-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-[ 2 H3]methylmethionine and enteral L-[1-13 C]methionine. The ratio of [13 C]homocysteine to [ 13 C]methionine enrichment was 1.0 Ϯ 0.15, 0.80 Ϯ 0.20, and 0.66 Ϯ 0.10, respectively, for the infants, children, and adolescents, and it was different between the infants and adolescents (P Ͻ 0.01). Methionine splanchnic uptake was 63, 45, and 36%, respectively, in the infants, children, and adolescents, and it was higher (P Ͻ 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 Ͻ 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 Ͻ 0.01) and decreased transulfuration rates in the infants (P Ͻ 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 THE PORTAL-DRAINED VISCERA involving the liver, stomach, and intestines is profoundly deranged during critical illness. Altered splanchnic function, whether elicited by hypoperfusion, hypoxia, or inflammation, has been associated with systemic inflammatory response syndrome and multiple organ dysfunction syndrome (10, 29). Under physiological conditions, the splanchnic tissues are important for whole body amino acid metabolism and selectively modify the pattern of absorbed amino acids that is subsequently presented to the peripheral circulation (9). Thus the pattern of amino acids in the diet is different from that in portal venous blood and does not reflect their availability to extraintestinal tissues. This concept has important implications for defining protein and amino acid requirements for nutritional and functional purposes. An extensive catabolism and/or utilization of dietary amino acids in the first pass by the small intestine results in decreased nutritional efficiency and will influence their requirements.The sulfur amino acids serve important protein and nonprotein functions (16,18,36,37). Methionine, an indispensable sulfur amino acid, serves as the precursor in the synthesis of S-...