Human thyroglobulin

evidence_access

Primary abstract

experimental_model

Human TG expressed in HEK293T cells; cryo-EM and in vitro hormone assays.

limitations

This does not mean free tyrosine is directly iodinated into circulating thyroid hormone.

nutrient_topic

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

plain_language

The thyroid uses selected tyrosines already built into a protein.

primary_references

The structure of human thyroglobulin. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32025030/ · DOI 10.1038/s41586-020-1995-4

L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 132–138

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human TG expressed in HEK293T cells; cryo-EM and in vitro hormone assays. · source_derived_draft · unverified_draft

## l-tyrosine-tg-iodinated-pairs The thyroid uses selected tyrosines already built into a protein. Human thyroglobulin cryo-EM and site-directed mutagenesis identified tyrosine donor-acceptor pairs supporting hormone formation in vitro. Model: Human TG expressed in HEK293T cells; cryo-EM and in vitro hormone assays. Limitations: This does not mean free tyrosine is directly iodinated into circulating thyroid hormone. Evidence access: Primary abstract The structure of human thyroglobulin. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32025030/ · DOI 10.1038/s41586-020-1995-4

availability_state

biomarker_context Imported condition classification; unverified.

cross_nutrient

false

evidence_location

Primary indexed abstract.

experimental_model

Assay-standardization study in 700 iodine-sufficient euthyroid anti-Tg-antibody-negative children aged 5–14 and separate 10-month iodized-salt intervention

exposure

International reference sample and longitudinal measurements before, 5 months and 10 months after salt iodization in deficient children.

limitations

Assay-specific pediatric reference distribution; not a universal adult/pregnancy threshold. Anti-Tg-antibody-positive children were excluded from the reference sample; antibody interference and other thyroid diseases remain relevant.

nutrient_topic

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

organism

Homo sapiens

plain_language

The study established a reference distribution for a particular pediatric assay.

primary_references

[iod-clin-tg2006] Assessment of iodine status using dried blood spot thyroglobulin: development of reference material and establishment of an international reference range in iodine-sufficient children. (2006). https://pubmed.ncbi.nlm.nih.gov/16968789/ DOI: 10.1210/jc.2006-1370

tissue_or_cell_type

Dried whole-blood thyroglobulin assay

trigger_kind

biomarker_context Imported condition classification; unverified.

Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 1594–1606

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Assay-standardization study in 700 iodine-sufficient euthyroid anti-Tg-antibody-negative children aged 5–14 and separate 10-month iodized-salt intervention · source_derived_draft · unverified_draft

### iod-clin-dbs-tg-reference The third and 97th percentiles of the standardized dried-blood-spot Tg assay were 4 and 40 micrograms/L in the 700 iodine-sufficient, euthyroid, anti-Tg-negative children. Condition category: biomarker_context nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The study established a reference distribution for a particular pediatric assay. organism: Homo sapiens tissue_or_cell_type: Dried whole-blood thyroglobulin assay experimental_model: Assay-standardization study in 700 iodine-sufficient euthyroid anti-Tg-antibody-negative children aged 5–14 and separate 10-month iodized-salt intervention limitations: Assay-specific pediatric reference distribution; not a universal adult/pregnancy threshold. Anti-Tg-antibody-positive children were excluded from the reference sample; antibody interference and other thyroid diseases remain relevant. exposure: International reference sample and longitudinal measurements before, 5 months and 10 months after salt iodization in deficient children. cross_nutrient: false evidence_location: Primary indexed abstract. [iod-clin-tg2006] Assessment of iodine status using dried blood spot thyroglobulin: development of reference material and establishment of an international reference range in iodine-sufficient children. (2006). https://pubmed.ncbi.nlm.nih.gov/16968789/ DOI: 10.1210/jc.2006-1370

evidence_span

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experimental_model

Thyroid safety analysis within a randomized beverage trial

exposure

Baseline and 84 days of glucoraphanin/sulforaphane-rich beverage

limitations

Subsample safety analysis; not all populations, iodine-deficient states, products, doses or lifelong exposure.

nutrient_topic

Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. · Sulforaphane / SFN, stereochemistry specified per study

organism

Human, 45 women

plain_language

This preparation showed no thyroid signal under the conditions tested; that is not universal thyroid safety proof.

