Nutrient chapter

Phosphorus

Phosphorus. Species, exposure and limitations are retained in each linked claim.

114 recorded mechanisms · 12 availability situations · 12 preserved sources. Draft and verified records are labeled separately.

Read recorded mechanisms Open recursive mind map

The mechanisms

What the sources say this nutrient does, one relationship at a time. Plain wording comes first; the technical statement follows.

Raising extracellular phosphate inhibited CaSR activity through noncompetitive antagonism in the experimental system.
Inorganic phosphate (Pi; protonation depends on pH) → Calcium-sensing receptor / CaSR source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/phosphorus-research/31619668.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e4fe1ed7eb92175f99f446afa19fb184147ceed0413f3a6dffa85aa80927015d", "start_char": 0, "end_char": 1144, "text_sha256": "e4fe1ed7eb92175f99f446afa19fb184147ceed0413f3a6dffa85aa80927015d"}
experimental_model
CaSR expression/mutagenesis and isolated human/mouse parathyroid experiments
exposure
Extracellular phosphate in pathophysiologic CKD ranges; R62A substitution and mouse Casr deletion
limitations
Direct phosphate antagonism was tested separately from calcium regulation; concentrations and model are not dietary thresholds.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Human CaSR expression system
plain_language
Phosphate can act on the calcium-sensing receptor itself, not only change how much calcium is present.
primary_references
[phosphorus-p31619668] Phosphate acts directly on the calcium-sensing receptor to stimulate parathyroid hormone secretion. (2019). https://pubmed.ncbi.nlm.nih.gov/31619668/ DOI: 10.1038/s41467-019-12399-9
tissue_or_cell_type
CaSR reporter cells and freshly isolated parathyroid cells/glands
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 438–449
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · CaSR expression/mutagenesis and isolated human/mouse parathyroid experiments · source_derived_draft · unverified_draft
### phosphorus-casr-antagonism Raising extracellular phosphate inhibited CaSR activity through noncompetitive antagonism in the experimental system. Condition category: normal nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: Phosphate can act on the calcium-sensing receptor itself, not only change how much calcium is present. organism: Human CaSR expression system tissue_or_cell_type: CaSR reporter cells and freshly isolated parathyroid cells/glands experimental_model: CaSR expression/mutagenesis and isolated human/mouse parathyroid experiments limitations: Direct phosphate antagonism was tested separately from calcium regulation; concentrations and model are not dietary thresholds. exposure: Extracellular phosphate in pathophysiologic CKD ranges; R62A substitution and mouse Casr deletion evidence_span: {"source_cache": "artifacts/phosphorus-research/31619668.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e4fe1ed7eb92175f99f446afa19fb184147ceed0413f3a6dffa85aa80927015d", "start_char": 0, "end_char": 1144, "text_sha256": "e4fe1ed7eb92175f99f446afa19fb184147ceed0413f3a6dffa85aa80927015d"} [phosphorus-p31619668] Phosphate acts directly on the calcium-sensing receptor to stimulate parathyroid hormone secretion. (2019). https://pubmed.ncbi.nlm.nih.gov/31619668/ DOI: 10.1038/s41467-019-12399-9
Complete structured claim and evidence
Human MAT2A formed S-adenosylmethionine before rapid triphosphate hydrolysis and product release in the kinetic study.
Human methionine adenosyltransferase 2A / MAT2A → S-Adenosyl-L-methionine source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/phosphorus-research/33656855.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1d45073f7187a06cfb9b2d630f94fa651239f0a9a5ae353b37d9af90750f2f38", "start_char": 0, "end_char": 1520, "text_sha256": "1d45073f7187a06cfb9b2d630f94fa651239f0a9a5ae353b37d9af90750f2f38"}
experimental_model
Human MAT2A kinetics, isotope exchange and inhibitor-bound crystallography
exposure
ATP/methionine reactions and PNPNP ligand complexes
limitations
Phosphoryl chemistry is not evidence that phosphate supplements boost methylation. Metal contacts were resolved with an experimental ATP-site ligand.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Human recombinant enzyme
plain_language
Making the methyl donor SAM is coupled to ATP-derived phosphate chemistry.
primary_references
[phosphorus-p33656855] Mechanism and Inhibition of Human Methionine Adenosyltransferase 2A. (2021). https://pubmed.ncbi.nlm.nih.gov/33656855/ DOI: 10.1021/acs.biochem.0c00998
tissue_or_cell_type
Purified MAT2A active site
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 633–644
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human MAT2A kinetics, isotope exchange and inhibitor-bound crystallography · source_derived_draft · unverified_draft
### phosphorus-mat-sam Human MAT2A formed S-adenosylmethionine before rapid triphosphate hydrolysis and product release in the kinetic study. Condition category: normal nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: Making the methyl donor SAM is coupled to ATP-derived phosphate chemistry. organism: Human recombinant enzyme tissue_or_cell_type: Purified MAT2A active site experimental_model: Human MAT2A kinetics, isotope exchange and inhibitor-bound crystallography limitations: Phosphoryl chemistry is not evidence that phosphate supplements boost methylation. Metal contacts were resolved with an experimental ATP-site ligand. exposure: ATP/methionine reactions and PNPNP ligand complexes evidence_span: {"source_cache": "artifacts/phosphorus-research/33656855.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1d45073f7187a06cfb9b2d630f94fa651239f0a9a5ae353b37d9af90750f2f38", "start_char": 0, "end_char": 1520, "text_sha256": "1d45073f7187a06cfb9b2d630f94fa651239f0a9a5ae353b37d9af90750f2f38"} [phosphorus-p33656855] Mechanism and Inhibition of Human Methionine Adenosyltransferase 2A. (2021). https://pubmed.ncbi.nlm.nih.gov/33656855/ DOI: 10.1021/acs.biochem.0c00998
Complete structured claim and evidence
Reported serum FGF23 decreased during low-phosphate feeding and increased after oral phosphate loading in healthy men.
Phosphorus → Circulating FGF23 assay result, molecular form unresolved source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/phosphorus-research/15613425.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4a8c4110b9c57e9f8f54305eb77abb80dd90253fc99e2f5aa21a4a3f129983c2", "start_char": 0, "end_char": 1563, "text_sha256": "4a8c4110b9c57e9f8f54305eb77abb80dd90253fc99e2f5aa21a4a3f129983c2"}
experimental_model
Controlled sequential dietary intervention
exposure
Five-day low-phosphate diet plus binder, then phosphate loading; calcium adjusted to minimize PTH changes
limitations
FGF23 assay form not resolved from the indexed abstract; circulating FGF23 result must not be read as a quantified cleavage ratio.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
object_scope
FGF23 assay result; assay form unresolved from abstract
organism
Human
plain_language
Changing phosphorus exposure changed a hormone involved in phosphate handling.
primary_references
[phosphorus-p15613425] Fibroblast growth factor-23 relationship to dietary phosphate and renal phosphate handling in healthy young men. (2005). https://pubmed.ncbi.nlm.nih.gov/15613425/ DOI: 10.1210/jc.2004-1039
tissue_or_cell_type
29 healthy young men; serum hormones and renal handling
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 906–918
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Controlled sequential dietary intervention · source_derived_draft · unverified_draft
### phosphorus-diet-fgf23 Reported serum FGF23 decreased during low-phosphate feeding and increased after oral phosphate loading in healthy men. Condition category: normal nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: Changing phosphorus exposure changed a hormone involved in phosphate handling. organism: Human tissue_or_cell_type: 29 healthy young men; serum hormones and renal handling experimental_model: Controlled sequential dietary intervention limitations: FGF23 assay form not resolved from the indexed abstract; circulating FGF23 result must not be read as a quantified cleavage ratio. exposure: Five-day low-phosphate diet plus binder, then phosphate loading; calcium adjusted to minimize PTH changes object_scope: FGF23 assay result; assay form unresolved from abstract evidence_span: {"source_cache": "artifacts/phosphorus-research/15613425.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4a8c4110b9c57e9f8f54305eb77abb80dd90253fc99e2f5aa21a4a3f129983c2", "start_char": 0, "end_char": 1563, "text_sha256": "4a8c4110b9c57e9f8f54305eb77abb80dd90253fc99e2f5aa21a4a3f129983c2"} [phosphorus-p15613425] Fibroblast growth factor-23 relationship to dietary phosphate and renal phosphate handling in healthy young men. (2005). https://pubmed.ncbi.nlm.nih.gov/15613425/ DOI: 10.1210/jc.2004-1039
Complete structured claim and evidence
Marked erythrocyte ATP depletion below 1 mmol/L cells was observed only when cellular Pi was below 0.3 mmol/L cells and plasma Pi below 0.35 mmol/L in this dataset.
Plasma inorganic phosphate concentration → Human erythrocyte ATP concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/phosphorus-research/4042545.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "474d2b2722565fa0e4c2f0ddf4a332715ce176f9325b9af5c22027bd6ac93e43", "start_char": 0, "end_char": 1711, "text_sha256": "474d2b2722565fa0e4c2f0ddf4a332715ce176f9325b9af5c22027bd6ac93e43"}
experimental_model
ICU erythrocyte measurements and normal-donor cell incubation
exposure
Plasma Pi 0.1–4.2 mmol/L in patients; normal-donor cells incubated at 1 or 5 mmol/L Pi
limitations
Observed ranges are not universal thresholds; ATP concentration, ATP synthetic flux and 2,3-DPG are separate endpoints.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Human
plain_language
Severe phosphate depletion can accompany low red-cell ATP, but this study does not set a universal cutoff.
primary_references
[phosphorus-p4042545] Phosphate metabolism in erythrocytes of critically ill patients. (1985). https://pubmed.ncbi.nlm.nih.gov/4042545/ DOI: 10.1042/cs0690435
tissue_or_cell_type
Red blood cells
trigger_kind
biomarker_context Imported condition classification; unverified.
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 1063–1074
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · ICU erythrocyte measurements and normal-donor cell incubation · source_derived_draft · unverified_draft
### phosphorus-rbc-atp-low Marked erythrocyte ATP depletion below 1 mmol/L cells was observed only when cellular Pi was below 0.3 mmol/L cells and plasma Pi below 0.35 mmol/L in this dataset. Condition category: biomarker_context nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: Severe phosphate depletion can accompany low red-cell ATP, but this study does not set a universal cutoff. organism: Human tissue_or_cell_type: Red blood cells experimental_model: ICU erythrocyte measurements and normal-donor cell incubation limitations: Observed ranges are not universal thresholds; ATP concentration, ATP synthetic flux and 2,3-DPG are separate endpoints. exposure: Plasma Pi 0.1–4.2 mmol/L in patients; normal-donor cells incubated at 1 or 5 mmol/L Pi evidence_span: {"source_cache": "artifacts/phosphorus-research/4042545.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "474d2b2722565fa0e4c2f0ddf4a332715ce176f9325b9af5c22027bd6ac93e43", "start_char": 0, "end_char": 1711, "text_sha256": "474d2b2722565fa0e4c2f0ddf4a332715ce176f9325b9af5c22027bd6ac93e43"} [phosphorus-p4042545] Phosphate metabolism in erythrocytes of critically ill patients. (1985). https://pubmed.ncbi.nlm.nih.gov/4042545/ DOI: 10.1042/cs0690435
Complete structured claim and evidence
After low-phosphate feeding and an acute phosphate bolus, Slc34a2-null mice absorbed approximately 50% less phosphate than wild type.
Inducible mouse Slc34a2 knockout in the 2009 absorption study → Mouse intestinal phosphate absorption source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/phosphorus-research/19729436.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "db886399fafd3fc4da4c341765ec69ebb7948f4993e271ca6ee6855d8ba7616d", "start_char": 0, "end_char": 1402, "text_sha256": "db886399fafd3fc4da4c341765ec69ebb7948f4993e271ca6ee6855d8ba7616d"}
experimental_model
Inducible Slc34a2 knockout, balance measurements and isolated ileum transport
exposure
Knockout versus wild type; low-P diet followed by an acute phosphate bolus
limitations
Fraction of active transport is not the fraction of total absorption in every diet or species. Normal serum phosphate can coexist with impaired intestinal entry because the kidney compensates.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Mouse
plain_language
Removing the intestinal transporter reduced absorption under the specified feeding conditions.
primary_references
[phosphorus-p19729436] Intestinal npt2b plays a major role in phosphate absorption and homeostasis. (2009). https://pubmed.ncbi.nlm.nih.gov/19729436/ DOI: 10.1681/asn.2009050559
tissue_or_cell_type
Intestine and compensatory renal handling
trigger_kind
machinery_impairment Imported condition classification; unverified.
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 230–241
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Inducible Slc34a2 knockout, balance measurements and isolated ileum transport · source_derived_draft · unverified_draft
### phosphorus-npt2b-absorption After low-phosphate feeding and an acute phosphate bolus, Slc34a2-null mice absorbed approximately 50% less phosphate than wild type. Condition category: machinery_impairment nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: Removing the intestinal transporter reduced absorption under the specified feeding conditions. organism: Mouse tissue_or_cell_type: Intestine and compensatory renal handling experimental_model: Inducible Slc34a2 knockout, balance measurements and isolated ileum transport limitations: Fraction of active transport is not the fraction of total absorption in every diet or species. Normal serum phosphate can coexist with impaired intestinal entry because the kidney compensates. exposure: Knockout versus wild type; low-P diet followed by an acute phosphate bolus evidence_span: {"source_cache": "artifacts/phosphorus-research/19729436.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "db886399fafd3fc4da4c341765ec69ebb7948f4993e271ca6ee6855d8ba7616d", "start_char": 0, "end_char": 1402, "text_sha256": "db886399fafd3fc4da4c341765ec69ebb7948f4993e271ca6ee6855d8ba7616d"} [phosphorus-p19729436] Intestinal npt2b plays a major role in phosphate absorption and homeostasis. (2009). https://pubmed.ncbi.nlm.nih.gov/19729436/ DOI: 10.1681/asn.2009050559
Complete structured claim and evidence
Slc34a2-null mice excreted more phosphate in feces.
Inducible mouse Slc34a2 knockout in the 2009 absorption study → Mouse fecal phosphate excretion source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/phosphorus-research/19729436.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "db886399fafd3fc4da4c341765ec69ebb7948f4993e271ca6ee6855d8ba7616d", "start_char": 0, "end_char": 1402, "text_sha256": "db886399fafd3fc4da4c341765ec69ebb7948f4993e271ca6ee6855d8ba7616d"}
experimental_model
Inducible Slc34a2 knockout, balance measurements and isolated ileum transport
exposure
Knockout versus wild type; low-P diet followed by an acute phosphate bolus
limitations
Fraction of active transport is not the fraction of total absorption in every diet or species. Normal serum phosphate can coexist with impaired intestinal entry because the kidney compensates.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Mouse
plain_language
More phosphorus left through the gut.
primary_references
[phosphorus-p19729436] Intestinal npt2b plays a major role in phosphate absorption and homeostasis. (2009). https://pubmed.ncbi.nlm.nih.gov/19729436/ DOI: 10.1681/asn.2009050559
tissue_or_cell_type
Intestine and compensatory renal handling
trigger_kind
machinery_impairment Imported condition classification; unverified.
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 243–254
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Inducible Slc34a2 knockout, balance measurements and isolated ileum transport · source_derived_draft · unverified_draft
### phosphorus-npt2b-fecal Slc34a2-null mice excreted more phosphate in feces. Condition category: machinery_impairment nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: More phosphorus left through the gut. organism: Mouse tissue_or_cell_type: Intestine and compensatory renal handling experimental_model: Inducible Slc34a2 knockout, balance measurements and isolated ileum transport limitations: Fraction of active transport is not the fraction of total absorption in every diet or species. Normal serum phosphate can coexist with impaired intestinal entry because the kidney compensates. exposure: Knockout versus wild type; low-P diet followed by an acute phosphate bolus evidence_span: {"source_cache": "artifacts/phosphorus-research/19729436.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "db886399fafd3fc4da4c341765ec69ebb7948f4993e271ca6ee6855d8ba7616d", "start_char": 0, "end_char": 1402, "text_sha256": "db886399fafd3fc4da4c341765ec69ebb7948f4993e271ca6ee6855d8ba7616d"} [phosphorus-p19729436] Intestinal npt2b plays a major role in phosphate absorption and homeostasis. (2009). https://pubmed.ncbi.nlm.nih.gov/19729436/ DOI: 10.1681/asn.2009050559
Complete structured claim and evidence
Slc34a2-null mice excreted less phosphate in urine.
Inducible mouse Slc34a2 knockout in the 2009 absorption study → Mouse urinary phosphate excretion source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/phosphorus-research/19729436.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "db886399fafd3fc4da4c341765ec69ebb7948f4993e271ca6ee6855d8ba7616d", "start_char": 0, "end_char": 1402, "text_sha256": "db886399fafd3fc4da4c341765ec69ebb7948f4993e271ca6ee6855d8ba7616d"}
experimental_model
Inducible Slc34a2 knockout, balance measurements and isolated ileum transport
exposure
Knockout versus wild type; low-P diet followed by an acute phosphate bolus
limitations
Fraction of active transport is not the fraction of total absorption in every diet or species. Normal serum phosphate can coexist with impaired intestinal entry because the kidney compensates.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Mouse
plain_language
The kidneys conserved phosphate when gut uptake was impaired.
primary_references
[phosphorus-p19729436] Intestinal npt2b plays a major role in phosphate absorption and homeostasis. (2009). https://pubmed.ncbi.nlm.nih.gov/19729436/ DOI: 10.1681/asn.2009050559
tissue_or_cell_type
Intestine and compensatory renal handling
trigger_kind
machinery_impairment Imported condition classification; unverified.
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 256–267
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Inducible Slc34a2 knockout, balance measurements and isolated ileum transport · source_derived_draft · unverified_draft
### phosphorus-npt2b-urine Slc34a2-null mice excreted less phosphate in urine. Condition category: machinery_impairment nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: The kidneys conserved phosphate when gut uptake was impaired. organism: Mouse tissue_or_cell_type: Intestine and compensatory renal handling experimental_model: Inducible Slc34a2 knockout, balance measurements and isolated ileum transport limitations: Fraction of active transport is not the fraction of total absorption in every diet or species. Normal serum phosphate can coexist with impaired intestinal entry because the kidney compensates. exposure: Knockout versus wild type; low-P diet followed by an acute phosphate bolus evidence_span: {"source_cache": "artifacts/phosphorus-research/19729436.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "db886399fafd3fc4da4c341765ec69ebb7948f4993e271ca6ee6855d8ba7616d", "start_char": 0, "end_char": 1402, "text_sha256": "db886399fafd3fc4da4c341765ec69ebb7948f4993e271ca6ee6855d8ba7616d"} [phosphorus-p19729436] Intestinal npt2b plays a major role in phosphate absorption and homeostasis. (2009). https://pubmed.ncbi.nlm.nih.gov/19729436/ DOI: 10.1681/asn.2009050559
Complete structured claim and evidence
Serum phosphate remained unchanged in the Slc34a2-null mice despite altered intestinal and urinary handling.
Inducible mouse Slc34a2 knockout in the 2009 absorption study → Mouse serum inorganic phosphate concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/phosphorus-research/19729436.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "db886399fafd3fc4da4c341765ec69ebb7948f4993e271ca6ee6855d8ba7616d", "start_char": 0, "end_char": 1402, "text_sha256": "db886399fafd3fc4da4c341765ec69ebb7948f4993e271ca6ee6855d8ba7616d"}
experimental_model
Inducible Slc34a2 knockout, balance measurements and isolated ileum transport
exposure
Knockout versus wild type; low-P diet followed by an acute phosphate bolus
limitations
Fraction of active transport is not the fraction of total absorption in every diet or species. Normal serum phosphate can coexist with impaired intestinal entry because the kidney compensates.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Mouse
plain_language
A normal blood measurement did not mean the transport system was unchanged.
primary_references
[phosphorus-p19729436] Intestinal npt2b plays a major role in phosphate absorption and homeostasis. (2009). https://pubmed.ncbi.nlm.nih.gov/19729436/ DOI: 10.1681/asn.2009050559
tissue_or_cell_type
Intestine and compensatory renal handling
trigger_kind
machinery_impairment Imported condition classification; unverified.
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 269–280
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Inducible Slc34a2 knockout, balance measurements and isolated ileum transport · source_derived_draft · unverified_draft
### phosphorus-npt2b-serum Serum phosphate remained unchanged in the Slc34a2-null mice despite altered intestinal and urinary handling. Condition category: machinery_impairment nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: A normal blood measurement did not mean the transport system was unchanged. organism: Mouse tissue_or_cell_type: Intestine and compensatory renal handling experimental_model: Inducible Slc34a2 knockout, balance measurements and isolated ileum transport limitations: Fraction of active transport is not the fraction of total absorption in every diet or species. Normal serum phosphate can coexist with impaired intestinal entry because the kidney compensates. exposure: Knockout versus wild type; low-P diet followed by an acute phosphate bolus evidence_span: {"source_cache": "artifacts/phosphorus-research/19729436.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "db886399fafd3fc4da4c341765ec69ebb7948f4993e271ca6ee6855d8ba7616d", "start_char": 0, "end_char": 1402, "text_sha256": "db886399fafd3fc4da4c341765ec69ebb7948f4993e271ca6ee6855d8ba7616d"} [phosphorus-p19729436] Intestinal npt2b plays a major role in phosphate absorption and homeostasis. (2009). https://pubmed.ncbi.nlm.nih.gov/19729436/ DOI: 10.1681/asn.2009050559
Complete structured claim and evidence
The Slc34a2-null phenotype included reduced circulating FGF23.
Inducible mouse Slc34a2 knockout in the 2009 absorption study → Mouse fibroblast growth factor 23 / Fgf23 source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/phosphorus-research/19729436.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "db886399fafd3fc4da4c341765ec69ebb7948f4993e271ca6ee6855d8ba7616d", "start_char": 0, "end_char": 1402, "text_sha256": "db886399fafd3fc4da4c341765ec69ebb7948f4993e271ca6ee6855d8ba7616d"}
experimental_model
Inducible Slc34a2 knockout, balance measurements and isolated ileum transport
exposure
Knockout versus wild type; low-P diet followed by an acute phosphate bolus
limitations
Fraction of active transport is not the fraction of total absorption in every diet or species. Normal serum phosphate can coexist with impaired intestinal entry because the kidney compensates.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Mouse
plain_language
A phosphate-wasting hormone fell as part of the compensatory pattern.
primary_references
[phosphorus-p19729436] Intestinal npt2b plays a major role in phosphate absorption and homeostasis. (2009). https://pubmed.ncbi.nlm.nih.gov/19729436/ DOI: 10.1681/asn.2009050559
tissue_or_cell_type
Intestine and compensatory renal handling
trigger_kind
machinery_impairment Imported condition classification; unverified.
