Protein-incorporated selenocysteine residue

cross_nutrient

Selenium-containing DIO2 metabolizes iodine-containing T4.

evidence_locator

Primary abstract

evidence_spans

[{"source_document": "artifacts/iodine-metabolism-sources/8755651.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1406}]

experimental_model

Rat and human DIO2 cDNA cloning and characterization

exposure

DIO2 sequence and functional characterization; no nutritional intervention.

limitations

Protein composition does not establish a dietary threshold, benefit from extra selenium, or species-independent regulation.

nutrient_topic

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

organism

Human DIO2; study also characterized rat orthologue

plain_language

The T4-activating enzyme contains selenium as part of its protein structure.

primary_references

[i-met-8755651] Cloning of the mammalian type II iodothyronine deiodinase. A selenoprotein differentially expressed and regulated in human and rat brain and other tissues. (1996). https://pubmed.ncbi.nlm.nih.gov/8755651/ DOI: 10.1172/jci118806

tissue_or_cell_type

Human cDNA and expression characterization

Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 1114–1127

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat and human DIO2 cDNA cloning and characterization · source_derived_draft · unverified_draft

### i-met-human-dio2-selenoprotein Cloning and characterization of human DIO2 cDNA identified DIO2 as a selenoprotein. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The T4-activating enzyme contains selenium as part of its protein structure. organism: Human DIO2; study also characterized rat orthologue tissue_or_cell_type: Human cDNA and expression characterization experimental_model: Rat and human DIO2 cDNA cloning and characterization limitations: Protein composition does not establish a dietary threshold, benefit from extra selenium, or species-independent regulation. exposure: DIO2 sequence and functional characterization; no nutritional intervention. cross_nutrient: Selenium-containing DIO2 metabolizes iodine-containing T4. evidence_locator: Primary abstract evidence_spans: [{"source_document": "artifacts/iodine-metabolism-sources/8755651.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1406}] [i-met-8755651] Cloning of the mammalian type II iodothyronine deiodinase. A selenoprotein differentially expressed and regulated in human and rat brain and other tissues. (1996). https://pubmed.ncbi.nlm.nih.gov/8755651/ DOI: 10.1172/jci118806

evidence_span

{"source_cache": "artifacts/curcumin-research/15879598.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "be68f9ed2b0741db356a6bc020304fe832121f92dfd9c423ce8a305e984e995c", "start_char": 0, "end_char": 1659, "text_sha256": "be68f9ed2b0741db356a6bc020304fe832121f92dfd9c423ce8a305e984e995c"}

experimental_model

Purified rat enzyme and separate HeLa-cell assays

exposure

Rat enzyme: two-hour incubation, IC50 3.6 micromolar; HeLa activity IC50 about 15 micromolar

limitations

Rat residue numbering Cys496/Sec497 is source-specific and must not replace numbering in other TrxR constructs. Cellular enzyme activity does not prove clinical cancer benefit.

nutrient_topic

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

organism

Rattus norvegicus

plain_language

The interaction included the selenium-containing active-site residue.

primary_references

[curcumin-p15879598] Thioredoxin reductase is irreversibly modified by curcumin: a novel molecular mechanism for its anticancer activity. (2005). https://pubmed.ncbi.nlm.nih.gov/15879598/ DOI: 10.1074/jbc.m414645200

tissue_or_cell_type

Purified enzyme

Curcumin: metabolism, signaling and nutrient connections (2026-09-17) · lines 515–526

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified rat enzyme and separate HeLa-cell assays · source_derived_draft · unverified_draft

### curcumin-trx-adduct Mass spectrometry and blotting supported modification of Cys496 and Sec497 in the rat enzyme. Condition category: normal nutrient_topic: Curcumin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The interaction included the selenium-containing active-site residue. organism: Rattus norvegicus tissue_or_cell_type: Purified enzyme experimental_model: Purified rat enzyme and separate HeLa-cell assays limitations: Rat residue numbering Cys496/Sec497 is source-specific and must not replace numbering in other TrxR constructs. Cellular enzyme activity does not prove clinical cancer benefit. exposure: Rat enzyme: two-hour incubation, IC50 3.6 micromolar; HeLa activity IC50 about 15 micromolar evidence_span: {"source_cache": "artifacts/curcumin-research/15879598.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "be68f9ed2b0741db356a6bc020304fe832121f92dfd9c423ce8a305e984e995c", "start_char": 0, "end_char": 1659, "text_sha256": "be68f9ed2b0741db356a6bc020304fe832121f92dfd9c423ce8a305e984e995c"} [curcumin-p15879598] Thioredoxin reductase is irreversibly modified by curcumin: a novel molecular mechanism for its anticancer activity. (2005). https://pubmed.ncbi.nlm.nih.gov/15879598/ DOI: 10.1074/jbc.m414645200

