Histidine is a source of the antioxidant, α-ketoglutarate, in Pseudomonas fluorescens challenged by oxidative stress
Bibliographic record
Abstract
The role of alpha-ketoglutarate (KG) in the detoxification of reactive oxygen species (ROS) has only recently begun to be appreciated. This ketoacid neutralizes ROS in an NADPH-independent manner with the concomitant formation of succinate and CO(2). To further probe this intriguing attribute of KG in living systems, we have evaluated the significance of histidine metabolism in the model organism, Pseudomonas fluorescens, challenged by hydrogen peroxide (H(2)O(2)). Here, we show that this amino acid does contribute to KG homeostasis and appears to be earmarked for the production of KG during oxidative stress. Both the NAD- and the NADP-dependent glutamate dehydrogenases were upregulated in the stressed cells despite the sharp decline in the activities of numerous enzymes mediating the tricarboxylic acid cycle and oxidative phosphorylation. Enzymes such as isocitrate dehydrogenase-NAD dependent, succinate dehydrogenase, alpha-ketoglutarate dehydrogenase, Complex I, and Complex IV were severely affected in the P. fluorescens grown in the presence of H(2)O(2). Studies with fluorocitrate, a potent inhibitor of citrate metabolism, clearly revealed that histidine was preferentially utilized in the production of KG in the H(2)O(2)-challenged cells. Regulation experiments also helped confirm that the metabolic reprogramming, resulting in the enhanced production of KG was induced by H(2)O(2) stress. These data further establish the pivotal role that KG plays in antioxidative defense.
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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) | 0.001 | 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) | 0.000 | 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".