Ontogeny of methionine utilization and splanchnic uptake in critically ill children

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-[ 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-...

Current recommended parenteral protein intakes do not support protein synthesis in critically ill septic, insulin-resistant adolescents with tight glucose control

“…Protein accretion will not occur without a sufficient energy supply, and a sufficient energy supply will not support anabolism in the absence of adequate protein (nitrogen) intake. We have shown that the parenteral protein requirements of critically ill children have been based on limited data (13) and that, at currently recommended enteral protein intakes, critically ill pediatric patients remain in significantly negative protein balance (14).…”

“…Hyperglycemic (Ͼ120 mg dL Ϫ1 , Ͼ6.7 mM) adolescents (13-18 yrs of age) with a diagnosis of severe sepsis, septic shock, or systemic inflammatory response syndrome (19) and receiving total parenteral nutrition were considered eligible. Only adolescents aged 13-18 yrs were included in the study as we have previously observed that metabolic processes greatly vary with age (14). All patients had drawing and infusing intravascular catheters and had received complete parenteral feedings for at least 24 hrs before the study.…”

Splanchnic First Pass Disappearance of Threonine and Lysine Do Not Differ in Healthy Men in the Fed State

“…Studies with methods that did not provide time for adaptation to either the protein or amino acid intakes prior to the study period were also not included. One study (19) met all methodological criteria as described previously but was not included, because the jn.nutrition.org subjects were patients in an intensive care unit and were not comparable to the clinically stable subjects in the studies listed in Table 3. There were 14 studies that qualified for inclusion in this review.…”

Protein Requirements of the Critically Ill Pediatric Patient

“…Critically ill children have an increased protein turnover due to an increase in whole‐body protein synthesis and breakdown 25 , 38 , 39 . During inflammatory conditions, there is a decrease in protein synthesis at the skeletal muscle level and an increase in protein degradation to shuttle amino acids and nitrogen to the tissues 38 , 40 . Protein degradation can be greater than muscle protein synthesis and create a negative protein balance.…”

“…While these methods are very accurate to measure protein kinetics, they require specialized equipment and expertise to conduct the studies. Several authors have reported the use of stable isotopes to assess protein metabolism and needs in critically ill children 15 , 25 , 26 , 40 , 54 , 115 , 116 …”