Kankayaliyan Thillayampalam - September 26
Sources of creatine and amino acids sparing in piglets
Arginine and methionine are indispensable amino acids in neonates that have a metabolic role in creatine synthesis other than protein synthesis. Arginine transfers its amidino group to glycine to form guanidinoaceticacid (GAA) which is then transmethylated to creatine. Methionine is the primary methyl donor for transmethylation reactions via S-adenosylmethionine (SAM). SAM is demethylated to S-adenosylhomocysteine and transfers its methyl group to synthesize creatine, phosphatidylcholine (PC) and methylated DNA. In rapidly growing animals, the balance between requirements for growth versus those for maintenance becomes more precarious as growth demands more amino acids for expansion of body protein mass as well as for the increase need for other critical metabolites. Therefore, our hypothesisis that dietary creatine and its precursor GAA can spare methionine for protein synthesis. L-[methyl-3H]methionine was infused to understand the sparing effect of dietary creatine and GAA on protein synthesis and to quantify the partitioning of transmethylation reactions. The rate of 3H-methyl incorporation to creatine, PC, DNA and protein was measured using isotope kinetics. Creatine supplementation increases the availability of methyl groups for other transmethylation reactions by reducing the labile methyl groups needed for creatine synthesis. GAA supplementation increased creatine synthesis, but only when methionine is not limited. Excess dietary methionine had a significant impact on PC synthesis but not on hepatic protein synthesis. Sparing methionine with creatine or supplementing methionine did not increase hepatic protein synthesis, suggesting hepatic protein synthesis is conserved in neonates limiting in methionine. Therefore, creatine levels in neonatal piglets can be maintained by de novo creatine synthesis but is enhanced by GAA only with an increased availability of methionine.