Creatine synthesis in isolated hepatocytes
Bibliographic record
Abstract
Creatine (Cr) is a “high‐energy” phosphate buffer that is synthesized from glycine, arginine and methionine. The generally accepted pathway for Cr synthesis involves both the kidney and liver. Guanidinoacetate (GAA) is formed from glycine and arginine by the enzyme arginine:glycine amidinotransferase (AGAT) in the kidney. GAA is then transported to the liver where it is methylated by the enzyme guanidinoacetate methyltransferase (GAMT) to form Cr. Cr is also spontaneously, non‐enzymatically cyclized to creatinine(Crn), which is subsequently excreted in the urine. Daily loss of creatine is on the order of 1‐2% of the total body pool and it has been calculated that the replacement of lost Cr would require about 50% of daily arginine intake and 70% of daily methionine intake. While methionine can be recycled after methylation, the ornithine produced from arginine is largely oxidized in the kidney. However, if AGAT activity was present in the liver the ornithine produced could re‐enter the urea cycle and thus recycle arginine. It is the goal of this study to determine whether this occurs in rat hepatocytes. In addition, little is known about the transport of GAA and Cr in the liver and part of the goal of this study will be to investigate the transport of these compounds. We measured Cr synthesis in isolated hepatocytes using various substrates. When GAA and methionine were present Cr synthesis was determined to be 0.02 nmol/min/mg dry weight. Cr synthesis was inhibited by 46% in the presence of 3‐guanidinopropionic acid; a known inhibitor of Cr transport. Cr did not appear to be synthesized in the presence of NH4, arginine, glycine and methionine and therefore the entire synthetic pathway probably does not occur in rat hepatocytes. Supported by CIHR.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".