Creatine synthesis and amino acid sparing in neonatal piglets

Thillayampalam, Kankayaliyan (2015) Creatine synthesis and amino acid sparing in neonatal piglets. Masters thesis, Memorial University of Newfoundland.

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Abstract

Arginine and methionine are indispensable amino acids in neonates and have a metabolic role in creatine synthesis as well as protein synthesis. Arginine transfers its amidino group to glycine to form guanidinoacetic acid (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 critical as growth demands more amino acids for expansion of body protein mass as well as for the increased need for other critical metabolites. Therefore, our hypothesis is that dietary creatine and its precursor GAA can spare methionine and arginine. L-[methyl-³H] methionine was infused to measure the sparing effect of dietary creatine and GAA and to quantify the partitioning of transmethylation reactions. The fractional synthetic rate of creatine, PC, DNA and protein were measured using isotope kinetics. Creatine supplementation increased the availability of methyl groups for other transmethylation reactions by reducing the labile methyl groups needed for creatine synthesis. GAA supplementation increased hepatic creatine levels 5-fold, but only when methionine was not limited. Excess dietary methionine enhanced PC synthesis by double but not hepatic protein synthesis. Sparing methionine with creatine or supplementing methionine did not increase hepatic protein synthesis, suggesting that hepatic protein synthesis is conserved in neonates when methionine is limiting. Therefore, creatine levels in neonatal piglets can be maintained only when the supply of methyl groups is expanded in the diet.

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