR_P085050]. (doi:10.1194/jlr.P085050).

Record type: Article

Abstract

Acute respiratory distress syndrome (ARDS) is associated with a severe pro-inflammatory response; although decreased plasma cholesterol concentration has been linked to systemic inflammation, any association of phospholipid metabolic pathways with ARDS has not been characterized. Plasma phosphatidylcholine (PC), the major phospholipid of circulating lipoproteins, is synthesized in human liver by two biologically diverse pathways: the CDP:choline and phosphatidylethanolamine-N-methyltransferase (PEMT) pathways. Here, we used electrospray ionization–MS/MS both to characterize plasma PC compositions and to quantify metabolic fluxes of both pathways using stable isotopes in patients with severe ARDS and in healthy controls. Direct incorporation of methyl-D9-choline estimated CDP:choline pathway flux, while PEMT flux was determined from incorporations of one and two methyl-D3 groups derived from methyl-D9-choline. Results of MS/MS analysis showed significant alterations in plasma PC composition in patients with ARDS versus healthy controls. In particular, the increased overall methyl-D9-PC enrichment and—most important—the much lower methyl-D3-PC and methyl-D6-PC enrichments—suggest increased flux through the CDP:choline pathway and reduced flux through the PEMT pathway in ARDS. To our knowledge, this study is the first to demonstrate significant plasma PC molecular compositional changes combined with associated alterations in the dynamics of PC synthetic pathways in patients with ARDS.

Text
J. Lipid Res.-2018-Dushianthan-jlr.P085050 - Accepted Manuscript
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More information

Accepted/In Press date: 26 April 2018
e-pub ahead of print date: 1 May 2018
Published date: 4 May 2018
Keywords: mrthyl-D9-choline, Stable isotope

Identifiers

Local EPrints ID: 420879
URI: http://eprints.soton.ac.uk/id/eprint/420879
ISSN: 0022-2275
PURE UUID: 4885f6f6-4da3-4303-b3d4-6345e2473cf4
ORCID for Anthony Postle: ORCID iD orcid.org/0000-0001-7361-0756
ORCID for Ahilanandan Dushianthan: ORCID iD orcid.org/0000-0002-0165-3359
ORCID for Michael Grocott: ORCID iD orcid.org/0000-0002-9484-7581

Catalogue record

Date deposited: 17 May 2018 16:30
Last modified: 22 Nov 2021 06:23

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Contributors

Author: Anthony Postle ORCID iD
Author: Ahilanandan Dushianthan ORCID iD
Author: Rebecca Cusack
Author: Michael Grocott ORCID iD

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