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 282–293
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Inducible Slc34a2 knockout, balance measurements and isolated ileum transport · source_derived_draft · unverified_draft
### phosphorus-npt2b-fgf23 The Slc34a2-null phenotype included reduced circulating FGF23. Condition category: machinery_impairment nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: A phosphate-wasting hormone fell as part of the compensatory pattern. organism: Mouse tissue_or_cell_type: Intestine and compensatory renal handling experimental_model: Inducible Slc34a2 knockout, balance measurements and isolated ileum transport limitations: Fraction of active transport is not the fraction of total absorption in every diet or species. Normal serum phosphate can coexist with impaired intestinal entry because the kidney compensates. exposure: Knockout versus wild type; low-P diet followed by an acute phosphate bolus evidence_span: {"source_cache": "artifacts/phosphorus-research/19729436.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "db886399fafd3fc4da4c341765ec69ebb7948f4993e271ca6ee6855d8ba7616d", "start_char": 0, "end_char": 1402, "text_sha256": "db886399fafd3fc4da4c341765ec69ebb7948f4993e271ca6ee6855d8ba7616d"} [phosphorus-p19729436] Intestinal npt2b plays a major role in phosphate absorption and homeostasis. (2009). https://pubmed.ncbi.nlm.nih.gov/19729436/ DOI: 10.1681/asn.2009050559
Complete structured claim and evidence
Renal NaPi-IIa protein expression increased in Slc34a2-null mice.
Inducible mouse Slc34a2 knockout in the 2009 absorption study → Mouse sodium-phosphate cotransporter NaPi-IIa / Slc34a1 source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/phosphorus-research/19729436.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "db886399fafd3fc4da4c341765ec69ebb7948f4993e271ca6ee6855d8ba7616d", "start_char": 0, "end_char": 1402, "text_sha256": "db886399fafd3fc4da4c341765ec69ebb7948f4993e271ca6ee6855d8ba7616d"}
experimental_model
Inducible Slc34a2 knockout, balance measurements and isolated ileum transport
exposure
Knockout versus wild type; low-P diet followed by an acute phosphate bolus
limitations
Fraction of active transport is not the fraction of total absorption in every diet or species. Normal serum phosphate can coexist with impaired intestinal entry because the kidney compensates.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Mouse
plain_language
The renal transporter increased while intestinal transport was absent.
primary_references
[phosphorus-p19729436] Intestinal npt2b plays a major role in phosphate absorption and homeostasis. (2009). https://pubmed.ncbi.nlm.nih.gov/19729436/ DOI: 10.1681/asn.2009050559
tissue_or_cell_type
Intestine and compensatory renal handling
trigger_kind
machinery_impairment Imported condition classification; unverified.
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 295–306
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Inducible Slc34a2 knockout, balance measurements and isolated ileum transport · source_derived_draft · unverified_draft
### phosphorus-npt2b-npt2a Renal NaPi-IIa protein expression increased in Slc34a2-null mice. Condition category: machinery_impairment nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: The renal transporter increased while intestinal transport was absent. organism: Mouse tissue_or_cell_type: Intestine and compensatory renal handling experimental_model: Inducible Slc34a2 knockout, balance measurements and isolated ileum transport limitations: Fraction of active transport is not the fraction of total absorption in every diet or species. Normal serum phosphate can coexist with impaired intestinal entry because the kidney compensates. exposure: Knockout versus wild type; low-P diet followed by an acute phosphate bolus evidence_span: {"source_cache": "artifacts/phosphorus-research/19729436.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "db886399fafd3fc4da4c341765ec69ebb7948f4993e271ca6ee6855d8ba7616d", "start_char": 0, "end_char": 1402, "text_sha256": "db886399fafd3fc4da4c341765ec69ebb7948f4993e271ca6ee6855d8ba7616d"} [phosphorus-p19729436] Intestinal npt2b plays a major role in phosphate absorption and homeostasis. (2009). https://pubmed.ncbi.nlm.nih.gov/19729436/ DOI: 10.1681/asn.2009050559
Complete structured claim and evidence
NaPi-IIb accounted for more than 90% of measured active phosphate absorption in isolated mouse ileum segments.
Mouse intestinal NaPi-IIb / Slc34a2 → Mouse intestinal phosphate absorption source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/phosphorus-research/19729436.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "db886399fafd3fc4da4c341765ec69ebb7948f4993e271ca6ee6855d8ba7616d", "start_char": 0, "end_char": 1402, "text_sha256": "db886399fafd3fc4da4c341765ec69ebb7948f4993e271ca6ee6855d8ba7616d"}
experimental_model
Inducible Slc34a2 knockout, balance measurements and isolated ileum transport
exposure
Knockout versus wild type; low-P diet followed by an acute phosphate bolus
limitations
Fraction of active transport is not the fraction of total absorption in every diet or species. Normal serum phosphate can coexist with impaired intestinal entry because the kidney compensates.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Mouse
plain_language
This transporter dominated the active route in that assay; passive absorption is a separate route.
primary_references
[phosphorus-p19729436] Intestinal npt2b plays a major role in phosphate absorption and homeostasis. (2009). https://pubmed.ncbi.nlm.nih.gov/19729436/ DOI: 10.1681/asn.2009050559
tissue_or_cell_type
Intestine and compensatory renal handling
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 308–319
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Inducible Slc34a2 knockout, balance measurements and isolated ileum transport · source_derived_draft · unverified_draft
### phosphorus-npt2b-active NaPi-IIb accounted for more than 90% of measured active phosphate absorption in isolated mouse ileum segments. Condition category: normal nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: This transporter dominated the active route in that assay; passive absorption is a separate route. organism: Mouse tissue_or_cell_type: Intestine and compensatory renal handling experimental_model: Inducible Slc34a2 knockout, balance measurements and isolated ileum transport limitations: Fraction of active transport is not the fraction of total absorption in every diet or species. Normal serum phosphate can coexist with impaired intestinal entry because the kidney compensates. exposure: Knockout versus wild type; low-P diet followed by an acute phosphate bolus evidence_span: {"source_cache": "artifacts/phosphorus-research/19729436.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "db886399fafd3fc4da4c341765ec69ebb7948f4993e271ca6ee6855d8ba7616d", "start_char": 0, "end_char": 1402, "text_sha256": "db886399fafd3fc4da4c341765ec69ebb7948f4993e271ca6ee6855d8ba7616d"} [phosphorus-p19729436] Intestinal npt2b plays a major role in phosphate absorption and homeostasis. (2009). https://pubmed.ncbi.nlm.nih.gov/19729436/ DOI: 10.1681/asn.2009050559
Complete structured claim and evidence
Tenapanor inhibits intestinal NHE3, the sodium/hydrogen exchanger targeted in the phosphate-absorption study.
Tenapanor → Human sodium/hydrogen exchanger 3 / SLC9A3 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/phosphorus-research/30158152.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6e6950931f538331a62ce1a6b35ba66ddf0a6bcaec7fe4b4f8f81e8fd952ee0e", "start_char": 0, "end_char": 1701, "text_sha256": "6e6950931f538331a62ce1a6b35ba66ddf0a6bcaec7fe4b4f8f81e8fd952ee0e"}
experimental_model
Rodent physiology, human enteroid transport and healthy-volunteer intervention
exposure
Enteroid NHE3 perturbation; healthy volunteers 15 mg tenapanor twice daily for four days
limitations
Tenapanor inhibits NHE3 rather than binding phosphate. TEER is an epithelial assay measure, not a direct clinical permeability score.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Human-derived intestinal epithelial system
plain_language
A sodium-handling protein can change how phosphate crosses the gut wall.
primary_references
[phosphorus-p30158152] Inhibition of sodium/hydrogen exchanger 3 in the gastrointestinal tract by tenapanor reduces paracellular phosphate permeability. (2018). https://pubmed.ncbi.nlm.nih.gov/30158152/ DOI: 10.1126/scitranslmed.aam6474
tissue_or_cell_type
Intestinal epithelium; stool and urinary balance
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 321–332
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rodent physiology, human enteroid transport and healthy-volunteer intervention · source_derived_draft · unverified_draft
### phosphorus-tenapanor-nhe3 Tenapanor inhibits intestinal NHE3, the sodium/hydrogen exchanger targeted in the phosphate-absorption study. Condition category: normal nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: A sodium-handling protein can change how phosphate crosses the gut wall. organism: Human-derived intestinal epithelial system tissue_or_cell_type: Intestinal epithelium; stool and urinary balance experimental_model: Rodent physiology, human enteroid transport and healthy-volunteer intervention limitations: Tenapanor inhibits NHE3 rather than binding phosphate. TEER is an epithelial assay measure, not a direct clinical permeability score. exposure: Enteroid NHE3 perturbation; healthy volunteers 15 mg tenapanor twice daily for four days evidence_span: {"source_cache": "artifacts/phosphorus-research/30158152.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6e6950931f538331a62ce1a6b35ba66ddf0a6bcaec7fe4b4f8f81e8fd952ee0e", "start_char": 0, "end_char": 1701, "text_sha256": "6e6950931f538331a62ce1a6b35ba66ddf0a6bcaec7fe4b4f8f81e8fd952ee0e"} [phosphorus-p30158152] Inhibition of sodium/hydrogen exchanger 3 in the gastrointestinal tract by tenapanor reduces paracellular phosphate permeability. (2018). https://pubmed.ncbi.nlm.nih.gov/30158152/ DOI: 10.1126/scitranslmed.aam6474
Complete structured claim and evidence
Tenapanor increased transepithelial electrical resistance in the human intestinal enteroid model.
Tenapanor → Human intestinal enteroid transepithelial electrical resistance source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/phosphorus-research/30158152.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6e6950931f538331a62ce1a6b35ba66ddf0a6bcaec7fe4b4f8f81e8fd952ee0e", "start_char": 0, "end_char": 1701, "text_sha256": "6e6950931f538331a62ce1a6b35ba66ddf0a6bcaec7fe4b4f8f81e8fd952ee0e"}
experimental_model
Rodent physiology, human enteroid transport and healthy-volunteer intervention
exposure
Enteroid NHE3 perturbation; healthy volunteers 15 mg tenapanor twice daily for four days
limitations
Tenapanor inhibits NHE3 rather than binding phosphate. TEER is an epithelial assay measure, not a direct clinical permeability score.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Human-derived enteroids
plain_language
The epithelial barrier became less electrically conductive in this assay.
primary_references
[phosphorus-p30158152] Inhibition of sodium/hydrogen exchanger 3 in the gastrointestinal tract by tenapanor reduces paracellular phosphate permeability. (2018). https://pubmed.ncbi.nlm.nih.gov/30158152/ DOI: 10.1126/scitranslmed.aam6474
tissue_or_cell_type
Intestinal epithelium; stool and urinary balance
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 334–345
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rodent physiology, human enteroid transport and healthy-volunteer intervention · source_derived_draft · unverified_draft
### phosphorus-tenapanor-teer Tenapanor increased transepithelial electrical resistance in the human intestinal enteroid model. Condition category: normal nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: The epithelial barrier became less electrically conductive in this assay. organism: Human-derived enteroids tissue_or_cell_type: Intestinal epithelium; stool and urinary balance experimental_model: Rodent physiology, human enteroid transport and healthy-volunteer intervention limitations: Tenapanor inhibits NHE3 rather than binding phosphate. TEER is an epithelial assay measure, not a direct clinical permeability score. exposure: Enteroid NHE3 perturbation; healthy volunteers 15 mg tenapanor twice daily for four days evidence_span: {"source_cache": "artifacts/phosphorus-research/30158152.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6e6950931f538331a62ce1a6b35ba66ddf0a6bcaec7fe4b4f8f81e8fd952ee0e", "start_char": 0, "end_char": 1701, "text_sha256": "6e6950931f538331a62ce1a6b35ba66ddf0a6bcaec7fe4b4f8f81e8fd952ee0e"} [phosphorus-p30158152] Inhibition of sodium/hydrogen exchanger 3 in the gastrointestinal tract by tenapanor reduces paracellular phosphate permeability. (2018). https://pubmed.ncbi.nlm.nih.gov/30158152/ DOI: 10.1126/scitranslmed.aam6474
Complete structured claim and evidence
Tenapanor reduced paracellular phosphate permeability in the human intestinal enteroid model.
Tenapanor → Human intestinal enteroid paracellular phosphate flux source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/phosphorus-research/30158152.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6e6950931f538331a62ce1a6b35ba66ddf0a6bcaec7fe4b4f8f81e8fd952ee0e", "start_char": 0, "end_char": 1701, "text_sha256": "6e6950931f538331a62ce1a6b35ba66ddf0a6bcaec7fe4b4f8f81e8fd952ee0e"}
experimental_model
Rodent physiology, human enteroid transport and healthy-volunteer intervention
exposure
Enteroid NHE3 perturbation; healthy volunteers 15 mg tenapanor twice daily for four days
limitations
Tenapanor inhibits NHE3 rather than binding phosphate. TEER is an epithelial assay measure, not a direct clinical permeability score.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Human-derived enteroids
plain_language
Less phosphate crossed between the cells.
primary_references
[phosphorus-p30158152] Inhibition of sodium/hydrogen exchanger 3 in the gastrointestinal tract by tenapanor reduces paracellular phosphate permeability. (2018). https://pubmed.ncbi.nlm.nih.gov/30158152/ DOI: 10.1126/scitranslmed.aam6474
tissue_or_cell_type
Intestinal epithelium; stool and urinary balance
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 347–358
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rodent physiology, human enteroid transport and healthy-volunteer intervention · source_derived_draft · unverified_draft
### phosphorus-tenapanor-pi Tenapanor reduced paracellular phosphate permeability in the human intestinal enteroid model. Condition category: normal nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: Less phosphate crossed between the cells. organism: Human-derived enteroids tissue_or_cell_type: Intestinal epithelium; stool and urinary balance experimental_model: Rodent physiology, human enteroid transport and healthy-volunteer intervention limitations: Tenapanor inhibits NHE3 rather than binding phosphate. TEER is an epithelial assay measure, not a direct clinical permeability score. exposure: Enteroid NHE3 perturbation; healthy volunteers 15 mg tenapanor twice daily for four days evidence_span: {"source_cache": "artifacts/phosphorus-research/30158152.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6e6950931f538331a62ce1a6b35ba66ddf0a6bcaec7fe4b4f8f81e8fd952ee0e", "start_char": 0, "end_char": 1701, "text_sha256": "6e6950931f538331a62ce1a6b35ba66ddf0a6bcaec7fe4b4f8f81e8fd952ee0e"} [phosphorus-p30158152] Inhibition of sodium/hydrogen exchanger 3 in the gastrointestinal tract by tenapanor reduces paracellular phosphate permeability. (2018). https://pubmed.ncbi.nlm.nih.gov/30158152/ DOI: 10.1126/scitranslmed.aam6474
Complete structured claim and evidence
NHE3-deficient monolayers mimicked the phosphate phenotype and showed no further tenapanor effect on phosphate flux or TEER.
NHE3-deficient human intestinal enteroid monolayers → Human intestinal enteroid paracellular phosphate flux source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/phosphorus-research/30158152.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6e6950931f538331a62ce1a6b35ba66ddf0a6bcaec7fe4b4f8f81e8fd952ee0e", "start_char": 0, "end_char": 1701, "text_sha256": "6e6950931f538331a62ce1a6b35ba66ddf0a6bcaec7fe4b4f8f81e8fd952ee0e"}
experimental_model
Rodent physiology, human enteroid transport and healthy-volunteer intervention
exposure
Enteroid NHE3 perturbation; healthy volunteers 15 mg tenapanor twice daily for four days
limitations
Tenapanor inhibits NHE3 rather than binding phosphate. TEER is an epithelial assay measure, not a direct clinical permeability score.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Human-derived enteroids
plain_language
When the drug’s target was missing, adding the drug no longer changed these measurements.
primary_references
[phosphorus-p30158152] Inhibition of sodium/hydrogen exchanger 3 in the gastrointestinal tract by tenapanor reduces paracellular phosphate permeability. (2018). https://pubmed.ncbi.nlm.nih.gov/30158152/ DOI: 10.1126/scitranslmed.aam6474
tissue_or_cell_type
Intestinal epithelium; stool and urinary balance
trigger_kind
machinery_impairment Imported condition classification; unverified.
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 360–371
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rodent physiology, human enteroid transport and healthy-volunteer intervention · source_derived_draft · unverified_draft
### phosphorus-nhe3-null NHE3-deficient monolayers mimicked the phosphate phenotype and showed no further tenapanor effect on phosphate flux or TEER. Condition category: machinery_impairment nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: When the drug’s target was missing, adding the drug no longer changed these measurements. organism: Human-derived enteroids tissue_or_cell_type: Intestinal epithelium; stool and urinary balance experimental_model: Rodent physiology, human enteroid transport and healthy-volunteer intervention limitations: Tenapanor inhibits NHE3 rather than binding phosphate. TEER is an epithelial assay measure, not a direct clinical permeability score. exposure: Enteroid NHE3 perturbation; healthy volunteers 15 mg tenapanor twice daily for four days evidence_span: {"source_cache": "artifacts/phosphorus-research/30158152.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6e6950931f538331a62ce1a6b35ba66ddf0a6bcaec7fe4b4f8f81e8fd952ee0e", "start_char": 0, "end_char": 1701, "text_sha256": "6e6950931f538331a62ce1a6b35ba66ddf0a6bcaec7fe4b4f8f81e8fd952ee0e"} [phosphorus-p30158152] Inhibition of sodium/hydrogen exchanger 3 in the gastrointestinal tract by tenapanor reduces paracellular phosphate permeability. (2018). https://pubmed.ncbi.nlm.nih.gov/30158152/ DOI: 10.1126/scitranslmed.aam6474
Complete structured claim and evidence
Tenapanor increased stool phosphorus in the four-day healthy-volunteer study.
Tenapanor → Human stool phosphorus excretion source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/phosphorus-research/30158152.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6e6950931f538331a62ce1a6b35ba66ddf0a6bcaec7fe4b4f8f81e8fd952ee0e", "start_char": 0, "end_char": 1701, "text_sha256": "6e6950931f538331a62ce1a6b35ba66ddf0a6bcaec7fe4b4f8f81e8fd952ee0e"}
experimental_model
Rodent physiology, human enteroid transport and healthy-volunteer intervention
exposure
Enteroid NHE3 perturbation; healthy volunteers 15 mg tenapanor twice daily for four days
limitations
Tenapanor inhibits NHE3 rather than binding phosphate. TEER is an epithelial assay measure, not a direct clinical permeability score.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Human
plain_language
More phosphorus was eliminated in stool.
primary_references
[phosphorus-p30158152] Inhibition of sodium/hydrogen exchanger 3 in the gastrointestinal tract by tenapanor reduces paracellular phosphate permeability. (2018). https://pubmed.ncbi.nlm.nih.gov/30158152/ DOI: 10.1126/scitranslmed.aam6474
tissue_or_cell_type
Intestinal epithelium; stool and urinary balance
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 373–384
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rodent physiology, human enteroid transport and healthy-volunteer intervention · source_derived_draft · unverified_draft
### phosphorus-tenapanor-stool Tenapanor increased stool phosphorus in the four-day healthy-volunteer study. Condition category: normal nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: More phosphorus was eliminated in stool. organism: Human tissue_or_cell_type: Intestinal epithelium; stool and urinary balance experimental_model: Rodent physiology, human enteroid transport and healthy-volunteer intervention limitations: Tenapanor inhibits NHE3 rather than binding phosphate. TEER is an epithelial assay measure, not a direct clinical permeability score. exposure: Enteroid NHE3 perturbation; healthy volunteers 15 mg tenapanor twice daily for four days evidence_span: {"source_cache": "artifacts/phosphorus-research/30158152.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6e6950931f538331a62ce1a6b35ba66ddf0a6bcaec7fe4b4f8f81e8fd952ee0e", "start_char": 0, "end_char": 1701, "text_sha256": "6e6950931f538331a62ce1a6b35ba66ddf0a6bcaec7fe4b4f8f81e8fd952ee0e"} [phosphorus-p30158152] Inhibition of sodium/hydrogen exchanger 3 in the gastrointestinal tract by tenapanor reduces paracellular phosphate permeability. (2018). https://pubmed.ncbi.nlm.nih.gov/30158152/ DOI: 10.1126/scitranslmed.aam6474
Complete structured claim and evidence
Tenapanor decreased urinary phosphorus in the four-day healthy-volunteer study.
Tenapanor → Urinary phosphate excretion source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/phosphorus-research/30158152.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6e6950931f538331a62ce1a6b35ba66ddf0a6bcaec7fe4b4f8f81e8fd952ee0e", "start_char": 0, "end_char": 1701, "text_sha256": "6e6950931f538331a62ce1a6b35ba66ddf0a6bcaec7fe4b4f8f81e8fd952ee0e"}
experimental_model
Rodent physiology, human enteroid transport and healthy-volunteer intervention
exposure
Enteroid NHE3 perturbation; healthy volunteers 15 mg tenapanor twice daily for four days
limitations
Tenapanor inhibits NHE3 rather than binding phosphate. TEER is an epithelial assay measure, not a direct clinical permeability score.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Human
plain_language
The urinary result was consistent with less intestinal absorption, not direct proof of renal-transporter inhibition.
primary_references
[phosphorus-p30158152] Inhibition of sodium/hydrogen exchanger 3 in the gastrointestinal tract by tenapanor reduces paracellular phosphate permeability. (2018). https://pubmed.ncbi.nlm.nih.gov/30158152/ DOI: 10.1126/scitranslmed.aam6474
tissue_or_cell_type
Intestinal epithelium; stool and urinary balance
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 386–397
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rodent physiology, human enteroid transport and healthy-volunteer intervention · source_derived_draft · unverified_draft
### phosphorus-tenapanor-urine Tenapanor decreased urinary phosphorus in the four-day healthy-volunteer study. Condition category: normal nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: The urinary result was consistent with less intestinal absorption, not direct proof of renal-transporter inhibition. organism: Human tissue_or_cell_type: Intestinal epithelium; stool and urinary balance experimental_model: Rodent physiology, human enteroid transport and healthy-volunteer intervention limitations: Tenapanor inhibits NHE3 rather than binding phosphate. TEER is an epithelial assay measure, not a direct clinical permeability score. exposure: Enteroid NHE3 perturbation; healthy volunteers 15 mg tenapanor twice daily for four days evidence_span: {"source_cache": "artifacts/phosphorus-research/30158152.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6e6950931f538331a62ce1a6b35ba66ddf0a6bcaec7fe4b4f8f81e8fd952ee0e", "start_char": 0, "end_char": 1701, "text_sha256": "6e6950931f538331a62ce1a6b35ba66ddf0a6bcaec7fe4b4f8f81e8fd952ee0e"} [phosphorus-p30158152] Inhibition of sodium/hydrogen exchanger 3 in the gastrointestinal tract by tenapanor reduces paracellular phosphate permeability. (2018). https://pubmed.ncbi.nlm.nih.gov/30158152/ DOI: 10.1126/scitranslmed.aam6474
Complete structured claim and evidence
PTH-(1–34) induced NaPi-IIa internalization in both wild-type and Nherf1-deficient mice.
