Jason Robinson - Feb. 15
The role of methyl donors in methionine metabolism in the neonatal piglet
Methionine is an essential amino acid that is incorporated into protein. It is also the primary methyl donor for transmethylation (TM) reactions once it is converted to S-adenosylmethionine (SAM). SAM is demethylated to form S-adenosylhomocysteine (SAH) with the majority of methyl groups either being transferred to DNA, or used for the synthesis of creatine and phosphatidylcholine (PC). SAH is converted to the amino acid homocysteine, which is a risk factor for cardiovascular disease when elevated in the plasma. Homocysteine is removed through two means; it can be oxidized to cysteine via transulphuration (TS), or remethylated (RM) back to methionine by the methyl donors folate and choline (via betaine). Interestingly, lowering plasma homocysteine through the provision of methyl donors does not ameliorate the risk of cardiovascular disease. My research focuses on quantifying TM, RM, and TS using tracer methodologies in young piglets that were fed a diet devoid or replete of methyl donors. After 5 days of feeding, dietary methionine was reduced to 80% of the requirement. On day 8 of trials, animals received a constant infusion of [3H]methyl-methionine to measure methylation to PC, creatine, and DNA through transmethylation. Creatine synthesis appears most sensitive to methyl supply and severe restriction of remethylation in piglets reduces methionine availability for synthesis of creatine. Moreover, PC synthesis was higher with methyl deficiency, suggesting this pathway is upregulated when choline is deficient. Future studies will measure TM, RM, and TS in methyl deficient piglets, that are subsequently "rescued" with either folate, betaine or folate + betaine. This will help determine which methyl donor is the most effective at altering the dynamics of methionine metabolism when methionine is limited.