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 with two-thirds for methylated products, both protein and nonprotein demands need to be considered when determining the methionine requirement.

OBJECTIVES

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

METHODS

Twenty surgically altered Yucatan miniature piglets (8 ± 2 d) were fed complete diets for 5 d and then randomly assigned to 20 test diets with methionine intakes ranging from 20% to 220% of requirement [0.32-3.55 g methionine/100 g total amino acids (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 a [3H]-phenylalanine flooding dose was administered to measure tissue-specific protein synthesis.

RESULTS

Breakpoint 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, whereas hepatic creatine synthesis maximized at 1.84 ± 0.22 g methionine/100 g total AAs. DNA methylation rate maximized at 1.52 ± 0.38 g methionine/100 g total AAs. Plasma concentrations of homocysteine were positively correlated with dietary methionine concentrations. These data suggest that DNA methylation is prioritized over hepatic creatine synthesis, whereas 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 because more methionine is required to meet nonprotein demands for methionine.