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Survey of the GLUT2 translocation pore for substrate selectivity determinants

2008· article· en· W2270133993 on OpenAlexaff
Kate Witkowska, Chris I. Cheeseman

Bibliographic record

VenueThe FASEB Journal · 2008
Typearticle
Languageen
FieldMedicine
TopicPancreatic function and diabetes
Canadian institutionsUniversity of Alberta
Fundersnot available
KeywordsGLUT2Chromosomal translocationChemistrySubstrate (aquarium)SelectivityKineticsFructoseXenopusBiophysicsBiochemistryBiologyGeneGene expressionCatalysis

Abstract

fetched live from OpenAlex

GLUT2 plays a major role in the absorption of nutrient hexoses, being expressed constitutively in the BLM and transiently in the apical membrane. This study's objective was to characterize motifs within TM 7 of GLUT2 which determine substrate specificity. When expressed in Xenopus oocytes, hGLUT1 transports fructose (FRU) at a rate of only 0.1% relative to glucose (GLU), while in GLUT2 they are equivalent. Mutating the NAV motif to NAI in GLUT1 increased FRU transport to approximately 0.9% (2.5 pmoles/oocyte/30 min with 100 μM substrate) relative to that of GLU. Mutating the molecular filter QLS in hGLUT1 to HVA also increased the relative rate of FRU transport (up to 0.5%) but to a lesser extent than the NAI mutation. Further, the combined hGLUT1 HVA‐NAI mutant had a relative FRU transport rate of 1.1 % (6 pmoles/oocyte/30 min at 100 μM substrate). Kinetic analysis for the hGLUT1 HVA‐NAI revealed that the Km for GLU was comparable to that of hGLUT1wt (1.5mM), while the Km for FRU was comparable to that for hGLUT2 (~70 mM). Thus, we have successfully introduced hGLUT2‐like FRU kinetics into hGLUT1, without affecting the GLU transport by this isoform. These results point to the presence of, at least two, selectivity filters within class I hGLUTs. NAV/NAI is the exofacial access filter, while QLS/HVA seems to allow FRU translocation beyond the substrate binding site without influencing GLU binding and/or translocation.

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 score0.004

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)0.0010.001

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 head0.056
GPT teacher head0.283
Teacher spread0.226 · 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
Published2008
Admission routes1
Has abstractyes

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