primary_references

[sulforaphane-p30735751] Broccoli sprout beverage is safe for thyroid hormonal and autoimmune status: Results of a 12-week randomized trial. (2019). https://pubmed.ncbi.nlm.nih.gov/30735751/ DOI: 10.1016/j.fct.2019.02.004

tissue_or_cell_type

Serum thyroid hormones, thyroglobulin and autoimmunity

Sulforaphane: formation, electrophile sensing and nutrient connections (2026-09-17) · lines 1217–1228

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Thyroid safety analysis within a randomized beverage trial · source_derived_draft · unverified_draft

### sulforaphane-thyroid-markers TSH, free thyroxine, thyroglobulin and thyroid autoimmunity status were not affected in this 84-day analysis. Condition category: normal nutrient_topic: Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. plain_language: This preparation showed no thyroid signal under the conditions tested; that is not universal thyroid safety proof. organism: Human, 45 women tissue_or_cell_type: Serum thyroid hormones, thyroglobulin and autoimmunity experimental_model: Thyroid safety analysis within a randomized beverage trial limitations: Subsample safety analysis; not all populations, iodine-deficient states, products, doses or lifelong exposure. exposure: Baseline and 84 days of glucoraphanin/sulforaphane-rich beverage evidence_span: {"source_cache": "artifacts/sulforaphane-research/30735751.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0797bbf31c4a1fa8cf002b8752410e80a92e8a351c44273335bc52f19e66b2ea", "start_char": 0, "end_char": 1494, "text_sha256": "0797bbf31c4a1fa8cf002b8752410e80a92e8a351c44273335bc52f19e66b2ea"} [sulforaphane-p30735751] Broccoli sprout beverage is safe for thyroid hormonal and autoimmune status: Results of a 12-week randomized trial. (2019). https://pubmed.ncbi.nlm.nih.gov/30735751/ DOI: 10.1016/j.fct.2019.02.004

evidence_access

Primary abstract

experimental_model

Human TG and engineered bacterial maltose-binding-protein hormone-production assays.

limitations

The engineered bacterial scaffold is an in vitro demonstration, not a physiological human alternative.

nutrient_topic

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

plain_language

Having the building blocks is not enough; their arrangement matters.

primary_references

The structure of human thyroglobulin. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32025030/ · DOI 10.1038/s41586-020-1995-4

L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 140–146

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human TG and engineered bacterial maltose-binding-protein hormone-production assays. · source_derived_draft · unverified_draft

## l-tyrosine-tg-geometry Having the building blocks is not enough; their arrangement matters. Mutational and engineered-scaffold experiments implicated tyrosine proximity, flexibility and solvent exposure in hormone formation. Model: Human TG and engineered bacterial maltose-binding-protein hormone-production assays. Limitations: The engineered bacterial scaffold is an in vitro demonstration, not a physiological human alternative. Evidence access: Primary abstract The structure of human thyroglobulin. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32025030/ · DOI 10.1038/s41586-020-1995-4

availability_state

biomarker_context Imported condition classification; unverified.

cross_nutrient

false

evidence_location

Primary indexed abstract.

experimental_model

Assay-standardization study in 700 iodine-sufficient euthyroid anti-Tg-antibody-negative children aged 5–14 and separate 10-month iodized-salt intervention

exposure

International reference sample and longitudinal measurements before, 5 months and 10 months after salt iodization in deficient children.

limitations

Assay-specific pediatric reference distribution; not a universal adult/pregnancy threshold. Anti-Tg-antibody-positive children were excluded from the reference sample; antibody interference and other thyroid diseases remain relevant.

nutrient_topic

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

organism

Homo sapiens

plain_language

This thyroglobulin assay tracked the population’s response to iodine repletion.

primary_references

[iod-clin-tg2006] Assessment of iodine status using dried blood spot thyroglobulin: development of reference material and establishment of an international reference range in iodine-sufficient children. (2006). https://pubmed.ncbi.nlm.nih.gov/16968789/ DOI: 10.1210/jc.2006-1370

tissue_or_cell_type

Dried whole-blood thyroglobulin assay

trigger_kind

biomarker_context Imported condition classification; unverified.

Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 1580–1592

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Assay-standardization study in 700 iodine-sufficient euthyroid anti-Tg-antibody-negative children aged 5–14 and separate 10-month iodized-salt intervention · source_derived_draft · unverified_draft

### iod-clin-dbs-tg-response Median dried-blood-spot thyroglobulin fell from 49 to 13 and 8 micrograms/L at 5 and 10 months after iodized salt introduction; proportions above 40 micrograms/L fell from over two thirds to 7% and 3%. Condition category: biomarker_context nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: This thyroglobulin assay tracked the population’s response to iodine repletion. organism: Homo sapiens tissue_or_cell_type: Dried whole-blood thyroglobulin assay experimental_model: Assay-standardization study in 700 iodine-sufficient euthyroid anti-Tg-antibody-negative children aged 5–14 and separate 10-month iodized-salt intervention limitations: Assay-specific pediatric reference distribution; not a universal adult/pregnancy threshold. Anti-Tg-antibody-positive children were excluded from the reference sample; antibody interference and other thyroid diseases remain relevant. exposure: International reference sample and longitudinal measurements before, 5 months and 10 months after salt iodization in deficient children. cross_nutrient: false evidence_location: Primary indexed abstract. [iod-clin-tg2006] Assessment of iodine status using dried blood spot thyroglobulin: development of reference material and establishment of an international reference range in iodine-sufficient children. (2006). https://pubmed.ncbi.nlm.nih.gov/16968789/ DOI: 10.1210/jc.2006-1370

cross_nutrient

false

evidence_span

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experimental_model

Purified hog TPO with human goiter TG or tyrosine-radiolabeled hog TG; chromatographic hormone and dehydroalanine analyses

exposure

Hog TPO with human goiter TG and radiolabeled hog TG; dehydroalanine quantified after benzyl-mercaptan addition or borohydride reduction and hydrolysis.

limitations

Chemical trapping identifies the retained donor remnant; it does not prove every proposed radical intermediate or identify individual T3 donor sites.

nutrient_topic

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

organism

Sus scrofa enzyme; Homo sapiens and Sus scrofa TG in separate experiments

plain_language

Coupling leaves a dehydroalanine remnant on the donor side of TG while creating a hormone residue.

primary_references

[iodine-syn-tpo-coupling1980] Formation of dehydroalanine residues during thyroid hormone synthesis in thyroglobulin. (1980). https://pubmed.ncbi.nlm.nih.gov/7372636/ DOI: 10.1016/S0021-9258(19)70782-0

tissue_or_cell_type

Purified-protein reactions

Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 870–882

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified hog TPO with human goiter TG or tyrosine-radiolabeled hog TG; chromatographic hormone and dehydroalanine analyses · source_derived_draft · unverified_draft

### iodine-syn-coupling-dehydroalanine During TPO-catalyzed hormone formation in TG, approximately one protein-bound dehydroalanine residue was formed per hormone residue. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Coupling leaves a dehydroalanine remnant on the donor side of TG while creating a hormone residue. organism: Sus scrofa enzyme; Homo sapiens and Sus scrofa TG in separate experiments tissue_or_cell_type: Purified-protein reactions experimental_model: Purified hog TPO with human goiter TG or tyrosine-radiolabeled hog TG; chromatographic hormone and dehydroalanine analyses limitations: Chemical trapping identifies the retained donor remnant; it does not prove every proposed radical intermediate or identify individual T3 donor sites. exposure: Hog TPO with human goiter TG and radiolabeled hog TG; dehydroalanine quantified after benzyl-mercaptan addition or borohydride reduction and hydrolysis. cross_nutrient: false evidence_span: {"source_cache": "artifacts/iodine-synthesis-sources/7372636.txt", "start_char": 1081, "end_char": 2101, "text_sha256": "5ea5287db6f28391150ad5b783a0be5e450fd71f22b92028fefb7900c686c636", "text_characters": 1020, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."} [iodine-syn-tpo-coupling1980] Formation of dehydroalanine residues during thyroid hormone synthesis in thyroglobulin. (1980). https://pubmed.ncbi.nlm.nih.gov/7372636/ DOI: 10.1016/S0021-9258(19)70782-0

cross_nutrient

true

evidence_span

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experimental_model

Human TG cryo-EM, recombinant HEK293T-expressed TG and site-directed mutants

exposure

Extended Data Fig.6c: 0.1 micromolar TG, 1 mM KI, glucose/glucose oxidase peroxide supply, 10 minutes at 37 C; TPO added at fivefold the LPO concentration to compensate for approximately 20% heme occupancy; T4 measured after Pronase digestion.

