Fatty acid oxidation drives hydrogen peroxide production by α-ketoglutarate dehydrogenase
Bibliographic record
Abstract
Here, we conducted the first in-depth investigation into sex effects on mitochondrial hydrogen peroxide (mH 2 O 2 ) generation in hepatic tissue. Female liver mitochondria produce less mH 2 O 2 when oxidizing pyruvate, palmitoyl-carnitine, and succinate when compared to male samples. This difference was attributed to superior coupling between fuel metabolism and oxidative phosphorylation (OxPhos) in female liver mitochondria. Examination of mH 2 O 2 production by individual sites of generation revealed that KGDH was a major source in both male and female liver mitochondria oxidizing pyruvate and malate. Surprisingly, α-keto-β-methyl-n-valeric acid (KMV), a site-specific inhibitor for KGDH, nearly abolished mH 2 O 2 generation in both male and female liver mitochondria oxidizing palmitoyl-carnitine. KMV did not interfere with the fatty acid oxidation (FAO) pathway and was specific to KGDH. KMV inhibited mH 2 O 2 production in liver mitochondria from male and female mice oxidizing myristoyl, octanoyl, and butyryl-carnitine. We also supply evidence that KGDH, not complex I or complex III, is the major mH 2 O 2 generator in liver mitochondria. Together, we discovered KGDH is a major mH 2 O 2 source, regardless of sex and during FAO.
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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 | 0.001 |
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.
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".