PTH-(1–34) experimental peptide → Mouse renal NaPi-IIa internalization from the brush border source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/phosphorus-research/16987995.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c5a055252ffc61da98e24d1de3a1733ee7aea678aded8cbdf071d18ad707d0bc", "start_char": 0, "end_char": 1699, "text_sha256": "c5a055252ffc61da98e24d1de3a1733ee7aea678aded8cbdf071d18ad707d0bc"}
experimental_model
Receptor-fragment stimulation, knockout and signaling-bypass experiments
exposure
PTH-(1–34), apically selective PTH-(3–34), PKC/PKA pathway stimulation
limitations
Apical and basolateral receptor routes differ. Loss of one scaffold does not eliminate every PTH response.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Mouse
plain_language
PTH could remove the transporter from the brush border even when one scaffold was absent.
primary_references
[phosphorus-p16987995] Defective coupling of apical PTH receptors to phospholipase C prevents internalization of the Na+-phosphate cotransporter NaPi-IIa in Nherf1-deficient mice. (2007). https://pubmed.ncbi.nlm.nih.gov/16987995/ DOI: 10.1152/ajpcell.00126.2006
tissue_or_cell_type
Renal proximal tubule brush-border membrane
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 399–410
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Receptor-fragment stimulation, knockout and signaling-bypass experiments · source_derived_draft · unverified_draft
### phosphorus-pth-internalization PTH-(1–34) induced NaPi-IIa internalization in both wild-type and Nherf1-deficient mice. Condition category: normal nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: PTH could remove the transporter from the brush border even when one scaffold was absent. organism: Mouse tissue_or_cell_type: Renal proximal tubule brush-border membrane experimental_model: Receptor-fragment stimulation, knockout and signaling-bypass experiments limitations: Apical and basolateral receptor routes differ. Loss of one scaffold does not eliminate every PTH response. exposure: PTH-(1–34), apically selective PTH-(3–34), PKC/PKA pathway stimulation evidence_span: {"source_cache": "artifacts/phosphorus-research/16987995.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c5a055252ffc61da98e24d1de3a1733ee7aea678aded8cbdf071d18ad707d0bc", "start_char": 0, "end_char": 1699, "text_sha256": "c5a055252ffc61da98e24d1de3a1733ee7aea678aded8cbdf071d18ad707d0bc"} [phosphorus-p16987995] Defective coupling of apical PTH receptors to phospholipase C prevents internalization of the Na+-phosphate cotransporter NaPi-IIa in Nherf1-deficient mice. (2007). https://pubmed.ncbi.nlm.nih.gov/16987995/ DOI: 10.1152/ajpcell.00126.2006
Complete structured claim and evidence
Apical PTH-receptor stimulation of PLC was impaired in Nherf1-deficient mice.
Experimental mouse Nherf1 knockout → Mouse apical PTH-receptor coupling to phospholipase C source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/phosphorus-research/16987995.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c5a055252ffc61da98e24d1de3a1733ee7aea678aded8cbdf071d18ad707d0bc", "start_char": 0, "end_char": 1699, "text_sha256": "c5a055252ffc61da98e24d1de3a1733ee7aea678aded8cbdf071d18ad707d0bc"}
experimental_model
Receptor-fragment stimulation, knockout and signaling-bypass experiments
exposure
PTH-(1–34), apically selective PTH-(3–34), PKC/PKA pathway stimulation
limitations
Apical and basolateral receptor routes differ. Loss of one scaffold does not eliminate every PTH response.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Mouse
plain_language
The receptor needed its local signaling scaffold for this route.
primary_references
[phosphorus-p16987995] Defective coupling of apical PTH receptors to phospholipase C prevents internalization of the Na+-phosphate cotransporter NaPi-IIa in Nherf1-deficient mice. (2007). https://pubmed.ncbi.nlm.nih.gov/16987995/ DOI: 10.1152/ajpcell.00126.2006
tissue_or_cell_type
Renal proximal tubule brush-border membrane
trigger_kind
machinery_impairment Imported condition classification; unverified.
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 412–423
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Receptor-fragment stimulation, knockout and signaling-bypass experiments · source_derived_draft · unverified_draft
### phosphorus-nherf-plc Apical PTH-receptor stimulation of PLC was impaired in Nherf1-deficient mice. Condition category: machinery_impairment nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: The receptor needed its local signaling scaffold for this route. organism: Mouse tissue_or_cell_type: Renal proximal tubule brush-border membrane experimental_model: Receptor-fragment stimulation, knockout and signaling-bypass experiments limitations: Apical and basolateral receptor routes differ. Loss of one scaffold does not eliminate every PTH response. exposure: PTH-(1–34), apically selective PTH-(3–34), PKC/PKA pathway stimulation evidence_span: {"source_cache": "artifacts/phosphorus-research/16987995.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c5a055252ffc61da98e24d1de3a1733ee7aea678aded8cbdf071d18ad707d0bc", "start_char": 0, "end_char": 1699, "text_sha256": "c5a055252ffc61da98e24d1de3a1733ee7aea678aded8cbdf071d18ad707d0bc"} [phosphorus-p16987995] Defective coupling of apical PTH receptors to phospholipase C prevents internalization of the Na+-phosphate cotransporter NaPi-IIa in Nherf1-deficient mice. (2007). https://pubmed.ncbi.nlm.nih.gov/16987995/ DOI: 10.1152/ajpcell.00126.2006
Complete structured claim and evidence
PTH-(3–34), used to stimulate apical receptors, failed to induce NaPi-IIa internalization in Nherf1-deficient mice.
PTH-(3–34) experimental peptide → Mouse renal NaPi-IIa internalization from the brush border source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/phosphorus-research/16987995.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c5a055252ffc61da98e24d1de3a1733ee7aea678aded8cbdf071d18ad707d0bc", "start_char": 0, "end_char": 1699, "text_sha256": "c5a055252ffc61da98e24d1de3a1733ee7aea678aded8cbdf071d18ad707d0bc"}
experimental_model
Receptor-fragment stimulation, knockout and signaling-bypass experiments
exposure
PTH-(1–34), apically selective PTH-(3–34), PKC/PKA pathway stimulation
limitations
Apical and basolateral receptor routes differ. Loss of one scaffold does not eliminate every PTH response.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Mouse
plain_language
The isolated apical route failed, unlike the broader PTH-(1–34) stimulation.
primary_references
[phosphorus-p16987995] Defective coupling of apical PTH receptors to phospholipase C prevents internalization of the Na+-phosphate cotransporter NaPi-IIa in Nherf1-deficient mice. (2007). https://pubmed.ncbi.nlm.nih.gov/16987995/ DOI: 10.1152/ajpcell.00126.2006
tissue_or_cell_type
Renal proximal tubule brush-border membrane
trigger_kind
machinery_impairment Imported condition classification; unverified.
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 425–436
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Receptor-fragment stimulation, knockout and signaling-bypass experiments · source_derived_draft · unverified_draft
### phosphorus-nherf-napi PTH-(3–34), used to stimulate apical receptors, failed to induce NaPi-IIa internalization in Nherf1-deficient mice. Condition category: machinery_impairment nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: The isolated apical route failed, unlike the broader PTH-(1–34) stimulation. organism: Mouse tissue_or_cell_type: Renal proximal tubule brush-border membrane experimental_model: Receptor-fragment stimulation, knockout and signaling-bypass experiments limitations: Apical and basolateral receptor routes differ. Loss of one scaffold does not eliminate every PTH response. exposure: PTH-(1–34), apically selective PTH-(3–34), PKC/PKA pathway stimulation evidence_span: {"source_cache": "artifacts/phosphorus-research/16987995.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c5a055252ffc61da98e24d1de3a1733ee7aea678aded8cbdf071d18ad707d0bc", "start_char": 0, "end_char": 1699, "text_sha256": "c5a055252ffc61da98e24d1de3a1733ee7aea678aded8cbdf071d18ad707d0bc"} [phosphorus-p16987995] Defective coupling of apical PTH receptors to phospholipase C prevents internalization of the Na+-phosphate cotransporter NaPi-IIa in Nherf1-deficient mice. (2007). https://pubmed.ncbi.nlm.nih.gov/16987995/ DOI: 10.1152/ajpcell.00126.2006
Complete structured claim and evidence
Pathophysiologic phosphate concentrations rapidly and reversibly increased PTH secretion from freshly isolated human parathyroid cells.
Inorganic phosphate (Pi; protonation depends on pH) → Human parathyroid hormone secretion source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/phosphorus-research/31619668.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e4fe1ed7eb92175f99f446afa19fb184147ceed0413f3a6dffa85aa80927015d", "start_char": 0, "end_char": 1144, "text_sha256": "e4fe1ed7eb92175f99f446afa19fb184147ceed0413f3a6dffa85aa80927015d"}
experimental_model
CaSR expression/mutagenesis and isolated human/mouse parathyroid experiments
exposure
Extracellular phosphate in pathophysiologic CKD ranges; R62A substitution and mouse Casr deletion
limitations
Direct phosphate antagonism was tested separately from calcium regulation; concentrations and model are not dietary thresholds.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Human
plain_language
Human parathyroid cells responded directly to the phosphate challenge.
primary_references
[phosphorus-p31619668] Phosphate acts directly on the calcium-sensing receptor to stimulate parathyroid hormone secretion. (2019). https://pubmed.ncbi.nlm.nih.gov/31619668/ DOI: 10.1038/s41467-019-12399-9
tissue_or_cell_type
CaSR reporter cells and freshly isolated parathyroid cells/glands
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 451–462
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · CaSR expression/mutagenesis and isolated human/mouse parathyroid experiments · source_derived_draft · unverified_draft
### phosphorus-human-pth Pathophysiologic phosphate concentrations rapidly and reversibly increased PTH secretion from freshly isolated human parathyroid cells. Condition category: normal nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: Human parathyroid cells responded directly to the phosphate challenge. organism: Human tissue_or_cell_type: CaSR reporter cells and freshly isolated parathyroid cells/glands experimental_model: CaSR expression/mutagenesis and isolated human/mouse parathyroid experiments limitations: Direct phosphate antagonism was tested separately from calcium regulation; concentrations and model are not dietary thresholds. exposure: Extracellular phosphate in pathophysiologic CKD ranges; R62A substitution and mouse Casr deletion evidence_span: {"source_cache": "artifacts/phosphorus-research/31619668.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e4fe1ed7eb92175f99f446afa19fb184147ceed0413f3a6dffa85aa80927015d", "start_char": 0, "end_char": 1144, "text_sha256": "e4fe1ed7eb92175f99f446afa19fb184147ceed0413f3a6dffa85aa80927015d"} [phosphorus-p31619668] Phosphate acts directly on the calcium-sensing receptor to stimulate parathyroid hormone secretion. (2019). https://pubmed.ncbi.nlm.nih.gov/31619668/ DOI: 10.1038/s41467-019-12399-9
Complete structured claim and evidence
The R62A CaSR construct lost the phosphate-induced receptor inhibition observed with wild-type receptor.
Human CaSR R62A construct → Inorganic phosphate (Pi; protonation depends on pH) source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/phosphorus-research/31619668.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e4fe1ed7eb92175f99f446afa19fb184147ceed0413f3a6dffa85aa80927015d", "start_char": 0, "end_char": 1144, "text_sha256": "e4fe1ed7eb92175f99f446afa19fb184147ceed0413f3a6dffa85aa80927015d"}
experimental_model
CaSR expression/mutagenesis and isolated human/mouse parathyroid experiments
exposure
Extracellular phosphate in pathophysiologic CKD ranges; R62A substitution and mouse Casr deletion
limitations
R62A identity resolved in full text; not a common variant or a dietary model.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Human CaSR construct
plain_language
Altering a specific receptor site removed the phosphate response.
primary_references
[phosphorus-p31619668] Phosphate acts directly on the calcium-sensing receptor to stimulate parathyroid hormone secretion. (2019). https://pubmed.ncbi.nlm.nih.gov/31619668/ DOI: 10.1038/s41467-019-12399-9
tissue_or_cell_type
CaSR reporter cells and freshly isolated parathyroid cells/glands
trigger_kind
machinery_impairment Imported condition classification; unverified.
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 464–475
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · CaSR expression/mutagenesis and isolated human/mouse parathyroid experiments · source_derived_draft · unverified_draft
### phosphorus-casr-r62 The R62A CaSR construct lost the phosphate-induced receptor inhibition observed with wild-type receptor. Condition category: machinery_impairment nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: Altering a specific receptor site removed the phosphate response. organism: Human CaSR construct tissue_or_cell_type: CaSR reporter cells and freshly isolated parathyroid cells/glands experimental_model: CaSR expression/mutagenesis and isolated human/mouse parathyroid experiments limitations: R62A identity resolved in full text; not a common variant or a dietary model. exposure: Extracellular phosphate in pathophysiologic CKD ranges; R62A substitution and mouse Casr deletion evidence_span: {"source_cache": "artifacts/phosphorus-research/31619668.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e4fe1ed7eb92175f99f446afa19fb184147ceed0413f3a6dffa85aa80927015d", "start_char": 0, "end_char": 1144, "text_sha256": "e4fe1ed7eb92175f99f446afa19fb184147ceed0413f3a6dffa85aa80927015d"} [phosphorus-p31619668] Phosphate acts directly on the calcium-sensing receptor to stimulate parathyroid hormone secretion. (2019). https://pubmed.ncbi.nlm.nih.gov/31619668/ DOI: 10.1038/s41467-019-12399-9
Complete structured claim and evidence
The phosphate-induced PTH increase seen in wild-type mouse parathyroid glands was absent in Casr-knockout glands.
Mouse parathyroid Casr knockout → Mouse parathyroid hormone secretion source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/phosphorus-research/31619668.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e4fe1ed7eb92175f99f446afa19fb184147ceed0413f3a6dffa85aa80927015d", "start_char": 0, "end_char": 1144, "text_sha256": "e4fe1ed7eb92175f99f446afa19fb184147ceed0413f3a6dffa85aa80927015d"}
experimental_model
CaSR expression/mutagenesis and isolated human/mouse parathyroid experiments
exposure
Extracellular phosphate in pathophysiologic CKD ranges; R62A substitution and mouse Casr deletion
limitations
Direct phosphate antagonism was tested separately from calcium regulation; concentrations and model are not dietary thresholds.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Mouse
plain_language
The mouse glands needed CaSR for this response.
primary_references
[phosphorus-p31619668] Phosphate acts directly on the calcium-sensing receptor to stimulate parathyroid hormone secretion. (2019). https://pubmed.ncbi.nlm.nih.gov/31619668/ DOI: 10.1038/s41467-019-12399-9
tissue_or_cell_type
CaSR reporter cells and freshly isolated parathyroid cells/glands
trigger_kind
machinery_impairment Imported condition classification; unverified.
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 477–488
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · CaSR expression/mutagenesis and isolated human/mouse parathyroid experiments · source_derived_draft · unverified_draft
### phosphorus-casr-mouse-null The phosphate-induced PTH increase seen in wild-type mouse parathyroid glands was absent in Casr-knockout glands. Condition category: machinery_impairment nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: The mouse glands needed CaSR for this response. organism: Mouse tissue_or_cell_type: CaSR reporter cells and freshly isolated parathyroid cells/glands experimental_model: CaSR expression/mutagenesis and isolated human/mouse parathyroid experiments limitations: Direct phosphate antagonism was tested separately from calcium regulation; concentrations and model are not dietary thresholds. exposure: Extracellular phosphate in pathophysiologic CKD ranges; R62A substitution and mouse Casr deletion evidence_span: {"source_cache": "artifacts/phosphorus-research/31619668.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e4fe1ed7eb92175f99f446afa19fb184147ceed0413f3a6dffa85aa80927015d", "start_char": 0, "end_char": 1144, "text_sha256": "e4fe1ed7eb92175f99f446afa19fb184147ceed0413f3a6dffa85aa80927015d"} [phosphorus-p31619668] Phosphate acts directly on the calcium-sensing receptor to stimulate parathyroid hormone secretion. (2019). https://pubmed.ncbi.nlm.nih.gov/31619668/ DOI: 10.1038/s41467-019-12399-9
Complete structured claim and evidence
FAM20C directly phosphorylated FGF23 at Ser180 within its proteolytic processing motif.
FAM20C secretory-pathway kinase → FGF23 phosphorylated at Ser180 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/phosphorus-research/24706917.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7ccd1d1a23c74c980009e67ac6b0feafa3c30c28a99d8b240bef93bcc4cf29be", "start_char": 0, "end_char": 1346, "text_sha256": "7ccd1d1a23c74c980009e67ac6b0feafa3c30c28a99d8b240bef93bcc4cf29be"}
experimental_model
Recombinant processing and phosphorylation/glycosylation experiments
exposure
FAM20C, GalNAc-T3 and furin manipulation
limitations
Protein-modification control, not a claim that dietary phosphate directly phosphorylates FGF23. Construct scope is retained rather than assigning every result to intact human physiology.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Construct system; precise species not inferred from abstract
plain_language
A phosphate mark controls how this phosphate-regulating hormone is processed.
primary_references
[phosphorus-p24706917] Dynamic regulation of FGF23 by Fam20C phosphorylation, GalNAc-T3 glycosylation, and furin proteolysis. (2014). https://pubmed.ncbi.nlm.nih.gov/24706917/ DOI: 10.1073/pnas.1402218111
tissue_or_cell_type
Secretory protein processing
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 490–501
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant processing and phosphorylation/glycosylation experiments · source_derived_draft · unverified_draft
### phosphorus-fgf23-phosphorylation FAM20C directly phosphorylated FGF23 at Ser180 within its proteolytic processing motif. Condition category: normal nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: A phosphate mark controls how this phosphate-regulating hormone is processed. organism: Construct system; precise species not inferred from abstract tissue_or_cell_type: Secretory protein processing experimental_model: Recombinant processing and phosphorylation/glycosylation experiments limitations: Protein-modification control, not a claim that dietary phosphate directly phosphorylates FGF23. Construct scope is retained rather than assigning every result to intact human physiology. exposure: FAM20C, GalNAc-T3 and furin manipulation evidence_span: {"source_cache": "artifacts/phosphorus-research/24706917.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7ccd1d1a23c74c980009e67ac6b0feafa3c30c28a99d8b240bef93bcc4cf29be", "start_char": 0, "end_char": 1346, "text_sha256": "7ccd1d1a23c74c980009e67ac6b0feafa3c30c28a99d8b240bef93bcc4cf29be"} [phosphorus-p24706917] Dynamic regulation of FGF23 by Fam20C phosphorylation, GalNAc-T3 glycosylation, and furin proteolysis. (2014). https://pubmed.ncbi.nlm.nih.gov/24706917/ DOI: 10.1073/pnas.1402218111
Complete structured claim and evidence
Ser180 phosphorylation inhibited GalNAc-T3-mediated O-glycosylation of FGF23.
FGF23 phosphorylated at Ser180 → O-glycosylated FGF23 in the FAM20C processing study source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/phosphorus-research/24706917.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7ccd1d1a23c74c980009e67ac6b0feafa3c30c28a99d8b240bef93bcc4cf29be", "start_char": 0, "end_char": 1346, "text_sha256": "7ccd1d1a23c74c980009e67ac6b0feafa3c30c28a99d8b240bef93bcc4cf29be"}
experimental_model
Recombinant processing and phosphorylation/glycosylation experiments
exposure
FAM20C, GalNAc-T3 and furin manipulation
limitations
Protein-modification control, not a claim that dietary phosphate directly phosphorylates FGF23. Construct scope is retained rather than assigning every result to intact human physiology.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Construct system; precise species not inferred from abstract
plain_language
The phosphate mark interfered with a competing sugar modification.
primary_references
[phosphorus-p24706917] Dynamic regulation of FGF23 by Fam20C phosphorylation, GalNAc-T3 glycosylation, and furin proteolysis. (2014). https://pubmed.ncbi.nlm.nih.gov/24706917/ DOI: 10.1073/pnas.1402218111
tissue_or_cell_type
Secretory protein processing
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 503–514
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant processing and phosphorylation/glycosylation experiments · source_derived_draft · unverified_draft
### phosphorus-fgf23-glycosylation Ser180 phosphorylation inhibited GalNAc-T3-mediated O-glycosylation of FGF23. Condition category: normal nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: The phosphate mark interfered with a competing sugar modification. organism: Construct system; precise species not inferred from abstract tissue_or_cell_type: Secretory protein processing experimental_model: Recombinant processing and phosphorylation/glycosylation experiments limitations: Protein-modification control, not a claim that dietary phosphate directly phosphorylates FGF23. Construct scope is retained rather than assigning every result to intact human physiology. exposure: FAM20C, GalNAc-T3 and furin manipulation evidence_span: {"source_cache": "artifacts/phosphorus-research/24706917.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7ccd1d1a23c74c980009e67ac6b0feafa3c30c28a99d8b240bef93bcc4cf29be", "start_char": 0, "end_char": 1346, "text_sha256": "7ccd1d1a23c74c980009e67ac6b0feafa3c30c28a99d8b240bef93bcc4cf29be"} [phosphorus-p24706917] Dynamic regulation of FGF23 by Fam20C phosphorylation, GalNAc-T3 glycosylation, and furin proteolysis. (2014). https://pubmed.ncbi.nlm.nih.gov/24706917/ DOI: 10.1073/pnas.1402218111
Complete structured claim and evidence
FAM20C-dependent FGF23 phosphorylation promoted furin cleavage and hormone inactivation.
FGF23 phosphorylated at Ser180 → Proteolytically cleaved FGF23 products source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/phosphorus-research/24706917.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7ccd1d1a23c74c980009e67ac6b0feafa3c30c28a99d8b240bef93bcc4cf29be", "start_char": 0, "end_char": 1346, "text_sha256": "7ccd1d1a23c74c980009e67ac6b0feafa3c30c28a99d8b240bef93bcc4cf29be"}
experimental_model
Recombinant processing and phosphorylation/glycosylation experiments
exposure
FAM20C, GalNAc-T3 and furin manipulation
limitations
Protein-modification control, not a claim that dietary phosphate directly phosphorylates FGF23. Construct scope is retained rather than assigning every result to intact human physiology.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Construct system; precise species not inferred from abstract
plain_language
Changing the hormone’s processing reduced the amount of intact active signal.
primary_references
[phosphorus-p24706917] Dynamic regulation of FGF23 by Fam20C phosphorylation, GalNAc-T3 glycosylation, and furin proteolysis. (2014). https://pubmed.ncbi.nlm.nih.gov/24706917/ DOI: 10.1073/pnas.1402218111
tissue_or_cell_type
Secretory protein processing
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 516–527
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant processing and phosphorylation/glycosylation experiments · source_derived_draft · unverified_draft
### phosphorus-fgf23-cleavage FAM20C-dependent FGF23 phosphorylation promoted furin cleavage and hormone inactivation. Condition category: normal nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: Changing the hormone’s processing reduced the amount of intact active signal. organism: Construct system; precise species not inferred from abstract tissue_or_cell_type: Secretory protein processing experimental_model: Recombinant processing and phosphorylation/glycosylation experiments limitations: Protein-modification control, not a claim that dietary phosphate directly phosphorylates FGF23. Construct scope is retained rather than assigning every result to intact human physiology. exposure: FAM20C, GalNAc-T3 and furin manipulation evidence_span: {"source_cache": "artifacts/phosphorus-research/24706917.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7ccd1d1a23c74c980009e67ac6b0feafa3c30c28a99d8b240bef93bcc4cf29be", "start_char": 0, "end_char": 1346, "text_sha256": "7ccd1d1a23c74c980009e67ac6b0feafa3c30c28a99d8b240bef93bcc4cf29be"} [phosphorus-p24706917] Dynamic regulation of FGF23 by Fam20C phosphorylation, GalNAc-T3 glycosylation, and furin proteolysis. (2014). https://pubmed.ncbi.nlm.nih.gov/24706917/ DOI: 10.1073/pnas.1402218111
Complete structured claim and evidence
SLC25A3 supplies inorganic phosphate to the mitochondrial matrix for aerobic ATP synthesis; the family study localized the defect to the muscle-expressed isoform.
