Partitioning of [methyl-3H]methionine to methylated products and protein is altered during high methyl demand conditions in young Yucatan miniature pigs.

Methionine is the main source of methyl groups that are partitioned to synthesize various methylated products including creatine, phosphatidylcholine (PC), and methylated DNA. Whether increased methylation of 1 product can divert methionine from protein synthesis or other methylation products was the aim of this experiment. We used an excess of guanidinoacetate (GAA) to synthesize creatine to create a higher demand for available methyl groups in normal-weight (NW) (n = 10) and intrauterine growth-restricted (IUGR) (n = 10) piglets. Anesthetized piglets (15-18 d old) were intraportally infused with either GAA or saline for 2 h. A bolus of l-[methyl-(3)H]methionine was intraportally infused at 1 h, and hepatic metabolites were analyzed for methyl-(3)H incorporation 1 h later. Overall, 50-75% of label was recovered in creatine and PC with negligible amounts in DNA. In both NW and IUGR piglets, excess GAA led to an ≈ 80-120% increase in methyl incorporation into creatine (P < 0.05) with a concomitant decrease by ≈ 75-85% in methyl incorporation into PC (P < 0.05) as well as a 40% decrease in methyl incorporation into protein (P < 0.05), suggesting methyl groups were limited for PC synthesis and that methionine was diverted from protein synthesis. Compared with NW piglets, IUGR piglets had lower methyl incorporation into PC (P < 0.05), but not DNA or protein, suggesting IUGR affects methyl metabolism and could potentially impact lipid metabolism. The partitioning of methionine is sensitive to methyl supply in neonates, which has implications in infant diet composition and growth.