Arginine or Guanidinoacetic Acid Can Serve as Precursors for Creatine Synthesis in Parenteral Nutrition, but Only with Excess Methionine to Facilitate Transmethylation
Bibliographic record
Abstract
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
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".