limitations

This identifies the TPO-containing assay arm; most TG mutagenesis experiments used LPO. The measured T4 was liberated by assay proteolysis after formation on TG.

nutrient_topic

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

organism

Homo sapiens TG and TPO; HEK293T TG expression and insect-cell TPO expression

plain_language

Human TPO can drive hormone formation on human thyroglobulin.

primary_references

[iodine-syn-tg2020] The structure of human thyroglobulin. (2020). https://pubmed.ncbi.nlm.nih.gov/32025030/ DOI: 10.1038/s41586-020-1995-4

tissue_or_cell_type

Purified-protein reconstitution

Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 842–854

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human TG cryo-EM, recombinant HEK293T-expressed TG and site-directed mutants · source_derived_draft · unverified_draft

### iodine-syn-human-tpo-t4-synthesis Recombinant human TPO catalyzed T4 formation from recombinant human TG in the direct TPO-versus-lactoperoxidase comparison. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Human TPO can drive hormone formation on human thyroglobulin. organism: Homo sapiens TG and TPO; HEK293T TG expression and insect-cell TPO expression tissue_or_cell_type: Purified-protein reconstitution experimental_model: Human TG cryo-EM, recombinant HEK293T-expressed TG and site-directed mutants limitations: This identifies the TPO-containing assay arm; most TG mutagenesis experiments used LPO. The measured T4 was liberated by assay proteolysis after formation on TG. exposure: Extended Data Fig.6c: 0.1 micromolar TG, 1 mM KI, glucose/glucose oxidase peroxide supply, 10 minutes at 37 C; TPO added at fivefold the LPO concentration to compensate for approximately 20% heme occupancy; T4 measured after Pronase digestion. cross_nutrient: true evidence_span: {"source_cache": "artifacts/iodine-synthesis-sources/32025030.txt", "start_char": 37661, "end_char": 38631, "text_sha256": "edbab2cbd62ebd263ef59f543f10aad3692d3a3983ef5abad904e697ea34ca04", "text_characters": 970, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."} [iodine-syn-tg2020] The structure of human thyroglobulin. (2020). https://pubmed.ncbi.nlm.nih.gov/32025030/ DOI: 10.1038/s41586-020-1995-4

cross_nutrient

false

evidence_span

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experimental_model

Human TG cryo-EM, recombinant HEK293T-expressed TG and site-directed mutants

exposure

0.1 micromolar human TG, 1 mM KI, 24 mM glucose, 2 micrograms/mL glucose oxidase and 3 micrograms/mL lactoperoxidase; 10 minutes at 37 C followed by approximately 2.5 micrograms/mL Pronase and T4 ELISA. Most assays used lactoperoxidase after comparison with human TPO. Four acceptor substitutions.

limitations

Engineered multi-site mutant; no human congenital phenotype inferred.

nutrient_topic

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

organism

Homo sapiens TG

plain_language

Four hormone-forming acceptor sites account for the measured T4 production.

primary_references

[iodine-syn-tg2020] The structure of human thyroglobulin. (2020). https://pubmed.ncbi.nlm.nih.gov/32025030/ DOI: 10.1038/s41586-020-1995-4

tissue_or_cell_type

Purified-protein reaction

Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 632–644

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human TG cryo-EM, recombinant HEK293T-expressed TG and site-directed mutants · source_derived_draft · unverified_draft

### iodine-syn-tg-acceptor-mutants Replacing human TG acceptors Y24, Y2573, Y2766 and Y1310 with phenylalanine eliminated detectable T4 formation in the reconstituted assay. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Four hormone-forming acceptor sites account for the measured T4 production. organism: Homo sapiens TG tissue_or_cell_type: Purified-protein reaction experimental_model: Human TG cryo-EM, recombinant HEK293T-expressed TG and site-directed mutants limitations: Engineered multi-site mutant; no human congenital phenotype inferred. exposure: 0.1 micromolar human TG, 1 mM KI, 24 mM glucose, 2 micrograms/mL glucose oxidase and 3 micrograms/mL lactoperoxidase; 10 minutes at 37 C followed by approximately 2.5 micrograms/mL Pronase and T4 ELISA. Most assays used lactoperoxidase after comparison with human TPO. Four acceptor substitutions. cross_nutrient: false evidence_span: {"source_cache": "artifacts/iodine-synthesis-sources/32025030.txt", "start_char": 8677, "end_char": 9897, "text_sha256": "fcdc18c2b096fdd24073329828fe9c6681e101b7f29bf985938e538faf6fb3fe", "text_characters": 1220, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."} [iodine-syn-tg2020] The structure of human thyroglobulin. (2020). https://pubmed.ncbi.nlm.nih.gov/32025030/ DOI: 10.1038/s41586-020-1995-4

