Isomer‐specific retinoic acid biosynthesis in HeLa cells expressing recombinant class I aldehyde dehydrogenases
Bibliographic record
Abstract
Retinal dehydrogenase type 1 (RALDH1) catalyzes the oxidation of all‐trans and 9‐cis retinal to the respective retinoic acids (RAs), whereas another member of the aldehyde dehydrogenase family, the phenobarbital‐induced aldehyde dehydrogenase (PB‐ALDH), is very poorly active. We have previously generated chimeras between these two enzymes that displayed selectivity for retinal isomers in crude bacterial extracts. Here, we have characterized the kinetic properties of the corresponding purified recombinant proteins, and demonstrate that these chimeras catalyze oxidation of retinal isomers with high efficiency and selectivity. To examine whether the selectivity of the recombinant enzymes is retained in vivo, we first assessed whether retinoid‐isomerizing activity is present in cultured eukaryotic cells. Our results demonstrate that the only RA isomers detected in RALDH1‐expressing or non‐expressing cells corresponded to the same steric conformation as the supplied retinoids, indicating a lack of measurable 9‐cis/all‐trans retinoid‐isomerizing activity. Finally, HeLa cells transfected with RALDH1 derivatives that were retinal isomer‐selective in vitro produced only the corresponding isomers of RA in vivo, establishing these enzymes as useful tools to assess the respective roles of the two RA isomers in vivo. (supported by CIHR grant)
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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) | 0.000 | 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 teacher head, 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".