Component

Human MCT8 / SLC16A2

Human MCT8 / SLC16A2

3 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 it acts on

  1. Human MCT8 structure places the T3 carboxylate against Arg371 and its iodine atoms in hydrophobic pockets; substitutions of substrate-contact residues reduce cellular T3 uptake.

    Human MCT8 / SLC16A2 → T3 source_derived_draftungraded
    Experimental context and source evidence
    evidence_locator
    Results: T3 recognition, Figure 3; Methods
    evidence_spans
    [{"source_document": "artifacts/iodine-metabolism-sources/40140416.txt", "locator": "Results: T3 recognition, Figure 3; Methods", "start_char": 679, "end_char": 2779}]
    experimental_model
    Purified tagged human MCT8 from HEK293F cells; cryo-EM and cell-based mutagenesis
    exposure
    Cryo-EM preparation: 1.5 mM T3. HeLa uptake assay: human MCT8 and CRYM coexpression; 1 nM unlabeled T3 plus 0.02 microcuries 125I-T3 for 30 minutes at 37 C.
    limitations
    Purified structural occupancy is not a physiological concentration threshold. Individual mutations and their effects are not identical.
    nutrient_topic
    Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine
    organism
    Human
    plain_language
    The transporter recognizes the shape and chemical groups of iodine-containing T3.
    primary_references
    [i-met-40140416] Structural insights into thyroid hormone transporter MCT8. (2025). https://pubmed.ncbi.nlm.nih.gov/40140416/ DOI: 10.1038/s41467-025-58131-8
    tissue_or_cell_type
    HeLa cells for transport; HEK293F cells for protein production

    Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 912–924

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified tagged human MCT8 from HEK293F cells; cryo-EM and cell-based mutagenesis · source_derived_draft · unverified_draft

    ### i-met-mct8-t3-recognition Human MCT8 structure places the T3 carboxylate against Arg371 and its iodine atoms in hydrophobic pockets; substitutions of substrate-contact residues reduce cellular T3 uptake. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The transporter recognizes the shape and chemical groups of iodine-containing T3. organism: Human tissue_or_cell_type: HeLa cells for transport; HEK293F cells for protein production experimental_model: Purified tagged human MCT8 from HEK293F cells; cryo-EM and cell-based mutagenesis limitations: Purified structural occupancy is not a physiological concentration threshold. Individual mutations and their effects are not identical. exposure: Cryo-EM preparation: 1.5 mM T3. HeLa uptake assay: human MCT8 and CRYM coexpression; 1 nM unlabeled T3 plus 0.02 microcuries 125I-T3 for 30 minutes at 37 C. evidence_locator: Results: T3 recognition, Figure 3; Methods evidence_spans: [{"source_document": "artifacts/iodine-metabolism-sources/40140416.txt", "locator": "Results: T3 recognition, Figure 3; Methods", "start_char": 679, "end_char": 2779}] [i-met-40140416] Structural insights into thyroid hormone transporter MCT8. (2025). https://pubmed.ncbi.nlm.nih.gov/40140416/ DOI: 10.1038/s41467-025-58131-8
    Complete structured claim and evidence

Where it participates (unsigned role)

  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. 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.

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