evidence_span

{"source_cache": "artifacts/curcumin-research/15879598.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "be68f9ed2b0741db356a6bc020304fe832121f92dfd9c423ce8a305e984e995c", "start_char": 0, "end_char": 1659, "text_sha256": "be68f9ed2b0741db356a6bc020304fe832121f92dfd9c423ce8a305e984e995c"}

experimental_model

Purified rat enzyme and separate HeLa-cell assays

exposure

Rat enzyme: two-hour incubation, IC50 3.6 micromolar; HeLa activity IC50 about 15 micromolar

limitations

Rat residue numbering Cys496/Sec497 is source-specific and must not replace numbering in other TrxR constructs. Cellular enzyme activity does not prove clinical cancer benefit.

nutrient_topic

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

organism

Rattus norvegicus

plain_language

An enzyme that normally helps control oxidation was inhibited.

primary_references

[curcumin-p15879598] Thioredoxin reductase is irreversibly modified by curcumin: a novel molecular mechanism for its anticancer activity. (2005). https://pubmed.ncbi.nlm.nih.gov/15879598/ DOI: 10.1074/jbc.m414645200

tissue_or_cell_type

Purified enzyme

Curcumin: metabolism, signaling and nutrient connections (2026-09-17) · lines 502–513

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified rat enzyme and separate HeLa-cell assays · source_derived_draft · unverified_draft

### curcumin-trx-inhibition Curcumin inhibited NADPH-reduced rat TrxR1 and inhibition persisted after curcumin removal. Condition category: normal nutrient_topic: Curcumin research collection; topical membership is not evidence of a direct dietary effect. plain_language: An enzyme that normally helps control oxidation was inhibited. organism: Rattus norvegicus tissue_or_cell_type: Purified enzyme experimental_model: Purified rat enzyme and separate HeLa-cell assays limitations: Rat residue numbering Cys496/Sec497 is source-specific and must not replace numbering in other TrxR constructs. Cellular enzyme activity does not prove clinical cancer benefit. exposure: Rat enzyme: two-hour incubation, IC50 3.6 micromolar; HeLa activity IC50 about 15 micromolar evidence_span: {"source_cache": "artifacts/curcumin-research/15879598.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "be68f9ed2b0741db356a6bc020304fe832121f92dfd9c423ce8a305e984e995c", "start_char": 0, "end_char": 1659, "text_sha256": "be68f9ed2b0741db356a6bc020304fe832121f92dfd9c423ce8a305e984e995c"} [curcumin-p15879598] Thioredoxin reductase is irreversibly modified by curcumin: a novel molecular mechanism for its anticancer activity. (2005). https://pubmed.ncbi.nlm.nih.gov/15879598/ DOI: 10.1074/jbc.m414645200

evidence_span

{"source_cache": "artifacts/curcumin-research/15879598.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "be68f9ed2b0741db356a6bc020304fe832121f92dfd9c423ce8a305e984e995c", "start_char": 0, "end_char": 1659, "text_sha256": "be68f9ed2b0741db356a6bc020304fe832121f92dfd9c423ce8a305e984e995c"}

experimental_model

Purified rat enzyme and separate HeLa-cell assays

exposure

Rat enzyme: two-hour incubation, IC50 3.6 micromolar; HeLa activity IC50 about 15 micromolar

limitations

Rat residue numbering Cys496/Sec497 is source-specific and must not replace numbering in other TrxR constructs. Cellular enzyme activity does not prove clinical cancer benefit.

nutrient_topic

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

organism

Rattus norvegicus

plain_language

The modified protein could consume reducing power while promoting oxidation.

