Sec

evidence_span

{"source_cache": "artifacts/hbot-research/10801974.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1627b8b48962b6d2b9bead351b64b71fb60b9681378b44f77a3fc288d35119e3", "start_char": 0, "end_char": 1719, "text_sha256": "1627b8b48962b6d2b9bead351b64b71fb60b9681378b44f77a3fc288d35119e3"}

experimental_model

Chemical modification, peptide sequencing, mass spectrometry and redox titration of mammalian thioredoxin reductase

exposure

Oxidised and NADPH-reduced enzyme states

limitations

Enzyme chemistry on purified protein. It establishes the selenium-containing active site; it is not a statement about selenium intake.

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

Rat and human enzyme

plain_language

The enzyme’s working end is built from a selenium amino acid paired with a cysteine.

primary_references

[hbot-p10801974] Structure and mechanism of mammalian thioredoxin reductase: the active site is a redox-active selenolthiol/selenenylsulfide formed from the conserved cysteine-selenocysteine sequence. (2000). https://pubmed.ncbi.nlm.nih.gov/10801974/ DOI: 10.1073/pnas.100114897

tissue_or_cell_type

Purified enzyme

Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 452–463

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Chemical modification, peptide sequencing, mass spectrometry and redox titration of mammalian thioredoxin reductase · source_derived_draft · unverified_draft

### hbot-trxr-selenocysteine-site Mammalian thioredoxin reductase carries an essential selenocysteine in the conserved C-terminal sequence Gly-Cys-SeCys-Gly, forming a selenenylsulfide between Cys497 and SeCys498 that becomes a selenolthiol on reduction, alongside a separate Cys59-Cys64 disulfide identical to the glutathione reductase active site. 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 enzyme’s working end is built from a selenium amino acid paired with a cysteine. organism: Rat and human enzyme tissue_or_cell_type: Purified enzyme experimental_model: Chemical modification, peptide sequencing, mass spectrometry and redox titration of mammalian thioredoxin reductase limitations: Enzyme chemistry on purified protein. It establishes the selenium-containing active site; it is not a statement about selenium intake. exposure: Oxidised and NADPH-reduced enzyme states evidence_span: {"source_cache": "artifacts/hbot-research/10801974.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1627b8b48962b6d2b9bead351b64b71fb60b9681378b44f77a3fc288d35119e3", "start_char": 0, "end_char": 1719, "text_sha256": "1627b8b48962b6d2b9bead351b64b71fb60b9681378b44f77a3fc288d35119e3"} [hbot-p10801974] Structure and mechanism of mammalian thioredoxin reductase: the active site is a redox-active selenolthiol/selenenylsulfide formed from the conserved cysteine-selenocysteine sequence. (2000). https://pubmed.ncbi.nlm.nih.gov/10801974/ DOI: 10.1073/pnas.100114897

cell_type

liver-derived enzyme

experimental_model

Purified and recombinant enzyme

limitations

The original assay described elemental selenium; intracellular speciation remains separate.

organism

mouse

Selenium: literature corrections and mechanism additions · lines 510–520

Metabolic Ledger literature curation, 17 September 2026; primary papers linked individually · supports · Purified and recombinant enzyme · secondary_verified · secondary_verified

## scly-decomposes-selenocysteine SCLY recovers selenium from free selenocysteine. SCLY decomposes free L-selenocysteine, yielding L-alanine and released selenium. Organism: mouse Cell type: liver-derived enzyme Experimental model: Purified and recombinant enzyme Limitations: The original assay described elemental selenium; intracellular speciation remains separate. Primary reference: [cDNA cloning, purification, and characterization of mouse liver selenocysteine lyase. Candidate for selenium delivery protein in selenoprotein synthesis](https://pubmed.ncbi.nlm.nih.gov/10692412/)

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

Protein architecture distinguishes sulfur from selenium at a B6-dependent enzyme.

experimental_model

Recombinant human SCLY; structures and substrate assays

limitations

Engineered gain of function; physiological rates and clinical effects were not tested.

nutrient_topic

Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6

organism

Homo sapiens

plain_language

A specific enzyme residue helps distinguish selenium from sulfur substrates.

primary_references

[b6-scly-2012] Biochemical Discrimination between Selenium and Sulfur 1: A Single Residue Provides Selenium Specificity to Human Selenocysteine Lyase (2012). https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0030581 DOI: 10.1371/journal.pone.0030581

tissue_or_cell_type

Purified recombinant protein; no intact tissue

trigger_kind

machinery_impairment Imported condition classification; unverified.

Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 937–947

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human SCLY; structures and substrate assays · source_derived_draft · unverified_draft

### b6-met-scly-specificity Replacing Asp146 with lysine gave human SCLY detectable cysteine-desulfurase activity absent from wild-type activity assays. Condition category: machinery_impairment nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A specific enzyme residue helps distinguish selenium from sulfur substrates. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Recombinant human SCLY; structures and substrate assays limitations: Engineered gain of function; physiological rates and clinical effects were not tested. cross_nutrient: Protein architecture distinguishes sulfur from selenium at a B6-dependent enzyme. [b6-scly-2012] Biochemical Discrimination between Selenium and Sulfur 1: A Single Residue Provides Selenium Specificity to Human Selenocysteine Lyase (2012). https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0030581 DOI: 10.1371/journal.pone.0030581

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/hbot-research/10849437.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "13fe79ebefbddac9a76f4cae2e0f1aede8d648b6568adca72f0b0a550e66bc90", "start_char": 0, "end_char": 1374, "text_sha256": "13fe79ebefbddac9a76f4cae2e0f1aede8d648b6568adca72f0b0a550e66bc90"}

experimental_model

Recombinant rat thioredoxin reductase with selenocysteine mutations expressed in E. coli

exposure

SeCys498 replaced by cysteine or serine, and a truncated protein lacking the C-terminal SeCys-Gly dipeptide

limitations

The truncated construct is described by the authors as the form expected in selenium deficiency, which is what links this enzyme chemistry to nutrient supply. It remains a recombinant model, not a measurement in a selenium-deficient animal.

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

Rat enzyme in a bacterial expression host

plain_language

Swapping selenium for sulphur leaves an enzyme that barely works and only in the wrong conditions.

primary_references

[hbot-p10849437] Essential role of selenium in the catalytic activities of mammalian thioredoxin reductase revealed by characterization of recombinant enzymes with selenocysteine mutations. (2000). https://pubmed.ncbi.nlm.nih.gov/10849437/ DOI: 10.1074/jbc.m000690200

tissue_or_cell_type

Purified enzyme

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Hyperbaric oxygen: the exposure, its reactive species, the signals they carry, and the nutrient-dependent enzymes that handle them (2026-09-19) · lines 465–476

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant rat thioredoxin reductase with selenocysteine mutations expressed in E. coli · source_derived_draft · unverified_draft

### hbot-trxr-secys-mutant-activity The SeCys498 to Cys enzyme retained catalytic activity in thioredoxin reduction with a 100-fold lower kcat and a 10-fold lower Km, and its pH optimum shifted from 7 to 9, strongly suggesting involvement of the low-pKa selenol in the mechanism. Condition category: nutrient_deficiency 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: Swapping selenium for sulphur leaves an enzyme that barely works and only in the wrong conditions. organism: Rat enzyme in a bacterial expression host tissue_or_cell_type: Purified enzyme experimental_model: Recombinant rat thioredoxin reductase with selenocysteine mutations expressed in E. coli limitations: The truncated construct is described by the authors as the form expected in selenium deficiency, which is what links this enzyme chemistry to nutrient supply. It remains a recombinant model, not a measurement in a selenium-deficient animal. exposure: SeCys498 replaced by cysteine or serine, and a truncated protein lacking the C-terminal SeCys-Gly dipeptide evidence_span: {"source_cache": "artifacts/hbot-research/10849437.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "13fe79ebefbddac9a76f4cae2e0f1aede8d648b6568adca72f0b0a550e66bc90", "start_char": 0, "end_char": 1374, "text_sha256": "13fe79ebefbddac9a76f4cae2e0f1aede8d648b6568adca72f0b0a550e66bc90"} [hbot-p10849437] Essential role of selenium in the catalytic activities of mammalian thioredoxin reductase revealed by characterization of recombinant enzymes with selenocysteine mutations. (2000). https://pubmed.ncbi.nlm.nih.gov/10849437/ DOI: 10.1074/jbc.m000690200

evidence_access

Primary abstract

experimental_model

Human SepSecS–tRNA complex structure with enzyme assays.

limitations

Free phosphoserine and a phosphoserine residue on this specialized tRNA are not interchangeable substrates.

nutrient_topic

L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine

plain_language

The carrier and the cofactor are part of the reaction, not optional packaging.

primary_references

The human SepSecS-tRNASec complex reveals the mechanism of selenocysteine formation. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19608919/ · DOI 10.1126/science.1173755

L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 390–396

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human SepSecS–tRNA complex structure with enzyme assays. · source_derived_draft · unverified_draft

## l-serine-sepsecs-substrate The carrier and the cofactor are part of the reaction, not optional packaging. Human SepSecS structural and functional analysis supported correct positioning of tRNA-bound phosphoserine, but not free phosphoserine, for PLP-dependent selenocysteine formation. Model: Human SepSecS–tRNA complex structure with enzyme assays. Limitations: Free phosphoserine and a phosphoserine residue on this specialized tRNA are not interchangeable substrates. Evidence access: Primary abstract The human SepSecS-tRNASec complex reveals the mechanism of selenocysteine formation. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19608919/ · DOI 10.1126/science.1173755