Human sodium-dependent multivitamin transporter / SLC5A6

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

true

experimental_model

Human and monkey brain microvessel analyses; SLC5A6-siRNA experiments in human hCMEC/D3 endothelial cells

exposure

SLC5A6-specific siRNA and radiolabeled substrate uptake; tracer concentration not specified in the abstract.

limitations

Cellular luminal uptake is not itself a measurement of complete transendothelial delivery into brain tissue. Reported percentages apply to hCMEC/D3 under these assay conditions, not every human tissue.

nutrient_topic

Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. · Pantothenate (vitamin B5)

organism

Homo sapiens

plain_language

SMVT supplied most measured biotin uptake in the human brain endothelial cell model.

primary_references

[b5-trans-brain2015] Major involvement of Na(+) -dependent multivitamin transporter (SLC5A6/SMVT) in uptake of biotin and pantothenic acid by human brain capillary endothelial cells. (2015). https://pubmed.ncbi.nlm.nih.gov/25809983/ DOI: 10.1111/jnc.13092

tissue_or_cell_type

hCMEC/D3 cerebral microvascular endothelial cells

trigger_kind

machinery_impairment Imported condition classification; unverified.

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 288–299

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human and monkey brain microvessel analyses; SLC5A6-siRNA experiments in human hCMEC/D3 endothelial cells · source_derived_draft · unverified_draft

### b5-trans-brain-biotin SLC5A6 knockdown analysis attributed 88.7% of total radiolabeled biotin uptake to SLC5A6 in human hCMEC/D3 brain endothelial cells. Condition category: machinery_impairment nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: SMVT supplied most measured biotin uptake in the human brain endothelial cell model. organism: Homo sapiens tissue_or_cell_type: hCMEC/D3 cerebral microvascular endothelial cells experimental_model: Human and monkey brain microvessel analyses; SLC5A6-siRNA experiments in human hCMEC/D3 endothelial cells limitations: Cellular luminal uptake is not itself a measurement of complete transendothelial delivery into brain tissue. Reported percentages apply to hCMEC/D3 under these assay conditions, not every human tissue. exposure: SLC5A6-specific siRNA and radiolabeled substrate uptake; tracer concentration not specified in the abstract. cross_nutrient: true [b5-trans-brain2015] Major involvement of Na(+) -dependent multivitamin transporter (SLC5A6/SMVT) in uptake of biotin and pantothenic acid by human brain capillary endothelial cells. (2015). https://pubmed.ncbi.nlm.nih.gov/25809983/ DOI: 10.1111/jnc.13092

cross_nutrient

true

experimental_model

Human and monkey brain microvessel analyses; SLC5A6-siRNA experiments in human hCMEC/D3 endothelial cells

exposure

Antibody-free membrane-localization method, with human/monkey microvessel proteomics and human expression analyses.

limitations

Abstract does not resolve which species supplied every localization preparation. The result addresses blood-facing localization, not the unidentified abluminal export step.

nutrient_topic

Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. · Pantothenate (vitamin B5)

organism

Homo sapiens and monkey microvessel preparations; localization sample allocation not detailed in abstract

plain_language

Brain capillary SMVT is concentrated on the side facing the blood.

primary_references

[b5-trans-brain2015] Major involvement of Na(+) -dependent multivitamin transporter (SLC5A6/SMVT) in uptake of biotin and pantothenic acid by human brain capillary endothelial cells. (2015). https://pubmed.ncbi.nlm.nih.gov/25809983/ DOI: 10.1111/jnc.13092

tissue_or_cell_type

Brain capillary endothelium

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 301–312

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human and monkey brain microvessel analyses; SLC5A6-siRNA experiments in human hCMEC/D3 endothelial cells · source_derived_draft · unverified_draft

### b5-trans-brain-luminal-localization The brain-microvessel study localized SLC5A6 preferentially to the luminal membrane of brain capillary endothelium. Condition category: normal nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Brain capillary SMVT is concentrated on the side facing the blood. organism: Homo sapiens and monkey microvessel preparations; localization sample allocation not detailed in abstract tissue_or_cell_type: Brain capillary endothelium experimental_model: Human and monkey brain microvessel analyses; SLC5A6-siRNA experiments in human hCMEC/D3 endothelial cells limitations: Abstract does not resolve which species supplied every localization preparation. The result addresses blood-facing localization, not the unidentified abluminal export step. exposure: Antibody-free membrane-localization method, with human/monkey microvessel proteomics and human expression analyses. cross_nutrient: true [b5-trans-brain2015] Major involvement of Na(+) -dependent multivitamin transporter (SLC5A6/SMVT) in uptake of biotin and pantothenic acid by human brain capillary endothelial cells. (2015). https://pubmed.ncbi.nlm.nih.gov/25809983/ DOI: 10.1111/jnc.13092

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

true

experimental_model

Human and monkey brain microvessel analyses; SLC5A6-siRNA experiments in human hCMEC/D3 endothelial cells

exposure

SLC5A6-specific siRNA and radiolabeled substrate uptake; tracer concentration not specified in the abstract.

limitations

Cellular luminal uptake is not itself a measurement of complete transendothelial delivery into brain tissue. Reported percentages apply to hCMEC/D3 under these assay conditions, not every human tissue.

nutrient_topic

Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. · Pantothenate (vitamin B5)

organism

Homo sapiens

plain_language

SMVT supplied most measured pantothenate uptake in the human brain endothelial cell model.

primary_references

[b5-trans-brain2015] Major involvement of Na(+) -dependent multivitamin transporter (SLC5A6/SMVT) in uptake of biotin and pantothenic acid by human brain capillary endothelial cells. (2015). https://pubmed.ncbi.nlm.nih.gov/25809983/ DOI: 10.1111/jnc.13092

tissue_or_cell_type

hCMEC/D3 cerebral microvascular endothelial cells

trigger_kind

machinery_impairment Imported condition classification; unverified.

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 275–286

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human and monkey brain microvessel analyses; SLC5A6-siRNA experiments in human hCMEC/D3 endothelial cells · source_derived_draft · unverified_draft

### b5-trans-brain-pantothenate SLC5A6 knockdown analysis attributed 98.6% of total radiolabeled pantothenate uptake to SLC5A6 in human hCMEC/D3 brain endothelial cells. Condition category: machinery_impairment nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: SMVT supplied most measured pantothenate uptake in the human brain endothelial cell model. organism: Homo sapiens tissue_or_cell_type: hCMEC/D3 cerebral microvascular endothelial cells experimental_model: Human and monkey brain microvessel analyses; SLC5A6-siRNA experiments in human hCMEC/D3 endothelial cells limitations: Cellular luminal uptake is not itself a measurement of complete transendothelial delivery into brain tissue. Reported percentages apply to hCMEC/D3 under these assay conditions, not every human tissue. exposure: SLC5A6-specific siRNA and radiolabeled substrate uptake; tracer concentration not specified in the abstract. cross_nutrient: true [b5-trans-brain2015] Major involvement of Na(+) -dependent multivitamin transporter (SLC5A6/SMVT) in uptake of biotin and pantothenic acid by human brain capillary endothelial cells. (2015). https://pubmed.ncbi.nlm.nih.gov/25809983/ DOI: 10.1111/jnc.13092

cross_nutrient

true

experimental_model

Functional human SMVT-GFP expression and imaging in polarized renal and intestinal epithelial cell lines

exposure

Full-length human SMVT-GFP expression and polarized membrane imaging.

limitations

Abstract-only; fluorescent fusion-protein localization in cell lines is not a measurement of net intestinal pantothenate absorption. The abstract does not name the intestinal cell line.

