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Analysis of the regulation of surfactant phosphatidylcholine metabolism using stable isotopes

Analysis of the regulation of surfactant phosphatidylcholine metabolism using stable isotopes
Analysis of the regulation of surfactant phosphatidylcholine metabolism using stable isotopes
The pathways and mechanisms that regulate pulmonary surfactant synthesis, processing, secretion and catabolism have been extensively characterised using classical biochemical and analytical approaches. These have constructed a model, largely in experimental animals, for surfactant phospholipid metabolism in the alveolar epithelial cell whereby phospholipid synthesised on the endoplasmic reticulum is selectively transported to lamellar body storage vesicles, where it is subsequently processed before secretion into the alveolus. Surfactant phospholipid is a complex mixture of individual molecular species defined by the combination of esterified fatty acid groups and a comprehensive description of surfactant phospholipid metabolism requires consideration of the interactions between such molecular species. However, until recently, lipid analytical techniques have not kept pace with the considerable advances in understanding of the enzymology and molecular biology of surfactant metabolism. Refinements in electrospray ionisation mass spectrometry (ESI-MS) can now provide very sensitive platforms for the rapid characterisation of surfactant phospholipid composition in molecular detail. The combination of ESI-MS and administration of phospholipid substrates labelled with stable isotopes extends this analytical approach to the quantification of synthesis and turnover of individual molecular species of surfactant phospholipid. As this methodology does not involve radioactivity, it is ideally suited to application in clinical studies. This review will provide an overview of the metabolic processes that regulate the molecular specificity of surfactant phosphatidylcholine together with examples of how the application of stable isotope technologies in vivo has, for the first time, begun to explore regulation of the molecular specificity of surfactant synthesis in human subjects.
176-183
Brandsma, Joost
b4c553dc-9444-466a-b352-25fd8fa25ee7
Postle, Anthony D.
0fa17988-b4a0-4cdc-819a-9ae15c5dad66
Brandsma, Joost
b4c553dc-9444-466a-b352-25fd8fa25ee7
Postle, Anthony D.
0fa17988-b4a0-4cdc-819a-9ae15c5dad66

Brandsma, Joost and Postle, Anthony D. (2017) Analysis of the regulation of surfactant phosphatidylcholine metabolism using stable isotopes. Annals of Anatomy, 211, 176-183. (doi:10.1016/j.aanat.2017.02.008).

Record type: Review

Abstract

The pathways and mechanisms that regulate pulmonary surfactant synthesis, processing, secretion and catabolism have been extensively characterised using classical biochemical and analytical approaches. These have constructed a model, largely in experimental animals, for surfactant phospholipid metabolism in the alveolar epithelial cell whereby phospholipid synthesised on the endoplasmic reticulum is selectively transported to lamellar body storage vesicles, where it is subsequently processed before secretion into the alveolus. Surfactant phospholipid is a complex mixture of individual molecular species defined by the combination of esterified fatty acid groups and a comprehensive description of surfactant phospholipid metabolism requires consideration of the interactions between such molecular species. However, until recently, lipid analytical techniques have not kept pace with the considerable advances in understanding of the enzymology and molecular biology of surfactant metabolism. Refinements in electrospray ionisation mass spectrometry (ESI-MS) can now provide very sensitive platforms for the rapid characterisation of surfactant phospholipid composition in molecular detail. The combination of ESI-MS and administration of phospholipid substrates labelled with stable isotopes extends this analytical approach to the quantification of synthesis and turnover of individual molecular species of surfactant phospholipid. As this methodology does not involve radioactivity, it is ideally suited to application in clinical studies. This review will provide an overview of the metabolic processes that regulate the molecular specificity of surfactant phosphatidylcholine together with examples of how the application of stable isotope technologies in vivo has, for the first time, begun to explore regulation of the molecular specificity of surfactant synthesis in human subjects.

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Surfactant PC metabolism stable isotope V2 - Accepted Manuscript
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Accepted/In Press date: 28 February 2017
e-pub ahead of print date: 25 March 2017
Published date: 25 March 2017

Identifiers

Local EPrints ID: 413547
URI: https://eprints.soton.ac.uk/id/eprint/413547
PURE UUID: 7d5d4035-4a8c-40cd-8e18-6060a38d333d
ORCID for Anthony D. Postle: ORCID iD orcid.org/0000-0001-7361-0756

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Date deposited: 25 Aug 2017 16:31
Last modified: 15 Aug 2019 04:54

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