Component

Cellular thyroxine uptake

Cellular thyroxine uptake

4 recorded relationships. Experimental role, claim status and evidence remain attached to each record.

Read recorded mechanisms Open recursive mind map

How nutrients influence it

Every nutrient with a recorded effect on this component, credited to the nutrient that acted rather than the chapter that recorded it. Open a nutrient to see the findings and the conditions they were measured under.

How nutrients reach it in more than one step

Chains of two or more recorded steps that end here, grouped by the nutrient they start from. Each step is a separate finding, so a chain is a route a mechanism could take, not proof that it does.

Tracing routes…

What it does

Every recorded relationship this component is part of, grouped by its role. Plain wording comes first; the technical statement follows.

Recorded relationships

What acts on it

  1. Human MCT8 D424N retained measurable T4 binding but had strongly impaired cellular T4 transport, showing that binding alone does not establish transport competence.

    Human MCT8 D424N (D498N in long isoform) → Cellular thyroxine uptake source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_locator
    Figure 3; Figure 5 caption and Results: MCT8 pathogenic mutant
    evidence_spans
    [{"source_document": "artifacts/iodine-metabolism-sources/40368961.txt", "locator": "Figure 3; Figure 5 caption and Results: MCT8 pathogenic mutant", "start_char": 16912, "end_char": 18212}]
    experimental_model
    Purified human MCT8 structures and microscale thermophoresis; transfected HeLa transport assays
    exposure
    Patient-derived D424N short isoform, equivalent to D498N long isoform; wild-type comparator.
    limitations
    The proposed conformational explanation is structural interpretation; no dietary intervention.
    nutrient_topic
    Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
    organism
    Human
    plain_language
    A transporter may still bind hormone while failing to deliver it into cells.
    primary_references
    [i-met-40368961] Molecular mechanism of thyroxine transport by monocarboxylate transporters. (2025). https://pubmed.ncbi.nlm.nih.gov/40368961/ DOI: 10.1038/s41467-025-59751-w
    tissue_or_cell_type
    Purified mutant and HeLa cells
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 940–952

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human MCT8 structures and microscale thermophoresis; transfected HeLa transport assays · source_derived_draft · unverified_draft

    ### i-met-mct8-d424n-binding-transport Human MCT8 D424N retained measurable T4 binding but had strongly impaired cellular T4 transport, showing that binding alone does not establish transport competence. Condition category: machinery_impairment nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A transporter may still bind hormone while failing to deliver it into cells. organism: Human tissue_or_cell_type: Purified mutant and HeLa cells experimental_model: Purified human MCT8 structures and microscale thermophoresis; transfected HeLa transport assays limitations: The proposed conformational explanation is structural interpretation; no dietary intervention. exposure: Patient-derived D424N short isoform, equivalent to D498N long isoform; wild-type comparator. evidence_locator: Figure 3; Figure 5 caption and Results: MCT8 pathogenic mutant evidence_spans: [{"source_document": "artifacts/iodine-metabolism-sources/40368961.txt", "locator": "Figure 3; Figure 5 caption and Results: MCT8 pathogenic mutant", "start_char": 16912, "end_char": 18212}] [i-met-40368961] Molecular mechanism of thyroxine transport by monocarboxylate transporters. (2025). https://pubmed.ncbi.nlm.nih.gov/40368961/ DOI: 10.1038/s41467-025-59751-w
    Complete structured claim and evidence

  2. Human OATP1C1 K376A abolished measured radiolabeled-T4 uptake without lowering cell-surface expression relative to wild type.

    Human OATP1C1 K376A → Cellular thyroxine uptake source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_locator
    Figure 3E and Supplemental Figure S3B
    evidence_spans
    [{"source_document": "artifacts/iodine-metabolism-sources/40680733.txt", "locator": "Figure 3E and Supplemental Figure S3B", "start_char": 30544, "end_char": 32244}]
    experimental_model
    Human OATP1C1 cryo-EM and stable HEK293 wild-type/mutant uptake assays
    exposure
    K376A versus wild type; 0.5 nM 125I-T4 for 30 minutes at 37 C in DMEM with 0.1% BSA; three independent uptake experiments.
    limitations
    Engineered alanine mutant; no in-vivo dose or dietary threshold inferred.
    nutrient_topic
    Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
    organism
    Human
    plain_language
    This pocket residue affects transport function even when the carrier reaches the membrane.
    primary_references
    [i-met-40680733] Structural insights into brain thyroid hormone transport via MCT8 and OATP1C1. (2025). https://pubmed.ncbi.nlm.nih.gov/40680733/ DOI: 10.1016/j.cell.2025.06.032
    tissue_or_cell_type
    Stable HEK293 cells
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 968–980

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human OATP1C1 cryo-EM and stable HEK293 wild-type/mutant uptake assays · source_derived_draft · unverified_draft

    ### i-met-oatp-k376a Human OATP1C1 K376A abolished measured radiolabeled-T4 uptake without lowering cell-surface expression relative to wild type. Condition category: machinery_impairment nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: This pocket residue affects transport function even when the carrier reaches the membrane. organism: Human tissue_or_cell_type: Stable HEK293 cells experimental_model: Human OATP1C1 cryo-EM and stable HEK293 wild-type/mutant uptake assays limitations: Engineered alanine mutant; no in-vivo dose or dietary threshold inferred. exposure: K376A versus wild type; 0.5 nM 125I-T4 for 30 minutes at 37 C in DMEM with 0.1% BSA; three independent uptake experiments. evidence_locator: Figure 3E and Supplemental Figure S3B evidence_spans: [{"source_document": "artifacts/iodine-metabolism-sources/40680733.txt", "locator": "Figure 3E and Supplemental Figure S3B", "start_char": 30544, "end_char": 32244}] [i-met-40680733] Structural insights into brain thyroid hormone transport via MCT8 and OATP1C1. (2025). https://pubmed.ncbi.nlm.nih.gov/40680733/ DOI: 10.1016/j.cell.2025.06.032
    Complete structured claim and evidence

