Impact of the AMPK gamma2 R302Q Mutation on Human Skeletal Muscle Metabolism
Bibliographic record
Abstract
AMP-activated protein kinase, AMPK, is a heterotrimeric protein complex comprised of an alpha catalytic, and of beta and gamma regulatory subunits. It is widely conserved across most organisms and is commonly referred to as the master regulator of cellular metabolism. By responding to increases in the AMP:ATP ratio, AMPK promotes ATP producing catabolic pathways, while simultaneously inhibiting ATP consuming anabolic pathways. Naturally occurring mutations in AMPK exist in various organisms and these can have a severe impact on fuel storage and metabolism. One such mutation in humans is the R302Q mutation in the gamma2 subunit; the outcome is accelerated glycogen production and impaired electrical conductance within the heart, resulting in Wolff-Parkinson White (WPW) syndrome. The impact of this rare mutation on AMPK activity is not well understood. By examining skeletal muscle samples from affected patients from the Ottawa region, we strove to determine the impact of the R302Q mutation on AMPK activity, and skeletal muscle metabolism. Skeletal muscle biopsies were utilized for histological analyses and cell culture determinations of fuel storage and AMPK activity. Trends for decreased triglyceride storage and increased glycogen storage, as well as impaired basal and AMP-stimulated AMPK activity were observed in the affected patient populations. Corollary work done in an adenoviral infected C2C12 muscle cell line expressing human gamma2 WT or the R302Q variant yielded no difference between groups in fuel storage or protein phosphorylation due to limitations (infection efficiency) of this model.
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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 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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".