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Arginine or Guanidinoacetic Acid Can Serve as Precursors for Creatine Synthesis in Parenteral Nutrition, but Only with Excess Methionine to Facilitate Transmethylation
Author(s) -
Bray Scott D.,
Aljaroudi Alaa,
Dinesh O. Chandani,
Kankayaliyan Thillayampalam,
Brunton Janet A.,
Bertolo Robert F.
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.909.11
Subject(s) - creatine , methionine , transmethylation , arginine , medicine , amino acid , endocrinology , chemistry , biochemistry , biology
Creatine synthesis in neonates demands high amounts of its precursors, arginine and methionine. Parenteral nutrition (PN) is typically marginal in these amino acids and devoid in creatine. The present study investigated the effectiveness of creatine supplementation of PN compared to supplementation with arginine, methionine and the unmethylated intermediate guanidinoacetic acid (GAA). The goal of this study was to determine if PN supplementation with creatine or GAA can spare methionine and/or arginine for other functions. Yucatan miniature‐piglets (6–10 d old; n=31) were fed 1 of 5 elemental PN diets: 1) low arginine and low methionine (Low Arg&Met), 2) low arginine and methionine plus GAA, 3) low arginine and methionine plus creatine, 4) high arginine and high methionine (High Arg&Met), or 5) low arginine with high methionine plus GAA (Met&GAA). After 7 d of feeding, a primed, constant infusion of [ 3 H‐methyl]‐methionine was intravenously infused for 4 h and label incorporation in transmethylation products (creatine, phosphatidylcholine, DNA) and protein were measured. Both High Arg&Met and Met&GAA pigs had greater daily weight gain compared to GAA‐ and creatine‐supplemented pigs (p < 0.05), indicating methionine was deficient in low methionine groups. Moreover, 72‐h nitrogen retention was significantly greater in High Met&Arg and Met&GAA pigs compared to GAA (p < 0.05). These results suggest that because methionine is heavily transmethylated in the neonatal piglet, excess methionine is needed to promote protein synthesis and increase growth. As expected, plasma methionine and arginine concentrations were significantly higher in High Met&Arg compared to Low Arg&Met, GAA and creatine treatments (p < 0.05). Plasma levels of ornithine were significantly higher and glutamine levels were significantly lower in High Met&Arg compared to all other treatments (p < 0.05) suggesting urea cycle metabolism was limited in the low arginine groups. Hepatic fractional synthetic rate of creatine was ~30–40% higher in High Met&Arg and Met&GAA pigs, suggesting creatine synthesis was limited by precursor availability. These results also suggest that PN supplementation of GAA requires excess levels of methionine to facilitate transmethylation to creatine. These results suggest that arginine or GAA is needed to adequately synthesize creatine in PN‐fed piglets, but only when sufficient methionine is fed to provide methyl groups. Moreover, it is clear that the methionine and arginine requirements during PN feeding need to accommodate creatine synthesis. Support or Funding Information Supported by Canadian Institutes of Health Research and the Janeway Research Foundation