Spectrofluorometric Analysis of CYP2A6-Catalyzed Coumarin 7-Hydroxylation
Bibliographic record
Abstract
CYP2A6 has been isolated and purified to apparent homogeneity from human liver (1, 2). The level of CYP2A6 protein expressed in liver is low (∼4% of total hepatic P450 content) (3), although substantial intermdividual variation exists (3–5). This P450 is primarily a hepatic protein, as suggested by its absence from several extrahepatic tissues, including adult human lung, colon, breast, kidney, and placenta microsomes (2). According to experiments with primary cultures of human hepatocytes, CYP2A6 is mducible by phenobarbital, dexamethasone, and rifampm (rifampicin) (6). Experiments with individual cDNA-expressed human P450 forms have indicated that CYP2A6 is a major catalyst of coumarm 7-hydroxylation (7). Among the other recombinant human P450s examined, CYPlAl, lA2, 2C8, 2C9, 2D6, 2E1, 3A3, 3A4, and 3A5 are catalytically inactive with respect to coumarm 7-hydroxylation, whereas CYP2B6 is active at only ∼5% the rate of CYP2A6 (7). Immunoinhibition studies have validated the use of coumarm 7-hydroxylase activity as a diagnostic catalytic marker for human hepatic CYP2A6. Antihuman CYP2A6 IgG inhibits coumarm 7-hydroxylase activity by >90% in human liver microsomes (2), indicating that CYP2A6 is the principal and perhaps the sole catalyst of human liver microsomal coumarin 7-hydroxylase activity. This activity can be inhibited by a variety of compounds, includmg 8-methoxypsoralen (8), tranylcypromme (8), α-naphthoflavone (8–11) and diethyldithiocarbamate (8, 10, 11). This chapter describes a modification (12) of a spectrofluorometric method (13) for the determination of coumarm 7-hydroxylase activity.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 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) | 0.001 | 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".