Methionine Requirement to Maximize Protein Synthesis and Transmethylated Products Synthesis in Neonatal Piglets

Methionine is an indispensable sulphur-containing amino acid required for synthesizing protein as well as a number of other critical nutrients. Methionine acts as a precursor for more than 50 transmethylation reactions to produce metabolites such as creatine, phosphatidylcholine (PC), and methylated DNA. The overall purpose of my research is to understand how dietary methionine is used for these pathways since it is critical to defining the nutritional requirements of neonates. In neonatal piglets, because a lower fraction of methionine flux is incorporated into protein synthesis (~1/3) compared to that used for methylation reactions (~2/3), both protein and non protein demands need to be considered when determining the methionine requirement. Our major objective is to quantify how much dietary methionine is required to maximize synthesis of protein as well as key transmethylated products such as creatine, PC and methylated DNA. Yucatan miniature- piglets (5-12d old; n=20) were fed 20 test diets with different levels of methionine (20%- 220% estimated requirement intragastrically (IG). After feeding the test diet, a primed, constant infusion of stable isotopes of phenylalanine and tyrosine was given IG for 6h to measure whole body protein dynamics. The following day, a primed, constant infusion of [3H-methyl]-methionine was given IG for 6h to measure methyl incorporation into transmethylated products such as creatine, PC and methylated DNA. After the constant infusion, a 3H-phenylalanine flooding dose was given to measure tissue-specific protein synthesis. We hypothesize that a higher level of dietary methionine will be needed to maximize creatine synthesis, with lower levels required to maximize PC and protein synthesis. The aim of this research is to re-evaluate the nutritional recommendations for infants and if this hypothesis holds true, we should increase the methionine requirement estimate to not only accommodate the protein synthesis demands, but also non-protein demands for methionine.