nutrient_topic

Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. · Pantothenate (vitamin B5)

organism

Homo sapiens (transporter); expression-host species not specified in the retrieved abstract

plain_language

In the intestinal cell models, SMVT sits on the surface facing the intestinal contents.

primary_references

[b5-trans-targeting2009] Membrane targeting and intracellular trafficking of the human sodium-dependent multivitamin transporter in polarized epithelial cells. (2009). https://pubmed.ncbi.nlm.nih.gov/19211916/ DOI: 10.1152/ajpcell.00396.2008

tissue_or_cell_type

Polarized intestinal epithelial cell model

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 223–234

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Functional human SMVT-GFP expression and imaging in polarized renal and intestinal epithelial cell lines · source_derived_draft · unverified_draft

### b5-trans-epithelial-apical-targeting Functional full-length human SMVT-GFP localized to the apical membrane in the studied polarized intestinal epithelial cell lines. Condition category: normal nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: In the intestinal cell models, SMVT sits on the surface facing the intestinal contents. organism: Homo sapiens (transporter); expression-host species not specified in the retrieved abstract tissue_or_cell_type: Polarized intestinal epithelial cell model experimental_model: Functional human SMVT-GFP expression and imaging in polarized renal and intestinal epithelial cell lines limitations: Abstract-only; fluorescent fusion-protein localization in cell lines is not a measurement of net intestinal pantothenate absorption. The abstract does not name the intestinal cell line. exposure: Full-length human SMVT-GFP expression and polarized membrane imaging. cross_nutrient: true [b5-trans-targeting2009] Membrane targeting and intracellular trafficking of the human sodium-dependent multivitamin transporter in polarized epithelial cells. (2009). https://pubmed.ncbi.nlm.nih.gov/19211916/ DOI: 10.1152/ajpcell.00396.2008

cross_nutrient

true

experimental_model

Cryo-EM of engineered human SMVT with nanobody-assisted alignment; functional uptake assays in HEK293T cells

exposure

3.7-angstrom cryo-EM pantothenate complex; molecular-dynamics support for the binding model.

limitations

Engineered, purified transporter structure supports a binding mechanism; it does not establish nutritional competition severity in vivo. The structural construct has altered biotin transport kinetics relative to wild type. Atom-level interactions are structural-model interpretations; no specific dietary threshold follows.

nutrient_topic

Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. · Pantothenate (vitamin B5)

organism

Homo sapiens

plain_language

SMVT anchors the charged end of B5 through specific contacts in its binding pocket.

primary_references

[b5-trans-structure2026] Structural basis for multivitamin recognition and transport by human SMVT. (2026). https://pubmed.ncbi.nlm.nih.gov/42364996/ DOI: 10.1038/s41467-026-74948-3

tissue_or_cell_type

Purified human SMVT ligand-binding pocket

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 418–429

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cryo-EM of engineered human SMVT with nanobody-assisted alignment; functional uptake assays in HEK293T cells · source_derived_draft · unverified_draft

### b5-trans-pantothenate-carboxyl-recognition In the human SMVT–pantothenate structural model, the substrate carboxyl group interacts with backbone amino groups of Ser81/Ala84 and hydrogen-bonds to Tyr156. Condition category: normal nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: SMVT anchors the charged end of B5 through specific contacts in its binding pocket. organism: Homo sapiens tissue_or_cell_type: Purified human SMVT ligand-binding pocket experimental_model: Cryo-EM of engineered human SMVT with nanobody-assisted alignment; functional uptake assays in HEK293T cells limitations: Engineered, purified transporter structure supports a binding mechanism; it does not establish nutritional competition severity in vivo. The structural construct has altered biotin transport kinetics relative to wild type. Atom-level interactions are structural-model interpretations; no specific dietary threshold follows. exposure: 3.7-angstrom cryo-EM pantothenate complex; molecular-dynamics support for the binding model. cross_nutrient: true [b5-trans-structure2026] Structural basis for multivitamin recognition and transport by human SMVT. (2026). https://pubmed.ncbi.nlm.nih.gov/42364996/ DOI: 10.1038/s41467-026-74948-3

cross_nutrient

true

experimental_model

Cryo-EM of engineered human SMVT with nanobody-assisted alignment; functional uptake assays in HEK293T cells

exposure

SMVTEM/NbALFA complexes incubated with 2 mM D-pantothenic acid, 4 mM biotin or 22 mM oxidized alpha-lipoic acid for separate structures.

limitations

Engineered, purified transporter structure supports a binding mechanism; it does not establish nutritional competition severity in vivo. The structural construct has altered biotin transport kinetics relative to wild type. These are separate ligand-bound complexes, not simultaneous occupancy.

nutrient_topic

Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. · Pantothenate (vitamin B5)

organism

Homo sapiens

plain_language

B5, biotin and free lipoate use the same binding pocket in SMVT.

primary_references

[b5-trans-structure2026] Structural basis for multivitamin recognition and transport by human SMVT. (2026). https://pubmed.ncbi.nlm.nih.gov/42364996/ DOI: 10.1038/s41467-026-74948-3

tissue_or_cell_type

Purified human SMVT; HEK293-derived expression system

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 405–416

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cryo-EM of engineered human SMVT with nanobody-assisted alignment; functional uptake assays in HEK293T cells · source_derived_draft · unverified_draft

### b5-trans-shared-substrate-site Human SMVT cryo-EM complexes placed pantothenate, biotin and oxidized lipoate in substantially overlapping positions within one central substrate-binding pocket. Condition category: normal nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: B5, biotin and free lipoate use the same binding pocket in SMVT. organism: Homo sapiens tissue_or_cell_type: Purified human SMVT; HEK293-derived expression system experimental_model: Cryo-EM of engineered human SMVT with nanobody-assisted alignment; functional uptake assays in HEK293T cells limitations: Engineered, purified transporter structure supports a binding mechanism; it does not establish nutritional competition severity in vivo. The structural construct has altered biotin transport kinetics relative to wild type. These are separate ligand-bound complexes, not simultaneous occupancy. exposure: SMVTEM/NbALFA complexes incubated with 2 mM D-pantothenic acid, 4 mM biotin or 22 mM oxidized alpha-lipoic acid for separate structures. cross_nutrient: true [b5-trans-structure2026] Structural basis for multivitamin recognition and transport by human SMVT. (2026). https://pubmed.ncbi.nlm.nih.gov/42364996/ DOI: 10.1038/s41467-026-74948-3

cross_nutrient

true

experimental_model

Human SMVT cloned from JAR cells, expressed in human retinal pigment epithelial cells and Xenopus laevis oocytes

exposure

Human SMVT cDNA expression; substrate concentrations not specified in the abstract.

limitations

Heterologous human-protein experiments establish transport properties; they do not quantify whole-body absorption or nutrient deficiency from supplement competition.

nutrient_topic

Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. · Pantothenate (vitamin B5)

organism

Homo sapiens (protein and HRPE expression cells)

plain_language

SMVT carries biotin into cells using sodium-dependent transport.

primary_references

[b5-trans-wang1999] Human placental Na+-dependent multivitamin transporter. Cloning, functional expression, gene structure, and chromosomal localization. (1999). https://pubmed.ncbi.nlm.nih.gov/10329687/ DOI: 10.1074/jbc.274.21.14875

tissue_or_cell_type

HRPE cell plasma membrane

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 171–182

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human SMVT cloned from JAR cells, expressed in human retinal pigment epithelial cells and Xenopus laevis oocytes · source_derived_draft · unverified_draft

