GPX1

experimental_model

Animal selenium status and erythrocyte glutathione-peroxidase biochemistry.

limitations

This experiment-specific relationship does not establish a human dietary-deficiency threshold or supplementation benefit.

organism

Rat

Selenium: literature corrections and mechanism additions · lines 954–963

Metabolic Ledger literature curation, 17 September 2026; primary papers linked individually · supports · Animal selenium status and erythrocyte glutathione-peroxidase biochemistry. · secondary_verified · secondary_verified

## gpx1-peroxide-reduction GPX1 uses glutathione to remove hydrogen peroxide. Classical GPX1 couples hydrogen-peroxide reduction to oxidation of reduced glutathione; water and glutathione disulfide are products. Experimental model: Animal selenium status and erythrocyte glutathione-peroxidase biochemistry. Organism: Rat Limitations: This experiment-specific relationship does not establish a human dietary-deficiency threshold or supplementation benefit. Primary reference: [Selenium: biochemical role as a component of glutathione peroxidase](https://pubmed.ncbi.nlm.nih.gov/4686466/)

availability_state

Selenium supply is restricted for a defined tissue, species, and duration.

experimental_scope

Predominantly animal and cell models; ranking varies with tissue, species, development, duration, and measurement.

limitations

Relative preservation does not mean immunity to severe loss. Um34 alone does not implement a universal ranking, and no plasma-to-protein cutoff is assigned.

trigger_kind

nutrient_deficiency

Selenium deficiency: a mechanism-first reference · lines 101–117

Supplied selenium deficiency reference · supports · Supplied reference; verify the primary study and experimental context. · source_derived_draft · unverified_draft

2.1 Protein hierarchy: useful, but schematic Different selenoproteins respond differently to selenium restriction. A useful conceptual grouping is: More selenium-responsive in many models Intermediate / context-dependent Relatively preserved in severe restriction GPX1, SELENOW GPX3, SELENOP, DIO1, SELENOK, SELENOM GPX4, TXNRD1, DIO2, SEPHS2 This is a schematic hierarchy, not a literal universal sequence of death. Ordering varies with tissue, species, developmental stage, duration of deficiency, and how the endpoint is measured.

Selenium deficiency: a mechanism-first reference · lines 287–293

Supplied selenium deficiency reference · supports · Supplied reference; verify the primary study and experimental context. · source_derived_draft · unverified_draft

GPX1 activity ↓ Often strongly selenium-responsive GPX1 mRNA ↓ in susceptible models NMD can contribute

cell_type

intestinal epithelium

experimental_model

Gpx2 knockout

limitations

Compensation did not erase the crypt phenotype.

organism

mouse

Selenium: literature corrections and mechanism additions · lines 666–676

Metabolic Ledger literature curation, 17 September 2026; primary papers linked individually · supports · Gpx2 knockout · secondary_verified · secondary_verified

## gpx2-loss-increases-gpx1-protein GPX1 protein rose as an incomplete compensatory response. Gpx2 deletion increased intestinal GPX1 protein without a matching mRNA increase. Organism: mouse Cell type: intestinal epithelium Experimental model: Gpx2 knockout Limitations: Compensation did not erase the crypt phenotype. Primary reference: [Loss of GPx2 increases apoptosis, mitosis, and GPx1 expression in the intestine of mice](https://pubmed.ncbi.nlm.nih.gov/20828612/)

cell_type

Mouse tissues and human melanoma cells

experimental_model

Transgenic mouse tRNA replacement; mutant affects i6A37 as well as Um34; Biochemistry, human melanoma cells and mouse metastasis/xenograft models

limitations

Older tRNA mutant also affects i6A37; no universal exclusive stress/housekeeping routing.

organism

Mus musculus and Homo sapiens

Selenium: literature corrections and mechanism additions · lines 1178–1189

Metabolic Ledger literature curation, 17 September 2026; primary papers linked individually · supports · Transgenic mouse tRNA replacement; mutant affects i6A37 as well as Um34; Biochemistry, human melanoma cells and mouse metastasis/xenograft models · secondary_verified · secondary_verified