cross_nutrient

false

evidence_span

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experimental_model

Human TG cryo-EM, recombinant HEK293T-expressed TG and site-directed mutants

exposure

0.1 micromolar human TG, 1 mM KI, 24 mM glucose, 2 micrograms/mL glucose oxidase and 3 micrograms/mL lactoperoxidase; 10 minutes at 37 C followed by approximately 2.5 micrograms/mL Pronase and T4 ELISA. Most assays used lactoperoxidase after comparison with human TPO. Five donor substitutions.

limitations

Multi-site mutagenesis supports the donor set; not an isolated rate for every individual site.

nutrient_topic

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

organism

Homo sapiens TG

plain_language

The paired donor tyrosines are also needed to assemble T4.

primary_references

[iodine-syn-tg2020] The structure of human thyroglobulin. (2020). https://pubmed.ncbi.nlm.nih.gov/32025030/ DOI: 10.1038/s41586-020-1995-4

tissue_or_cell_type

Purified-protein reaction

Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 646–658

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human TG cryo-EM, recombinant HEK293T-expressed TG and site-directed mutants · source_derived_draft · unverified_draft

### iodine-syn-tg-donor-mutants Replacing human TG donor residues Y2540, Y2766, Y108, Y234 and Y149 with phenylalanine suppressed significant T4 synthesis. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The paired donor tyrosines are also needed to assemble T4. organism: Homo sapiens TG tissue_or_cell_type: Purified-protein reaction experimental_model: Human TG cryo-EM, recombinant HEK293T-expressed TG and site-directed mutants limitations: Multi-site mutagenesis supports the donor set; not an isolated rate for every individual site. exposure: 0.1 micromolar human TG, 1 mM KI, 24 mM glucose, 2 micrograms/mL glucose oxidase and 3 micrograms/mL lactoperoxidase; 10 minutes at 37 C followed by approximately 2.5 micrograms/mL Pronase and T4 ELISA. Most assays used lactoperoxidase after comparison with human TPO. Five donor substitutions. cross_nutrient: false evidence_span: {"source_cache": "artifacts/iodine-synthesis-sources/32025030.txt", "start_char": 9120, "end_char": 9940, "text_sha256": "8b8cd3eb09e3950bb40977268ed2a95e242386b632a9d45ccd8a2e156aead2b1", "text_characters": 820, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."} [iodine-syn-tg2020] The structure of human thyroglobulin. (2020). https://pubmed.ncbi.nlm.nih.gov/32025030/ DOI: 10.1038/s41586-020-1995-4

cross_nutrient

false

evidence_span

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experimental_model

Human TG cryo-EM, recombinant HEK293T-expressed TG and site-directed mutants

exposure

0.1 micromolar human TG, 1 mM KI, 24 mM glucose, 2 micrograms/mL glucose oxidase and 3 micrograms/mL lactoperoxidase; 10 minutes at 37 C followed by approximately 2.5 micrograms/mL Pronase and T4 ELISA. Most assays used lactoperoxidase after comparison with human TPO.

limitations

Artificial reaction with lactoperoxidase in most assays; not an intake-response curve.

nutrient_topic

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

organism

Homo sapiens TG expressed in HEK293T cells

plain_language

Iodide supplies the iodine needed to build T4 on thyroglobulin.

primary_references

[iodine-syn-tg2020] The structure of human thyroglobulin. (2020). https://pubmed.ncbi.nlm.nih.gov/32025030/ DOI: 10.1038/s41586-020-1995-4

tissue_or_cell_type

Purified-protein reaction

Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 618–630

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human TG cryo-EM, recombinant HEK293T-expressed TG and site-directed mutants · source_derived_draft · unverified_draft