### b5-trans-smvt-biotin Expression of cloned human SLC5A6 in HRPE cells conferred sodium-dependent uptake of biotin. Condition category: normal nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: SMVT carries biotin into cells using sodium-dependent transport. organism: Homo sapiens (protein and HRPE expression cells) tissue_or_cell_type: HRPE cell plasma membrane experimental_model: Human SMVT cloned from JAR cells, expressed in human retinal pigment epithelial cells and Xenopus laevis oocytes limitations: Heterologous human-protein experiments establish transport properties; they do not quantify whole-body absorption or nutrient deficiency from supplement competition. exposure: Human SMVT cDNA expression; substrate concentrations not specified in the abstract. cross_nutrient: true [b5-trans-wang1999] Human placental Na+-dependent multivitamin transporter. Cloning, functional expression, gene structure, and chromosomal localization. (1999). https://pubmed.ncbi.nlm.nih.gov/10329687/ DOI: 10.1074/jbc.274.21.14875

cross_nutrient

true

experimental_model

Human SMVT cloned from JAR cells, expressed in human retinal pigment epithelial cells and Xenopus laevis oocytes

exposure

Human SMVT cDNA expression; substrate concentrations not specified in the abstract.

limitations

Heterologous human-protein experiments establish transport properties; they do not quantify whole-body absorption or nutrient deficiency from supplement competition.

nutrient_topic

Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. · Pantothenate (vitamin B5)

organism

Homo sapiens (protein and HRPE expression cells)

plain_language

SMVT carries lipoate into cells using sodium-dependent transport.

primary_references

[b5-trans-wang1999] Human placental Na+-dependent multivitamin transporter. Cloning, functional expression, gene structure, and chromosomal localization. (1999). https://pubmed.ncbi.nlm.nih.gov/10329687/ DOI: 10.1074/jbc.274.21.14875

tissue_or_cell_type

HRPE cell plasma membrane

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 184–195

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human SMVT cloned from JAR cells, expressed in human retinal pigment epithelial cells and Xenopus laevis oocytes · source_derived_draft · unverified_draft

### b5-trans-smvt-lipoate Expression of cloned human SLC5A6 in HRPE cells conferred sodium-dependent uptake of lipoate. Condition category: normal nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: SMVT carries lipoate into cells using sodium-dependent transport. organism: Homo sapiens (protein and HRPE expression cells) tissue_or_cell_type: HRPE cell plasma membrane experimental_model: Human SMVT cloned from JAR cells, expressed in human retinal pigment epithelial cells and Xenopus laevis oocytes limitations: Heterologous human-protein experiments establish transport properties; they do not quantify whole-body absorption or nutrient deficiency from supplement competition. exposure: Human SMVT cDNA expression; substrate concentrations not specified in the abstract. cross_nutrient: true [b5-trans-wang1999] Human placental Na+-dependent multivitamin transporter. Cloning, functional expression, gene structure, and chromosomal localization. (1999). https://pubmed.ncbi.nlm.nih.gov/10329687/ DOI: 10.1074/jbc.274.21.14875

cross_nutrient

true

experimental_model

Human SMVT cloned from JAR cells, expressed in human retinal pigment epithelial cells and Xenopus laevis oocytes

exposure

Human SMVT cDNA expression; substrate concentrations not specified in the abstract.

limitations

Heterologous human-protein experiments establish transport properties; they do not quantify whole-body absorption or nutrient deficiency from supplement competition.

nutrient_topic

Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. · Pantothenate (vitamin B5)

organism

Homo sapiens (protein and HRPE expression cells)

plain_language

SMVT carries pantothenate into cells using sodium-dependent transport.

primary_references

[b5-trans-wang1999] Human placental Na+-dependent multivitamin transporter. Cloning, functional expression, gene structure, and chromosomal localization. (1999). https://pubmed.ncbi.nlm.nih.gov/10329687/ DOI: 10.1074/jbc.274.21.14875

tissue_or_cell_type

HRPE cell plasma membrane

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 158–169

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human SMVT cloned from JAR cells, expressed in human retinal pigment epithelial cells and Xenopus laevis oocytes · source_derived_draft · unverified_draft

### b5-trans-smvt-pantothenate Expression of cloned human SLC5A6 in HRPE cells conferred sodium-dependent uptake of pantothenate. Condition category: normal nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: SMVT carries pantothenate into cells using sodium-dependent transport. organism: Homo sapiens (protein and HRPE expression cells) tissue_or_cell_type: HRPE cell plasma membrane experimental_model: Human SMVT cloned from JAR cells, expressed in human retinal pigment epithelial cells and Xenopus laevis oocytes limitations: Heterologous human-protein experiments establish transport properties; they do not quantify whole-body absorption or nutrient deficiency from supplement competition. exposure: Human SMVT cDNA expression; substrate concentrations not specified in the abstract. cross_nutrient: true [b5-trans-wang1999] Human placental Na+-dependent multivitamin transporter. Cloning, functional expression, gene structure, and chromosomal localization. (1999). https://pubmed.ncbi.nlm.nih.gov/10329687/ DOI: 10.1074/jbc.274.21.14875

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

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experimental_model

Chronic ethanol exposure in rodents and human Caco-2 cells

exposure

Chronic ethanol feeding or culture exposure

limitations

Animal feeding and human cell experiments are separate; no human dietary depletion threshold was established.

nutrient_topic

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

organism

Homo sapiens

plain_language

Alcohol exposure reduced the cell signals that produce the shared vitamin transporter.

primary_references

[b7-p21148397] Inhibition of intestinal biotin absorption by chronic alcohol feeding: cellular and molecular mechanisms. (2011). https://pubmed.ncbi.nlm.nih.gov/21148397/ DOI: 10.1152/ajpgi.00465.2010

tissue_or_cell_type

Caco-2 intestinal epithelial cells

trigger_kind

machinery_impairment Imported condition classification; unverified.

Biotin: carboxylases, recycling, deficiency and nutrient interactions (2026-09-17) · lines 221–232

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Chronic ethanol exposure in rodents and human Caco-2 cells · source_derived_draft · unverified_draft

### b7-alcohol-promoters Chronic ethanol exposure reduced activity of both SLC5A6 promoters P1 and P2 in human Caco-2 cells. Condition category: machinery_impairment nutrient_topic: Biotin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Alcohol exposure reduced the cell signals that produce the shared vitamin transporter. organism: Homo sapiens tissue_or_cell_type: Caco-2 intestinal epithelial cells experimental_model: Chronic ethanol exposure in rodents and human Caco-2 cells limitations: Animal feeding and human cell experiments are separate; no human dietary depletion threshold was established. exposure: Chronic ethanol feeding or culture exposure evidence_span: {"source_cache": "artifacts/biotin-research/21148397.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2398f4926e678d4650eba6488cab945c2d651a7c8e6c2f8fd00794c0ea891d4d", "start_char": 0, "end_char": 1829, "text_sha256": "2398f4926e678d4650eba6488cab945c2d651a7c8e6c2f8fd00794c0ea891d4d"} [b7-p21148397] Inhibition of intestinal biotin absorption by chronic alcohol feeding: cellular and molecular mechanisms. (2011). https://pubmed.ncbi.nlm.nih.gov/21148397/ DOI: 10.1152/ajpgi.00465.2010

evidence_span

{"source_cache": "artifacts/biotin-research/9814986.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7cc679e31b95ae919c15fadf0d56933d2ed8074664e11cd80a96e910181857be", "start_char": 0, "end_char": 1676, "text_sha256": "7cc679e31b95ae919c15fadf0d56933d2ed8074664e11cd80a96e910181857be"}

experimental_model

Transport and inhibitor experiments in human NCM460 colonic epithelial cells

exposure

Radiolabeled biotin with sodium replacement, pantothenate and kinase modulators

limitations

Cell-line kinetics do not quantify microbiome contributions or demonstrate competition at ordinary dietary intakes.