## um34-selective This tRNA modification helps make some selenium proteins more than others. Sec-tRNA Um34 modification contributes to efficient expression of selected stress-responsive selenoproteins including GPX1. Organism: Mus musculus and Homo sapiens Cell type: Mouse tissues and human melanoma cells Experimental model: Transgenic mouse tRNA replacement; mutant affects i6A37 as well as Um34; Biochemistry, human melanoma cells and mouse metastasis/xenograft models Limitations: Older tRNA mutant also affects i6A37; no universal exclusive stress/housekeeping routing. Primary reference: [Selective rescue of selenoprotein expression in mice lacking a highly specialized methyl group in selenocysteine tRNA](https://digitalcommons.unl.edu/biochemgladyshev/54/) Primary reference: [Selenocysteine tRNA methylation promotes oxidative stress resistance in melanoma metastasis](https://www.nature.com/articles/s43018-024-00844-8)

evidence_span

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experimental_model

Twelve patients sampled at the first and fifteenth hyperbaric session

exposure

Fifteen hyperbaric oxygen treatments without antioxidant supplementation

limitations

A small human series without a control group. The fall in enzyme activity may reflect oxidative modification of the enzymes themselves, which the authors state was still under investigation.

nutrient_topic

Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

organism

Human

plain_language

The selenium-dependent enzyme and the vitamin pools held steady while two other enzymes fell.

primary_references

[hbot-p15003734] Oxidative stress and antioxidant status in patients undergoing prolonged exposure to hyperbaric oxygen. (2004). https://pubmed.ncbi.nlm.nih.gov/15003734/ DOI: 10.1016/j.clinbiochem.2003.12.001

tissue_or_cell_type

Plasma and erythrocytes

Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 270–281

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Twelve patients sampled at the first and fifteenth hyperbaric session · source_derived_draft · unverified_draft

### hbot-gpx-unchanged Glutathione peroxidase activity remained almost unchanged, and no relevant differences were detected in reduced glutathione, alpha-tocopherol or retinol plasma levels. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: The selenium-dependent enzyme and the vitamin pools held steady while two other enzymes fell. organism: Human tissue_or_cell_type: Plasma and erythrocytes experimental_model: Twelve patients sampled at the first and fifteenth hyperbaric session limitations: A small human series without a control group. The fall in enzyme activity may reflect oxidative modification of the enzymes themselves, which the authors state was still under investigation. exposure: Fifteen hyperbaric oxygen treatments without antioxidant supplementation evidence_span: {"source_cache": "artifacts/hbot-research/15003734.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5e4b6cef5c64b735c97ae362e7a90c76433e3f8fef2978d3b3b2a584016e506f", "start_char": 0, "end_char": 1432, "text_sha256": "5e4b6cef5c64b735c97ae362e7a90c76433e3f8fef2978d3b3b2a584016e506f"} [hbot-p15003734] Oxidative stress and antioxidant status in patients undergoing prolonged exposure to hyperbaric oxygen. (2004). https://pubmed.ncbi.nlm.nih.gov/15003734/ DOI: 10.1016/j.clinbiochem.2003.12.001

evidence_span

{"source_cache": "artifacts/hbot-research/15642322.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e3bc035a17e4e19dd92d4fadb1a79f8e3801619dac24fb91dcf985728afaf995", "start_char": 0, "end_char": 2646, "text_sha256": "e3bc035a17e4e19dd92d4fadb1a79f8e3801619dac24fb91dcf985728afaf995"}

experimental_model

Cultured human lens epithelial cells exposed to extreme hyperbaric oxygen with enzyme assays and real-time PCR

exposure

99% oxygen at 50 atmospheres for 3 hours, then normal culture for up to 11 days

limitations

Fifty atmospheres is an extreme experimental exposure far above therapy, chosen to probe which defences matter. The selenoenzyme result is the informative part; the pressure is not clinically relevant.

nutrient_topic

Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Hyperbaric oxygen therapy

organism

Human cells

plain_language

The cell rebuilt exactly three proteins: the heme enzyme, the manganese enzyme and the selenium enzyme.

