EVALUATION OF PHENYLALANINE ISOTOPES USING AN ISOLATED ORGAN PERFUSION MODEL
Bibliographic record
Abstract
The objective of the research was to evaluate the possibility of isotopic discrimination between two isotopomers of phenylalanine during the hydroxylation to tyrosine. Phenylalanine hydroxylation of L-[1-13C]phenylalanine and L-{ring- 2H5]phenylalanine were evaluated in three in vitro experiments, as well as an isolated liver perfusion model. The in vitro experiment involved an assay system using purified phenylalanine hydroxylase enzyme in a buffer medium. The isolated liver perfusion was set up to examine the first-pass hepatic metabolism of phenylalanine. Tyrosine production from the unlabeled phenylalanine as well as the two isotopomers was measured by spectrophotometric assay and high-performance liquid chromatography (HPLC). Gas chromatography-mass spectrometry (GC-MS) analysis was used to measure the enrichment of 13C-tyrosine and 2H4-tyrosine in a third in vitro experiment as well as labeled tyrosine and phenylalanine enrichments in the liver perfusion experiments. In a kinetic assay, the rate of production of 2H4-tyrosine (from hydroxylation 2H5- phenylalanine), was found to be significantly lower (p < 0.01) than the rate of production of unlabeled or 13C-tyrosine. When overall tyrosine production was measured by HPLC, the 2H4 -tyrosine production was found to be significantly lower than from both unlabeled and 13C-tyrosine (p < 0.01). 13C-Tyrosine was also found to be significantly lower than unlabeled tyrosine (p < 0.05). When measured by GC-MS, the enrichment of 13C- tyrosine was found to be significantly greater than the enrichment of 2H4-tyrosine (p < 0.05) indicating more production of tyrosine from 13C-phenylalanine than from 2H5- phenylalanine. In the liver perfusion experiments, mean phenylalanine enrichments were 15.57 ± 2.99 and 15.94 ± 3.16 for 13C-phenylalanine and 2H5-phenylalanine, respectively. Mean tyrosine enrichments were 12.18 ± 2.04 and 11.61 ± 1.94 for 13C- tyrosine and 2H4-tyrosine, respectively. There was no significant difference for either the phenylalanine (p > 0.05) or tyrosine (p > 0.05) enrichments. The lack of significant difference between enrichments of 13C-phenylalanine and 2H5-phenylalanine, or 13C- tyrosine and 2H4-tyrosine indicates that the discrimination at the enzymatic level is not large enough to affect hepatic enrichment. This study suggests that, although discrimination may exist between L-[1-13C]phenylalanine and L-[ring-2H5]phenylalanine, the liver is not likely the site for such discrimination.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".