Adverse Outcome Pathway on Aryl hydrogen receptor activation leading to uroporphyria
Bibliographic record
Abstract
Hepatic uroporphyria is a disorder where the disturbance of heme biosynthesis results in accumulation and excretion of uroporphyrin, heptacarboxyl- and hexacarboxyl porphyrin: collectively referred to as highly carboxylated porphyrins (HCPs). The disorder is due to a homozygous mutation in uroporphyrinogen decarboxylase (UROD), an enzyme involved in the heme biosynthesis pathway, or may be chemically induced, which involves the inhibition of UROD. This AOP describes the linkages leading to chemically induced porphyria through the activation of the aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor. AHR activation leads to the induction of cytochrome P450 1A2, a phase I metabolising enzyme, which in turn results in excessive oxidation of uroporphyrinogen. This oxidation produces a UROD inhibitor, preventing the conversion of uroporphyrinogen to coprouroporphyrinogen and increasing the synthesis of the UROD inhibitor in a positive feedback loop. The accumulation of uroporphyrinogen leads to its preferential oxidation and accumulation of HCP in various organs (Uroporphyria).
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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) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.072 |
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; both teacher heads agree on what is shown here.
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".