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Mass spectrometric analysis of surfactant metabolism in human volunteers using deuteriated choline

Mass spectrometric analysis of surfactant metabolism in human volunteers using deuteriated choline
Mass spectrometric analysis of surfactant metabolism in human volunteers using deuteriated choline
urfactant reduces surface tension at pulmonary air–liquid interfaces. Although its major component is dipalmitoyl–phosphatidylcholine (PC16:0/16:0), other PC species, principally palmitoylmyristoyl–PC, palmitoylpalmitoleoyl–PC, and palmitoyloleoyl–PC, are integral components of surfactant. The composition and metabolism of PC species depend on pulmonary development, respiratory rate, and pathologic alterations, which have largely been investigated in animals using radiolabeled precursors. Recent advances in mass spectrometry and availability of precursors carrying stable isotopes make metabolic experiments in human subjects ethically feasible. We introduce a technique to quantify surfactant PC synthesis in vivo using deuteriated choline coupled with electrospray ionization tandem mass spectrometry. Endogenous PC from induced sputa of healthy volunteers comprised 54.0 ± 1.5% PC16:0/16:0, 9.7 ± 0.7% palmitoylmyristoyl–PC, 10.0 ± 1.0% palmitoylpalmitoleoyl–PC, and 13.1 ± 0.3% palmitoyloleoyl–PC. Infusion of deuteriated choline chloride (3.6 mg/kg body weight) over 3 hours resulted in linear incorporation into PC over 30 hours. After a plateau of 0.61 ± 0.04% labeled PC between 30 and 48 hours, incorporation decreased to 0.30 ± 0.02% within 7 days. Compared with native PC, fractional label was initially lower for PC16:0/16:0 (31.9 ± 8.3%) but was higher for palmitoyloleoyl–PC (21.0 ± 1.2%), and equilibrium was achieved after only 48 hours. We conclude that infusion of deuteriated choline and electrospray ionization tandem mass spectrometry is useful to investigate surfactant metabolism in humans in vivo.
human surfactant metabolism, induced sputum, stable isotopes, mass spectrometry, phosphatidylcholine molecular species
1073-449X
54-58
Bernhard, Wolfgang
a93ed9d7-1f32-42e8-bf9c-c9f0f14ad2a2
Pynn, Christopher J.
fc15bc36-c549-4cc8-9482-5b5459ac12e5
Jaworski, Andreas
ee98f487-ed98-4ef8-b833-a0b0b7956ab7
Rau, Gunnar A.
025ddf77-417e-47e8-901f-0bf239f291a9
Hohlfeld, Jens M.
93e4d137-a7b0-43f4-85cd-bfc1e9714407
Freihorst, Joachim
e2d603aa-3710-4865-84b6-3865d48d145d
Poets, Christian F.
611dc9d4-8d1b-4f68-8d82-c18e13fb92ba
Stoll, Dieter
17226e0f-58b9-4e6b-a196-4a12dd531c22
Postle, Anthony D.
0fa17988-b4a0-4cdc-819a-9ae15c5dad66
Bernhard, Wolfgang
a93ed9d7-1f32-42e8-bf9c-c9f0f14ad2a2
Pynn, Christopher J.
fc15bc36-c549-4cc8-9482-5b5459ac12e5
Jaworski, Andreas
ee98f487-ed98-4ef8-b833-a0b0b7956ab7
Rau, Gunnar A.
025ddf77-417e-47e8-901f-0bf239f291a9
Hohlfeld, Jens M.
93e4d137-a7b0-43f4-85cd-bfc1e9714407
Freihorst, Joachim
e2d603aa-3710-4865-84b6-3865d48d145d
Poets, Christian F.
611dc9d4-8d1b-4f68-8d82-c18e13fb92ba
Stoll, Dieter
17226e0f-58b9-4e6b-a196-4a12dd531c22
Postle, Anthony D.
0fa17988-b4a0-4cdc-819a-9ae15c5dad66

Bernhard, Wolfgang, Pynn, Christopher J., Jaworski, Andreas, Rau, Gunnar A., Hohlfeld, Jens M., Freihorst, Joachim, Poets, Christian F., Stoll, Dieter and Postle, Anthony D. (2004) Mass spectrometric analysis of surfactant metabolism in human volunteers using deuteriated choline. American Journal of Respiratory and Critical Care Medicine, 170 (1), 54-58. (doi:10.1164/rccm.200401-089OC).

Record type: Article

Abstract

urfactant reduces surface tension at pulmonary air–liquid interfaces. Although its major component is dipalmitoyl–phosphatidylcholine (PC16:0/16:0), other PC species, principally palmitoylmyristoyl–PC, palmitoylpalmitoleoyl–PC, and palmitoyloleoyl–PC, are integral components of surfactant. The composition and metabolism of PC species depend on pulmonary development, respiratory rate, and pathologic alterations, which have largely been investigated in animals using radiolabeled precursors. Recent advances in mass spectrometry and availability of precursors carrying stable isotopes make metabolic experiments in human subjects ethically feasible. We introduce a technique to quantify surfactant PC synthesis in vivo using deuteriated choline coupled with electrospray ionization tandem mass spectrometry. Endogenous PC from induced sputa of healthy volunteers comprised 54.0 ± 1.5% PC16:0/16:0, 9.7 ± 0.7% palmitoylmyristoyl–PC, 10.0 ± 1.0% palmitoylpalmitoleoyl–PC, and 13.1 ± 0.3% palmitoyloleoyl–PC. Infusion of deuteriated choline chloride (3.6 mg/kg body weight) over 3 hours resulted in linear incorporation into PC over 30 hours. After a plateau of 0.61 ± 0.04% labeled PC between 30 and 48 hours, incorporation decreased to 0.30 ± 0.02% within 7 days. Compared with native PC, fractional label was initially lower for PC16:0/16:0 (31.9 ± 8.3%) but was higher for palmitoyloleoyl–PC (21.0 ± 1.2%), and equilibrium was achieved after only 48 hours. We conclude that infusion of deuteriated choline and electrospray ionization tandem mass spectrometry is useful to investigate surfactant metabolism in humans in vivo.

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Published date: 2004
Keywords: human surfactant metabolism, induced sputum, stable isotopes, mass spectrometry, phosphatidylcholine molecular species

Identifiers

Local EPrints ID: 26941
URI: http://eprints.soton.ac.uk/id/eprint/26941
ISSN: 1073-449X
PURE UUID: 8a4b05f0-4b77-41ee-9532-ea3fddab66cd
ORCID for Anthony D. Postle: ORCID iD orcid.org/0000-0001-7361-0756

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Date deposited: 25 Apr 2006
Last modified: 10 Dec 2019 01:59

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Contributors

Author: Wolfgang Bernhard
Author: Christopher J. Pynn
Author: Andreas Jaworski
Author: Gunnar A. Rau
Author: Jens M. Hohlfeld
Author: Joachim Freihorst
Author: Christian F. Poets
Author: Dieter Stoll

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