primary_references

[hbot-p15642322] Thioredoxin reductase may be essential for the normal growth of hyperbaric oxygen-treated human lens epithelial cells. (2004). https://pubmed.ncbi.nlm.nih.gov/15642322/ DOI: 10.1016/j.exer.2004.07.001

tissue_or_cell_type

Lens epithelium

Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 426–437

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cultured human lens epithelial cells exposed to extreme hyperbaric oxygen with enzyme assays and real-time PCR · source_derived_draft · unverified_draft

### hbot-trxr-mrna-response Messenger RNA for heme oxygenase-1, manganese superoxide dismutase and cytoplasmic thioredoxin reductase 1 rose three- to six-fold nine hours after exposure, with heme oxygenase-1 rising a few hours before manganese superoxide dismutase, while catalase, copper-zinc superoxide dismutase, glutathione reductase, glutathione peroxidase and thioredoxin did not change. Condition category: normal nutrient_topic: Hyperbaric oxygen research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: The cell rebuilt exactly three proteins: the heme enzyme, the manganese enzyme and the selenium enzyme. organism: Human cells tissue_or_cell_type: Lens epithelium experimental_model: Cultured human lens epithelial cells exposed to extreme hyperbaric oxygen with enzyme assays and real-time PCR limitations: Fifty atmospheres is an extreme experimental exposure far above therapy, chosen to probe which defences matter. The selenoenzyme result is the informative part; the pressure is not clinically relevant. exposure: 99% oxygen at 50 atmospheres for 3 hours, then normal culture for up to 11 days evidence_span: {"source_cache": "artifacts/hbot-research/15642322.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e3bc035a17e4e19dd92d4fadb1a79f8e3801619dac24fb91dcf985728afaf995", "start_char": 0, "end_char": 2646, "text_sha256": "e3bc035a17e4e19dd92d4fadb1a79f8e3801619dac24fb91dcf985728afaf995"} [hbot-p15642322] Thioredoxin reductase may be essential for the normal growth of hyperbaric oxygen-treated human lens epithelial cells. (2004). https://pubmed.ncbi.nlm.nih.gov/15642322/ DOI: 10.1016/j.exer.2004.07.001

duration

Not stated here

evidence_access

Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.

experimental_model

RAW 264.7 murine macrophages

exposure

(+)-Lariciresinol

limitations

Expression levels, not enzyme activity assays.

organism

RAW 264.7 murine macrophages

plain_language

(+)-Lariciresinol raised superoxide dismutase, glutathione peroxidase and catalase at transcript and protein level.

primary_references

Antioxidant efficacy and the upregulation of Nrf2-mediated HO-1 expression by (+)-lariciresinol, a lignan isolated from Rubia philippinensis, through the activation of p38. (2017). https://pubmed.ncbi.nlm.nih.gov/28378774/ DOI: 10.1038/srep46035

route

In vitro

tissue

Antioxidant enzyme expression

Lariciresinol: five molecules under one name, and the mechanisms each one carries (2026-09-22) · lines 55–64

Original AI-assisted curation of twelve primary studies, every abstract read and all DOIs cross-checked against live PubMed metadata. Mechanism edges only, with no conclusion or claim of benefit recorded. Three author clusters account for eight of the twelve and carry shared laboratory keys. Study-specific concentrations, negative findings and limitations retained. Not publisher full text. · supports · · source_derived_draft · unverified_draft

## plus-lariciresinol-raises-antioxidant-enzymes (+)-Lariciresinol raised superoxide dismutase, glutathione peroxidase and catalase at transcript and protein level. Model/species: RAW 264.7 murine macrophages Tissue/system: Antioxidant enzyme expression Exposure: (+)-Lariciresinol Route: In vitro Duration: Not stated here Limits: Expression levels, not enzyme activity assays. Primary reference: Antioxidant efficacy and the upregulation of Nrf2-mediated HO-1 expression by (+)-lariciresinol, a lignan isolated from Rubia philippinensis, through the activation of p38. (2017). https://pubmed.ncbi.nlm.nih.gov/28378774/ DOI: 10.1038/srep46035 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.