primary_references

[curcumin-p15879598] Thioredoxin reductase is irreversibly modified by curcumin: a novel molecular mechanism for its anticancer activity. (2005). https://pubmed.ncbi.nlm.nih.gov/15879598/ DOI: 10.1074/jbc.m414645200

tissue_or_cell_type

Purified enzyme

Curcumin: metabolism, signaling and nutrient connections (2026-09-17) · lines 528–539

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified rat enzyme and separate HeLa-cell assays · source_derived_draft · unverified_draft

### curcumin-trx-oxidase The modified enzyme acquired increased NADPH oxidase activity associated with reactive oxygen species production. Condition category: normal nutrient_topic: Curcumin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The modified protein could consume reducing power while promoting oxidation. organism: Rattus norvegicus tissue_or_cell_type: Purified enzyme experimental_model: Purified rat enzyme and separate HeLa-cell assays limitations: Rat residue numbering Cys496/Sec497 is source-specific and must not replace numbering in other TrxR constructs. Cellular enzyme activity does not prove clinical cancer benefit. exposure: Rat enzyme: two-hour incubation, IC50 3.6 micromolar; HeLa activity IC50 about 15 micromolar evidence_span: {"source_cache": "artifacts/curcumin-research/15879598.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "be68f9ed2b0741db356a6bc020304fe832121f92dfd9c423ce8a305e984e995c", "start_char": 0, "end_char": 1659, "text_sha256": "be68f9ed2b0741db356a6bc020304fe832121f92dfd9c423ce8a305e984e995c"} [curcumin-p15879598] Thioredoxin reductase is irreversibly modified by curcumin: a novel molecular mechanism for its anticancer activity. (2005). https://pubmed.ncbi.nlm.nih.gov/15879598/ DOI: 10.1074/jbc.m414645200

evidence_access

Primary abstract and publisher methods/results

experimental_model

Rat TrxR biochemical experiments.

limitations

Semiquinone mediation was proposed; do not treat the precise intermediate as directly proven.

nutrient_topic

Myricetin collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Myricetin

plain_language

The enzyme’s chemical state affects vulnerability.

primary_references

Inhibition of Mammalian thioredoxin reductase by some flavonoids: implications for myricetin and quercetin anticancer activity. · 2006 · https://pubmed.ncbi.nlm.nih.gov/16618767/ · DOI 10.1158/0008-5472.CAN-05-3310

Myricetin: metabolism, immune signaling, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 260–266

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat TrxR biochemical experiments. · source_derived_draft · unverified_draft

## myricetin-txnrd-active-site The enzyme’s chemical state affects vulnerability. Myricetin inhibition was time- and NADPH-dependent and involved the reduced C-terminal Cys-Sec-Gly active site. Model: Rat TrxR biochemical experiments. Limitations: Semiquinone mediation was proposed; do not treat the precise intermediate as directly proven. Evidence access: Primary abstract and publisher methods/results Inhibition of Mammalian thioredoxin reductase by some flavonoids: implications for myricetin and quercetin anticancer activity. · 2006 · https://pubmed.ncbi.nlm.nih.gov/16618767/ · DOI 10.1158/0008-5472.CAN-05-3310

evidence_access

Primary abstract and publisher methods/results

experimental_model

Recombinant rat TrxR; one-hour preincubation and DTNB assay.

limitations

Enzyme potency differs from cellular exposure; not human dietary selenium depletion.

nutrient_topic

Myricetin collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Myricetin

plain_language

A selenium-containing defense enzyme can be inhibited.

primary_references

Inhibition of Mammalian thioredoxin reductase by some flavonoids: implications for myricetin and quercetin anticancer activity. · 2006 · https://pubmed.ncbi.nlm.nih.gov/16618767/ · DOI 10.1158/0008-5472.CAN-05-3310

Myricetin: metabolism, immune signaling, redox chemistry and cross-nutrient mechanisms (2026-09-19) · lines 252–258

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Recombinant rat TrxR; one-hour preincubation and DTNB assay. · source_derived_draft · unverified_draft

