Sparing effect of betaine on methionine availability for PC synthesis in TPN fed neonatal piglets

Methionine is an essential amino acid required not only for protein synthesis, but also as the primary source of methyl groups. These methyl groups are used for methylation to creatine, phosphatidylcholine (PC) and for regulating gene expression. A significant proportion of methionine metabolism occurs in the gut which is severely diminished with total parenteral nutrition (TPN). Also, TPN is known to induce fatty liver.
PC is the most abundant phospholipid in mammalian cells. It can be formed via two pathways: CDP choline pathway (70%) or the phosphatidylethanolamine methyltransferase (PEMT) pathway (30%). PC synthesis is sensitive to methyl supply and is critical during TPN to prevent fatty liver. Moreover, PEMT-derived PC is rich in arachidonic acid and docosahexaenoic acid, both of which are critical to the developing brain in infants. Thus, it is important to maximize the PEMT pathway to ensure the adequate delivery of these essential polyunsaturated fatty acids to the brain.
Betaine is also a potent methyl donor. It can remethylate homocysteine to form methionine. Betaine has also been shown to have hepatoprotective properties. The principal hypothesis of this study is that dietary betaine can spare methionine in neonates for PC synthesis during TPN feeding, while preventing hyperhomocysteinemia. Our major objective is to assess the effects of betaine supplementation in TPN on development of fatty liver and long chain fatty acid status. We are particularly interested in the sparing effect of betaine on methionine for enhanced PC synthesis via PEMT pathway, which would be evident through the hepatic and brain phospholipid fatty acid profile.