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Record W2051802466 · doi:10.1074/jbc.m000562200

Molecular Characterization of a First Human 3(α→β)-Hydroxysteroid Epimerase

2000· article· en· W2051802466 on OpenAlex

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.

Bibliographic record

VenueJournal of Biological Chemistry · 2000
Typearticle
Languageen
FieldMedicine
TopicHormonal Regulation and Hypertension
Canadian institutionsUniversité Laval
Fundersnot available
KeywordsAndrosteroneHydroxysteroid DehydrogenasesEnzymeNAD+ kinaseChemistryHydroxysteroid dehydrogenaseComplementary DNAAndrostaneBiochemistryCofactorDehydrogenaseSteroidBiologyMolecular biologyStereochemistryGeneHormone

Abstract

fetched live from OpenAlex

In this report, we describe the isolation and characterization of a cDNA encoding an enzyme that exhibits catalytic characteristics of a 3(alpha-->beta)-hydroxysteroid epimerase (3(alpha-->beta)-HSE). The enzyme overexpressed in human 293 embryonic kidney cells transforms androsterone into epi-androsterone in two steps: the oxidation of androsterone to 5 alpha-androstane-3,17-dione, followed by the reduction of the latter to epi-androsterone. The reverse reaction, 3(beta-->alpha)-hydroxysteroid epimeration, is approximately 10-fold weaker. These results are confirmed by V(max)/K(m) determination, which shows that the enzyme catalyzes the oxidation of androsterone to 5 alpha-androstane-3,17-dione and the reduction of 5 alpha-androstane-3,17-dione to epi-androsterone more efficiently than the reverse reactions. The selective catalysis of the reaction following the 3(alpha-->beta) direction is also observed in intact transfected cells in culture, which better reflect physiological conditions. In vitro assays reveal that the recombinant enzyme prefers NAD(+) and NADH as cofactors and could recognize both C-19 and C-21 3 alpha-hydroxysteroids as substrates. DNA sequence analysis predicts a protein of 317 amino acids. Tissue distribution analysis using RT-PCR reveals that the mRNA of the enzyme is expressed in various tissues, including liver, brain, prostate, adrenal, and uterus, with the most abundant expression in the liver. Because active hydroxysteroids generally exert their effect in a stereo-specific manner, 3(alpha-->beta)-HSE could thus potentially play an important role in regulating the biological activities of various steroids.

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.

Full frame distilled prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesInsufficient payload (model declined to judge)
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 score0.069
Threshold uncertainty score0.999

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
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)0.0020.000

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.

Opus teacher head0.022
GPT teacher head0.259
Teacher spread0.237 · 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