The Amount of Dietary Methionine Required to Maximize Synthesis of Transmethylated Products Is Higher Than That Needed for Protein Synthesis in Neonatal Piglets

OBJECTIVES: Methionine is an indispensable sulfur-containing amino acid required for synthesizing protein as well as other critical nutrients. Methionine is the primary methyl donor for >50 transmethylation reactions to produce metabolites including creatine, phosphatidylcholine (PC), and methylated DNA. In piglets, because only one-third of methionine flux is incorporated into protein compared to transmethylation reactions (∼2/3), non-protein demands need to be considered when determining methionine requirement. Our objective was to quantify how much dietary methionine is required to maximize synthesis of protein as well as key transmethylated products. We hypothesized that more dietary methionine will be needed to maximize creatine synthesis, with lower levels required to maximize PC and protein synthesis. METHODS: Twenty surgically altered Yucatan miniature piglets (∼8 d old; ∼1.6 kg) were fed complete diets for 5 d and then randomized to 20 test diets with methionine intakes ranging from 20%-220% of requirement (0.05–0.55 g/kg/d). After 24 h of test diet, [(3)H-methyl]-methionine was infused for 6 h to measure methyl incorporation into creatine, PC, and methylated DNA, and then a(3)H-phenylalanine flooding dose was given to measure protein synthesis. Break-point analysis was used to identify the methionine required to maximize product synthesis. RESULTS: Plasma methionine increased above 0.3 g methionine/kg/d, reflecting the whole body requirement. Creatine synthesis maximized at ∼0.3 g methionine/kg/d, while muscle protein synthesis was maximized at 0.2 g methionine/kg/d, suggesting growth is prioritized when methionine is limiting. PC synthesis was low up to 0.35 g methionine/kg/d and increased linearly with higher intakes, suggesting PC synthesis was not maximized at 200% of requirement.(3)H-DNA did not change with dietary methionine, and plasma homocysteine was positively correlated with dietary methionine. CONCLUSIONS: These data suggest that more methionine is required to accommodate demands for creatine and PC synthesis than that for protein synthesis. Therefore, methionine requirement estimates for infants, which rely on protein synthesis outcomes, are likely insufficient to achieve maximal synthesis of key methylated metabolites creatine and PC. FUNDING SOURCES: NSERC.