### iodine-syn-tg-iodide-required Recombinant human TG produced a T4 signal after in-vitro iodination and proteolysis, whereas omission of iodide prevented the reaction. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Iodide supplies the iodine needed to build T4 on thyroglobulin. organism: Homo sapiens TG expressed in HEK293T cells tissue_or_cell_type: Purified-protein reaction experimental_model: Human TG cryo-EM, recombinant HEK293T-expressed TG and site-directed mutants limitations: Artificial reaction with lactoperoxidase in most assays; not an intake-response curve. exposure: 0.1 micromolar human TG, 1 mM KI, 24 mM glucose, 2 micrograms/mL glucose oxidase and 3 micrograms/mL lactoperoxidase; 10 minutes at 37 C followed by approximately 2.5 micrograms/mL Pronase and T4 ELISA. Most assays used lactoperoxidase after comparison with human TPO. cross_nutrient: false evidence_span: {"source_cache": "artifacts/iodine-synthesis-sources/32025030.txt", "start_char": 37603, "end_char": 38323, "text_sha256": "dfd7b409d46dbfe4e78cf481b6074477d36d70e14b5731f95a6b99ef0c43b33a", "text_characters": 720, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."} [iodine-syn-tg2020] The structure of human thyroglobulin. (2020). https://pubmed.ncbi.nlm.nih.gov/32025030/ DOI: 10.1038/s41586-020-1995-4

cross_nutrient

false

evidence_span

{"source_cache": "artifacts/iodine-synthesis-sources/7372636.txt", "start_char": 6216, "end_char": 8536, "text_sha256": "753e684061b9063528196c840b23404015abc2b7b836a3887497aea0f8fe20a6", "text_characters": 2320, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."}

experimental_model

Purified hog TPO with human goiter TG or tyrosine-radiolabeled hog TG; chromatographic hormone and dehydroalanine analyses

exposure

Human goiter TG initially 0.04% iodine, iodinated for 90 minutes to approximately 60 iodine atoms per TG; the same preparation contained 2.6 T4 residues per molecule.

limitations

Reconstituted mixed-species experiment. Hormone residues are protein-bound before hydrolysis; the assay is not evidence that free MIT and DIT are routinely coupled in blood.

nutrient_topic

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

organism

Sus scrofa enzyme; Homo sapiens substrate

plain_language

TPO-driven chemistry can make T3 directly within TG, before the hormone is released.

primary_references

[iodine-syn-tpo-coupling1980] Formation of dehydroalanine residues during thyroid hormone synthesis in thyroglobulin. (1980). https://pubmed.ncbi.nlm.nih.gov/7372636/ DOI: 10.1016/S0021-9258(19)70782-0

tissue_or_cell_type

Purified TPO and human goiter TG

Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 856–868

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified hog TPO with human goiter TG or tyrosine-radiolabeled hog TG; chromatographic hormone and dehydroalanine analyses · source_derived_draft · unverified_draft

### iodine-syn-tpo-t3-formation Iodinating human goiter TG with hog TPO for 90 minutes produced 0.3 T3 residues per TG molecule, measured after enzymatic hydrolysis. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: TPO-driven chemistry can make T3 directly within TG, before the hormone is released. organism: Sus scrofa enzyme; Homo sapiens substrate tissue_or_cell_type: Purified TPO and human goiter TG experimental_model: Purified hog TPO with human goiter TG or tyrosine-radiolabeled hog TG; chromatographic hormone and dehydroalanine analyses limitations: Reconstituted mixed-species experiment. Hormone residues are protein-bound before hydrolysis; the assay is not evidence that free MIT and DIT are routinely coupled in blood. exposure: Human goiter TG initially 0.04% iodine, iodinated for 90 minutes to approximately 60 iodine atoms per TG; the same preparation contained 2.6 T4 residues per molecule. cross_nutrient: false evidence_span: {"source_cache": "artifacts/iodine-synthesis-sources/7372636.txt", "start_char": 6216, "end_char": 8536, "text_sha256": "753e684061b9063528196c840b23404015abc2b7b836a3887497aea0f8fe20a6", "text_characters": 2320, "note": "Exact publisher passage retained in the cited local source cache; locator and digest supplied here."} [iodine-syn-tpo-coupling1980] Formation of dehydroalanine residues during thyroid hormone synthesis in thyroglobulin. (1980). https://pubmed.ncbi.nlm.nih.gov/7372636/ DOI: 10.1016/S0021-9258(19)70782-0