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Am J Physiol Endocrinol Metab 297: E1046-E1055, 2009. First published September 1, 2009; doi:10.1152/ajpendo.00396.2009
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Ontogeny of methionine utilization and splanchnic uptake in critically ill children

Sascha Verbruggen,1,2,3 Jama Sy,1,2 William E. Gordon,1,2 Jean Hsu,2 Manhong Wu,1,2 Shaji Chacko,2 David Zurakowski,4 Douglas Burrin,2 and Leticia Castillo1,2

1Critical Care Section, Department of Pediatrics, Texas Children's Hospital, Baylor College of Medicine; 2Children's Nutrition Research Center, United States Department of Agriculture, Houston; Texas; 3Department of Pediatrics, Erasmus Medical Center, Sophia Children's Hospital, Rotterdam, The Netherlands; and 4Departments of Anesthesia and Surgery, Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts

Submitted 2 June 2009 ; accepted in final form 23 August 2009

To determine the rates of methionine splanchnic uptake and utilization in critically ill pediatric patients we used two kinetic models: the plasma methionine enrichment and the "intracellular" homocysteine enrichment. Twenty four patients, eight infants, eight children, and eight adolescents, were studied. They received simultaneous, primed, constant, intravenous infusions of L-[2H3]methylmethionine and enteral L-[1-13C]methionine. The ratio of [13C]homocysteine to [13C]methionine enrichment was 1.0 ± 0.15, 0.80 ± 0.20, and 0.66 ± 0.10, respectively, for the infants, children, and adolescents, and it was different between the infants and adolescents (P < 0.01). Methionine splanchnic uptake was 63, 45, and 36%, respectively, in the infants, children, and adolescents, and it was higher (P < 0.01) in the infants compared with the adolescents. The infants utilized 73% of methionine flux for nonoxidative disposal, while 27% was used for transulfuration (P < 0.001). Conversely, in the adolescents, 40% was utilized for nonoxidative disposal, while 60% was used for transulfuration. There is ontogeny on the rates of methionine splanchnic uptake and on the fate of methionine utilization in critically ill children, with greater methionine utilization for synthesis of proteins and methionine-derived compounds (P < 0.01) and decreased transulfuration rates in the infants (P < 0.01), while the opposite was observed in the adolescents. The plasma model underestimated methionine kinetics in children and adolescents but not in the infants, suggesting lesser dilution and greater compartmentation of methionine metabolism in the infant population. All patients were in negative methionine balance, indicating that the current enteral nutritional support is inadequate in these patients.

isotopes; transulfuration; oxidation; kinetic model



Address for reprint requests and other correspondence: L. Castillo, Texas Children's Hospital, Children's Nutrition Research Center, USDA/ARS at Baylor College Medicine, 1100 Bates St., Houston, TX 77030 (e-mail: Lcastill{at}BCM.edu).







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