Hepatic and Biliary Glucuronidation of Bisphenol A in Mice: A Reaction Catalyzed by the UDP-Glucuronosyltransferase (Ugt2b)1 and Ugt2b34 Enzymes
Bibliographic record
Abstract
Bisphenol A (BPA) is an important industrial chemical used in the manufacture of polycarbonate plastic and epoxy resin-based products. This endocrine disruptor molecule is metabolized and eliminated primarily as a monoglucuronide. The purpose of this study was to identify those of murine tissues and UDP-glucuronosyltransferase (UGT) enzymes involved in BPA-glucuronide (-G) formation. A series of in vitro glucuronidation assays were performed using homogenates or microsomal fractions from murine tissues or HEK293 cells expressing each of the 7 murine Ugt2b isoforms. From the 29 tissues tested, the most reactive were the liver, gallbladder, caecum and colon. A low BPA-G formation was also detected in the ileum, oviduct and testis. KM values ranged from 19.6±7.5 (gallbladder) to 85.8±16.0µM (caecum), while with 190.3µL/min/mg proteins the gallbladder exhibited the highest intrinsic clearance value. From the 7 murine Ugt2bs, the highest BPA-G formation rates were obtained with the Ugt2b1 and Ugt2b34 isoforms. These 2 enzymes displayed important differences in terms of kinetic parameters: Ugt2b1 exhibited lower KM and Vmaxapp. values (2.5±0.2µM and 389.4±79.0pmol/min/mg proteins, respectively) than Ug2b34 (KM=98.4±3.3µM and Vmaxapp.=9,681.3±1,507.3pmol/min/mg proteins). However, CLINT. values revealed that both enzymes exhibit similar BPA glucuronidation efficiencies. Quantitative RT-PCR experiments further revealed that the profile of the Ugt2b34 mRNA expression correlates with BPA-G formation in tissues of the gastro-intestinal tract. In conclusion, the present study identifies tissues of the hepato-biliary-intestinal tract as well as the Ugt2b1 and Ugt2b34 isoforms as major contributors for bisphenol A glucuronidation in mice Surprisingly, gallbladder was very reactive with this substrate.
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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 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| 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".