The amount of dietary methionine required to maximize synthesis of transmethylated products is higher than that needed for protein synthesis in neonatal piglets.

Background: Methionine is required for synthesizing protein and other critical metabolites, acting as a precursor for >50 transmethylation reactions to produce metabolites such as creatine, phosphatidylcholine (PC), and methylated DNA. In neonatal piglets, because only one-third of dietary methionine is incorporated into protein compared to two-thirds for methylated products, both protein and non-protein demands need to be considered when determining the methionine requirement.

Objective: Our major objective was to quantify how much dietary methionine is required to maximize protein synthesis and key transmethylated products (creatine, PC, methylated DNA).

Methods: Twenty surgically altered Yucatan miniature piglets (8 ± 2 d) were fed complete diets for 5 d and then randomized to 20 test diets with methionine intakes ranging from 20%-220% of requirement (0.32 - 3.55 g methionine/100 g total AAs). Stable isotopes of phenylalanine and tyrosine were administered to determine whole-body protein synthesis. [³H-methyl]-methionine was infused to measure methyl incorporation into transmethylated products, and ³H-phenylalanine flooding dose was given to measure tissue-specific protein synthesis.

Results: Break-point analysis indicated a whole-body requirement of 1.73 ± 0.27 g methionine/100 g total AAs. [³H-methyl] incorporation into PC increased linearly with dietary methionine, while hepatic creatine synthesis maximized at 1.84 ± 0.22 g methionine/100 g total AAs. DNA methylation rate was maximized at 1.52 ± 0.38 g methionine/100 g total AAs. Plasma concentrations of homocysteine were positively correlated with dietary methionine levels. These data suggest that DNA methylation is prioritized over hepatic creatine synthesis, while PC synthesis continuously increases with methionine intake with no discernible maximum rate. When methionine intake was limited, liver protein synthesis was prioritized, followed by kidney and muscle protein synthesis.

Conclusions: These data suggest that protein synthesis should not be used to determine whole-body requirements since more methionine is required to meet non-protein demands for methionine.