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Journal of Lipid Research, Vol. 46, 1257-1265, June 2005
Copyright © 2005 by American Society for Biochemistry and Molecular Biology

Metabolic kinetics of pulmonary surfactant in newborn infants using endogenous stable isotope techniques

Kajsa Bohlin^1,*,, Bruce W. Patterson^1,, Kimberly L. Spence^*, Assaad Merchak^*, James C. G. Zozobrado^*, Luc J. I. Zimmermann^**, Virgilio P. Carnielli and Aaron Hamvas^2,*

^* Division of Newborn Medicine, Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine and St. Louis Children's Hospital, St. Louis, MO
Division of Pediatrics, Karolinska University Hospital Huddinge and the Karolinska Institute, Stockholm, Sweden
Center for Human Nutrition, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO
^** Division of Neonatology, Maastricht University, Maastricht, The Netherlands
Division of Neonatal Medicine, Ospedale Salesi, Ancona, Italy

Published, JLR Papers in Press, March 16, 2005. DOI 10.1194/jlr.M400481-JLR200

¹ K. Bohlin and B. W. Patterson contributed equally to this work.

² To whom correspondence should be addressed. e-mail: hamvas{at}kids.wustl.edu

We compared kinetic indices of pulmonary surfactant metabolism in premature infants (n = 41) with respect to i) tracer ([1-¹³C₁]acetate, [U-¹³C₆]glucose, and [1,2,3,4-¹³C₄] palmitate), ii) phospholipid (PL) pool (total PLs or disaturated PLs), or iii) instrumentation [gas chromatography/mass spectrometry (GC/MS) or GC-combustion-isotope ratio mass spectometry (GC-C-IRMS)]. Tracer incorporation was measured in PLs extracted from serial tracheal aspirates after a 24 h tracer infusion. The fractional catabolic rate (FCR), representing the total fractional turnover from all sources of surfactant production, was independent of tracer. The fractional synthesis rate of surfactant PL from plasma palmitate was significantly higher than that from palmitate synthesized de novo from acetate, and these two sources of palmitate together accounted for only half of the total surfactant production in preterm infants. [U-¹³C₆]glucose showed significant recycling of the ¹³C label in intermediary metabolism, distinguishable by GC-MS but not by GC-C-IRMS, resulting in a slower apparent FCR when GC-C-IRMS was used. The extracted PL pool did not affect the surfactant metabolic indices.

We suggest that FCR should be used as a primary measure of surfactant turnover kinetics and that tracers labeling both de novo synthesis (acetate and glucose) and preformed pathways (plasma palmitate) can be used to partition the fractional contribution of each pathway to total production.

Abbreviations: DSPL, disaturated phospholipid; FCR, fractional catabolic rate; FSR, fractional synthesis rate; GC-C-IRMS, gas chromatography-combustion-isotope ratio mass spectrometry; MIDA, mass isotopomer distribution analysis; PC, phosphatidylcholine; PL, phospholipid; T_1/2, half-life; TTR, tracer-to-tracee ratio

Supplementary key words acetate • palmitate • mass isotopomer distribution analysis • turnover

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