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

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 cytidine diphosphocholine (CDP):choline and phosphatidylethanolamine N-methyltransferase (PEMT) pathways. Here, we used ESI-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. The 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 importantly, 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.

journal_name

J Lipid Res

authors

Dushianthan A,Cusack R,Grocott MPW,Postle AD

doi

10.1194/jlr.P085050

subject

Has Abstract

pub_date

2018-06-01 00:00:00

pages

1034-1045

issue

6

eissn

0022-2275

issn

1539-7262

pii

jlr.P085050

journal_volume

59

pub_type

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