  3. Rat MCT8 expression increased uptake of 10 nM radiolabeled T4 approximately tenfold in Xenopus oocytes.

    Rat MCT8 / Slc16a2 → Cellular thyroxine uptake source_derived_draftungraded
    Experimental context and source evidence
    evidence_locator
    Primary abstract
    evidence_spans
    [{"source_document": "artifacts/iodine-metabolism-sources/12871948.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1490}]
    experimental_model
    Rat MCT8 cRNA expressed in Xenopus laevis oocytes
    exposure
    MCT8 cRNA; assay three days later with 10 nM 125I-labeled hormone; uptake linear for less than four minutes.
    limitations
    Rat transporter in an expression host; this is hormone transport, not intestinal iodide uptake.
    nutrient_topic
    Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
    organism
    Rat protein in Xenopus laevis
    plain_language
    MCT8 carries T4 across the cell membrane.
    primary_references
    [i-met-12871948] Identification of monocarboxylate transporter 8 as a specific thyroid hormone transporter. (2003). https://pubmed.ncbi.nlm.nih.gov/12871948/ DOI: 10.1074/jbc.m300909200
    tissue_or_cell_type
    Oocyte plasma membrane

    Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 884–896

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat MCT8 cRNA expressed in Xenopus laevis oocytes · source_derived_draft · unverified_draft

    ### i-met-rat-t4 Rat MCT8 expression increased uptake of 10 nM radiolabeled T4 approximately tenfold in Xenopus oocytes. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: MCT8 carries T4 across the cell membrane. organism: Rat protein in Xenopus laevis tissue_or_cell_type: Oocyte plasma membrane experimental_model: Rat MCT8 cRNA expressed in Xenopus laevis oocytes limitations: Rat transporter in an expression host; this is hormone transport, not intestinal iodide uptake. exposure: MCT8 cRNA; assay three days later with 10 nM 125I-labeled hormone; uptake linear for less than four minutes. evidence_locator: Primary abstract evidence_spans: [{"source_document": "artifacts/iodine-metabolism-sources/12871948.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1490}] [i-met-12871948] Identification of monocarboxylate transporter 8 as a specific thyroid hormone transporter. (2003). https://pubmed.ncbi.nlm.nih.gov/12871948/ DOI: 10.1074/jbc.m300909200
    Complete structured claim and evidence

  4. Silychristin inhibited human MCT8-mediated T4 uptake in transfected HeLa cells; structural and binding experiments support trapping an outward-facing transporter state.

    Silychristin → Cellular thyroxine uptake source_derived_draftungraded
    Experimental context and source evidence
    evidence_locator
    Figures 1a-b and 4; Results: inhibitor mechanism
    evidence_spans
    [{"source_document": "artifacts/iodine-metabolism-sources/40368961.txt", "locator": "Figures 1a-b and 4; Results: inhibitor mechanism", "start_char": 17453, "end_char": 22253}]
    experimental_model
    Purified human MCT8 structures and microscale thermophoresis; transfected HeLa transport assays
    exposure
    Cell assays used 10 micromolar T4 with or without 10 micromolar silychristin.
    limitations
    Drug-compound experiment; does not establish dietary milk-thistle effects or an iodine-supplement interaction at usual exposure.
    nutrient_topic
    Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
    organism
    Human
    plain_language
    An experimental inhibitor can block hormone passage through MCT8.
    primary_references
    [i-met-40368961] Molecular mechanism of thyroxine transport by monocarboxylate transporters. (2025). https://pubmed.ncbi.nlm.nih.gov/40368961/ DOI: 10.1038/s41467-025-59751-w
    tissue_or_cell_type
    HeLa cells and purified MCT8

    Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 926–938

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human MCT8 structures and microscale thermophoresis; transfected HeLa transport assays · source_derived_draft · unverified_draft

    ### i-met-silychristin-mct8 Silychristin inhibited human MCT8-mediated T4 uptake in transfected HeLa cells; structural and binding experiments support trapping an outward-facing transporter state. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: An experimental inhibitor can block hormone passage through MCT8. organism: Human tissue_or_cell_type: HeLa cells and purified MCT8 experimental_model: Purified human MCT8 structures and microscale thermophoresis; transfected HeLa transport assays limitations: Drug-compound experiment; does not establish dietary milk-thistle effects or an iodine-supplement interaction at usual exposure. exposure: Cell assays used 10 micromolar T4 with or without 10 micromolar silychristin. evidence_locator: Figures 1a-b and 4; Results: inhibitor mechanism evidence_spans: [{"source_document": "artifacts/iodine-metabolism-sources/40368961.txt", "locator": "Figures 1a-b and 4; Results: inhibitor mechanism", "start_char": 17453, "end_char": 22253}] [i-met-40368961] Molecular mechanism of thyroxine transport by monocarboxylate transporters. (2025). https://pubmed.ncbi.nlm.nih.gov/40368961/ DOI: 10.1038/s41467-025-59751-w
    Complete structured claim and evidence

In the sources

Preserved passages that mention this component, quoted exactly. Open one to read it in context.

    This is a research prototype built from draft material. It is not medical advice, and its statements still await verification against the original studies.

    Evidence, AI assistance and curation standards