Human mitochondrial phosphate/copper carrier SLC25A3 → Inorganic phosphate (Pi; protonation depends on pH) source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/phosphorus-research/17273968.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ff20a374b5c0a96a013cb9dd52c86c9dcc63d157e35e8aac58266dd26da9c0a2", "start_char": 0, "end_char": 805, "text_sha256": "ff20a374b5c0a96a013cb9dd52c86c9dcc63d157e35e8aac58266dd26da9c0a2"}
experimental_model
Human family genetics, mitochondrial functional assay and yeast complementation
exposure
Two siblings with homozygous SLC25A3 exon-3A c.215G>A, p.Gly72Glu
limitations
Isoform- and tissue-specific inherited transport defect; normal dietary phosphorus cannot be assumed to repair the carrier.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Human; yeast functional complementation
plain_language
Phosphate must enter the mitochondrion before it can support ATP production.
primary_references
[phosphorus-p17273968] Mitochondrial phosphate-carrier deficiency: a novel disorder of oxidative phosphorylation. (2007). https://pubmed.ncbi.nlm.nih.gov/17273968/ DOI: 10.1086/511788
tissue_or_cell_type
Muscle compared with fibroblasts
transport_effect
raises Recorded as supplying inorganic phosphate to the matrix.
transport_pool
the mitochondrial matrix Recorded as supplying inorganic phosphate to the matrix.
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 529–540
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human family genetics, mitochondrial functional assay and yeast complementation · source_derived_draft · unverified_draft
### phosphorus-mitochondrial-entry SLC25A3 supplies inorganic phosphate to the mitochondrial matrix for aerobic ATP synthesis; the family study localized the defect to the muscle-expressed isoform. Condition category: normal nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: Phosphate must enter the mitochondrion before it can support ATP production. organism: Human; yeast functional complementation tissue_or_cell_type: Muscle compared with fibroblasts experimental_model: Human family genetics, mitochondrial functional assay and yeast complementation limitations: Isoform- and tissue-specific inherited transport defect; normal dietary phosphorus cannot be assumed to repair the carrier. exposure: Two siblings with homozygous SLC25A3 exon-3A c.215G>A, p.Gly72Glu evidence_span: {"source_cache": "artifacts/phosphorus-research/17273968.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ff20a374b5c0a96a013cb9dd52c86c9dcc63d157e35e8aac58266dd26da9c0a2", "start_char": 0, "end_char": 805, "text_sha256": "ff20a374b5c0a96a013cb9dd52c86c9dcc63d157e35e8aac58266dd26da9c0a2"} [phosphorus-p17273968] Mitochondrial phosphate-carrier deficiency: a novel disorder of oxidative phosphorylation. (2007). https://pubmed.ncbi.nlm.nih.gov/17273968/ DOI: 10.1086/511788
Complete structured claim and evidence
Intact muscle mitochondria from the affected siblings showed deficient ATP synthesis.
Human SLC25A3 isoform A Gly72Glu variant → Human muscle mitochondrial ATP synthesis in the SLC25A3 assay source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/phosphorus-research/17273968.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ff20a374b5c0a96a013cb9dd52c86c9dcc63d157e35e8aac58266dd26da9c0a2", "start_char": 0, "end_char": 805, "text_sha256": "ff20a374b5c0a96a013cb9dd52c86c9dcc63d157e35e8aac58266dd26da9c0a2"}
experimental_model
Human family genetics, mitochondrial functional assay and yeast complementation
exposure
Two siblings with homozygous SLC25A3 exon-3A c.215G>A, p.Gly72Glu
limitations
Isoform- and tissue-specific inherited transport defect; normal dietary phosphorus cannot be assumed to repair the carrier.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Human; yeast functional complementation
plain_language
The defect appeared in the tissue using the affected carrier isoform.
primary_references
[phosphorus-p17273968] Mitochondrial phosphate-carrier deficiency: a novel disorder of oxidative phosphorylation. (2007). https://pubmed.ncbi.nlm.nih.gov/17273968/ DOI: 10.1086/511788
tissue_or_cell_type
Muscle compared with fibroblasts
trigger_kind
machinery_impairment Imported condition classification; unverified.
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 542–553
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human family genetics, mitochondrial functional assay and yeast complementation · source_derived_draft · unverified_draft
### phosphorus-slc25a3-muscle Intact muscle mitochondria from the affected siblings showed deficient ATP synthesis. Condition category: machinery_impairment nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: The defect appeared in the tissue using the affected carrier isoform. organism: Human; yeast functional complementation tissue_or_cell_type: Muscle compared with fibroblasts experimental_model: Human family genetics, mitochondrial functional assay and yeast complementation limitations: Isoform- and tissue-specific inherited transport defect; normal dietary phosphorus cannot be assumed to repair the carrier. exposure: Two siblings with homozygous SLC25A3 exon-3A c.215G>A, p.Gly72Glu evidence_span: {"source_cache": "artifacts/phosphorus-research/17273968.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ff20a374b5c0a96a013cb9dd52c86c9dcc63d157e35e8aac58266dd26da9c0a2", "start_char": 0, "end_char": 805, "text_sha256": "ff20a374b5c0a96a013cb9dd52c86c9dcc63d157e35e8aac58266dd26da9c0a2"} [phosphorus-p17273968] Mitochondrial phosphate-carrier deficiency: a novel disorder of oxidative phosphorylation. (2007). https://pubmed.ncbi.nlm.nih.gov/17273968/ DOI: 10.1086/511788
Complete structured claim and evidence
Fibroblast mitochondrial ATP synthesis was preserved, correlating with use of the alternative exon-3B isoform.
Human SLC25A3 isoform A Gly72Glu variant → Human fibroblast mitochondrial ATP synthesis in the SLC25A3 assay source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/phosphorus-research/17273968.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ff20a374b5c0a96a013cb9dd52c86c9dcc63d157e35e8aac58266dd26da9c0a2", "start_char": 0, "end_char": 805, "text_sha256": "ff20a374b5c0a96a013cb9dd52c86c9dcc63d157e35e8aac58266dd26da9c0a2"}
experimental_model
Human family genetics, mitochondrial functional assay and yeast complementation
exposure
Two siblings with homozygous SLC25A3 exon-3A c.215G>A, p.Gly72Glu
limitations
Isoform- and tissue-specific inherited transport defect; normal dietary phosphorus cannot be assumed to repair the carrier.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Human; yeast functional complementation
plain_language
A preserved result in fibroblasts did not rule out the muscle defect.
primary_references
[phosphorus-p17273968] Mitochondrial phosphate-carrier deficiency: a novel disorder of oxidative phosphorylation. (2007). https://pubmed.ncbi.nlm.nih.gov/17273968/ DOI: 10.1086/511788
tissue_or_cell_type
Muscle compared with fibroblasts
trigger_kind
machinery_impairment Imported condition classification; unverified.
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 555–566
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human family genetics, mitochondrial functional assay and yeast complementation · source_derived_draft · unverified_draft
### phosphorus-slc25a3-fibroblast Fibroblast mitochondrial ATP synthesis was preserved, correlating with use of the alternative exon-3B isoform. Condition category: machinery_impairment nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: A preserved result in fibroblasts did not rule out the muscle defect. organism: Human; yeast functional complementation tissue_or_cell_type: Muscle compared with fibroblasts experimental_model: Human family genetics, mitochondrial functional assay and yeast complementation limitations: Isoform- and tissue-specific inherited transport defect; normal dietary phosphorus cannot be assumed to repair the carrier. exposure: Two siblings with homozygous SLC25A3 exon-3A c.215G>A, p.Gly72Glu evidence_span: {"source_cache": "artifacts/phosphorus-research/17273968.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ff20a374b5c0a96a013cb9dd52c86c9dcc63d157e35e8aac58266dd26da9c0a2", "start_char": 0, "end_char": 805, "text_sha256": "ff20a374b5c0a96a013cb9dd52c86c9dcc63d157e35e8aac58266dd26da9c0a2"} [phosphorus-p17273968] Mitochondrial phosphate-carrier deficiency: a novel disorder of oxidative phosphorylation. (2007). https://pubmed.ncbi.nlm.nih.gov/17273968/ DOI: 10.1086/511788
Complete structured claim and evidence
Diet-induced hypophosphatemic mice had approximately 50% lower basal and insulin-stimulated muscle ATP synthetic flux.
Low-phosphate feeding in the 2016 mouse ATP-flux study → Mouse skeletal-muscle ATP synthetic flux by 31P-MRS source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/phosphorus-research/27338702.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "634bc9a26ebb8d6a911692bcb98a05432db2bc08455c0a02f1ef5e4b953150fe", "start_char": 0, "end_char": 1786, "text_sha256": "634bc9a26ebb8d6a911692bcb98a05432db2bc08455c0a02f1ef5e4b953150fe"}
experimental_model
31P-MRS ATP-flux measurements, repletion and cellular/mitochondrial experiments
exposure
Diet-induced low phosphate, NaPi-IIa knockout, phosphate repletion; one SLC34A3-associated human case
limitations
ATP synthetic flux is not ATP pool size or direct proof that all measured flux is mitochondrial oxidative phosphorylation. One human case cannot define a population threshold.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Mouse
plain_language
In this mouse experiment, phosphate shortage limited the measured ATP-making flux.
primary_references
[phosphorus-p27338702] Hypophosphatemia promotes lower rates of muscle ATP synthesis. (2016). https://pubmed.ncbi.nlm.nih.gov/27338702/ DOI: 10.1096/fj.201600473r
tissue_or_cell_type
Skeletal muscle
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 568–579
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 31P-MRS ATP-flux measurements, repletion and cellular/mitochondrial experiments · source_derived_draft · unverified_draft
### phosphorus-diet-atp Diet-induced hypophosphatemic mice had approximately 50% lower basal and insulin-stimulated muscle ATP synthetic flux. Condition category: nutrient_deficiency nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: In this mouse experiment, phosphate shortage limited the measured ATP-making flux. organism: Mouse tissue_or_cell_type: Skeletal muscle experimental_model: 31P-MRS ATP-flux measurements, repletion and cellular/mitochondrial experiments limitations: ATP synthetic flux is not ATP pool size or direct proof that all measured flux is mitochondrial oxidative phosphorylation. One human case cannot define a population threshold. exposure: Diet-induced low phosphate, NaPi-IIa knockout, phosphate repletion; one SLC34A3-associated human case evidence_span: {"source_cache": "artifacts/phosphorus-research/27338702.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "634bc9a26ebb8d6a911692bcb98a05432db2bc08455c0a02f1ef5e4b953150fe", "start_char": 0, "end_char": 1786, "text_sha256": "634bc9a26ebb8d6a911692bcb98a05432db2bc08455c0a02f1ef5e4b953150fe"} [phosphorus-p27338702] Hypophosphatemia promotes lower rates of muscle ATP synthesis. (2016). https://pubmed.ncbi.nlm.nih.gov/27338702/ DOI: 10.1096/fj.201600473r
Complete structured claim and evidence
NaPi-IIa-knockout mice had approximately 50% lower plasma phosphate and muscle ATP synthetic flux than controls.
Experimental mouse Slc34a1 / NaPi-IIa knockout → Mouse skeletal-muscle ATP synthetic flux by 31P-MRS source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/phosphorus-research/27338702.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "634bc9a26ebb8d6a911692bcb98a05432db2bc08455c0a02f1ef5e4b953150fe", "start_char": 0, "end_char": 1786, "text_sha256": "634bc9a26ebb8d6a911692bcb98a05432db2bc08455c0a02f1ef5e4b953150fe"}
experimental_model
31P-MRS ATP-flux measurements, repletion and cellular/mitochondrial experiments
exposure
Diet-induced low phosphate, NaPi-IIa knockout, phosphate repletion; one SLC34A3-associated human case
limitations
ATP synthetic flux is not ATP pool size or direct proof that all measured flux is mitochondrial oxidative phosphorylation. One human case cannot define a population threshold.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Mouse
plain_language
A kidney transport defect affected a measurement in muscle.
primary_references
[phosphorus-p27338702] Hypophosphatemia promotes lower rates of muscle ATP synthesis. (2016). https://pubmed.ncbi.nlm.nih.gov/27338702/ DOI: 10.1096/fj.201600473r
tissue_or_cell_type
Skeletal muscle
trigger_kind
machinery_impairment Imported condition classification; unverified.
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 581–592
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 31P-MRS ATP-flux measurements, repletion and cellular/mitochondrial experiments · source_derived_draft · unverified_draft
### phosphorus-napi2a-atp NaPi-IIa-knockout mice had approximately 50% lower plasma phosphate and muscle ATP synthetic flux than controls. Condition category: machinery_impairment nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: A kidney transport defect affected a measurement in muscle. organism: Mouse tissue_or_cell_type: Skeletal muscle experimental_model: 31P-MRS ATP-flux measurements, repletion and cellular/mitochondrial experiments limitations: ATP synthetic flux is not ATP pool size or direct proof that all measured flux is mitochondrial oxidative phosphorylation. One human case cannot define a population threshold. exposure: Diet-induced low phosphate, NaPi-IIa knockout, phosphate repletion; one SLC34A3-associated human case evidence_span: {"source_cache": "artifacts/phosphorus-research/27338702.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "634bc9a26ebb8d6a911692bcb98a05432db2bc08455c0a02f1ef5e4b953150fe", "start_char": 0, "end_char": 1786, "text_sha256": "634bc9a26ebb8d6a911692bcb98a05432db2bc08455c0a02f1ef5e4b953150fe"} [phosphorus-p27338702] Hypophosphatemia promotes lower rates of muscle ATP synthesis. (2016). https://pubmed.ncbi.nlm.nih.gov/27338702/ DOI: 10.1096/fj.201600473r
Complete structured claim and evidence
Restoring plasma phosphate normalized muscle ATP synthetic flux in both mouse hypophosphatemia models.
Study-specific phosphate repletion interventions → Mouse skeletal-muscle ATP synthetic flux by 31P-MRS source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/phosphorus-research/27338702.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "634bc9a26ebb8d6a911692bcb98a05432db2bc08455c0a02f1ef5e4b953150fe", "start_char": 0, "end_char": 1786, "text_sha256": "634bc9a26ebb8d6a911692bcb98a05432db2bc08455c0a02f1ef5e4b953150fe"}
experimental_model
31P-MRS ATP-flux measurements, repletion and cellular/mitochondrial experiments
exposure
Diet-induced low phosphate, NaPi-IIa knockout, phosphate repletion; one SLC34A3-associated human case
limitations
ATP synthetic flux is not ATP pool size or direct proof that all measured flux is mitochondrial oxidative phosphorylation. One human case cannot define a population threshold.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Mouse
plain_language
The reduced flux was reversible when phosphate availability was restored.
primary_references
[phosphorus-p27338702] Hypophosphatemia promotes lower rates of muscle ATP synthesis. (2016). https://pubmed.ncbi.nlm.nih.gov/27338702/ DOI: 10.1096/fj.201600473r
tissue_or_cell_type
Skeletal muscle
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 594–605
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 31P-MRS ATP-flux measurements, repletion and cellular/mitochondrial experiments · source_derived_draft · unverified_draft
### phosphorus-mouse-atp-rescue Restoring plasma phosphate normalized muscle ATP synthetic flux in both mouse hypophosphatemia models. Condition category: normal nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: The reduced flux was reversible when phosphate availability was restored. organism: Mouse tissue_or_cell_type: Skeletal muscle experimental_model: 31P-MRS ATP-flux measurements, repletion and cellular/mitochondrial experiments limitations: ATP synthetic flux is not ATP pool size or direct proof that all measured flux is mitochondrial oxidative phosphorylation. One human case cannot define a population threshold. exposure: Diet-induced low phosphate, NaPi-IIa knockout, phosphate repletion; one SLC34A3-associated human case evidence_span: {"source_cache": "artifacts/phosphorus-research/27338702.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "634bc9a26ebb8d6a911692bcb98a05432db2bc08455c0a02f1ef5e4b953150fe", "start_char": 0, "end_char": 1786, "text_sha256": "634bc9a26ebb8d6a911692bcb98a05432db2bc08455c0a02f1ef5e4b953150fe"} [phosphorus-p27338702] Hypophosphatemia promotes lower rates of muscle ATP synthesis. (2016). https://pubmed.ncbi.nlm.nih.gov/27338702/ DOI: 10.1096/fj.201600473r
Complete structured claim and evidence
The patient with SLC34A3-associated chronic hypophosphatemia had approximately 50% lower serum phosphate and muscle ATP synthetic flux.
SLC34A3-associated phosphate wasting in the 2016 ATP-flux patient → Human skeletal-muscle ATP synthetic flux by 31P-MRS source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/phosphorus-research/27338702.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "634bc9a26ebb8d6a911692bcb98a05432db2bc08455c0a02f1ef5e4b953150fe", "start_char": 0, "end_char": 1786, "text_sha256": "634bc9a26ebb8d6a911692bcb98a05432db2bc08455c0a02f1ef5e4b953150fe"}
experimental_model
31P-MRS ATP-flux measurements, repletion and cellular/mitochondrial experiments
exposure
Diet-induced low phosphate, NaPi-IIa knockout, phosphate repletion; one SLC34A3-associated human case
limitations
ATP synthetic flux is not ATP pool size or direct proof that all measured flux is mitochondrial oxidative phosphorylation. One human case cannot define a population threshold.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Human
plain_language
The study found a similar pattern in one person with inherited renal phosphate wasting.
primary_references
[phosphorus-p27338702] Hypophosphatemia promotes lower rates of muscle ATP synthesis. (2016). https://pubmed.ncbi.nlm.nih.gov/27338702/ DOI: 10.1096/fj.201600473r
tissue_or_cell_type
Skeletal muscle
trigger_kind
machinery_impairment Imported condition classification; unverified.
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 607–618
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 31P-MRS ATP-flux measurements, repletion and cellular/mitochondrial experiments · source_derived_draft · unverified_draft
### phosphorus-human-atp-defect The patient with SLC34A3-associated chronic hypophosphatemia had approximately 50% lower serum phosphate and muscle ATP synthetic flux. Condition category: machinery_impairment nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: The study found a similar pattern in one person with inherited renal phosphate wasting. organism: Human tissue_or_cell_type: Skeletal muscle experimental_model: 31P-MRS ATP-flux measurements, repletion and cellular/mitochondrial experiments limitations: ATP synthetic flux is not ATP pool size or direct proof that all measured flux is mitochondrial oxidative phosphorylation. One human case cannot define a population threshold. exposure: Diet-induced low phosphate, NaPi-IIa knockout, phosphate repletion; one SLC34A3-associated human case evidence_span: {"source_cache": "artifacts/phosphorus-research/27338702.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "634bc9a26ebb8d6a911692bcb98a05432db2bc08455c0a02f1ef5e4b953150fe", "start_char": 0, "end_char": 1786, "text_sha256": "634bc9a26ebb8d6a911692bcb98a05432db2bc08455c0a02f1ef5e4b953150fe"} [phosphorus-p27338702] Hypophosphatemia promotes lower rates of muscle ATP synthesis. (2016). https://pubmed.ncbi.nlm.nih.gov/27338702/ DOI: 10.1096/fj.201600473r
Complete structured claim and evidence
After oral phosphate repletion normalized serum phosphate, measured muscle ATP synthetic flux normalized in the single patient.
Study-specific phosphate repletion interventions → Human skeletal-muscle ATP synthetic flux by 31P-MRS source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/phosphorus-research/27338702.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "634bc9a26ebb8d6a911692bcb98a05432db2bc08455c0a02f1ef5e4b953150fe", "start_char": 0, "end_char": 1786, "text_sha256": "634bc9a26ebb8d6a911692bcb98a05432db2bc08455c0a02f1ef5e4b953150fe"}
experimental_model
31P-MRS ATP-flux measurements, repletion and cellular/mitochondrial experiments
exposure
Diet-induced low phosphate, NaPi-IIa knockout, phosphate repletion; one SLC34A3-associated human case
limitations
ATP synthetic flux is not ATP pool size or direct proof that all measured flux is mitochondrial oxidative phosphorylation. One human case cannot define a population threshold.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Human
plain_language
Correcting the shortage restored the measured flux in this individual.
primary_references
[phosphorus-p27338702] Hypophosphatemia promotes lower rates of muscle ATP synthesis. (2016). https://pubmed.ncbi.nlm.nih.gov/27338702/ DOI: 10.1096/fj.201600473r
tissue_or_cell_type
Skeletal muscle
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 620–631
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 31P-MRS ATP-flux measurements, repletion and cellular/mitochondrial experiments · source_derived_draft · unverified_draft
### phosphorus-human-atp-rescue After oral phosphate repletion normalized serum phosphate, measured muscle ATP synthetic flux normalized in the single patient. Condition category: normal nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: Correcting the shortage restored the measured flux in this individual. organism: Human tissue_or_cell_type: Skeletal muscle experimental_model: 31P-MRS ATP-flux measurements, repletion and cellular/mitochondrial experiments limitations: ATP synthetic flux is not ATP pool size or direct proof that all measured flux is mitochondrial oxidative phosphorylation. One human case cannot define a population threshold. exposure: Diet-induced low phosphate, NaPi-IIa knockout, phosphate repletion; one SLC34A3-associated human case evidence_span: {"source_cache": "artifacts/phosphorus-research/27338702.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "634bc9a26ebb8d6a911692bcb98a05432db2bc08455c0a02f1ef5e4b953150fe", "start_char": 0, "end_char": 1786, "text_sha256": "634bc9a26ebb8d6a911692bcb98a05432db2bc08455c0a02f1ef5e4b953150fe"} [phosphorus-p27338702] Hypophosphatemia promotes lower rates of muscle ATP synthesis. (2016). https://pubmed.ncbi.nlm.nih.gov/27338702/ DOI: 10.1096/fj.201600473r
Complete structured claim and evidence
After SAM formation, MAT2A rapidly hydrolyzed the beta–gamma bond of triphosphate and released phosphate and pyrophosphate.