nutrient_topic

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

organism

Homo sapiens

plain_language

B5 and biotin can compete for entry in this colon-cell assay.

primary_references

[b7-p9814986] Biotin uptake by human colonic epithelial NCM460 cells: a carrier-mediated process shared with pantothenic acid. (1998). https://pubmed.ncbi.nlm.nih.gov/9814986/ DOI: 10.1152/ajpcell.1998.275.5.c1365

tissue_or_cell_type

Colonic epithelium; NCM460 culture

Biotin: carboxylases, recycling, deficiency and nutrient interactions (2026-09-17) · lines 195–206

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Transport and inhibitor experiments in human NCM460 colonic epithelial cells · source_derived_draft · unverified_draft

### b7-colon-b5-competition Pantothenic acid competitively inhibited biotin uptake in NCM460 cells, with Ki 14.4 micromolar. Condition category: normal nutrient_topic: Biotin research collection; topical membership is not evidence of a direct dietary effect. plain_language: B5 and biotin can compete for entry in this colon-cell assay. organism: Homo sapiens tissue_or_cell_type: Colonic epithelium; NCM460 culture experimental_model: Transport and inhibitor experiments in human NCM460 colonic epithelial cells limitations: Cell-line kinetics do not quantify microbiome contributions or demonstrate competition at ordinary dietary intakes. exposure: Radiolabeled biotin with sodium replacement, pantothenate and kinase modulators evidence_span: {"source_cache": "artifacts/biotin-research/9814986.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7cc679e31b95ae919c15fadf0d56933d2ed8074664e11cd80a96e910181857be", "start_char": 0, "end_char": 1676, "text_sha256": "7cc679e31b95ae919c15fadf0d56933d2ed8074664e11cd80a96e910181857be"} [b7-p9814986] Biotin uptake by human colonic epithelial NCM460 cells: a carrier-mediated process shared with pantothenic acid. (1998). https://pubmed.ncbi.nlm.nih.gov/9814986/ DOI: 10.1152/ajpcell.1998.275.5.c1365

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/biotin-research/21209005.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b42defcb27acffce0c264240e14b0535770f94627ee5a4836b284e4e0971b5a0", "start_char": 0, "end_char": 1797, "text_sha256": "b42defcb27acffce0c264240e14b0535770f94627ee5a4836b284e4e0971b5a0"}

experimental_model

Chronic ethanol exposure in renal HK-2 cells and separate rodents

exposure

Chronic ethanol exposure

limitations

HK-2 uptake is a model of renal handling, not a measured whole-body biotin loss in people.

nutrient_topic

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

organism

Homo sapiens

plain_language

Reduced transporter production is one explanation for the impaired uptake.

primary_references

[b7-p21209005] Chronic alcohol exposure negatively impacts the physiological and molecular parameters of the renal biotin reabsorption process. (2011). https://pubmed.ncbi.nlm.nih.gov/21209005/ DOI: 10.1152/ajprenal.00707.2010

tissue_or_cell_type

Human HK-2 proximal-tubular epithelial cells

trigger_kind

machinery_impairment Imported condition classification; unverified.

Biotin: carboxylases, recycling, deficiency and nutrient interactions (2026-09-17) · lines 260–271

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Chronic ethanol exposure in renal HK-2 cells and separate rodents · source_derived_draft · unverified_draft

### b7-kidney-alcohol-transcription Ethanol-exposed HK-2 cells showed reduced activity of the human SLC5A6 regulatory region. Condition category: machinery_impairment nutrient_topic: Biotin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Reduced transporter production is one explanation for the impaired uptake. organism: Homo sapiens tissue_or_cell_type: Human HK-2 proximal-tubular epithelial cells experimental_model: Chronic ethanol exposure in renal HK-2 cells and separate rodents limitations: HK-2 uptake is a model of renal handling, not a measured whole-body biotin loss in people. exposure: Chronic ethanol exposure evidence_span: {"source_cache": "artifacts/biotin-research/21209005.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b42defcb27acffce0c264240e14b0535770f94627ee5a4836b284e4e0971b5a0", "start_char": 0, "end_char": 1797, "text_sha256": "b42defcb27acffce0c264240e14b0535770f94627ee5a4836b284e4e0971b5a0"} [b7-p21209005] Chronic alcohol exposure negatively impacts the physiological and molecular parameters of the renal biotin reabsorption process. (2011). https://pubmed.ncbi.nlm.nih.gov/21209005/ DOI: 10.1152/ajprenal.00707.2010

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/biotin-research/21209005.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b42defcb27acffce0c264240e14b0535770f94627ee5a4836b284e4e0971b5a0", "start_char": 0, "end_char": 1797, "text_sha256": "b42defcb27acffce0c264240e14b0535770f94627ee5a4836b284e4e0971b5a0"}

experimental_model

Chronic ethanol exposure in renal HK-2 cells and separate rodents

exposure

Chronic ethanol exposure

limitations

HK-2 uptake is a model of renal handling, not a measured whole-body biotin loss in people.

nutrient_topic

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

organism

Homo sapiens

plain_language

Kidney cells reclaimed less biotin in this alcohol-exposure model.

primary_references

[b7-p21209005] Chronic alcohol exposure negatively impacts the physiological and molecular parameters of the renal biotin reabsorption process. (2011). https://pubmed.ncbi.nlm.nih.gov/21209005/ DOI: 10.1152/ajprenal.00707.2010

tissue_or_cell_type

Human HK-2 proximal-tubular epithelial cells

trigger_kind

machinery_impairment Imported condition classification; unverified.

Biotin: carboxylases, recycling, deficiency and nutrient interactions (2026-09-17) · lines 247–258

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Chronic ethanol exposure in renal HK-2 cells and separate rodents · source_derived_draft · unverified_draft

### b7-kidney-alcohol-uptake Chronic ethanol exposure reduced carrier-mediated biotin uptake in human HK-2 cells. Condition category: machinery_impairment nutrient_topic: Biotin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Kidney cells reclaimed less biotin in this alcohol-exposure model. organism: Homo sapiens tissue_or_cell_type: Human HK-2 proximal-tubular epithelial cells experimental_model: Chronic ethanol exposure in renal HK-2 cells and separate rodents limitations: HK-2 uptake is a model of renal handling, not a measured whole-body biotin loss in people. exposure: Chronic ethanol exposure evidence_span: {"source_cache": "artifacts/biotin-research/21209005.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b42defcb27acffce0c264240e14b0535770f94627ee5a4836b284e4e0971b5a0", "start_char": 0, "end_char": 1797, "text_sha256": "b42defcb27acffce0c264240e14b0535770f94627ee5a4836b284e4e0971b5a0"} [b7-p21209005] Chronic alcohol exposure negatively impacts the physiological and molecular parameters of the renal biotin reabsorption process. (2011). https://pubmed.ncbi.nlm.nih.gov/21209005/ DOI: 10.1152/ajprenal.00707.2010

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/biotin-research/28052864.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2f27f27a7730837eff6529a7eccf67b3587df28af01ac0507d1b692410483703", "start_char": 0, "end_char": 1549, "text_sha256": "2f27f27a7730837eff6529a7eccf67b3587df28af01ac0507d1b692410483703"}

experimental_model

LPS exposure of human NCM460 cells with separate mouse experiments

exposure

LPS, CK2 inhibitors and SMVT Thr78Ala mutation

limitations

CK2 involvement is supported experimentally but the full causal sequence remains qualified; whole-body human deficiency was not measured.

nutrient_topic

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

organism

Homo sapiens

plain_language

Total transporter abundance can look normal while functional surface availability falls.

primary_references

[b7-p28052864] Lipopolysaccharide inhibits colonic biotin uptake via interference with membrane expression of its transporter: a role for a casein kinase 2-mediated pathway. (2017). https://pubmed.ncbi.nlm.nih.gov/28052864/ DOI: 10.1152/ajpcell.00300.2016

tissue_or_cell_type

Colonic epithelial NCM460 cells

trigger_kind

machinery_impairment Imported condition classification; unverified.

