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Hydrophobic residues as a key determinant in hexoses exchange urate mechanism mediated by human glucose transporter 9, hSLC2A9

2013· article· en· W3171428211 on OpenAlexafffund
Wentong Long, Chris I. Cheeseman, Kate Witkowska

Bibliographic record

VenueThe FASEB Journal · 2013
Typearticle
Languageen
FieldMedicine
TopicGout, Hyperuricemia, Uric Acid
Canadian institutionsUniversity of Alberta
FundersCanadian Institutes of Health Research
KeywordsHyperuricemiaEffluxChemistryFructoseHexoseTransporterBiochemistryGlucose transporterMutantUric acidEnzymeBiologyEndocrinologyGeneInsulin

Abstract

fetched live from OpenAlex

Human GLUT9 (hSLC2A9) is a urate/hexose transporter expressed predominantly in the liver and kidney where human urate homeostasis is achieved. hSLC2A9 has two splice variants: 9a and 9b differing in their N‐termini and targeted differentially within polarized epithelia. The transporter shows trans‐acceleration between urate and hexoses, however, the mechanism is unknown. Hydrophobic residues in TM7 of GLUTs have been shown to play a role in hexose selectivity. Objective To investigate urate/hexose exchange mediated by SLC2A9 isoforms and their mutants. Methods hSLC2A9 isoforms and I335V mutants were overexpressed in X. laevis oocytes. Urate induced currents and I‐V curves were obtained using Two Micro‐Electrode Voltage Clamp (TEVC) recordings. Urate transport and hexose trans‐stimulation activities were determined by radiolabelled urate uptake and efflux measurements. Results TEVC studies demonstrated that the membrane potential plays a major role in urate transport mediated by hSLC2A9. Fructose was found to trans‐stimulate urate uptake and efflux in wild type hSLC2A9a; whereas it stimulates only urate efflux in the I335V mutant. These finding advance our understanding of how fructose intake is linked with serum urate levels and implicates hSLC2A9 as an important transporter that may contribute to pathophysiological conditions involving urate or fructose. Supported by CIHR.

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 score0.001
Threshold uncertainty score0.003

Distilled classifier scores by category (both heads)

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)0.0010.000

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 head0.014
GPT teacher head0.247
Teacher spread0.233 · 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
Published2013
Admission routes2
Has abstractyes

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