Inorganic triphosphate → Inorganic phosphate (Pi; protonation depends on pH) source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/phosphorus-research/33656855.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1d45073f7187a06cfb9b2d630f94fa651239f0a9a5ae353b37d9af90750f2f38", "start_char": 0, "end_char": 1520, "text_sha256": "1d45073f7187a06cfb9b2d630f94fa651239f0a9a5ae353b37d9af90750f2f38"}
experimental_model
Human MAT2A kinetics, isotope exchange and inhibitor-bound crystallography
exposure
ATP/methionine reactions and PNPNP ligand complexes
limitations
Phosphoryl chemistry is not evidence that phosphate supplements boost methylation. Metal contacts were resolved with an experimental ATP-site ligand.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Human recombinant enzyme
plain_language
ATP’s phosphate chain is processed into two separately tracked products.
primary_references
[phosphorus-p33656855] Mechanism and Inhibition of Human Methionine Adenosyltransferase 2A. (2021). https://pubmed.ncbi.nlm.nih.gov/33656855/ DOI: 10.1021/acs.biochem.0c00998
tissue_or_cell_type
Purified MAT2A active site
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 646–657
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human MAT2A kinetics, isotope exchange and inhibitor-bound crystallography · source_derived_draft · unverified_draft
### phosphorus-mat-pi After SAM formation, MAT2A rapidly hydrolyzed the beta–gamma bond of triphosphate and released phosphate and pyrophosphate. Condition category: normal nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: ATP’s phosphate chain is processed into two separately tracked products. organism: Human recombinant enzyme tissue_or_cell_type: Purified MAT2A active site experimental_model: Human MAT2A kinetics, isotope exchange and inhibitor-bound crystallography limitations: Phosphoryl chemistry is not evidence that phosphate supplements boost methylation. Metal contacts were resolved with an experimental ATP-site ligand. exposure: ATP/methionine reactions and PNPNP ligand complexes evidence_span: {"source_cache": "artifacts/phosphorus-research/33656855.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1d45073f7187a06cfb9b2d630f94fa651239f0a9a5ae353b37d9af90750f2f38", "start_char": 0, "end_char": 1520, "text_sha256": "1d45073f7187a06cfb9b2d630f94fa651239f0a9a5ae353b37d9af90750f2f38"} [phosphorus-p33656855] Mechanism and Inhibition of Human Methionine Adenosyltransferase 2A. (2021). https://pubmed.ncbi.nlm.nih.gov/33656855/ DOI: 10.1021/acs.biochem.0c00998
Complete structured claim and evidence
Two Mg2+ ions chelated the alpha- and gamma-phosphoryl groups of PNPNP in the human MAT2A structure.
Mg2+ → Diimido triphosphate / PNPNP, experimental MAT2A ligand source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/phosphorus-research/33656855.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1d45073f7187a06cfb9b2d630f94fa651239f0a9a5ae353b37d9af90750f2f38", "start_char": 0, "end_char": 1520, "text_sha256": "1d45073f7187a06cfb9b2d630f94fa651239f0a9a5ae353b37d9af90750f2f38"}
experimental_model
Human MAT2A kinetics, isotope exchange and inhibitor-bound crystallography
exposure
ATP/methionine reactions and PNPNP ligand complexes
limitations
Phosphoryl chemistry is not evidence that phosphate supplements boost methylation. Metal contacts were resolved with an experimental ATP-site ligand.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Human recombinant enzyme
plain_language
Magnesium helped position the experimental phosphate-chain mimic at the enzyme site.
primary_references
[phosphorus-p33656855] Mechanism and Inhibition of Human Methionine Adenosyltransferase 2A. (2021). https://pubmed.ncbi.nlm.nih.gov/33656855/ DOI: 10.1021/acs.biochem.0c00998
tissue_or_cell_type
Purified MAT2A active site
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 659–670
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human MAT2A kinetics, isotope exchange and inhibitor-bound crystallography · source_derived_draft · unverified_draft
### phosphorus-mat-magnesium Two Mg2+ ions chelated the alpha- and gamma-phosphoryl groups of PNPNP in the human MAT2A structure. Condition category: normal nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: Magnesium helped position the experimental phosphate-chain mimic at the enzyme site. organism: Human recombinant enzyme tissue_or_cell_type: Purified MAT2A active site experimental_model: Human MAT2A kinetics, isotope exchange and inhibitor-bound crystallography limitations: Phosphoryl chemistry is not evidence that phosphate supplements boost methylation. Metal contacts were resolved with an experimental ATP-site ligand. exposure: ATP/methionine reactions and PNPNP ligand complexes evidence_span: {"source_cache": "artifacts/phosphorus-research/33656855.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1d45073f7187a06cfb9b2d630f94fa651239f0a9a5ae353b37d9af90750f2f38", "start_char": 0, "end_char": 1520, "text_sha256": "1d45073f7187a06cfb9b2d630f94fa651239f0a9a5ae353b37d9af90750f2f38"} [phosphorus-p33656855] Mechanism and Inhibition of Human Methionine Adenosyltransferase 2A. (2021). https://pubmed.ncbi.nlm.nih.gov/33656855/ DOI: 10.1021/acs.biochem.0c00998
Complete structured claim and evidence
The beta-phosphoryl oxygen of the MAT2A-bound PNPNP ligand contacted the essential potassium ion.
Potassium ion → Diimido triphosphate / PNPNP, experimental MAT2A ligand source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/phosphorus-research/33656855.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1d45073f7187a06cfb9b2d630f94fa651239f0a9a5ae353b37d9af90750f2f38", "start_char": 0, "end_char": 1520, "text_sha256": "1d45073f7187a06cfb9b2d630f94fa651239f0a9a5ae353b37d9af90750f2f38"}
experimental_model
Human MAT2A kinetics, isotope exchange and inhibitor-bound crystallography
exposure
ATP/methionine reactions and PNPNP ligand complexes
limitations
Phosphoryl chemistry is not evidence that phosphate supplements boost methylation. Metal contacts were resolved with an experimental ATP-site ligand.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Human recombinant enzyme
plain_language
Potassium and magnesium had distinct contacts in the same phosphate-handling active site.
primary_references
[phosphorus-p33656855] Mechanism and Inhibition of Human Methionine Adenosyltransferase 2A. (2021). https://pubmed.ncbi.nlm.nih.gov/33656855/ DOI: 10.1021/acs.biochem.0c00998
tissue_or_cell_type
Purified MAT2A active site
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 672–683
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human MAT2A kinetics, isotope exchange and inhibitor-bound crystallography · source_derived_draft · unverified_draft
### phosphorus-mat-potassium The beta-phosphoryl oxygen of the MAT2A-bound PNPNP ligand contacted the essential potassium ion. Condition category: normal nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: Potassium and magnesium had distinct contacts in the same phosphate-handling active site. organism: Human recombinant enzyme tissue_or_cell_type: Purified MAT2A active site experimental_model: Human MAT2A kinetics, isotope exchange and inhibitor-bound crystallography limitations: Phosphoryl chemistry is not evidence that phosphate supplements boost methylation. Metal contacts were resolved with an experimental ATP-site ligand. exposure: ATP/methionine reactions and PNPNP ligand complexes evidence_span: {"source_cache": "artifacts/phosphorus-research/33656855.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1d45073f7187a06cfb9b2d630f94fa651239f0a9a5ae353b37d9af90750f2f38", "start_char": 0, "end_char": 1520, "text_sha256": "1d45073f7187a06cfb9b2d630f94fa651239f0a9a5ae353b37d9af90750f2f38"} [phosphorus-p33656855] Mechanism and Inhibition of Human Methionine Adenosyltransferase 2A. (2021). https://pubmed.ncbi.nlm.nih.gov/33656855/ DOI: 10.1021/acs.biochem.0c00998
Complete structured claim and evidence
Changing pyrophosphate-mimicking nucleotide leaving groups altered POLB chemical-step kinetics in a base-pair-dependent manner.
dNTP beta/gamma leaving-group analogues in the 2014 POLB study → POLB nucleotide-addition chemical-step kinetics in the 2014 study source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/phosphorus-research/24580380.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7ffa6a3c6ccf9f3a9d52240080160bfcf00d832210168f91b7ac0b9a39be30a2", "start_char": 0, "end_char": 1081, "text_sha256": "7ffa6a3c6ccf9f3a9d52240080160bfcf00d832210168f91b7ac0b9a39be30a2"}
experimental_model
dNTP leaving-group analogue kinetics
exposure
Beta/gamma pyrophosphate-mimicking dNTP analogues across matched and mismatched base pairs
limitations
Chemistry with designed nucleotide analogues, not a measurement of dietary phosphorus and DNA repair; no free-phosphate-to-DNA shortcut is asserted.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Purified DNA polymerase beta; construct species unresolved in the inspected text
plain_language
The nucleotide’s phosphate-chain chemistry is part of DNA synthesis fidelity, not merely structural packaging.
primary_references
[phosphorus-p24580380] Transition state in DNA polymerase β catalysis: rate-limiting chemistry altered by base-pair configuration. (2014). https://pubmed.ncbi.nlm.nih.gov/24580380/ DOI: 10.1021/bi500101z
tissue_or_cell_type
Purified enzyme–primer–template system
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 685–696
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · dNTP leaving-group analogue kinetics · source_derived_draft · unverified_draft
### phosphorus-dna-phosphate-chemistry Changing pyrophosphate-mimicking nucleotide leaving groups altered POLB chemical-step kinetics in a base-pair-dependent manner. Condition category: normal nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: The nucleotide’s phosphate-chain chemistry is part of DNA synthesis fidelity, not merely structural packaging. organism: Purified DNA polymerase beta; construct species unresolved in the inspected text tissue_or_cell_type: Purified enzyme–primer–template system experimental_model: dNTP leaving-group analogue kinetics limitations: Chemistry with designed nucleotide analogues, not a measurement of dietary phosphorus and DNA repair; no free-phosphate-to-DNA shortcut is asserted. exposure: Beta/gamma pyrophosphate-mimicking dNTP analogues across matched and mismatched base pairs evidence_span: {"source_cache": "artifacts/phosphorus-research/24580380.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7ffa6a3c6ccf9f3a9d52240080160bfcf00d832210168f91b7ac0b9a39be30a2", "start_char": 0, "end_char": 1081, "text_sha256": "7ffa6a3c6ccf9f3a9d52240080160bfcf00d832210168f91b7ac0b9a39be30a2"} [phosphorus-p24580380] Transition state in DNA polymerase β catalysis: rate-limiting chemistry altered by base-pair configuration. (2014). https://pubmed.ncbi.nlm.nih.gov/24580380/ DOI: 10.1021/bi500101z
Complete structured claim and evidence
Human CCTbeta expression increased CCT activity and cellular CDP-choline accumulation in COS-7 cells.
Human CTP:phosphocholine cytidylyltransferase beta / PCYT1B → CDP-choline source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/phosphorus-research/9593753.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6ed2c0c0ceaa7eb2efb90c66565bae51b71023f77cdd0224159fd9814e3b7d45", "start_char": 0, "end_char": 1766, "text_sha256": "6ed2c0c0ceaa7eb2efb90c66565bae51b71023f77cdd0224159fd9814e3b7d45"}
experimental_model
Human isoform cloning and COS-7 expression studies
exposure
CCTbeta transfection and catalytic assays with lipid regulators
limitations
Expression-system findings; maximum activity required lipid regulators. Do not generalize the early clone to every subsequently described splice variant.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Human PCYT1B expressed in African-green-monkey-derived COS-7 cells
plain_language
A separately identified enzyme activates the phosphocholine building block.
primary_references
[phosphorus-p9593753] Cloning and characterization of a second human CTP:phosphocholine cytidylyltransferase. (1998). https://pubmed.ncbi.nlm.nih.gov/9593753/ DOI: 10.1074/jbc.273.22.14022
tissue_or_cell_type
Cytoplasm and phospholipid biosynthesis
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 698–709
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human isoform cloning and COS-7 expression studies · source_derived_draft · unverified_draft
### phosphorus-pcyt-cdp Human CCTbeta expression increased CCT activity and cellular CDP-choline accumulation in COS-7 cells. Condition category: normal nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: A separately identified enzyme activates the phosphocholine building block. organism: Human PCYT1B expressed in African-green-monkey-derived COS-7 cells tissue_or_cell_type: Cytoplasm and phospholipid biosynthesis experimental_model: Human isoform cloning and COS-7 expression studies limitations: Expression-system findings; maximum activity required lipid regulators. Do not generalize the early clone to every subsequently described splice variant. exposure: CCTbeta transfection and catalytic assays with lipid regulators evidence_span: {"source_cache": "artifacts/phosphorus-research/9593753.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6ed2c0c0ceaa7eb2efb90c66565bae51b71023f77cdd0224159fd9814e3b7d45", "start_char": 0, "end_char": 1766, "text_sha256": "6ed2c0c0ceaa7eb2efb90c66565bae51b71023f77cdd0224159fd9814e3b7d45"} [phosphorus-p9593753] Cloning and characterization of a second human CTP:phosphocholine cytidylyltransferase. (1998). https://pubmed.ncbi.nlm.nih.gov/9593753/ DOI: 10.1074/jbc.273.22.14022
Complete structured claim and evidence
Human CCTbeta expression enhanced radiolabeling of phosphatidylcholine in COS-7 cells.
Human CTP:phosphocholine cytidylyltransferase beta / PCYT1B → Phosphatidylcholine source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/phosphorus-research/9593753.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6ed2c0c0ceaa7eb2efb90c66565bae51b71023f77cdd0224159fd9814e3b7d45", "start_char": 0, "end_char": 1766, "text_sha256": "6ed2c0c0ceaa7eb2efb90c66565bae51b71023f77cdd0224159fd9814e3b7d45"}
experimental_model
Human isoform cloning and COS-7 expression studies
exposure
CCTbeta transfection and catalytic assays with lipid regulators
limitations
Expression-system findings; maximum activity required lipid regulators. Do not generalize the early clone to every subsequently described splice variant.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Human PCYT1B expressed in African-green-monkey-derived COS-7 cells
plain_language
The pathway feeds a phosphorus-containing membrane lipid; it is distinct from free phosphate transport.
primary_references
[phosphorus-p9593753] Cloning and characterization of a second human CTP:phosphocholine cytidylyltransferase. (1998). https://pubmed.ncbi.nlm.nih.gov/9593753/ DOI: 10.1074/jbc.273.22.14022
tissue_or_cell_type
Cytoplasm and phospholipid biosynthesis
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 711–722
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human isoform cloning and COS-7 expression studies · source_derived_draft · unverified_draft
### phosphorus-pcyt-lipid Human CCTbeta expression enhanced radiolabeling of phosphatidylcholine in COS-7 cells. Condition category: normal nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: The pathway feeds a phosphorus-containing membrane lipid; it is distinct from free phosphate transport. organism: Human PCYT1B expressed in African-green-monkey-derived COS-7 cells tissue_or_cell_type: Cytoplasm and phospholipid biosynthesis experimental_model: Human isoform cloning and COS-7 expression studies limitations: Expression-system findings; maximum activity required lipid regulators. Do not generalize the early clone to every subsequently described splice variant. exposure: CCTbeta transfection and catalytic assays with lipid regulators evidence_span: {"source_cache": "artifacts/phosphorus-research/9593753.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6ed2c0c0ceaa7eb2efb90c66565bae51b71023f77cdd0224159fd9814e3b7d45", "start_char": 0, "end_char": 1766, "text_sha256": "6ed2c0c0ceaa7eb2efb90c66565bae51b71023f77cdd0224159fd9814e3b7d45"} [phosphorus-p9593753] Cloning and characterization of a second human CTP:phosphocholine cytidylyltransferase. (1998). https://pubmed.ncbi.nlm.nih.gov/9593753/ DOI: 10.1074/jbc.273.22.14022
Complete structured claim and evidence
XPR1 was identified as a binding partner of the phosphate-uptake transporter PiT1.
XPR1 (human phosphate exporter) → Human phosphate transporter PiT-1 / SLC20A1 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/phosphorus-research/38833370.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5c093accfcc7194268c0fbd19d3ee39aae4206e9b2feed48b76b2a95eee33b78", "start_char": 0, "end_char": 1103, "text_sha256": "5c093accfcc7194268c0fbd19d3ee39aae4206e9b2feed48b76b2a95eee33b78"}
experimental_model
Protein interaction, localization and phosphate-challenge cell experiments
exposure
Genetic manipulation and pharmacological mimic of phosphate homeostatic challenge
limitations
Temporal regulatory model in cultured cells; endogenous InsP8 signaling is not equivalent to taking an inositol or phytate supplement.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Human cultured HCT116, U2OS and Saos-2 systems
plain_language
The phosphate exit system can physically connect to the entry system.
primary_references
[phosphorus-p38833370] Homeostatic coordination of cellular phosphate uptake and efflux requires an organelle-based receptor for the inositol pyrophosphate IP8. (2024). https://pubmed.ncbi.nlm.nih.gov/38833370/ DOI: 10.1016/j.celrep.2024.114316
tissue_or_cell_type
Cellular phosphate uptake/export and LAMP1-positive puncta
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 724–735
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Protein interaction, localization and phosphate-challenge cell experiments · source_derived_draft · unverified_draft
### phosphorus-xpr1-pit1 XPR1 was identified as a binding partner of the phosphate-uptake transporter PiT1. Condition category: normal nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: The phosphate exit system can physically connect to the entry system. organism: Human cultured HCT116, U2OS and Saos-2 systems tissue_or_cell_type: Cellular phosphate uptake/export and LAMP1-positive puncta experimental_model: Protein interaction, localization and phosphate-challenge cell experiments limitations: Temporal regulatory model in cultured cells; endogenous InsP8 signaling is not equivalent to taking an inositol or phytate supplement. exposure: Genetic manipulation and pharmacological mimic of phosphate homeostatic challenge evidence_span: {"source_cache": "artifacts/phosphorus-research/38833370.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5c093accfcc7194268c0fbd19d3ee39aae4206e9b2feed48b76b2a95eee33b78", "start_char": 0, "end_char": 1103, "text_sha256": "5c093accfcc7194268c0fbd19d3ee39aae4206e9b2feed48b76b2a95eee33b78"} [phosphorus-p38833370] Homeostatic coordination of cellular phosphate uptake and efflux requires an organelle-based receptor for the inositol pyrophosphate IP8. (2024). https://pubmed.ncbi.nlm.nih.gov/38833370/ DOI: 10.1016/j.celrep.2024.114316
Complete structured claim and evidence
XPR1 localized to a subset of intracellular LAMP1-positive puncta designated XLPVs.
XPR1 (human phosphate exporter) → Human XPR1 localization in LAMP1-positive intracellular puncta source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/phosphorus-research/38833370.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5c093accfcc7194268c0fbd19d3ee39aae4206e9b2feed48b76b2a95eee33b78", "start_char": 0, "end_char": 1103, "text_sha256": "5c093accfcc7194268c0fbd19d3ee39aae4206e9b2feed48b76b2a95eee33b78"}
experimental_model
Protein interaction, localization and phosphate-challenge cell experiments
exposure
Genetic manipulation and pharmacological mimic of phosphate homeostatic challenge
limitations
Temporal regulatory model in cultured cells; endogenous InsP8 signaling is not equivalent to taking an inositol or phytate supplement.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Human cultured HCT116, U2OS and Saos-2 systems
plain_language
Some of the control system operated in an intracellular compartment.
primary_references
[phosphorus-p38833370] Homeostatic coordination of cellular phosphate uptake and efflux requires an organelle-based receptor for the inositol pyrophosphate IP8. (2024). https://pubmed.ncbi.nlm.nih.gov/38833370/ DOI: 10.1016/j.celrep.2024.114316
tissue_or_cell_type
Cellular phosphate uptake/export and LAMP1-positive puncta
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 737–748
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Protein interaction, localization and phosphate-challenge cell experiments · source_derived_draft · unverified_draft
### phosphorus-xpr1-location XPR1 localized to a subset of intracellular LAMP1-positive puncta designated XLPVs. Condition category: normal nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: Some of the control system operated in an intracellular compartment. organism: Human cultured HCT116, U2OS and Saos-2 systems tissue_or_cell_type: Cellular phosphate uptake/export and LAMP1-positive puncta experimental_model: Protein interaction, localization and phosphate-challenge cell experiments limitations: Temporal regulatory model in cultured cells; endogenous InsP8 signaling is not equivalent to taking an inositol or phytate supplement. exposure: Genetic manipulation and pharmacological mimic of phosphate homeostatic challenge evidence_span: {"source_cache": "artifacts/phosphorus-research/38833370.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5c093accfcc7194268c0fbd19d3ee39aae4206e9b2feed48b76b2a95eee33b78", "start_char": 0, "end_char": 1103, "text_sha256": "5c093accfcc7194268c0fbd19d3ee39aae4206e9b2feed48b76b2a95eee33b78"} [phosphorus-p38833370] Homeostatic coordination of cellular phosphate uptake and efflux requires an organelle-based receptor for the inositol pyrophosphate IP8. (2024). https://pubmed.ncbi.nlm.nih.gov/38833370/ DOI: 10.1016/j.celrep.2024.114316
Complete structured claim and evidence
In the challenge model, InsP8-dependent XPR1 regulation first adjusted phosphate efflux.
1,5-bisdiphosphoinositol tetrakisphosphate (1,5-InsP8) → Cellular inorganic phosphate export source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/phosphorus-research/38833370.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5c093accfcc7194268c0fbd19d3ee39aae4206e9b2feed48b76b2a95eee33b78", "start_char": 0, "end_char": 1103, "text_sha256": "5c093accfcc7194268c0fbd19d3ee39aae4206e9b2feed48b76b2a95eee33b78"}
experimental_model
Protein interaction, localization and phosphate-challenge cell experiments
exposure
Genetic manipulation and pharmacological mimic of phosphate homeostatic challenge
limitations
Temporal regulatory model in cultured cells; endogenous InsP8 signaling is not equivalent to taking an inositol or phytate supplement.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Human cultured HCT116, U2OS and Saos-2 systems
plain_language
An inositol pyrophosphate signal changed phosphate export.
primary_references
[phosphorus-p38833370] Homeostatic coordination of cellular phosphate uptake and efflux requires an organelle-based receptor for the inositol pyrophosphate IP8. (2024). https://pubmed.ncbi.nlm.nih.gov/38833370/ DOI: 10.1016/j.celrep.2024.114316
tissue_or_cell_type
Cellular phosphate uptake/export and LAMP1-positive puncta
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 750–761
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Protein interaction, localization and phosphate-challenge cell experiments · source_derived_draft · unverified_draft
### phosphorus-ip8-export In the challenge model, InsP8-dependent XPR1 regulation first adjusted phosphate efflux. Condition category: normal nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: An inositol pyrophosphate signal changed phosphate export. organism: Human cultured HCT116, U2OS and Saos-2 systems tissue_or_cell_type: Cellular phosphate uptake/export and LAMP1-positive puncta experimental_model: Protein interaction, localization and phosphate-challenge cell experiments limitations: Temporal regulatory model in cultured cells; endogenous InsP8 signaling is not equivalent to taking an inositol or phytate supplement. exposure: Genetic manipulation and pharmacological mimic of phosphate homeostatic challenge evidence_span: {"source_cache": "artifacts/phosphorus-research/38833370.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5c093accfcc7194268c0fbd19d3ee39aae4206e9b2feed48b76b2a95eee33b78", "start_char": 0, "end_char": 1103, "text_sha256": "5c093accfcc7194268c0fbd19d3ee39aae4206e9b2feed48b76b2a95eee33b78"} [phosphorus-p38833370] Homeostatic coordination of cellular phosphate uptake and efflux requires an organelle-based receptor for the inositol pyrophosphate IP8. (2024). https://pubmed.ncbi.nlm.nih.gov/38833370/ DOI: 10.1016/j.celrep.2024.114316
Complete structured claim and evidence
The study reported later XPR1-dependent modulation of PiT1 turnover, resetting phosphate uptake after the earlier efflux response.
