The importance of thiol availability to transsulfuration, antioxidant systems and mitochondrial H2S formation in the rat
Bibliographic record
Abstract
Sulphur containing amino acids play numerous roles in cellular system including protein synthesis, cell replication, a cellular defence mechanism and energy metabolism. Of the two-major sulphur containing amino acids, methionine is indispensable whereas cysteine is semi-essential considering cysteine can be synthesized from dietary methionine. During the metabolism of methionine, homocysteine is formed as an intermediate which holds a critical position between transsulfuration and transmethylation pathways. Metabolism of homocysteine through transsulfuration leads to the formation of cysteine which serves as a precursor for the major antioxidant glutathione (GSH) or hydrogen sulphide (H2S). A diet low in sulphur amino acids, known as methionine restriction (MR), increases lifespan in diverse species. Unconventional to lifespan extension mechanism, methionine restriction causes hyperhomocysteinemia and decreases tissue GSH levels in rodents. Linking the significance of sulphur amino acids, longevity and H2S, previously it has been proposed that increased H2S production delays the onset of aging and age-related aspects in nutritional restriction diets. Additionally, it has been suggested that the upregulation of transsulfuration pathway produces H2S in MR mice while hyperhomocysteinemia and low tissue GSH in MR animals indicate the opposite. Despite a declination of a major antioxidant GSH, how MR protects the cellular environment from pro-oxidants is not clear. Apart from transsulfuration, H2S can also be produced by the mercaptopyruvate sulfurtransferase (MPST). Along with other functions, H2S is reported to increase mitochondrial respiration rate. To generate H2S in in vitro, MPST require accessory reductant(s) and it is not known whether mitochondria also needs reductant(s) to release H2S which in turn enhances respiration rate. To investigate the link between homocysteine, H2S and GSH, we fed Fischer 344 rats MR and control diets. We found that MR impedes transsulfuration by inhibiting the cystathionine-β-synthase and simultaneously maintains H2S production capacity by enhancing alternate pathways. Methionine restriction increases the activity of thioredoxin reductase and glutathione reductase which can compensate for the low GSH level in cytosol and parallelly reduces reactive oxygen species production in mitochondria presumably by enhancing proton leak. Liver mitochondria assays from Sprague-Dawley rat further suggested that MPST require thioredoxin to enhance mitochondrial bioenergetics.
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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 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".