Biotin: carboxylases, recycling, deficiency and nutrient interactions (2026-09-17) · lines 1105–1116

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · LPS exposure of human NCM460 cells with separate mouse experiments · source_derived_draft · unverified_draft

### b7-lps-surface LPS reduced the cell-surface fraction of SMVT in NCM460 cells without reducing total SMVT protein or RNA. Condition category: machinery_impairment nutrient_topic: Biotin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Total transporter abundance can look normal while functional surface availability falls. organism: Homo sapiens tissue_or_cell_type: Colonic epithelial NCM460 cells experimental_model: LPS exposure of human NCM460 cells with separate mouse experiments limitations: CK2 involvement is supported experimentally but the full causal sequence remains qualified; whole-body human deficiency was not measured. exposure: LPS, CK2 inhibitors and SMVT Thr78Ala mutation evidence_span: {"source_cache": "artifacts/biotin-research/28052864.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2f27f27a7730837eff6529a7eccf67b3587df28af01ac0507d1b692410483703", "start_char": 0, "end_char": 1549, "text_sha256": "2f27f27a7730837eff6529a7eccf67b3587df28af01ac0507d1b692410483703"} [b7-p28052864] Lipopolysaccharide inhibits colonic biotin uptake via interference with membrane expression of its transporter: a role for a casein kinase 2-mediated pathway. (2017). https://pubmed.ncbi.nlm.nih.gov/28052864/ DOI: 10.1152/ajpcell.00300.2016

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/biotin-research/28052864.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2f27f27a7730837eff6529a7eccf67b3587df28af01ac0507d1b692410483703", "start_char": 0, "end_char": 1549, "text_sha256": "2f27f27a7730837eff6529a7eccf67b3587df28af01ac0507d1b692410483703"}

experimental_model

LPS exposure of human NCM460 cells with separate mouse experiments

exposure

LPS, CK2 inhibitors and SMVT Thr78Ala mutation

limitations

CK2 involvement is supported experimentally but the full causal sequence remains qualified; whole-body human deficiency was not measured.

nutrient_topic

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

organism

Homo sapiens

plain_language

Inflammatory exposure interfered with biotin entry in this model.

primary_references

[b7-p28052864] Lipopolysaccharide inhibits colonic biotin uptake via interference with membrane expression of its transporter: a role for a casein kinase 2-mediated pathway. (2017). https://pubmed.ncbi.nlm.nih.gov/28052864/ DOI: 10.1152/ajpcell.00300.2016

tissue_or_cell_type

Colonic epithelial NCM460 cells

trigger_kind

machinery_impairment Imported condition classification; unverified.

Biotin: carboxylases, recycling, deficiency and nutrient interactions (2026-09-17) · lines 1118–1129

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · LPS exposure of human NCM460 cells with separate mouse experiments · source_derived_draft · unverified_draft

### b7-lps-uptake LPS reduced carrier-mediated biotin uptake in NCM460 cells; CK2 inhibition and a putative CK2-site SMVT mutant supported a CK2-related trafficking mechanism. Condition category: machinery_impairment nutrient_topic: Biotin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Inflammatory exposure interfered with biotin entry in this model. organism: Homo sapiens tissue_or_cell_type: Colonic epithelial NCM460 cells experimental_model: LPS exposure of human NCM460 cells with separate mouse experiments limitations: CK2 involvement is supported experimentally but the full causal sequence remains qualified; whole-body human deficiency was not measured. exposure: LPS, CK2 inhibitors and SMVT Thr78Ala mutation evidence_span: {"source_cache": "artifacts/biotin-research/28052864.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2f27f27a7730837eff6529a7eccf67b3587df28af01ac0507d1b692410483703", "start_char": 0, "end_char": 1549, "text_sha256": "2f27f27a7730837eff6529a7eccf67b3587df28af01ac0507d1b692410483703"} [b7-p28052864] Lipopolysaccharide inhibits colonic biotin uptake via interference with membrane expression of its transporter: a role for a casein kinase 2-mediated pathway. (2017). https://pubmed.ncbi.nlm.nih.gov/28052864/ DOI: 10.1152/ajpcell.00300.2016

cross_nutrient

Distinguishes thiamine transport from biotin transport; no shared-substrate mechanism demonstrated.

evidence-scope

Caco-2 and MDCK epithelial models

evidence_locator

Abstract

evidence_spans

[{"source_document": "artifacts/thiamine_transport_sources/subramanian-2006-biotin-specificity-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1656}]

experimental_model

Human transporter constructs in epithelial cell lines; uptake and surface targeting.

limitations

Tested cell models; clinical biotin-response mechanism remains unresolved.

nutrient_topic

Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)

organism

Human proteins in human and canine cell lines

plain_language

The name biotin-responsive disease does not make SLC19A3 a biotin carrier.

primary_references

[subramanian-2006-biotin-specificity] Biotin-responsive basal ganglia disease-linked mutations inhibit thiamine transport via hTHTR2: biotin is not a substrate for hTHTR2 (2006). https://pubmed.ncbi.nlm.nih.gov/16790503/ DOI: 10.1152/ajpcell.00105.2006

tissue_or_cell_type

Caco-2 and MDCK epithelial models

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 294–307

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human transporter constructs in epithelial cell lines; uptake and surface targeting. · source_derived_draft · unverified_draft

### b1-slc19a3-not-biotin-transporter Wild-type SLC19A3 did not confer detectable biotin uptake, whereas the SLC5A6 positive control did. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The name biotin-responsive disease does not make SLC19A3 a biotin carrier. organism: Human proteins in human and canine cell lines tissue_or_cell_type: Caco-2 and MDCK epithelial models experimental_model: Human transporter constructs in epithelial cell lines; uptake and surface targeting. limitations: Tested cell models; clinical biotin-response mechanism remains unresolved. cross_nutrient: Distinguishes thiamine transport from biotin transport; no shared-substrate mechanism demonstrated. evidence_spans: [{"source_document": "artifacts/thiamine_transport_sources/subramanian-2006-biotin-specificity-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1656}] evidence_locator: Abstract evidence-scope: Caco-2 and MDCK epithelial models [subramanian-2006-biotin-specificity] Biotin-responsive basal ganglia disease-linked mutations inhibit thiamine transport via hTHTR2: biotin is not a substrate for hTHTR2 (2006). https://pubmed.ncbi.nlm.nih.gov/16790503/ DOI: 10.1152/ajpcell.00105.2006

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

true

experimental_model

Human JAr choriocarcinoma cells cultured for three weeks with deficient, physiological or pharmacological biotin

exposure

Three weeks at 25 pmol/L deficient, 250 pmol/L physiological, or 10000 pmol/L pharmacological biotin.

limitations

Tumor-derived placental cell model. The paper also measured biotin uptake and promoter activity, but a resulting change in pantothenate uptake or whole-placenta fetal delivery is not demonstrated by this abstract.

