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Record W3184558961 · doi:10.22215/etd/2021-14487

The Metabolism of 6:2 Fluorotelomer Alcohol by CYP 2A6

2021· dissertation· en· W3184558961 on OpenAlexaff
Oluwadamilola Daramola

Bibliographic record

Venuenot available
Typedissertation
Languageen
FieldEnvironmental Science
TopicPer- and polyfluoroalkyl substances research
Canadian institutionsCarleton University
Fundersnot available
KeywordsTranylcypromineChemistryMetabolismEnzymeAlcoholBiochemistryToxicityPharmacologyChromatographyBiologyOrganic chemistryMonoamine oxidase

Abstract

fetched live from OpenAlex

For well-known toxicants such as perfluorooctanoic acid (PFOA) and its precursor, 8:2 fluorotelomer alcohol (8:2 FTOH), identification of the CYPs driving the metabolism, from the FTOH to the PFOA, could be used to identify the possibility of localized toxicity.This is based on the varying distribution of CYPs in organs and cell membranes.Due to environmental regulations, PFOA and 8:2 FTOH have been phased out in favour of compounds with shorter fluorinated chain lengths, considered less bioaccumulative and toxic.However, there is currently insufficient knowledge of enzyme catalysed metabolism of these replacements.One replacement for 8:2 FTOH is the 6:2 FTOH [4] .This project identifies CYP 3A4 and CYP 2A6 as possible cytochrome P450s responsible for the phase I metabolism of 6:2 FTOH.A Michaelis Menten curve is generated for the metabolism of 6:2 FTOH by CYP 2A6 metabolism.This provided a KM and VMax of 4076.4 ± 581.9 ng/mL and 68.8 ± 2.8 ng/mL/min, respectively.Once inhibited with 35 𝜇M of tranylcypromine, HCl, a selective inhibitor of CYP 2A6, the KM and VMax were determined to be 8796.2± 1366.1 ng/mL and 69.5 ± 4.1 ng/mL/min, representing competitive inhibition.We further demonstrated that CYP 2A6 was responsible for 6:2 FTOH metabolism using human recombinant assays with purified CYP 2A6.These assays yielded a 6:2 FTOH metabolic conversion rate of 0.42 ng/mL/min.This rate significantly decreased with the addition of Tranylcypromine HCl.This confirms CYP 2A6 as an active enzyme for the metabolism of 6:2 FTOH in the human liver.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.008

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.001
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.001

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.

Opus teacher head0.010
GPT teacher head0.281
Teacher spread0.272 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

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".

Quick stats

Citations0
Published2021
Admission routes1
Has abstractyes

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