XPR1 (human phosphate exporter) → Human PiT1 protein turnover source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/phosphorus-research/38833370.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5c093accfcc7194268c0fbd19d3ee39aae4206e9b2feed48b76b2a95eee33b78", "start_char": 0, "end_char": 1103, "text_sha256": "5c093accfcc7194268c0fbd19d3ee39aae4206e9b2feed48b76b2a95eee33b78"}
experimental_model
Protein interaction, localization and phosphate-challenge cell experiments
exposure
Genetic manipulation and pharmacological mimic of phosphate homeostatic challenge
limitations
Temporal regulatory model in cultured cells; endogenous InsP8 signaling is not equivalent to taking an inositol or phytate supplement.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Human cultured HCT116, U2OS and Saos-2 systems
plain_language
Changing transporter turnover adjusted how much phosphate entered later.
primary_references
[phosphorus-p38833370] Homeostatic coordination of cellular phosphate uptake and efflux requires an organelle-based receptor for the inositol pyrophosphate IP8. (2024). https://pubmed.ncbi.nlm.nih.gov/38833370/ DOI: 10.1016/j.celrep.2024.114316
tissue_or_cell_type
Cellular phosphate uptake/export and LAMP1-positive puncta
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 763–774
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Protein interaction, localization and phosphate-challenge cell experiments · source_derived_draft · unverified_draft
### phosphorus-ip8-uptake The study reported later XPR1-dependent modulation of PiT1 turnover, resetting phosphate uptake after the earlier efflux response. Condition category: normal nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: Changing transporter turnover adjusted how much phosphate entered later. organism: Human cultured HCT116, U2OS and Saos-2 systems tissue_or_cell_type: Cellular phosphate uptake/export and LAMP1-positive puncta experimental_model: Protein interaction, localization and phosphate-challenge cell experiments limitations: Temporal regulatory model in cultured cells; endogenous InsP8 signaling is not equivalent to taking an inositol or phytate supplement. exposure: Genetic manipulation and pharmacological mimic of phosphate homeostatic challenge evidence_span: {"source_cache": "artifacts/phosphorus-research/38833370.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5c093accfcc7194268c0fbd19d3ee39aae4206e9b2feed48b76b2a95eee33b78", "start_char": 0, "end_char": 1103, "text_sha256": "5c093accfcc7194268c0fbd19d3ee39aae4206e9b2feed48b76b2a95eee33b78"} [phosphorus-p38833370] Homeostatic coordination of cellular phosphate uptake and efflux requires an organelle-based receptor for the inositol pyrophosphate IP8. (2024). https://pubmed.ncbi.nlm.nih.gov/38833370/ DOI: 10.1016/j.celrep.2024.114316
Complete structured claim and evidence
Elevated extracellular phosphate induced concentration-dependent mineral deposition in human aortic smooth-muscle cultures; 1.4 mmol/L control cultures did not mineralize.
Inorganic phosphate (Pi; protonation depends on pH) → Human vascular smooth-muscle-cell matrix mineralization source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/phosphorus-research/11009570.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b677e361792cc961c217b0437e58c9d5f54b3c0953b539a61c2b2bb732e51291", "start_char": 0, "end_char": 1607, "text_sha256": "b677e361792cc961c217b0437e58c9d5f54b3c0953b539a61c2b2bb732e51291"}
experimental_model
Concentration-response calcification in cultured aortic smooth muscle
exposure
Media phosphate 1.4 mmol/L versus elevated concentrations; phosphonoformic-acid inhibition
limitations
Culture mineralization is not a clinical intake threshold; the inhibitor does not establish one universally necessary transporter isoform.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Human
plain_language
High phosphate promoted mineral deposition in this cell model.
primary_references
[phosphorus-p11009570] Phosphate regulation of vascular smooth muscle cell calcification. (2000). https://pubmed.ncbi.nlm.nih.gov/11009570/ DOI: 10.1161/01.res.87.7.e10
tissue_or_cell_type
Aortic smooth-muscle-cell matrix
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 776–787
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Concentration-response calcification in cultured aortic smooth muscle · source_derived_draft · unverified_draft
### phosphorus-vascular-mineralization Elevated extracellular phosphate induced concentration-dependent mineral deposition in human aortic smooth-muscle cultures; 1.4 mmol/L control cultures did not mineralize. Condition category: normal nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: High phosphate promoted mineral deposition in this cell model. organism: Human tissue_or_cell_type: Aortic smooth-muscle-cell matrix experimental_model: Concentration-response calcification in cultured aortic smooth muscle limitations: Culture mineralization is not a clinical intake threshold; the inhibitor does not establish one universally necessary transporter isoform. exposure: Media phosphate 1.4 mmol/L versus elevated concentrations; phosphonoformic-acid inhibition evidence_span: {"source_cache": "artifacts/phosphorus-research/11009570.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b677e361792cc961c217b0437e58c9d5f54b3c0953b539a61c2b2bb732e51291", "start_char": 0, "end_char": 1607, "text_sha256": "b677e361792cc961c217b0437e58c9d5f54b3c0953b539a61c2b2bb732e51291"} [phosphorus-p11009570] Phosphate regulation of vascular smooth muscle cell calcification. (2000). https://pubmed.ncbi.nlm.nih.gov/11009570/ DOI: 10.1161/01.res.87.7.e10
Complete structured claim and evidence
Elevated phosphate increased osteocalcin and Cbfa1/RUNX2 expression in cultured human aortic smooth-muscle cells.
Inorganic phosphate (Pi; protonation depends on pH) → Human vascular smooth-muscle osteocalcin and RUNX2/Cbfa1 expression source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/phosphorus-research/11009570.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b677e361792cc961c217b0437e58c9d5f54b3c0953b539a61c2b2bb732e51291", "start_char": 0, "end_char": 1607, "text_sha256": "b677e361792cc961c217b0437e58c9d5f54b3c0953b539a61c2b2bb732e51291"}
experimental_model
Concentration-response calcification in cultured aortic smooth muscle
exposure
Media phosphate 1.4 mmol/L versus elevated concentrations; phosphonoformic-acid inhibition
limitations
Culture mineralization is not a clinical intake threshold; the inhibitor does not establish one universally necessary transporter isoform.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Human
plain_language
The cells increased markers associated with a bone-forming program.
primary_references
[phosphorus-p11009570] Phosphate regulation of vascular smooth muscle cell calcification. (2000). https://pubmed.ncbi.nlm.nih.gov/11009570/ DOI: 10.1161/01.res.87.7.e10
tissue_or_cell_type
Aortic smooth-muscle-cell matrix
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 789–800
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Concentration-response calcification in cultured aortic smooth muscle · source_derived_draft · unverified_draft
### phosphorus-vascular-program Elevated phosphate increased osteocalcin and Cbfa1/RUNX2 expression in cultured human aortic smooth-muscle cells. Condition category: normal nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: The cells increased markers associated with a bone-forming program. organism: Human tissue_or_cell_type: Aortic smooth-muscle-cell matrix experimental_model: Concentration-response calcification in cultured aortic smooth muscle limitations: Culture mineralization is not a clinical intake threshold; the inhibitor does not establish one universally necessary transporter isoform. exposure: Media phosphate 1.4 mmol/L versus elevated concentrations; phosphonoformic-acid inhibition evidence_span: {"source_cache": "artifacts/phosphorus-research/11009570.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b677e361792cc961c217b0437e58c9d5f54b3c0953b539a61c2b2bb732e51291", "start_char": 0, "end_char": 1607, "text_sha256": "b677e361792cc961c217b0437e58c9d5f54b3c0953b539a61c2b2bb732e51291"} [phosphorus-p11009570] Phosphate regulation of vascular smooth muscle cell calcification. (2000). https://pubmed.ncbi.nlm.nih.gov/11009570/ DOI: 10.1161/01.res.87.7.e10
Complete structured claim and evidence
Aortic medial PiT2 mRNA increased approximately twofold after smooth-muscle PiT1 deletion.
Mouse vascular smooth-muscle Slc20a1 knockout → Mouse phosphate transporter PiT-2 / Slc20a2 source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/phosphorus-research/23968976.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6704ac0400a286d5137384f4339dd6dffb0061a41a121b6c72a0b23353cbc6f9", "start_char": 0, "end_char": 1852, "text_sha256": "6704ac0400a286d5137384f4339dd6dffb0061a41a121b6c72a0b23353cbc6f9"}
experimental_model
Smooth-muscle-specific knockout and transporter compensation experiments
exposure
Mouse CKD plus dietary phosphate loading; PiT2 knockdown or expression rescue
limitations
Loss of one transporter can be masked by another. This refines a single-transporter model without proving every calcification pathway requires transport.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Mouse
plain_language
The backup transporter increased when the first transporter was absent.
primary_references
[phosphorus-p23968976] Sodium-dependent phosphate cotransporters and phosphate-induced calcification of vascular smooth muscle cells: redundant roles for PiT-1 and PiT-2. (2013). https://pubmed.ncbi.nlm.nih.gov/23968976/ DOI: 10.1161/atvbaha.113.302249
tissue_or_cell_type
Vascular smooth muscle
trigger_kind
machinery_impairment Imported condition classification; unverified.
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 802–813
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Smooth-muscle-specific knockout and transporter compensation experiments · source_derived_draft · unverified_draft
### phosphorus-pit2-compensation Aortic medial PiT2 mRNA increased approximately twofold after smooth-muscle PiT1 deletion. Condition category: machinery_impairment nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: The backup transporter increased when the first transporter was absent. organism: Mouse tissue_or_cell_type: Vascular smooth muscle experimental_model: Smooth-muscle-specific knockout and transporter compensation experiments limitations: Loss of one transporter can be masked by another. This refines a single-transporter model without proving every calcification pathway requires transport. exposure: Mouse CKD plus dietary phosphate loading; PiT2 knockdown or expression rescue evidence_span: {"source_cache": "artifacts/phosphorus-research/23968976.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6704ac0400a286d5137384f4339dd6dffb0061a41a121b6c72a0b23353cbc6f9", "start_char": 0, "end_char": 1852, "text_sha256": "6704ac0400a286d5137384f4339dd6dffb0061a41a121b6c72a0b23353cbc6f9"} [phosphorus-p23968976] Sodium-dependent phosphate cotransporters and phosphate-induced calcification of vascular smooth muscle cells: redundant roles for PiT-1 and PiT-2. (2013). https://pubmed.ncbi.nlm.nih.gov/23968976/ DOI: 10.1161/atvbaha.113.302249
Complete structured claim and evidence
PiT1 deletion did not reduce aortic calcification in the mouse CKD/phosphate-loading model.
Mouse vascular smooth-muscle Slc20a1 knockout → Mouse vascular smooth-muscle matrix mineralization source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/phosphorus-research/23968976.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6704ac0400a286d5137384f4339dd6dffb0061a41a121b6c72a0b23353cbc6f9", "start_char": 0, "end_char": 1852, "text_sha256": "6704ac0400a286d5137384f4339dd6dffb0061a41a121b6c72a0b23353cbc6f9"}
experimental_model
Smooth-muscle-specific knockout and transporter compensation experiments
exposure
Mouse CKD plus dietary phosphate loading; PiT2 knockdown or expression rescue
limitations
Loss of one transporter can be masked by another. This refines a single-transporter model without proving every calcification pathway requires transport.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Mouse
plain_language
Removing PiT1 alone did not protect these mice from calcification.
primary_references
[phosphorus-p23968976] Sodium-dependent phosphate cotransporters and phosphate-induced calcification of vascular smooth muscle cells: redundant roles for PiT-1 and PiT-2. (2013). https://pubmed.ncbi.nlm.nih.gov/23968976/ DOI: 10.1161/atvbaha.113.302249
tissue_or_cell_type
Vascular smooth muscle
trigger_kind
machinery_impairment Imported condition classification; unverified.
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 815–826
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Smooth-muscle-specific knockout and transporter compensation experiments · source_derived_draft · unverified_draft
### phosphorus-pit1-null-calcification PiT1 deletion did not reduce aortic calcification in the mouse CKD/phosphate-loading model. Condition category: machinery_impairment nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: Removing PiT1 alone did not protect these mice from calcification. organism: Mouse tissue_or_cell_type: Vascular smooth muscle experimental_model: Smooth-muscle-specific knockout and transporter compensation experiments limitations: Loss of one transporter can be masked by another. This refines a single-transporter model without proving every calcification pathway requires transport. exposure: Mouse CKD plus dietary phosphate loading; PiT2 knockdown or expression rescue evidence_span: {"source_cache": "artifacts/phosphorus-research/23968976.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6704ac0400a286d5137384f4339dd6dffb0061a41a121b6c72a0b23353cbc6f9", "start_char": 0, "end_char": 1852, "text_sha256": "6704ac0400a286d5137384f4339dd6dffb0061a41a121b6c72a0b23353cbc6f9"} [phosphorus-p23968976] Sodium-dependent phosphate cotransporters and phosphate-induced calcification of vascular smooth muscle cells: redundant roles for PiT-1 and PiT-2. (2013). https://pubmed.ncbi.nlm.nih.gov/23968976/ DOI: 10.1161/atvbaha.113.302249
Complete structured claim and evidence
PiT2 knockdown reduced phosphate uptake in PiT1-deficient mouse vascular smooth-muscle cells.
Experimental mouse Slc20a2 knockdown → Mouse vascular smooth-muscle phosphate uptake source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/phosphorus-research/23968976.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6704ac0400a286d5137384f4339dd6dffb0061a41a121b6c72a0b23353cbc6f9", "start_char": 0, "end_char": 1852, "text_sha256": "6704ac0400a286d5137384f4339dd6dffb0061a41a121b6c72a0b23353cbc6f9"}
experimental_model
Smooth-muscle-specific knockout and transporter compensation experiments
exposure
Mouse CKD plus dietary phosphate loading; PiT2 knockdown or expression rescue
limitations
Loss of one transporter can be masked by another. This refines a single-transporter model without proving every calcification pathway requires transport.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Mouse
plain_language
Removing the backup reduced uptake.
primary_references
[phosphorus-p23968976] Sodium-dependent phosphate cotransporters and phosphate-induced calcification of vascular smooth muscle cells: redundant roles for PiT-1 and PiT-2. (2013). https://pubmed.ncbi.nlm.nih.gov/23968976/ DOI: 10.1161/atvbaha.113.302249
tissue_or_cell_type
Vascular smooth muscle
trigger_kind
machinery_impairment Imported condition classification; unverified.
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 828–839
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Smooth-muscle-specific knockout and transporter compensation experiments · source_derived_draft · unverified_draft
### phosphorus-pit2-knockdown-uptake PiT2 knockdown reduced phosphate uptake in PiT1-deficient mouse vascular smooth-muscle cells. Condition category: machinery_impairment nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: Removing the backup reduced uptake. organism: Mouse tissue_or_cell_type: Vascular smooth muscle experimental_model: Smooth-muscle-specific knockout and transporter compensation experiments limitations: Loss of one transporter can be masked by another. This refines a single-transporter model without proving every calcification pathway requires transport. exposure: Mouse CKD plus dietary phosphate loading; PiT2 knockdown or expression rescue evidence_span: {"source_cache": "artifacts/phosphorus-research/23968976.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6704ac0400a286d5137384f4339dd6dffb0061a41a121b6c72a0b23353cbc6f9", "start_char": 0, "end_char": 1852, "text_sha256": "6704ac0400a286d5137384f4339dd6dffb0061a41a121b6c72a0b23353cbc6f9"} [phosphorus-p23968976] Sodium-dependent phosphate cotransporters and phosphate-induced calcification of vascular smooth muscle cells: redundant roles for PiT-1 and PiT-2. (2013). https://pubmed.ncbi.nlm.nih.gov/23968976/ DOI: 10.1161/atvbaha.113.302249
Complete structured claim and evidence
PiT2 knockdown reduced phosphate-induced calcification in PiT1-deficient mouse vascular smooth-muscle cells.
Experimental mouse Slc20a2 knockdown → Mouse vascular smooth-muscle matrix mineralization source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/phosphorus-research/23968976.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6704ac0400a286d5137384f4339dd6dffb0061a41a121b6c72a0b23353cbc6f9", "start_char": 0, "end_char": 1852, "text_sha256": "6704ac0400a286d5137384f4339dd6dffb0061a41a121b6c72a0b23353cbc6f9"}
experimental_model
Smooth-muscle-specific knockout and transporter compensation experiments
exposure
Mouse CKD plus dietary phosphate loading; PiT2 knockdown or expression rescue
limitations
Loss of one transporter can be masked by another. This refines a single-transporter model without proving every calcification pathway requires transport.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Mouse
plain_language
Removing the backup also reduced mineral deposition.
primary_references
[phosphorus-p23968976] Sodium-dependent phosphate cotransporters and phosphate-induced calcification of vascular smooth muscle cells: redundant roles for PiT-1 and PiT-2. (2013). https://pubmed.ncbi.nlm.nih.gov/23968976/ DOI: 10.1161/atvbaha.113.302249
tissue_or_cell_type
Vascular smooth muscle
trigger_kind
machinery_impairment Imported condition classification; unverified.
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 841–852
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Smooth-muscle-specific knockout and transporter compensation experiments · source_derived_draft · unverified_draft
### phosphorus-pit2-knockdown-mineral PiT2 knockdown reduced phosphate-induced calcification in PiT1-deficient mouse vascular smooth-muscle cells. Condition category: machinery_impairment nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: Removing the backup also reduced mineral deposition. organism: Mouse tissue_or_cell_type: Vascular smooth muscle experimental_model: Smooth-muscle-specific knockout and transporter compensation experiments limitations: Loss of one transporter can be masked by another. This refines a single-transporter model without proving every calcification pathway requires transport. exposure: Mouse CKD plus dietary phosphate loading; PiT2 knockdown or expression rescue evidence_span: {"source_cache": "artifacts/phosphorus-research/23968976.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6704ac0400a286d5137384f4339dd6dffb0061a41a121b6c72a0b23353cbc6f9", "start_char": 0, "end_char": 1852, "text_sha256": "6704ac0400a286d5137384f4339dd6dffb0061a41a121b6c72a0b23353cbc6f9"} [phosphorus-p23968976] Sodium-dependent phosphate cotransporters and phosphate-induced calcification of vascular smooth muscle cells: redundant roles for PiT-1 and PiT-2. (2013). https://pubmed.ncbi.nlm.nih.gov/23968976/ DOI: 10.1161/atvbaha.113.302249
Complete structured claim and evidence
PiT2 overexpression restored phosphate uptake and phosphate-induced calcification in human PiT1-deficient vascular smooth-muscle cells.
PiT-2 / SLC20A2 → Human vascular smooth-muscle-cell matrix mineralization source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/phosphorus-research/23968976.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6704ac0400a286d5137384f4339dd6dffb0061a41a121b6c72a0b23353cbc6f9", "start_char": 0, "end_char": 1852, "text_sha256": "6704ac0400a286d5137384f4339dd6dffb0061a41a121b6c72a0b23353cbc6f9"}
experimental_model
Smooth-muscle-specific knockout and transporter compensation experiments
exposure
Mouse CKD plus dietary phosphate loading; PiT2 knockdown or expression rescue
limitations
Loss of one transporter can be masked by another. This refines a single-transporter model without proving every calcification pathway requires transport.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Human
plain_language
The human-cell rescue supported a backup role for PiT2.
primary_references
[phosphorus-p23968976] Sodium-dependent phosphate cotransporters and phosphate-induced calcification of vascular smooth muscle cells: redundant roles for PiT-1 and PiT-2. (2013). https://pubmed.ncbi.nlm.nih.gov/23968976/ DOI: 10.1161/atvbaha.113.302249
tissue_or_cell_type
Vascular smooth muscle
trigger_kind
machinery_impairment Imported condition classification; unverified.
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 854–865
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Smooth-muscle-specific knockout and transporter compensation experiments · source_derived_draft · unverified_draft
### phosphorus-human-pit2-rescue PiT2 overexpression restored phosphate uptake and phosphate-induced calcification in human PiT1-deficient vascular smooth-muscle cells. Condition category: machinery_impairment nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: The human-cell rescue supported a backup role for PiT2. organism: Human tissue_or_cell_type: Vascular smooth muscle experimental_model: Smooth-muscle-specific knockout and transporter compensation experiments limitations: Loss of one transporter can be masked by another. This refines a single-transporter model without proving every calcification pathway requires transport. exposure: Mouse CKD plus dietary phosphate loading; PiT2 knockdown or expression rescue evidence_span: {"source_cache": "artifacts/phosphorus-research/23968976.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6704ac0400a286d5137384f4339dd6dffb0061a41a121b6c72a0b23353cbc6f9", "start_char": 0, "end_char": 1852, "text_sha256": "6704ac0400a286d5137384f4339dd6dffb0061a41a121b6c72a0b23353cbc6f9"} [phosphorus-p23968976] Sodium-dependent phosphate cotransporters and phosphate-induced calcification of vascular smooth muscle cells: redundant roles for PiT-1 and PiT-2. (2013). https://pubmed.ncbi.nlm.nih.gov/23968976/ DOI: 10.1161/atvbaha.113.302249
Complete structured claim and evidence
The study linked phosphate entry into mitochondria to increased hydrogen-peroxide production in the FGFR1 activation pathway.
Inorganic phosphate (Pi; protonation depends on pH) → Mitochondrial hydrogen-peroxide production in the 2026 osteosarcoma study source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/phosphorus-research/42247296.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a8d4221d8a5c56a5937ab8262e3ece5ed87692cb876ddcc0a08e7f68b66a9b76", "start_char": 0, "end_char": 1041, "text_sha256": "a8d4221d8a5c56a5937ab8262e3ece5ed87692cb876ddcc0a08e7f68b66a9b76"}
experimental_model
Osteosarcoma-cell signaling with in-vivo tumor experiments
exposure
Elevated phosphate challenges and receptor activation experiments
limitations
New 2026 mechanism in tumor models; blood-Pi/tumor-growth association is not proof that dietary phosphorus causes human cancer. No specific transporter or oxidized residue number is invented from the abstract.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Osteosarcoma cellular and animal systems; precise species not fully resolved from abstract
plain_language
Mitochondrial phosphate handling fed a redox signal in these tumor models.
primary_references
[phosphorus-p42247296] Unconventional activation of the proto-oncogene FGFR1 by extracellular phosphate via H2O2-mediated kinase oxidation. (2026). https://pubmed.ncbi.nlm.nih.gov/42247296/ DOI: 10.1016/j.celrep.2026.117504
tissue_or_cell_type
Plasma-membrane/mitochondrial phosphate handling and FGFR1 signaling
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 867–878
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Osteosarcoma-cell signaling with in-vivo tumor experiments · source_derived_draft · unverified_draft
### phosphorus-pi-mito-peroxide The study linked phosphate entry into mitochondria to increased hydrogen-peroxide production in the FGFR1 activation pathway. Condition category: normal nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: Mitochondrial phosphate handling fed a redox signal in these tumor models. organism: Osteosarcoma cellular and animal systems; precise species not fully resolved from abstract tissue_or_cell_type: Plasma-membrane/mitochondrial phosphate handling and FGFR1 signaling experimental_model: Osteosarcoma-cell signaling with in-vivo tumor experiments limitations: New 2026 mechanism in tumor models; blood-Pi/tumor-growth association is not proof that dietary phosphorus causes human cancer. No specific transporter or oxidized residue number is invented from the abstract. exposure: Elevated phosphate challenges and receptor activation experiments evidence_span: {"source_cache": "artifacts/phosphorus-research/42247296.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a8d4221d8a5c56a5937ab8262e3ece5ed87692cb876ddcc0a08e7f68b66a9b76", "start_char": 0, "end_char": 1041, "text_sha256": "a8d4221d8a5c56a5937ab8262e3ece5ed87692cb876ddcc0a08e7f68b66a9b76"} [phosphorus-p42247296] Unconventional activation of the proto-oncogene FGFR1 by extracellular phosphate via H2O2-mediated kinase oxidation. (2026). https://pubmed.ncbi.nlm.nih.gov/42247296/ DOI: 10.1016/j.celrep.2026.117504
Complete structured claim and evidence
The phosphate-associated hydrogen-peroxide burst oxidized critical cysteine and methionine residues of FGFR1.