## myricetin-txnrd-inhibition A selenium-containing defense enzyme can be inhibited. Myricetin inhibited NADPH-reduced recombinant rat TrxR1, IC50 0.62 micromolar after the reported preincubation. Model: Recombinant rat TrxR; one-hour preincubation and DTNB assay. Limitations: Enzyme potency differs from cellular exposure; not human dietary selenium depletion. Evidence access: Primary abstract and publisher methods/results Inhibition of Mammalian thioredoxin reductase by some flavonoids: implications for myricetin and quercetin anticancer activity. · 2006 · https://pubmed.ncbi.nlm.nih.gov/16618767/ · DOI 10.1158/0008-5472.CAN-05-3310

cross_nutrient

Selenium incorporation supports an enzyme that inactivates iodine-containing hormones.

evidence_locator

Primary abstract

evidence_spans

[{"source_document": "artifacts/iodine-metabolism-sources/7593630.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1405}]

experimental_model

Human placental DIO3 cDNA and heterologous expression, selenium labeling and SECIS manipulation

exposure

Cloned 2.1-kb DIO3 cDNA; 75Se labeling and SECIS-dependent expression.

limitations

Expression machinery experiment; not evidence for selenium dosing in pregnancy.

nutrient_topic

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

organism

Human placental protein in transfected cells

plain_language

The hormone-inactivating enzyme also needs the cellular system that incorporates selenium into proteins.

primary_references

[i-met-7593630] Type 3 lodothyronine deiodinase: cloning, in vitro expression, and functional analysis of the placental selenoenzyme. (1995). https://pubmed.ncbi.nlm.nih.gov/7593630/ DOI: 10.1172/jci118299

tissue_or_cell_type

DIO3 expression system

Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 1129–1142

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human placental DIO3 cDNA and heterologous expression, selenium labeling and SECIS manipulation · source_derived_draft · unverified_draft

### i-met-dio3-secis-expression The 3-prime-untranslated-region SECIS element was required for expression of cloned human placental DIO3, which incorporated 75Se in transfected cells. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The hormone-inactivating enzyme also needs the cellular system that incorporates selenium into proteins. organism: Human placental protein in transfected cells tissue_or_cell_type: DIO3 expression system experimental_model: Human placental DIO3 cDNA and heterologous expression, selenium labeling and SECIS manipulation limitations: Expression machinery experiment; not evidence for selenium dosing in pregnancy. exposure: Cloned 2.1-kb DIO3 cDNA; 75Se labeling and SECIS-dependent expression. cross_nutrient: Selenium incorporation supports an enzyme that inactivates iodine-containing hormones. evidence_locator: Primary abstract evidence_spans: [{"source_document": "artifacts/iodine-metabolism-sources/7593630.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1405}] [i-met-7593630] Type 3 lodothyronine deiodinase: cloning, in vitro expression, and functional analysis of the placental selenoenzyme. (1995). https://pubmed.ncbi.nlm.nih.gov/7593630/ DOI: 10.1172/jci118299

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_locator

Figure 3B and Results: Analysis of TH content and metabolism in the brain

evidence_spans

[{"source_document": "artifacts/iodine-metabolism-sources/24691440.txt", "locator": "Figure 3B and Results: Analysis of TH content and metabolism in the brain", "start_char": 26251, "end_char": 27951}]

experimental_model

Global Mct8 and Oatp1c1 single/double knockout mice, adult tracer experiments and P21 tissue assays

exposure

P21, n=8 per genotype; hormone content measurements.

limitations

The content result is local to mouse forebrain and this developmental time.

nutrient_topic

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

organism

Mus musculus

plain_language

Losing both transport routes overwhelms the compensation seen after one loss.

primary_references

[i-met-24691440] Transporters MCT8 and OATP1C1 maintain murine brain thyroid hormone homeostasis. (2014). https://pubmed.ncbi.nlm.nih.gov/24691440/ DOI: 10.1172/jci70324

tissue_or_cell_type

Perfused forebrain

trigger_kind

machinery_impairment Imported condition classification; unverified.

Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 996–1008

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Global Mct8 and Oatp1c1 single/double knockout mice, adult tracer experiments and P21 tissue assays · source_derived_draft · unverified_draft

### i-met-double-ko-brain-t3 At postnatal day 21, double-knockout forebrain T3 content was approximately 10% of wild type, whereas Oatp1c1 single-knockout forebrain T3 was preserved. Condition category: machinery_impairment nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Losing both transport routes overwhelms the compensation seen after one loss. organism: Mus musculus tissue_or_cell_type: Perfused forebrain experimental_model: Global Mct8 and Oatp1c1 single/double knockout mice, adult tracer experiments and P21 tissue assays limitations: The content result is local to mouse forebrain and this developmental time. exposure: P21, n=8 per genotype; hormone content measurements. evidence_locator: Figure 3B and Results: Analysis of TH content and metabolism in the brain evidence_spans: [{"source_document": "artifacts/iodine-metabolism-sources/24691440.txt", "locator": "Figure 3B and Results: Analysis of TH content and metabolism in the brain", "start_char": 26251, "end_char": 27951}] [i-met-24691440] Transporters MCT8 and OATP1C1 maintain murine brain thyroid hormone homeostasis. (2014). https://pubmed.ncbi.nlm.nih.gov/24691440/ DOI: 10.1172/jci70324

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

Selenium-containing D2 processes iodine-containing T4; genetic transport failure persists despite increased enzyme activity.

evidence_locator

Figure 4A and Results: Analysis of TH content and metabolism in the brain

evidence_spans

[{"source_document": "artifacts/iodine-metabolism-sources/24691440.txt", "locator": "Figure 4A and Results: Analysis of TH content and metabolism in the brain", "start_char": 26902, "end_char": 28402}]

experimental_model

Global Mct8 and Oatp1c1 single/double knockout mice, adult tracer experiments and P21 tissue assays

exposure

P21 double knockout versus wild type; D2 activity assay.

limitations

This is compensatory enzyme activity, not demonstration that selenium supplementation repairs transporter loss.

nutrient_topic

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

organism

Mus musculus

plain_language

The brain increases local hormone activation machinery, but this cannot replace missing substrate delivery.

primary_references

[i-met-24691440] Transporters MCT8 and OATP1C1 maintain murine brain thyroid hormone homeostasis. (2014). https://pubmed.ncbi.nlm.nih.gov/24691440/ DOI: 10.1172/jci70324

tissue_or_cell_type

Forebrain and cerebellum homogenates

trigger_kind

machinery_impairment Imported condition classification; unverified.

Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 1010–1023

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Global Mct8 and Oatp1c1 single/double knockout mice, adult tracer experiments and P21 tissue assays · source_derived_draft · unverified_draft

### i-met-double-ko-dio2-response D2 activity in P21 forebrain and cerebellum rose almost tenfold in Mct8/Oatp1c1 double-knockout mice despite persistent severe brain hormone depletion. Condition category: machinery_impairment nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The brain increases local hormone activation machinery, but this cannot replace missing substrate delivery. organism: Mus musculus tissue_or_cell_type: Forebrain and cerebellum homogenates experimental_model: Global Mct8 and Oatp1c1 single/double knockout mice, adult tracer experiments and P21 tissue assays limitations: This is compensatory enzyme activity, not demonstration that selenium supplementation repairs transporter loss. exposure: P21 double knockout versus wild type; D2 activity assay. cross_nutrient: Selenium-containing D2 processes iodine-containing T4; genetic transport failure persists despite increased enzyme activity. evidence_locator: Figure 4A and Results: Analysis of TH content and metabolism in the brain evidence_spans: [{"source_document": "artifacts/iodine-metabolism-sources/24691440.txt", "locator": "Figure 4A and Results: Analysis of TH content and metabolism in the brain", "start_char": 26902, "end_char": 28402}] [i-met-24691440] Transporters MCT8 and OATP1C1 maintain murine brain thyroid hormone homeostasis. (2014). https://pubmed.ncbi.nlm.nih.gov/24691440/ DOI: 10.1172/jci70324

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_locator

Figure 3A and Results: In vivo T4 transport studies

evidence_spans

[{"source_document": "artifacts/iodine-metabolism-sources/24691440.txt", "locator": "Figure 3A and Results: In vivo T4 transport studies", "start_char": 23660, "end_char": 25360}]

experimental_model

Global Mct8 and Oatp1c1 single/double knockout mice, adult tracer experiments and P21 tissue assays

exposure

Adults received 1.2 microcuries 125I-T4 intraperitoneally; n=3 per genotype and time point.

limitations

Tracer accumulation is a transport measurement; murine redundancy is not proof of equivalent human compensation.

nutrient_topic

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

organism

Mus musculus

plain_language

The two mouse transporters provide partly overlapping routes into the brain.

primary_references

[i-met-24691440] Transporters MCT8 and OATP1C1 maintain murine brain thyroid hormone homeostasis. (2014). https://pubmed.ncbi.nlm.nih.gov/24691440/ DOI: 10.1172/jci70324

tissue_or_cell_type

Brain after systemic tracer injection

trigger_kind

machinery_impairment Imported condition classification; unverified.

Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 982–994

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Global Mct8 and Oatp1c1 single/double knockout mice, adult tracer experiments and P21 tissue assays · source_derived_draft · unverified_draft

### i-met-double-ko-t4-entry Brain uptake of injected radiolabeled T4 was strongly reduced in Mct8/Oatp1c1 double-knockout mice; either single knockout retained roughly half the wild-type uptake. Condition category: machinery_impairment nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The two mouse transporters provide partly overlapping routes into the brain. organism: Mus musculus tissue_or_cell_type: Brain after systemic tracer injection experimental_model: Global Mct8 and Oatp1c1 single/double knockout mice, adult tracer experiments and P21 tissue assays limitations: Tracer accumulation is a transport measurement; murine redundancy is not proof of equivalent human compensation. exposure: Adults received 1.2 microcuries 125I-T4 intraperitoneally; n=3 per genotype and time point. evidence_locator: Figure 3A and Results: In vivo T4 transport studies evidence_spans: [{"source_document": "artifacts/iodine-metabolism-sources/24691440.txt", "locator": "Figure 3A and Results: In vivo T4 transport studies", "start_char": 23660, "end_char": 25360}] [i-met-24691440] Transporters MCT8 and OATP1C1 maintain murine brain thyroid hormone homeostasis. (2014). https://pubmed.ncbi.nlm.nih.gov/24691440/ DOI: 10.1172/jci70324

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

Selenium-incorporation machinery is required for hormone-processing selenoproteins; this is not dietary selenium deficiency.

evidence_locator

Primary abstract

evidence_spans

[{"source_document": "artifacts/iodine-metabolism-sources/16228000.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1084}]

experimental_model

Two human families with recessive SECISBP2 variants; patient fibroblast enzyme assays and linkage analysis

exposure

Inherited SECISBP2 variants; no dietary deprivation exposure.

limitations

Abstract-only; variant-specific kinetics and dietary rescue were not established.

nutrient_topic

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

organism

Homo sapiens

plain_language

A defect in selenium-incorporation machinery can impair thyroid-hormone processing even when the deiodinase gene is not the cause.

primary_references

[i-met-16228000] Mutations in SECISBP2 result in abnormal thyroid hormone metabolism. (2005). https://pubmed.ncbi.nlm.nih.gov/16228000/ DOI: 10.1038/ng1654

tissue_or_cell_type

Patient fibroblasts

trigger_kind

machinery_impairment Imported condition classification; unverified.

Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 1099–1112

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Two human families with recessive SECISBP2 variants; patient fibroblast enzyme assays and linkage analysis · source_derived_draft · unverified_draft

### i-met-secisbp2-fibroblast-dio2 Fibroblasts from affected siblings with a recessive SECISBP2 defect had reduced DIO2 activity; linkage did not map the defect to DIO2 itself. Condition category: machinery_impairment nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A defect in selenium-incorporation machinery can impair thyroid-hormone processing even when the deiodinase gene is not the cause. organism: Homo sapiens tissue_or_cell_type: Patient fibroblasts experimental_model: Two human families with recessive SECISBP2 variants; patient fibroblast enzyme assays and linkage analysis limitations: Abstract-only; variant-specific kinetics and dietary rescue were not established. exposure: Inherited SECISBP2 variants; no dietary deprivation exposure. cross_nutrient: Selenium-incorporation machinery is required for hormone-processing selenoproteins; this is not dietary selenium deficiency. evidence_locator: Primary abstract evidence_spans: [{"source_document": "artifacts/iodine-metabolism-sources/16228000.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1084}] [i-met-16228000] Mutations in SECISBP2 result in abnormal thyroid hormone metabolism. (2005). https://pubmed.ncbi.nlm.nih.gov/16228000/ DOI: 10.1038/ng1654