The hexosamine biosynthetic pathway couples growth factor-induced glutamine uptake to glucose metabolism
Bibliographic record
Abstract
Glucose and glutamine serve as the two primary carbon sources in proliferating cells, and uptake of both nutrients is directed by growth factor signaling. Although either glucose or glutamine can potentially support mitochondrial tricarboxylic acid (TCA) cycle integrity and ATP production, we found that glucose deprivation led to a marked reduction in glutamine uptake and progressive cellular atrophy in multiple mammalian cell types. Despite the continuous presence of growth factor and an abundant supply of extracellular glutamine, interleukin-3 (IL-3)-dependent cells were unable to maintain TCA cycle metabolite pools or receptor-dependent signal transduction when deprived of glucose. This was due at least in part to down-regulation of IL-3 receptor α (IL-3Rα) surface expression in the absence of glucose. Treatment of glucose-starved cells with N-acetylglucosamine (GlcNAc) to maintain hexosamine biosynthesis restored mitochondrial metabolism and cell growth by promoting IL-3-dependent glutamine uptake and metabolism. Thus, glucose metabolism through the hexosamine biosynthetic pathway is required to sustain sufficient growth factor signaling and glutamine uptake to support cell growth and survival.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 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 source (direct Gemma or distilled Codex), 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".