Hydrogen peroxide → FGFR1 cysteine/methionine oxidation in the 2026 osteosarcoma study source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/phosphorus-research/42247296.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a8d4221d8a5c56a5937ab8262e3ece5ed87692cb876ddcc0a08e7f68b66a9b76", "start_char": 0, "end_char": 1041, "text_sha256": "a8d4221d8a5c56a5937ab8262e3ece5ed87692cb876ddcc0a08e7f68b66a9b76"}
experimental_model
Osteosarcoma-cell signaling with in-vivo tumor experiments
exposure
Elevated phosphate challenges and receptor activation experiments
limitations
New 2026 mechanism in tumor models; blood-Pi/tumor-growth association is not proof that dietary phosphorus causes human cancer. No specific transporter or oxidized residue number is invented from the abstract.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Osteosarcoma cellular and animal systems; precise species not fully resolved from abstract
plain_language
A redox change reached the receptor protein.
primary_references
[phosphorus-p42247296] Unconventional activation of the proto-oncogene FGFR1 by extracellular phosphate via H2O2-mediated kinase oxidation. (2026). https://pubmed.ncbi.nlm.nih.gov/42247296/ DOI: 10.1016/j.celrep.2026.117504
tissue_or_cell_type
Plasma-membrane/mitochondrial phosphate handling and FGFR1 signaling
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 880–891
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Osteosarcoma-cell signaling with in-vivo tumor experiments · source_derived_draft · unverified_draft
### phosphorus-peroxide-fgfr The phosphate-associated hydrogen-peroxide burst oxidized critical cysteine and methionine residues of FGFR1. Condition category: normal nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: A redox change reached the receptor protein. organism: Osteosarcoma cellular and animal systems; precise species not fully resolved from abstract tissue_or_cell_type: Plasma-membrane/mitochondrial phosphate handling and FGFR1 signaling experimental_model: Osteosarcoma-cell signaling with in-vivo tumor experiments limitations: New 2026 mechanism in tumor models; blood-Pi/tumor-growth association is not proof that dietary phosphorus causes human cancer. No specific transporter or oxidized residue number is invented from the abstract. exposure: Elevated phosphate challenges and receptor activation experiments evidence_span: {"source_cache": "artifacts/phosphorus-research/42247296.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a8d4221d8a5c56a5937ab8262e3ece5ed87692cb876ddcc0a08e7f68b66a9b76", "start_char": 0, "end_char": 1041, "text_sha256": "a8d4221d8a5c56a5937ab8262e3ece5ed87692cb876ddcc0a08e7f68b66a9b76"} [phosphorus-p42247296] Unconventional activation of the proto-oncogene FGFR1 by extracellular phosphate via H2O2-mediated kinase oxidation. (2026). https://pubmed.ncbi.nlm.nih.gov/42247296/ DOI: 10.1016/j.celrep.2026.117504
Complete structured claim and evidence
FGFR1 oxidation promoted receptor activation and downstream signaling in the phosphate-sensing tumor-model experiments.
FGFR1 cysteine/methionine oxidation in the 2026 osteosarcoma study → Fibroblast growth factor receptor 1 / FGFR1 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/phosphorus-research/42247296.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a8d4221d8a5c56a5937ab8262e3ece5ed87692cb876ddcc0a08e7f68b66a9b76", "start_char": 0, "end_char": 1041, "text_sha256": "a8d4221d8a5c56a5937ab8262e3ece5ed87692cb876ddcc0a08e7f68b66a9b76"}
experimental_model
Osteosarcoma-cell signaling with in-vivo tumor experiments
exposure
Elevated phosphate challenges and receptor activation experiments
limitations
New 2026 mechanism in tumor models; blood-Pi/tumor-growth association is not proof that dietary phosphorus causes human cancer. No specific transporter or oxidized residue number is invented from the abstract.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Osteosarcoma cellular and animal systems; precise species not fully resolved from abstract
plain_language
Phosphate triggered receptor signaling through an indirect chemical route.
primary_references
[phosphorus-p42247296] Unconventional activation of the proto-oncogene FGFR1 by extracellular phosphate via H2O2-mediated kinase oxidation. (2026). https://pubmed.ncbi.nlm.nih.gov/42247296/ DOI: 10.1016/j.celrep.2026.117504
tissue_or_cell_type
Plasma-membrane/mitochondrial phosphate handling and FGFR1 signaling
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 893–904
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Osteosarcoma-cell signaling with in-vivo tumor experiments · source_derived_draft · unverified_draft
### phosphorus-fgfr-activation FGFR1 oxidation promoted receptor activation and downstream signaling in the phosphate-sensing tumor-model experiments. Condition category: normal nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: Phosphate triggered receptor signaling through an indirect chemical route. organism: Osteosarcoma cellular and animal systems; precise species not fully resolved from abstract tissue_or_cell_type: Plasma-membrane/mitochondrial phosphate handling and FGFR1 signaling experimental_model: Osteosarcoma-cell signaling with in-vivo tumor experiments limitations: New 2026 mechanism in tumor models; blood-Pi/tumor-growth association is not proof that dietary phosphorus causes human cancer. No specific transporter or oxidized residue number is invented from the abstract. exposure: Elevated phosphate challenges and receptor activation experiments evidence_span: {"source_cache": "artifacts/phosphorus-research/42247296.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a8d4221d8a5c56a5937ab8262e3ece5ed87692cb876ddcc0a08e7f68b66a9b76", "start_char": 0, "end_char": 1041, "text_sha256": "a8d4221d8a5c56a5937ab8262e3ece5ed87692cb876ddcc0a08e7f68b66a9b76"} [phosphorus-p42247296] Unconventional activation of the proto-oncogene FGFR1 by extracellular phosphate via H2O2-mediated kinase oxidation. (2026). https://pubmed.ncbi.nlm.nih.gov/42247296/ DOI: 10.1016/j.celrep.2026.117504
Complete structured claim and evidence
Diet-related FGF23 changes correlated inversely with maximal tubular phosphate reabsorption and calcitriol, and positively with urinary phosphate excretion.
Phosphorus → Renal phosphate reabsorption source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/phosphorus-research/15613425.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4a8c4110b9c57e9f8f54305eb77abb80dd90253fc99e2f5aa21a4a3f129983c2", "start_char": 0, "end_char": 1563, "text_sha256": "4a8c4110b9c57e9f8f54305eb77abb80dd90253fc99e2f5aa21a4a3f129983c2"}
experimental_model
Controlled sequential dietary intervention
exposure
Five-day low-phosphate diet plus binder, then phosphate loading; calcium adjusted to minimize PTH changes
limitations
Phosphate intake and calcium/binder cointerventions are explicit; correlation of hormones with renal handling does not independently prove each mediator.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Human
plain_language
The hormone, kidney and vitamin D responses moved together during the intervention.
primary_references
[phosphorus-p15613425] Fibroblast growth factor-23 relationship to dietary phosphate and renal phosphate handling in healthy young men. (2005). https://pubmed.ncbi.nlm.nih.gov/15613425/ DOI: 10.1210/jc.2004-1039
tissue_or_cell_type
29 healthy young men; serum hormones and renal handling
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 920–931
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Controlled sequential dietary intervention · source_derived_draft · unverified_draft
### phosphorus-diet-renal-feedback Diet-related FGF23 changes correlated inversely with maximal tubular phosphate reabsorption and calcitriol, and positively with urinary phosphate excretion. Condition category: normal nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: The hormone, kidney and vitamin D responses moved together during the intervention. organism: Human tissue_or_cell_type: 29 healthy young men; serum hormones and renal handling experimental_model: Controlled sequential dietary intervention limitations: Phosphate intake and calcium/binder cointerventions are explicit; correlation of hormones with renal handling does not independently prove each mediator. exposure: Five-day low-phosphate diet plus binder, then phosphate loading; calcium adjusted to minimize PTH changes evidence_span: {"source_cache": "artifacts/phosphorus-research/15613425.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4a8c4110b9c57e9f8f54305eb77abb80dd90253fc99e2f5aa21a4a3f129983c2", "start_char": 0, "end_char": 1563, "text_sha256": "4a8c4110b9c57e9f8f54305eb77abb80dd90253fc99e2f5aa21a4a3f129983c2"} [phosphorus-p15613425] Fibroblast growth factor-23 relationship to dietary phosphate and renal phosphate handling in healthy young men. (2005). https://pubmed.ncbi.nlm.nih.gov/15613425/ DOI: 10.1210/jc.2004-1039
Complete structured claim and evidence
Serum phosphate rose from 1.11 to 1.32 mmol/L during the higher-phosphate/calcium regimen.
Paired low/high phosphate and calcium diets in the 2010 study → Serum inorganic phosphate concentration source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/phosphorus-research/21030580.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e51a1cd580ac4ea7b0232f65c73ac0814df6bff655bf7bd6d0d82f7f9f21a33e", "start_char": 0, "end_char": 1603, "text_sha256": "e51a1cd580ac4ea7b0232f65c73ac0814df6bff655bf7bd6d0d82f7f9f21a33e"}
experimental_model
Paired 36-hour dietary interventions
exposure
Low/high phosphate and calcium diets, separated by a week
limitations
Both calcium and phosphate changed; phosphate alone cannot be assigned the full effect. Timing and circadian variation matter.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Human
plain_language
The combined dietary change raised the blood phosphate measurement.
primary_references
[phosphorus-p21030580] Effects of dietary phosphate and calcium intake on fibroblast growth factor-23. (2011). https://pubmed.ncbi.nlm.nih.gov/21030580/ DOI: 10.2215/cjn.04730510
tissue_or_cell_type
Ten healthy adults; serial serum measurements and 24-hour urine
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 933–944
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Paired 36-hour dietary interventions · source_derived_draft · unverified_draft
### phosphorus-mixed-diet-pi Serum phosphate rose from 1.11 to 1.32 mmol/L during the higher-phosphate/calcium regimen. Condition category: normal nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: The combined dietary change raised the blood phosphate measurement. organism: Human tissue_or_cell_type: Ten healthy adults; serial serum measurements and 24-hour urine experimental_model: Paired 36-hour dietary interventions limitations: Both calcium and phosphate changed; phosphate alone cannot be assigned the full effect. Timing and circadian variation matter. exposure: Low/high phosphate and calcium diets, separated by a week evidence_span: {"source_cache": "artifacts/phosphorus-research/21030580.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e51a1cd580ac4ea7b0232f65c73ac0814df6bff655bf7bd6d0d82f7f9f21a33e", "start_char": 0, "end_char": 1603, "text_sha256": "e51a1cd580ac4ea7b0232f65c73ac0814df6bff655bf7bd6d0d82f7f9f21a33e"} [phosphorus-p21030580] Effects of dietary phosphate and calcium intake on fibroblast growth factor-23. (2011). https://pubmed.ncbi.nlm.nih.gov/21030580/ DOI: 10.2215/cjn.04730510
Complete structured claim and evidence
Intact FGF23 rose from 33 to 37 ng/L during the higher-phosphate/calcium regimen.
Paired low/high phosphate and calcium diets in the 2010 study → Circulating biologically active intact FGF23 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/phosphorus-research/21030580.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e51a1cd580ac4ea7b0232f65c73ac0814df6bff655bf7bd6d0d82f7f9f21a33e", "start_char": 0, "end_char": 1603, "text_sha256": "e51a1cd580ac4ea7b0232f65c73ac0814df6bff655bf7bd6d0d82f7f9f21a33e"}
experimental_model
Paired 36-hour dietary interventions
exposure
Low/high phosphate and calcium diets, separated by a week
limitations
Both calcium and phosphate changed; phosphate alone cannot be assigned the full effect. Timing and circadian variation matter.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Human
plain_language
The active hormone concentration also increased.
primary_references
[phosphorus-p21030580] Effects of dietary phosphate and calcium intake on fibroblast growth factor-23. (2011). https://pubmed.ncbi.nlm.nih.gov/21030580/ DOI: 10.2215/cjn.04730510
tissue_or_cell_type
Ten healthy adults; serial serum measurements and 24-hour urine
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 946–957
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Paired 36-hour dietary interventions · source_derived_draft · unverified_draft
### phosphorus-mixed-diet-fgf23 Intact FGF23 rose from 33 to 37 ng/L during the higher-phosphate/calcium regimen. Condition category: normal nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: The active hormone concentration also increased. organism: Human tissue_or_cell_type: Ten healthy adults; serial serum measurements and 24-hour urine experimental_model: Paired 36-hour dietary interventions limitations: Both calcium and phosphate changed; phosphate alone cannot be assigned the full effect. Timing and circadian variation matter. exposure: Low/high phosphate and calcium diets, separated by a week evidence_span: {"source_cache": "artifacts/phosphorus-research/21030580.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e51a1cd580ac4ea7b0232f65c73ac0814df6bff655bf7bd6d0d82f7f9f21a33e", "start_char": 0, "end_char": 1603, "text_sha256": "e51a1cd580ac4ea7b0232f65c73ac0814df6bff655bf7bd6d0d82f7f9f21a33e"} [phosphorus-p21030580] Effects of dietary phosphate and calcium intake on fibroblast growth factor-23. (2011). https://pubmed.ncbi.nlm.nih.gov/21030580/ DOI: 10.2215/cjn.04730510
Complete structured claim and evidence
Urinary phosphate rose from 21.6 to 28.8 mmol/day during the higher-phosphate/calcium regimen.
Paired low/high phosphate and calcium diets in the 2010 study → Urinary phosphate excretion source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/phosphorus-research/21030580.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e51a1cd580ac4ea7b0232f65c73ac0814df6bff655bf7bd6d0d82f7f9f21a33e", "start_char": 0, "end_char": 1603, "text_sha256": "e51a1cd580ac4ea7b0232f65c73ac0814df6bff655bf7bd6d0d82f7f9f21a33e"}
experimental_model
Paired 36-hour dietary interventions
exposure
Low/high phosphate and calcium diets, separated by a week
limitations
Both calcium and phosphate changed; phosphate alone cannot be assigned the full effect. Timing and circadian variation matter.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Human
plain_language
The kidneys excreted more phosphate.
primary_references
[phosphorus-p21030580] Effects of dietary phosphate and calcium intake on fibroblast growth factor-23. (2011). https://pubmed.ncbi.nlm.nih.gov/21030580/ DOI: 10.2215/cjn.04730510
tissue_or_cell_type
Ten healthy adults; serial serum measurements and 24-hour urine
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 959–970
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Paired 36-hour dietary interventions · source_derived_draft · unverified_draft
### phosphorus-mixed-diet-urine Urinary phosphate rose from 21.6 to 28.8 mmol/day during the higher-phosphate/calcium regimen. Condition category: normal nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: The kidneys excreted more phosphate. organism: Human tissue_or_cell_type: Ten healthy adults; serial serum measurements and 24-hour urine experimental_model: Paired 36-hour dietary interventions limitations: Both calcium and phosphate changed; phosphate alone cannot be assigned the full effect. Timing and circadian variation matter. exposure: Low/high phosphate and calcium diets, separated by a week evidence_span: {"source_cache": "artifacts/phosphorus-research/21030580.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e51a1cd580ac4ea7b0232f65c73ac0814df6bff655bf7bd6d0d82f7f9f21a33e", "start_char": 0, "end_char": 1603, "text_sha256": "e51a1cd580ac4ea7b0232f65c73ac0814df6bff655bf7bd6d0d82f7f9f21a33e"} [phosphorus-p21030580] Effects of dietary phosphate and calcium intake on fibroblast growth factor-23. (2011). https://pubmed.ncbi.nlm.nih.gov/21030580/ DOI: 10.2215/cjn.04730510
Complete structured claim and evidence
PTH declined during the higher-phosphate/calcium regimen even while FGF23 increased.
Paired low/high phosphate and calcium diets in the 2010 study → Serum PTH concentration source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/phosphorus-research/21030580.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e51a1cd580ac4ea7b0232f65c73ac0814df6bff655bf7bd6d0d82f7f9f21a33e", "start_char": 0, "end_char": 1603, "text_sha256": "e51a1cd580ac4ea7b0232f65c73ac0814df6bff655bf7bd6d0d82f7f9f21a33e"}
experimental_model
Paired 36-hour dietary interventions
exposure
Low/high phosphate and calcium diets, separated by a week
limitations
Both calcium and phosphate changed; phosphate alone cannot be assigned the full effect. Timing and circadian variation matter.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Human
plain_language
Changing calcium alongside phosphate produced a different PTH pattern than a phosphate-only cell challenge.
primary_references
[phosphorus-p21030580] Effects of dietary phosphate and calcium intake on fibroblast growth factor-23. (2011). https://pubmed.ncbi.nlm.nih.gov/21030580/ DOI: 10.2215/cjn.04730510
tissue_or_cell_type
Ten healthy adults; serial serum measurements and 24-hour urine
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 972–983
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Paired 36-hour dietary interventions · source_derived_draft · unverified_draft
### phosphorus-mixed-diet-pth PTH declined during the higher-phosphate/calcium regimen even while FGF23 increased. Condition category: normal nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: Changing calcium alongside phosphate produced a different PTH pattern than a phosphate-only cell challenge. organism: Human tissue_or_cell_type: Ten healthy adults; serial serum measurements and 24-hour urine experimental_model: Paired 36-hour dietary interventions limitations: Both calcium and phosphate changed; phosphate alone cannot be assigned the full effect. Timing and circadian variation matter. exposure: Low/high phosphate and calcium diets, separated by a week evidence_span: {"source_cache": "artifacts/phosphorus-research/21030580.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e51a1cd580ac4ea7b0232f65c73ac0814df6bff655bf7bd6d0d82f7f9f21a33e", "start_char": 0, "end_char": 1603, "text_sha256": "e51a1cd580ac4ea7b0232f65c73ac0814df6bff655bf7bd6d0d82f7f9f21a33e"} [phosphorus-p21030580] Effects of dietary phosphate and calcium intake on fibroblast growth factor-23. (2011). https://pubmed.ncbi.nlm.nih.gov/21030580/ DOI: 10.2215/cjn.04730510
Complete structured claim and evidence
The vegetarian diet produced lower serum phosphorus than the meat diet after one week.
Vegetarian diet in the 2011 CKD crossover trial → Serum inorganic phosphate concentration source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/phosphorus-research/21183586.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c1361f250bd0c2febcef675ba888387b4f2ea0b81b171150734d8f148982a660", "start_char": 0, "end_char": 1667, "text_sha256": "c1361f250bd0c2febcef675ba888387b4f2ea0b81b171150734d8f148982a660"}
experimental_model
Randomized-order crossover feeding trial
exposure
Seven-day vegetarian and meat diets with equivalent nutrients prepared by research staff
limitations
Small short-term CKD study; food source/form matters, but the trial does not isolate one phytate mechanism or establish that all plant phosphate is unabsorbed.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Human
plain_language
Equal listed nutrients did not produce identical blood phosphorus responses.
primary_references
[phosphorus-p21183586] Vegetarian compared with meat dietary protein source and phosphorus homeostasis in chronic kidney disease. (2011). https://pubmed.ncbi.nlm.nih.gov/21183586/ DOI: 10.2215/cjn.05040610
tissue_or_cell_type
Nine people with CKD; mean eGFR 32 mL/min
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 985–996
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized-order crossover feeding trial · source_derived_draft · unverified_draft
### phosphorus-plant-diet-pi The vegetarian diet produced lower serum phosphorus than the meat diet after one week. Condition category: normal nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: Equal listed nutrients did not produce identical blood phosphorus responses. organism: Human tissue_or_cell_type: Nine people with CKD; mean eGFR 32 mL/min experimental_model: Randomized-order crossover feeding trial limitations: Small short-term CKD study; food source/form matters, but the trial does not isolate one phytate mechanism or establish that all plant phosphate is unabsorbed. exposure: Seven-day vegetarian and meat diets with equivalent nutrients prepared by research staff evidence_span: {"source_cache": "artifacts/phosphorus-research/21183586.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c1361f250bd0c2febcef675ba888387b4f2ea0b81b171150734d8f148982a660", "start_char": 0, "end_char": 1667, "text_sha256": "c1361f250bd0c2febcef675ba888387b4f2ea0b81b171150734d8f148982a660"} [phosphorus-p21183586] Vegetarian compared with meat dietary protein source and phosphorus homeostasis in chronic kidney disease. (2011). https://pubmed.ncbi.nlm.nih.gov/21183586/ DOI: 10.2215/cjn.05040610
Complete structured claim and evidence
The vegetarian diet produced lower FGF23 than the meat diet after one week.
Vegetarian diet in the 2011 CKD crossover trial → Fibroblast growth factor 23 / FGF23 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/phosphorus-research/21183586.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c1361f250bd0c2febcef675ba888387b4f2ea0b81b171150734d8f148982a660", "start_char": 0, "end_char": 1667, "text_sha256": "c1361f250bd0c2febcef675ba888387b4f2ea0b81b171150734d8f148982a660"}
experimental_model
Randomized-order crossover feeding trial
exposure
Seven-day vegetarian and meat diets with equivalent nutrients prepared by research staff
limitations
Small short-term CKD study; food source/form matters, but the trial does not isolate one phytate mechanism or establish that all plant phosphate is unabsorbed.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Human
plain_language
The hormone response also depended on the food source.
primary_references
[phosphorus-p21183586] Vegetarian compared with meat dietary protein source and phosphorus homeostasis in chronic kidney disease. (2011). https://pubmed.ncbi.nlm.nih.gov/21183586/ DOI: 10.2215/cjn.05040610
tissue_or_cell_type
Nine people with CKD; mean eGFR 32 mL/min
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 998–1009
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized-order crossover feeding trial · source_derived_draft · unverified_draft
### phosphorus-plant-diet-fgf23 The vegetarian diet produced lower FGF23 than the meat diet after one week. Condition category: normal nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: The hormone response also depended on the food source. organism: Human tissue_or_cell_type: Nine people with CKD; mean eGFR 32 mL/min experimental_model: Randomized-order crossover feeding trial limitations: Small short-term CKD study; food source/form matters, but the trial does not isolate one phytate mechanism or establish that all plant phosphate is unabsorbed. exposure: Seven-day vegetarian and meat diets with equivalent nutrients prepared by research staff evidence_span: {"source_cache": "artifacts/phosphorus-research/21183586.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c1361f250bd0c2febcef675ba888387b4f2ea0b81b171150734d8f148982a660", "start_char": 0, "end_char": 1667, "text_sha256": "c1361f250bd0c2febcef675ba888387b4f2ea0b81b171150734d8f148982a660"} [phosphorus-p21183586] Vegetarian compared with meat dietary protein source and phosphorus homeostasis in chronic kidney disease. (2011). https://pubmed.ncbi.nlm.nih.gov/21183586/ DOI: 10.2215/cjn.05040610
Complete structured claim and evidence
Ferric carboxymaltose-associated intact-FGF23 elevation accompanied lower circulating calcitriol in the substudy.