nutrient_topic

Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. · Pantothenate (vitamin B5)

organism

Homo sapiens

plain_language

Cells exposed to less biotin made more of the transporter also used by B5.

primary_references

[b5-trans-biotin-supply2004] Biotin supply affects rates of cell proliferation, biotinylation of carboxylases and histones, and expression of the gene encoding the sodium-dependent multivitamin transporter in JAr choriocarcinoma cells. (2004). https://pubmed.ncbi.nlm.nih.gov/14991266/ DOI: 10.1007/s00394-004-0435-9

tissue_or_cell_type

JAr placental choriocarcinoma cells

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 327–338

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human JAr choriocarcinoma cells cultured for three weeks with deficient, physiological or pharmacological biotin · source_derived_draft · unverified_draft

### b5-trans-biotin-supply-smvt Across 25, 250 and 10000 pmol/L biotin culture conditions for three weeks, biotin availability correlated negatively with SMVT protein abundance in human JAr cells. Condition category: nutrient_deficiency nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Cells exposed to less biotin made more of the transporter also used by B5. organism: Homo sapiens tissue_or_cell_type: JAr placental choriocarcinoma cells experimental_model: Human JAr choriocarcinoma cells cultured for three weeks with deficient, physiological or pharmacological biotin limitations: Tumor-derived placental cell model. The paper also measured biotin uptake and promoter activity, but a resulting change in pantothenate uptake or whole-placenta fetal delivery is not demonstrated by this abstract. exposure: Three weeks at 25 pmol/L deficient, 250 pmol/L physiological, or 10000 pmol/L pharmacological biotin. cross_nutrient: true [b5-trans-biotin-supply2004] Biotin supply affects rates of cell proliferation, biotinylation of carboxylases and histones, and expression of the gene encoding the sodium-dependent multivitamin transporter in JAr choriocarcinoma cells. (2004). https://pubmed.ncbi.nlm.nih.gov/14991266/ DOI: 10.1007/s00394-004-0435-9

cross_nutrient

true

experimental_model

Cryo-EM of engineered human SMVT with nanobody-assisted alignment; functional uptake assays in HEK293T cells

exposure

Biotin uptake assay: 5 micromolar unlabeled biotin plus [3H]biotin at a 300:1 molar ratio; 30 degrees C for ten minutes; inhibitor concentration varied.

limitations

In-vitro IC50 depends on tracer/substrate concentration and expression conditions; it is not a human supplement dose, affinity constant, or threshold for biotin deficiency.

nutrient_topic

Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. · Pantothenate (vitamin B5)

organism

Homo sapiens

plain_language

Oxidized alpha-lipoic acid competed with biotin uptake in the SMVT cell assay.

primary_references

[b5-trans-structure2026] Structural basis for multivitamin recognition and transport by human SMVT. (2026). https://pubmed.ncbi.nlm.nih.gov/42364996/ DOI: 10.1038/s41467-026-74948-3

tissue_or_cell_type

HEK293T cells expressing human SMVT

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 444–455

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cryo-EM of engineered human SMVT with nanobody-assisted alignment; functional uptake assays in HEK293T cells · source_derived_draft · unverified_draft

### b5-trans-lipoate-inhibits-biotin Oxidized alpha-lipoic acid inhibited human SMVT-mediated radiolabeled biotin uptake with an IC50 of 9.1 micromolar in the 2026 HEK293T assay. Condition category: normal nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Oxidized alpha-lipoic acid competed with biotin uptake in the SMVT cell assay. organism: Homo sapiens tissue_or_cell_type: HEK293T cells expressing human SMVT experimental_model: Cryo-EM of engineered human SMVT with nanobody-assisted alignment; functional uptake assays in HEK293T cells limitations: In-vitro IC50 depends on tracer/substrate concentration and expression conditions; it is not a human supplement dose, affinity constant, or threshold for biotin deficiency. exposure: Biotin uptake assay: 5 micromolar unlabeled biotin plus [3H]biotin at a 300:1 molar ratio; 30 degrees C for ten minutes; inhibitor concentration varied. cross_nutrient: true [b5-trans-structure2026] Structural basis for multivitamin recognition and transport by human SMVT. (2026). https://pubmed.ncbi.nlm.nih.gov/42364996/ DOI: 10.1038/s41467-026-74948-3

cross_nutrient

true

experimental_model

Human SMVT cloned from JAR cells, expressed in human retinal pigment epithelial cells and Xenopus laevis oocytes

exposure

Electrophysiology after human SMVT expression; pantothenate and extracellular sodium varied.

limitations

Heterologous human-protein experiments establish transport properties; they do not quantify whole-body absorption or nutrient deficiency from supplement competition.

nutrient_topic

Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. · Pantothenate (vitamin B5)

organism

Homo sapiens (protein); Xenopus laevis (expression host)

plain_language

Pantothenate transport through human SMVT moves net positive charge inward.

primary_references

[b5-trans-wang1999] Human placental Na+-dependent multivitamin transporter. Cloning, functional expression, gene structure, and chromosomal localization. (1999). https://pubmed.ncbi.nlm.nih.gov/10329687/ DOI: 10.1074/jbc.274.21.14875

tissue_or_cell_type

Oocyte plasma membrane

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 210–221

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human SMVT cloned from JAR cells, expressed in human retinal pigment epithelial cells and Xenopus laevis oocytes · source_derived_draft · unverified_draft

### b5-trans-pantothenate-current Pantothenate evoked sodium-, concentration- and potential-dependent inward currents in Xenopus oocytes expressing human SLC5A6. Condition category: normal nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Pantothenate transport through human SMVT moves net positive charge inward. organism: Homo sapiens (protein); Xenopus laevis (expression host) tissue_or_cell_type: Oocyte plasma membrane experimental_model: Human SMVT cloned from JAR cells, expressed in human retinal pigment epithelial cells and Xenopus laevis oocytes limitations: Heterologous human-protein experiments establish transport properties; they do not quantify whole-body absorption or nutrient deficiency from supplement competition. exposure: Electrophysiology after human SMVT expression; pantothenate and extracellular sodium varied. cross_nutrient: true [b5-trans-wang1999] Human placental Na+-dependent multivitamin transporter. Cloning, functional expression, gene structure, and chromosomal localization. (1999). https://pubmed.ncbi.nlm.nih.gov/10329687/ DOI: 10.1074/jbc.274.21.14875

cross_nutrient

true

experimental_model

Cryo-EM of engineered human SMVT with nanobody-assisted alignment; functional uptake assays in HEK293T cells

exposure

Biotin uptake assay: 5 micromolar unlabeled biotin plus [3H]biotin at a 300:1 molar ratio; 30 degrees C for ten minutes; inhibitor concentration varied.

limitations

In-vitro IC50 depends on tracer/substrate concentration and expression conditions; it is not a human supplement dose, affinity constant, or threshold for biotin deficiency.

nutrient_topic

Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. · Pantothenate (vitamin B5)

organism

Homo sapiens

plain_language

D-pantothenic acid competed with biotin uptake in the SMVT cell assay.

primary_references

[b5-trans-structure2026] Structural basis for multivitamin recognition and transport by human SMVT. (2026). https://pubmed.ncbi.nlm.nih.gov/42364996/ DOI: 10.1038/s41467-026-74948-3

tissue_or_cell_type

HEK293T cells expressing human SMVT

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 431–442

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cryo-EM of engineered human SMVT with nanobody-assisted alignment; functional uptake assays in HEK293T cells · source_derived_draft · unverified_draft

