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Title: Ontogeny of methionine utilization and splanchnic uptake in critically ill children

Author
item VERBRUGGEN, SASCHA - Children'S Nutrition Research Center (CNRC)
item SY, JAMA - Children'S Nutrition Research Center (CNRC)
item GORDON, WILLIAM - Children'S Nutrition Research Center (CNRC)
item HSU, JEAN - Children'S Nutrition Research Center (CNRC)
item WU, MANHONG - Children'S Nutrition Research Center (CNRC)
item CHACKO, SHAJI - Children'S Nutrition Research Center (CNRC)
item ZURAKOWSKI, DAVID - Children'S Hospital - Boston, Massachusetts
item BURRIN, DOUGLAS - Children'S Nutrition Research Center (CNRC)
item CASTILLO, LETICIA - Children'S Nutrition Research Center (CNRC)

Submitted to: American Journal of Physiology - Endocrinology and Metabolism
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/23/2009
Publication Date: 9/1/2009
Citation: Verbruggen, S., Sy, J., Gordon, W.E., Hsu, J., Wu, M., Chacko, S., Zurakowski, D., Burrin, D., Castillo, L. 2009. Ontogeny of methionine utilization and splanchnic uptake in critically ill children. American Journal of Physiology - Endocrinology and Metabolism. 297(5):E1046-E1055.

Interpretive Summary: Rapidly growing infants have a critical need for adequate protein in the diet. The protein needs for infants can be significantly increased by critical illness. Methionine is a component amino acid of most proteins and cannot be made by the infant body and thus it is required in the diet. Methionine is also used to make another important amino acid, cysteine, contained in proteins. In addition to being a component of body protein, methionine is a key precursor for production of other important cellular metabolites that function in cell growth, replication, and defense against stress. Most of these metabolic processes occur in the liver and gut. Thus the aim of this study was to determine how much of the dietary methionine intake is used by the liver and gut tissues, also called the splanchnic organs, in twenty-four patients, including infants, children, and adolescents. We used a dual isotope approach by infusing different molecular forms of methionine into the gut and blood stream, which gives quantitative estimate of splanchnic metabolism. Our results showed that the splanchnic organs used a substantial amount (63%, 45%, and 36%) of the dietary methionine intake in infants, children, and adolescents, respectively. We also found that in infants vs. adolescents, most of the methionine used by the splanchnic organs was for production of protein rather than conversion to cysteine. Importantly, in all patients studied, the dietary methionine needs for normal growth were not achieved, suggesting that the recommended dietary methionine intake guidelines for growth in critically ill pediatric patients need to be increased.

Technical Abstract: 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] methyl methionine and enteral L-[1-13C] methionine. The ratio of [13C]homocysteine to [13C]methionine enrichment (13CHcy/13Cmeth) was 1.0+0.15, 0.80+0.20, and 0.66+0.10, respectively for the infants, children,and adolescents, and 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 higher (p<0.01) in the infants when compared to the adolescents. The infants utilized 73% of methionine flux for non-oxidative disposal (NOD), while 27% was used for transulfuration (p<0.001). Conversely, in the adolescents 40% was utilized for NOD 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.