### b5-trans-pantothenate-inhibits-biotin D-pantothenic acid inhibited human SMVT-mediated radiolabeled biotin uptake with an IC50 of 89.7 micromolar in the 2026 HEK293T assay. Condition category: normal nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: D-pantothenic acid competed with biotin uptake in the SMVT cell assay. organism: Homo sapiens tissue_or_cell_type: HEK293T cells expressing human SMVT experimental_model: Cryo-EM of engineered human SMVT with nanobody-assisted alignment; functional uptake assays in HEK293T cells limitations: In-vitro IC50 depends on tracer/substrate concentration and expression conditions; it is not a human supplement dose, affinity constant, or threshold for biotin deficiency. exposure: Biotin uptake assay: 5 micromolar unlabeled biotin plus [3H]biotin at a 300:1 molar ratio; 30 degrees C for ten minutes; inhibitor concentration varied. cross_nutrient: true [b5-trans-structure2026] Structural basis for multivitamin recognition and transport by human SMVT. (2026). https://pubmed.ncbi.nlm.nih.gov/42364996/ DOI: 10.1038/s41467-026-74948-3

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

true

experimental_model

Patient-derived fibroblasts in a human SLC5A6 family study; molecular and radiolabeled biotin uptake analysis

exposure

The p.Ser429Gly allele supplied canonically spliced transcripts in the compound-heterozygous proband; uptake compared with control fibroblasts.

limitations

Abstract-only transport extraction. This is one proband genotype, not an isolated p.Ser429Gly dose-response study; neither pantothenate uptake nor the relative contribution of individual supplements is quantified.

nutrient_topic

Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. · Pantothenate (vitamin B5)

organism

Homo sapiens

plain_language

A patient with two SLC5A6 variants had a large defect in cellular biotin entry.

primary_references

[b5-trans-neuropathy2024] Genome sequencing enables diagnosis and treatment of SLC5A6 neuropathy. (2024). https://pubmed.ncbi.nlm.nih.gov/38816490/ DOI: 10.1038/s41431-024-01641-8

tissue_or_cell_type

Patient-derived fibroblasts

trigger_kind

machinery_impairment Imported condition classification; unverified.

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 392–403

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Patient-derived fibroblasts in a human SLC5A6 family study; molecular and radiolabeled biotin uptake analysis · source_derived_draft · unverified_draft

### b5-trans-patient-fibroblast-biotin Fibroblasts from the proband with SLC5A6 c.393+2T>C and p.Ser429Gly variants showed approximately 90% lower biotin uptake than controls. Condition category: machinery_impairment nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: A patient with two SLC5A6 variants had a large defect in cellular biotin entry. organism: Homo sapiens tissue_or_cell_type: Patient-derived fibroblasts experimental_model: Patient-derived fibroblasts in a human SLC5A6 family study; molecular and radiolabeled biotin uptake analysis limitations: Abstract-only transport extraction. This is one proband genotype, not an isolated p.Ser429Gly dose-response study; neither pantothenate uptake nor the relative contribution of individual supplements is quantified. exposure: The p.Ser429Gly allele supplied canonically spliced transcripts in the compound-heterozygous proband; uptake compared with control fibroblasts. cross_nutrient: true [b5-trans-neuropathy2024] Genome sequencing enables diagnosis and treatment of SLC5A6 neuropathy. (2024). https://pubmed.ncbi.nlm.nih.gov/38816490/ DOI: 10.1038/s41431-024-01641-8

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

true

experimental_model

Human intestinal HuTu-80 and brain-derived U87 cell transfection and live-cell imaging of patient-derived SLC5A6 variants

exposure

Forty-eight hours after transfection; 5 nM [3H]biotin, pH 7.4, 37 degrees C, five-minute uptake.

limitations

Human transformed cell models expressing GFP-tagged constructs. Biotin is the measured substrate; impaired B5/lipoate transport is plausible through shared machinery but is not directly quantified here. Genetic dysfunction is not dietary B5 deficiency.

nutrient_topic

Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. · Pantothenate (vitamin B5)

organism

Homo sapiens

plain_language

The R123L SMVT variant lost the uptake activity seen with the normal transporter.

primary_references

[b5-trans-slc5a6-variants2017] Mutations in SLC5A6 associated with brain, immune, bone, and intestinal dysfunction in a young child. (2017). https://pubmed.ncbi.nlm.nih.gov/27904971/ DOI: 10.1007/s00439-016-1751-x

tissue_or_cell_type

HuTu-80 duodenal-derived epithelial and U87 brain-derived glioma cells

trigger_kind

machinery_impairment Imported condition classification; unverified.

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 353–364

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human intestinal HuTu-80 and brain-derived U87 cell transfection and live-cell imaging of patient-derived SLC5A6 variants · source_derived_draft · unverified_draft

### b5-trans-r123l-biotin Expression of human SLC5A6 R123L failed to induce biotin uptake above control in HuTu-80 and U87 cells, whereas wild-type SLC5A6 increased uptake. Condition category: machinery_impairment nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: The R123L SMVT variant lost the uptake activity seen with the normal transporter. organism: Homo sapiens tissue_or_cell_type: HuTu-80 duodenal-derived epithelial and U87 brain-derived glioma cells experimental_model: Human intestinal HuTu-80 and brain-derived U87 cell transfection and live-cell imaging of patient-derived SLC5A6 variants limitations: Human transformed cell models expressing GFP-tagged constructs. Biotin is the measured substrate; impaired B5/lipoate transport is plausible through shared machinery but is not directly quantified here. Genetic dysfunction is not dietary B5 deficiency. exposure: Forty-eight hours after transfection; 5 nM [3H]biotin, pH 7.4, 37 degrees C, five-minute uptake. cross_nutrient: true [b5-trans-slc5a6-variants2017] Mutations in SLC5A6 associated with brain, immune, bone, and intestinal dysfunction in a young child. (2017). https://pubmed.ncbi.nlm.nih.gov/27904971/ DOI: 10.1007/s00439-016-1751-x

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

false

experimental_model

Human intestinal HuTu-80 and brain-derived U87 cell transfection and live-cell imaging of patient-derived SLC5A6 variants

exposure

Live-cell confocal imaging 48 hours after transfection; hSMVT-GFP versus R123L-GFP and DsRed-ER.

limitations

Some mutant signal remained at the cell surface. Fluorescent-fusion localization does not prove zero residual activity or a dietary treatment response.

nutrient_topic

Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. · Pantothenate (vitamin B5)

organism

Homo sapiens

plain_language

The R123L transporter is largely trapped inside the cell instead of reaching its working surface.

primary_references

[b5-trans-slc5a6-variants2017] Mutations in SLC5A6 associated with brain, immune, bone, and intestinal dysfunction in a young child. (2017). https://pubmed.ncbi.nlm.nih.gov/27904971/ DOI: 10.1007/s00439-016-1751-x

tissue_or_cell_type

HuTu-80 and U87 cells; ER-marker colocalization shown in HuTu-80

trigger_kind

machinery_impairment Imported condition classification; unverified.

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 366–377

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human intestinal HuTu-80 and brain-derived U87 cell transfection and live-cell imaging of patient-derived SLC5A6 variants · source_derived_draft · unverified_draft

### b5-trans-r123l-er-retention Human SLC5A6 R123L-GFP was predominantly retained in the endoplasmic reticulum; ER-marker colocalization supported this localization. Condition category: machinery_impairment nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: The R123L transporter is largely trapped inside the cell instead of reaching its working surface. organism: Homo sapiens tissue_or_cell_type: HuTu-80 and U87 cells; ER-marker colocalization shown in HuTu-80 experimental_model: Human intestinal HuTu-80 and brain-derived U87 cell transfection and live-cell imaging of patient-derived SLC5A6 variants limitations: Some mutant signal remained at the cell surface. Fluorescent-fusion localization does not prove zero residual activity or a dietary treatment response. exposure: Live-cell confocal imaging 48 hours after transfection; hSMVT-GFP versus R123L-GFP and DsRed-ER. cross_nutrient: false [b5-trans-slc5a6-variants2017] Mutations in SLC5A6 associated with brain, immune, bone, and intestinal dysfunction in a young child. (2017). https://pubmed.ncbi.nlm.nih.gov/27904971/ DOI: 10.1007/s00439-016-1751-x

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

true

experimental_model

Human intestinal HuTu-80 and brain-derived U87 cell transfection and live-cell imaging of patient-derived SLC5A6 variants

exposure

Forty-eight hours after transfection; 5 nM [3H]biotin, pH 7.4, 37 degrees C, five-minute uptake.

limitations

Human transformed cell models expressing GFP-tagged constructs. Biotin is the measured substrate; impaired B5/lipoate transport is plausible through shared machinery but is not directly quantified here. Genetic dysfunction is not dietary B5 deficiency.

nutrient_topic

Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. · Pantothenate (vitamin B5)

organism

Homo sapiens

plain_language

The R94X SMVT variant lost the uptake activity seen with the normal transporter.

primary_references

[b5-trans-slc5a6-variants2017] Mutations in SLC5A6 associated with brain, immune, bone, and intestinal dysfunction in a young child. (2017). https://pubmed.ncbi.nlm.nih.gov/27904971/ DOI: 10.1007/s00439-016-1751-x

tissue_or_cell_type

HuTu-80 duodenal-derived epithelial and U87 brain-derived glioma cells

trigger_kind

machinery_impairment Imported condition classification; unverified.

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 340–351

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human intestinal HuTu-80 and brain-derived U87 cell transfection and live-cell imaging of patient-derived SLC5A6 variants · source_derived_draft · unverified_draft

### b5-trans-r94x-biotin Expression of human SLC5A6 R94X failed to induce biotin uptake above control in HuTu-80 and U87 cells, whereas wild-type SLC5A6 increased uptake. Condition category: machinery_impairment nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: The R94X SMVT variant lost the uptake activity seen with the normal transporter. organism: Homo sapiens tissue_or_cell_type: HuTu-80 duodenal-derived epithelial and U87 brain-derived glioma cells experimental_model: Human intestinal HuTu-80 and brain-derived U87 cell transfection and live-cell imaging of patient-derived SLC5A6 variants limitations: Human transformed cell models expressing GFP-tagged constructs. Biotin is the measured substrate; impaired B5/lipoate transport is plausible through shared machinery but is not directly quantified here. Genetic dysfunction is not dietary B5 deficiency. exposure: Forty-eight hours after transfection; 5 nM [3H]biotin, pH 7.4, 37 degrees C, five-minute uptake. cross_nutrient: true [b5-trans-slc5a6-variants2017] Mutations in SLC5A6 associated with brain, immune, bone, and intestinal dysfunction in a young child. (2017). https://pubmed.ncbi.nlm.nih.gov/27904971/ DOI: 10.1007/s00439-016-1751-x

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

false

experimental_model

Human intestinal HuTu-80 and brain-derived U87 cell transfection and live-cell imaging of patient-derived SLC5A6 variants

exposure

Live-cell confocal imaging of equal-DNA transfections under matched imaging settings.

limitations

Poor expression and localization were observed together; the experiment does not separately quantify synthesis, degradation and trafficking rates.

nutrient_topic

Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. · Pantothenate (vitamin B5)

organism

Homo sapiens

plain_language

The R94X truncation produced little transporter and failed to show normal membrane localization.

primary_references

[b5-trans-slc5a6-variants2017] Mutations in SLC5A6 associated with brain, immune, bone, and intestinal dysfunction in a young child. (2017). https://pubmed.ncbi.nlm.nih.gov/27904971/ DOI: 10.1007/s00439-016-1751-x

tissue_or_cell_type

HuTu-80 and U87 cells

trigger_kind

machinery_impairment Imported condition classification; unverified.

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 379–390

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human intestinal HuTu-80 and brain-derived U87 cell transfection and live-cell imaging of patient-derived SLC5A6 variants · source_derived_draft · unverified_draft

### b5-trans-r94x-cytoplasmic The truncated SLC5A6 R94X-GFP construct was poorly expressed, with the detected signal localized in the cytoplasm of HuTu-80 and U87 cells. Condition category: machinery_impairment nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: The R94X truncation produced little transporter and failed to show normal membrane localization. organism: Homo sapiens tissue_or_cell_type: HuTu-80 and U87 cells experimental_model: Human intestinal HuTu-80 and brain-derived U87 cell transfection and live-cell imaging of patient-derived SLC5A6 variants limitations: Poor expression and localization were observed together; the experiment does not separately quantify synthesis, degradation and trafficking rates. exposure: Live-cell confocal imaging of equal-DNA transfections under matched imaging settings. cross_nutrient: false [b5-trans-slc5a6-variants2017] Mutations in SLC5A6 associated with brain, immune, bone, and intestinal dysfunction in a young child. (2017). https://pubmed.ncbi.nlm.nih.gov/27904971/ DOI: 10.1007/s00439-016-1751-x

cross_nutrient

true

experimental_model

Human SMVT cloned from JAR cells, expressed in human retinal pigment epithelial cells and Xenopus laevis oocytes

exposure

Sodium concentration-response of cloned human SMVT-mediated vitamin uptake.

limitations

Heterologous human-protein experiments establish transport properties; they do not quantify whole-body absorption or nutrient deficiency from supplement competition. The ratio is inferred from transport kinetics, rather than direct counting of individual cotransport events.

nutrient_topic

Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. · Pantothenate (vitamin B5)

organism

Homo sapiens

plain_language

Two sodium ions accompany each pantothenate molecule in the reported SMVT transport model.

primary_references

[b5-trans-wang1999] Human placental Na+-dependent multivitamin transporter. Cloning, functional expression, gene structure, and chromosomal localization. (1999). https://pubmed.ncbi.nlm.nih.gov/10329687/ DOI: 10.1074/jbc.274.21.14875

tissue_or_cell_type

HRPE cell plasma membrane

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 197–208

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human SMVT cloned from JAR cells, expressed in human retinal pigment epithelial cells and Xenopus laevis oocytes · source_derived_draft · unverified_draft

### b5-trans-two-sodium-pantothenate Sodium-dependence kinetics of human SLC5A6-mediated pantothenate uptake supported a 2:1 sodium:pantothenate coupling ratio. Condition category: normal nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Two sodium ions accompany each pantothenate molecule in the reported SMVT transport model. organism: Homo sapiens tissue_or_cell_type: HRPE cell plasma membrane experimental_model: Human SMVT cloned from JAR cells, expressed in human retinal pigment epithelial cells and Xenopus laevis oocytes limitations: Heterologous human-protein experiments establish transport properties; they do not quantify whole-body absorption or nutrient deficiency from supplement competition. The ratio is inferred from transport kinetics, rather than direct counting of individual cotransport events. exposure: Sodium concentration-response of cloned human SMVT-mediated vitamin uptake. cross_nutrient: true [b5-trans-wang1999] Human placental Na+-dependent multivitamin transporter. Cloning, functional expression, gene structure, and chromosomal localization. (1999). https://pubmed.ncbi.nlm.nih.gov/10329687/ DOI: 10.1074/jbc.274.21.14875