Ferric carboxymaltose → Circulating calcitriol concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/phosphorus-research/30518682.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e1d37261355eedeff60d9715e7eb88b6718641ed868c5b3ab64fceaf62c15e6d", "start_char": 0, "end_char": 2381, "text_sha256": "e1d37261355eedeff60d9715e7eb88b6718641ed868c5b3ab64fceaf62c15e6d"}
experimental_model
Randomized iron-formulation comparison with physiological substudy
exposure
One trial course of ferric carboxymaltose or ferumoxytol; follow-up five weeks
limitations
Formulation-specific drug effect, not dietary iron. FGF23 was associated with the downstream changes; the exact reason the formulations differ was not settled.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Human
plain_language
The phosphate-wasting pattern also reduced active vitamin D.
primary_references
[phosphorus-p30518682] Randomized trial of intravenous iron-induced hypophosphatemia. (2018). https://pubmed.ncbi.nlm.nih.gov/30518682/ DOI: 10.1172/jci.insight.124486
tissue_or_cell_type
Iron-deficiency anemia; n=1997 parent trial, n=185 substudy
trigger_kind
machinery_impairment Imported condition classification; unverified.
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 1011–1022
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized iron-formulation comparison with physiological substudy · source_derived_draft · unverified_draft
### phosphorus-iron-calcitriol Ferric carboxymaltose-associated intact-FGF23 elevation accompanied lower circulating calcitriol in the substudy. Condition category: machinery_impairment nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: The phosphate-wasting pattern also reduced active vitamin D. organism: Human tissue_or_cell_type: Iron-deficiency anemia; n=1997 parent trial, n=185 substudy experimental_model: Randomized iron-formulation comparison with physiological substudy limitations: Formulation-specific drug effect, not dietary iron. FGF23 was associated with the downstream changes; the exact reason the formulations differ was not settled. exposure: One trial course of ferric carboxymaltose or ferumoxytol; follow-up five weeks evidence_span: {"source_cache": "artifacts/phosphorus-research/30518682.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e1d37261355eedeff60d9715e7eb88b6718641ed868c5b3ab64fceaf62c15e6d", "start_char": 0, "end_char": 2381, "text_sha256": "e1d37261355eedeff60d9715e7eb88b6718641ed868c5b3ab64fceaf62c15e6d"} [phosphorus-p30518682] Randomized trial of intravenous iron-induced hypophosphatemia. (2018). https://pubmed.ncbi.nlm.nih.gov/30518682/ DOI: 10.1172/jci.insight.124486
Complete structured claim and evidence
The ferric-carboxymaltose substudy found lower calcium accompanying the intact-FGF23 rise.
Ferric carboxymaltose → Serum calcium concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/phosphorus-research/30518682.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e1d37261355eedeff60d9715e7eb88b6718641ed868c5b3ab64fceaf62c15e6d", "start_char": 0, "end_char": 2381, "text_sha256": "e1d37261355eedeff60d9715e7eb88b6718641ed868c5b3ab64fceaf62c15e6d"}
experimental_model
Randomized iron-formulation comparison with physiological substudy
exposure
One trial course of ferric carboxymaltose or ferumoxytol; follow-up five weeks
limitations
Formulation-specific drug effect, not dietary iron. FGF23 was associated with the downstream changes; the exact reason the formulations differ was not settled.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Human
plain_language
Calcium regulation was affected along with phosphate.
primary_references
[phosphorus-p30518682] Randomized trial of intravenous iron-induced hypophosphatemia. (2018). https://pubmed.ncbi.nlm.nih.gov/30518682/ DOI: 10.1172/jci.insight.124486
tissue_or_cell_type
Iron-deficiency anemia; n=1997 parent trial, n=185 substudy
trigger_kind
machinery_impairment Imported condition classification; unverified.
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 1024–1035
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized iron-formulation comparison with physiological substudy · source_derived_draft · unverified_draft
### phosphorus-iron-calcium The ferric-carboxymaltose substudy found lower calcium accompanying the intact-FGF23 rise. Condition category: machinery_impairment nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: Calcium regulation was affected along with phosphate. organism: Human tissue_or_cell_type: Iron-deficiency anemia; n=1997 parent trial, n=185 substudy experimental_model: Randomized iron-formulation comparison with physiological substudy limitations: Formulation-specific drug effect, not dietary iron. FGF23 was associated with the downstream changes; the exact reason the formulations differ was not settled. exposure: One trial course of ferric carboxymaltose or ferumoxytol; follow-up five weeks evidence_span: {"source_cache": "artifacts/phosphorus-research/30518682.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e1d37261355eedeff60d9715e7eb88b6718641ed868c5b3ab64fceaf62c15e6d", "start_char": 0, "end_char": 2381, "text_sha256": "e1d37261355eedeff60d9715e7eb88b6718641ed868c5b3ab64fceaf62c15e6d"} [phosphorus-p30518682] Randomized trial of intravenous iron-induced hypophosphatemia. (2018). https://pubmed.ncbi.nlm.nih.gov/30518682/ DOI: 10.1172/jci.insight.124486
Complete structured claim and evidence
PTH increased in the ferric-carboxymaltose-associated phosphate-wasting cascade.
Ferric carboxymaltose → Serum PTH concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/phosphorus-research/30518682.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e1d37261355eedeff60d9715e7eb88b6718641ed868c5b3ab64fceaf62c15e6d", "start_char": 0, "end_char": 2381, "text_sha256": "e1d37261355eedeff60d9715e7eb88b6718641ed868c5b3ab64fceaf62c15e6d"}
experimental_model
Randomized iron-formulation comparison with physiological substudy
exposure
One trial course of ferric carboxymaltose or ferumoxytol; follow-up five weeks
limitations
Formulation-specific drug effect, not dietary iron. FGF23 was associated with the downstream changes; the exact reason the formulations differ was not settled.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Human
plain_language
The parathyroid response added another hormone affecting renal phosphate handling.
primary_references
[phosphorus-p30518682] Randomized trial of intravenous iron-induced hypophosphatemia. (2018). https://pubmed.ncbi.nlm.nih.gov/30518682/ DOI: 10.1172/jci.insight.124486
tissue_or_cell_type
Iron-deficiency anemia; n=1997 parent trial, n=185 substudy
trigger_kind
machinery_impairment Imported condition classification; unverified.
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 1037–1048
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized iron-formulation comparison with physiological substudy · source_derived_draft · unverified_draft
### phosphorus-iron-pth PTH increased in the ferric-carboxymaltose-associated phosphate-wasting cascade. Condition category: machinery_impairment nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: The parathyroid response added another hormone affecting renal phosphate handling. organism: Human tissue_or_cell_type: Iron-deficiency anemia; n=1997 parent trial, n=185 substudy experimental_model: Randomized iron-formulation comparison with physiological substudy limitations: Formulation-specific drug effect, not dietary iron. FGF23 was associated with the downstream changes; the exact reason the formulations differ was not settled. exposure: One trial course of ferric carboxymaltose or ferumoxytol; follow-up five weeks evidence_span: {"source_cache": "artifacts/phosphorus-research/30518682.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e1d37261355eedeff60d9715e7eb88b6718641ed868c5b3ab64fceaf62c15e6d", "start_char": 0, "end_char": 2381, "text_sha256": "e1d37261355eedeff60d9715e7eb88b6718641ed868c5b3ab64fceaf62c15e6d"} [phosphorus-p30518682] Randomized trial of intravenous iron-induced hypophosphatemia. (2018). https://pubmed.ncbi.nlm.nih.gov/30518682/ DOI: 10.1172/jci.insight.124486
Complete structured claim and evidence
After serum phosphorus rose from 0.55 to 1.33 mmol/L, mean stimulated transdiaphragmatic pressure increased from 9.75 to 17.25 cm H2O.
Study-specific phosphate repletion interventions → Human transdiaphragmatic pressure during phrenic-nerve stimulation source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/phosphorus-research/3860734.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "cf061281363419c0833fd3b160950e7f4c1a57ebeef46f3b73a0ad30f3b7f7e1", "start_char": 0, "end_char": 1400, "text_sha256": "cf061281363419c0833fd3b160950e7f4c1a57ebeef46f3b73a0ad30f3b7f7e1"}
experimental_model
Before/after phosphate correction with phrenic-nerve stimulation
exposure
Historical protocol: 10 mmol phosphorus as KH2PO4 infused over four hours
limitations
Small uncontrolled physiological experiment; potassium was also administered. Not a general infusion recommendation or proof of one intracellular mediator.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Human
plain_language
Correcting the low phosphate measurement accompanied stronger diaphragm contractions in these patients.
primary_references
[phosphorus-p3860734] Effect of hypophosphatemia on diaphragmatic contractility in patients with acute respiratory failure. (1985). https://pubmed.ncbi.nlm.nih.gov/3860734/ DOI: 10.1056/nejm198508153130705
tissue_or_cell_type
Eight ventilated patients with acute respiratory failure
trigger_kind
biomarker_context Imported condition classification; unverified.
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 1050–1061
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Before/after phosphate correction with phrenic-nerve stimulation · source_derived_draft · unverified_draft
### phosphorus-diaphragm-rescue After serum phosphorus rose from 0.55 to 1.33 mmol/L, mean stimulated transdiaphragmatic pressure increased from 9.75 to 17.25 cm H2O. Condition category: biomarker_context nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: Correcting the low phosphate measurement accompanied stronger diaphragm contractions in these patients. organism: Human tissue_or_cell_type: Eight ventilated patients with acute respiratory failure experimental_model: Before/after phosphate correction with phrenic-nerve stimulation limitations: Small uncontrolled physiological experiment; potassium was also administered. Not a general infusion recommendation or proof of one intracellular mediator. exposure: Historical protocol: 10 mmol phosphorus as KH2PO4 infused over four hours evidence_span: {"source_cache": "artifacts/phosphorus-research/3860734.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "cf061281363419c0833fd3b160950e7f4c1a57ebeef46f3b73a0ad30f3b7f7e1", "start_char": 0, "end_char": 1400, "text_sha256": "cf061281363419c0833fd3b160950e7f4c1a57ebeef46f3b73a0ad30f3b7f7e1"} [phosphorus-p3860734] Effect of hypophosphatemia on diaphragmatic contractility in patients with acute respiratory failure. (1985). https://pubmed.ncbi.nlm.nih.gov/3860734/ DOI: 10.1056/nejm198508153130705
Complete structured claim and evidence
No dependence of erythrocyte 2,3-DPG concentration on cellular Pi was detected in the ICU dataset.
Inorganic phosphate (Pi; protonation depends on pH) → Human erythrocyte 2,3-DPG concentration source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/phosphorus-research/4042545.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "474d2b2722565fa0e4c2f0ddf4a332715ce176f9325b9af5c22027bd6ac93e43", "start_char": 0, "end_char": 1711, "text_sha256": "474d2b2722565fa0e4c2f0ddf4a332715ce176f9325b9af5c22027bd6ac93e43"}
experimental_model
ICU erythrocyte measurements and normal-donor cell incubation
exposure
Plasma Pi 0.1–4.2 mmol/L in patients; normal-donor cells incubated at 1 or 5 mmol/L Pi
limitations
Observed ranges are not universal thresholds; ATP concentration, ATP synthetic flux and 2,3-DPG are separate endpoints.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Human
plain_language
A lower phosphate measurement did not automatically mean lower 2,3-DPG.
primary_references
[phosphorus-p4042545] Phosphate metabolism in erythrocytes of critically ill patients. (1985). https://pubmed.ncbi.nlm.nih.gov/4042545/ DOI: 10.1042/cs0690435
tissue_or_cell_type
Red blood cells
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 1076–1087
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · ICU erythrocyte measurements and normal-donor cell incubation · source_derived_draft · unverified_draft
### phosphorus-rbc-dpg-null No dependence of erythrocyte 2,3-DPG concentration on cellular Pi was detected in the ICU dataset. Condition category: normal nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: A lower phosphate measurement did not automatically mean lower 2,3-DPG. organism: Human tissue_or_cell_type: Red blood cells experimental_model: ICU erythrocyte measurements and normal-donor cell incubation limitations: Observed ranges are not universal thresholds; ATP concentration, ATP synthetic flux and 2,3-DPG are separate endpoints. exposure: Plasma Pi 0.1–4.2 mmol/L in patients; normal-donor cells incubated at 1 or 5 mmol/L Pi evidence_span: {"source_cache": "artifacts/phosphorus-research/4042545.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "474d2b2722565fa0e4c2f0ddf4a332715ce176f9325b9af5c22027bd6ac93e43", "start_char": 0, "end_char": 1711, "text_sha256": "474d2b2722565fa0e4c2f0ddf4a332715ce176f9325b9af5c22027bd6ac93e43"} [phosphorus-p4042545] Phosphate metabolism in erythrocytes of critically ill patients. (1985). https://pubmed.ncbi.nlm.nih.gov/4042545/ DOI: 10.1042/cs0690435
Complete structured claim and evidence
Raising incubation Pi from 1 to 5 mmol/L increased normal-donor erythrocyte lactate production from 2.09 to 3.11 mmol/hour/L cells.
Inorganic phosphate (Pi; protonation depends on pH) → Human erythrocyte lactate production rate source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/phosphorus-research/4042545.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "474d2b2722565fa0e4c2f0ddf4a332715ce176f9325b9af5c22027bd6ac93e43", "start_char": 0, "end_char": 1711, "text_sha256": "474d2b2722565fa0e4c2f0ddf4a332715ce176f9325b9af5c22027bd6ac93e43"}
experimental_model
ICU erythrocyte measurements and normal-donor cell incubation
exposure
Plasma Pi 0.1–4.2 mmol/L in patients; normal-donor cells incubated at 1 or 5 mmol/L Pi
limitations
Observed ranges are not universal thresholds; ATP concentration, ATP synthetic flux and 2,3-DPG are separate endpoints.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Human
plain_language
More phosphate accelerated the measured glycolytic output in this cell preparation.
primary_references
[phosphorus-p4042545] Phosphate metabolism in erythrocytes of critically ill patients. (1985). https://pubmed.ncbi.nlm.nih.gov/4042545/ DOI: 10.1042/cs0690435
tissue_or_cell_type
Red blood cells
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 1089–1100
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · ICU erythrocyte measurements and normal-donor cell incubation · source_derived_draft · unverified_draft
### phosphorus-rbc-lactate Raising incubation Pi from 1 to 5 mmol/L increased normal-donor erythrocyte lactate production from 2.09 to 3.11 mmol/hour/L cells. Condition category: normal nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: More phosphate accelerated the measured glycolytic output in this cell preparation. organism: Human tissue_or_cell_type: Red blood cells experimental_model: ICU erythrocyte measurements and normal-donor cell incubation limitations: Observed ranges are not universal thresholds; ATP concentration, ATP synthetic flux and 2,3-DPG are separate endpoints. exposure: Plasma Pi 0.1–4.2 mmol/L in patients; normal-donor cells incubated at 1 or 5 mmol/L Pi evidence_span: {"source_cache": "artifacts/phosphorus-research/4042545.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "474d2b2722565fa0e4c2f0ddf4a332715ce176f9325b9af5c22027bd6ac93e43", "start_char": 0, "end_char": 1711, "text_sha256": "474d2b2722565fa0e4c2f0ddf4a332715ce176f9325b9af5c22027bd6ac93e43"} [phosphorus-p4042545] Phosphate metabolism in erythrocytes of critically ill patients. (1985). https://pubmed.ncbi.nlm.nih.gov/4042545/ DOI: 10.1042/cs0690435
Complete structured claim and evidence
The 1-versus-5 mmol/L Pi incubation changed erythrocyte glycolytic output without a significant ATP-concentration change.
Inorganic phosphate (Pi; protonation depends on pH) → Human erythrocyte ATP concentration source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/phosphorus-research/4042545.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "474d2b2722565fa0e4c2f0ddf4a332715ce176f9325b9af5c22027bd6ac93e43", "start_char": 0, "end_char": 1711, "text_sha256": "474d2b2722565fa0e4c2f0ddf4a332715ce176f9325b9af5c22027bd6ac93e43"}
experimental_model
ICU erythrocyte measurements and normal-donor cell incubation
exposure
Plasma Pi 0.1–4.2 mmol/L in patients; normal-donor cells incubated at 1 or 5 mmol/L Pi
limitations
Observed ranges are not universal thresholds; ATP concentration, ATP synthetic flux and 2,3-DPG are separate endpoints.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Human
plain_language
A faster flux did not necessarily make the ATP pool larger.
primary_references
[phosphorus-p4042545] Phosphate metabolism in erythrocytes of critically ill patients. (1985). https://pubmed.ncbi.nlm.nih.gov/4042545/ DOI: 10.1042/cs0690435
tissue_or_cell_type
Red blood cells
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 1102–1113
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · ICU erythrocyte measurements and normal-donor cell incubation · source_derived_draft · unverified_draft
### phosphorus-rbc-atp-buffered The 1-versus-5 mmol/L Pi incubation changed erythrocyte glycolytic output without a significant ATP-concentration change. Condition category: normal nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: A faster flux did not necessarily make the ATP pool larger. organism: Human tissue_or_cell_type: Red blood cells experimental_model: ICU erythrocyte measurements and normal-donor cell incubation limitations: Observed ranges are not universal thresholds; ATP concentration, ATP synthetic flux and 2,3-DPG are separate endpoints. exposure: Plasma Pi 0.1–4.2 mmol/L in patients; normal-donor cells incubated at 1 or 5 mmol/L Pi evidence_span: {"source_cache": "artifacts/phosphorus-research/4042545.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "474d2b2722565fa0e4c2f0ddf4a332715ce176f9325b9af5c22027bd6ac93e43", "start_char": 0, "end_char": 1711, "text_sha256": "474d2b2722565fa0e4c2f0ddf4a332715ce176f9325b9af5c22027bd6ac93e43"} [phosphorus-p4042545] Phosphate metabolism in erythrocytes of critically ill patients. (1985). https://pubmed.ncbi.nlm.nih.gov/4042545/ DOI: 10.1042/cs0690435
Complete structured claim and evidence
Serum phosphate fell after surgery and during glucose infusion, particularly with continuous glucose administration.
Postoperative glucose-infusion regimens in the 1989 study → Serum inorganic phosphate concentration source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/phosphorus-research/2741619.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "62051650a8db9312feacd99776a0a1bc2b55587b371ede554ae61fbdf335de30", "start_char": 0, "end_char": 1180, "text_sha256": "62051650a8db9312feacd99776a0a1bc2b55587b371ede554ae61fbdf335de30"}
experimental_model
Randomized postoperative glucose-infusion timing study
exposure
Equal daily glucose supplied continuously versus in five-hour infusions
limitations
Acute redistribution and postoperative hypophosphatemia are not synonymous with severe whole-body phosphate depletion.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Human
plain_language
A glucose load can lower the blood phosphate measurement in this clinical context.
primary_references
[phosphorus-p2741619] Postoperative and glucose-induced hypophosphatemia in relation to adenosine triphosphate and 2,3-diphosphoglycerate in erythrocytes. (1989). https://pubmed.ncbi.nlm.nih.gov/2741619/
tissue_or_cell_type
Patients after elective colonic surgery; serum and red cells
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 1115–1126
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized postoperative glucose-infusion timing study · source_derived_draft · unverified_draft
### phosphorus-glucose-pi Serum phosphate fell after surgery and during glucose infusion, particularly with continuous glucose administration. Condition category: normal nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: A glucose load can lower the blood phosphate measurement in this clinical context. organism: Human tissue_or_cell_type: Patients after elective colonic surgery; serum and red cells experimental_model: Randomized postoperative glucose-infusion timing study limitations: Acute redistribution and postoperative hypophosphatemia are not synonymous with severe whole-body phosphate depletion. exposure: Equal daily glucose supplied continuously versus in five-hour infusions evidence_span: {"source_cache": "artifacts/phosphorus-research/2741619.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "62051650a8db9312feacd99776a0a1bc2b55587b371ede554ae61fbdf335de30", "start_char": 0, "end_char": 1180, "text_sha256": "62051650a8db9312feacd99776a0a1bc2b55587b371ede554ae61fbdf335de30"} [phosphorus-p2741619] Postoperative and glucose-induced hypophosphatemia in relation to adenosine triphosphate and 2,3-diphosphoglycerate in erythrocytes. (1989). https://pubmed.ncbi.nlm.nih.gov/2741619/
Complete structured claim and evidence
The postoperative and glucose-associated serum phosphate reductions were not accompanied by reduced red-cell ATP.
Postoperative glucose-infusion regimens in the 1989 study → Human erythrocyte ATP concentration source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/phosphorus-research/2741619.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "62051650a8db9312feacd99776a0a1bc2b55587b371ede554ae61fbdf335de30", "start_char": 0, "end_char": 1180, "text_sha256": "62051650a8db9312feacd99776a0a1bc2b55587b371ede554ae61fbdf335de30"}
experimental_model
Randomized postoperative glucose-infusion timing study
exposure
Equal daily glucose supplied continuously versus in five-hour infusions
limitations
Acute redistribution and postoperative hypophosphatemia are not synonymous with severe whole-body phosphate depletion.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Human
plain_language
Blood phosphate fell while the measured red-cell ATP pool remained preserved.
primary_references
[phosphorus-p2741619] Postoperative and glucose-induced hypophosphatemia in relation to adenosine triphosphate and 2,3-diphosphoglycerate in erythrocytes. (1989). https://pubmed.ncbi.nlm.nih.gov/2741619/
tissue_or_cell_type
Patients after elective colonic surgery; serum and red cells
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 1128–1139
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized postoperative glucose-infusion timing study · source_derived_draft · unverified_draft
### phosphorus-glucose-atp-null The postoperative and glucose-associated serum phosphate reductions were not accompanied by reduced red-cell ATP. Condition category: normal nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: Blood phosphate fell while the measured red-cell ATP pool remained preserved. organism: Human tissue_or_cell_type: Patients after elective colonic surgery; serum and red cells experimental_model: Randomized postoperative glucose-infusion timing study limitations: Acute redistribution and postoperative hypophosphatemia are not synonymous with severe whole-body phosphate depletion. exposure: Equal daily glucose supplied continuously versus in five-hour infusions evidence_span: {"source_cache": "artifacts/phosphorus-research/2741619.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "62051650a8db9312feacd99776a0a1bc2b55587b371ede554ae61fbdf335de30", "start_char": 0, "end_char": 1180, "text_sha256": "62051650a8db9312feacd99776a0a1bc2b55587b371ede554ae61fbdf335de30"} [phosphorus-p2741619] Postoperative and glucose-induced hypophosphatemia in relation to adenosine triphosphate and 2,3-diphosphoglycerate in erythrocytes. (1989). https://pubmed.ncbi.nlm.nih.gov/2741619/
Complete structured claim and evidence
The serum phosphate reductions were not accompanied by reduced red-cell 2,3-DPG.
Postoperative glucose-infusion regimens in the 1989 study → Human erythrocyte 2,3-DPG concentration source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/phosphorus-research/2741619.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "62051650a8db9312feacd99776a0a1bc2b55587b371ede554ae61fbdf335de30", "start_char": 0, "end_char": 1180, "text_sha256": "62051650a8db9312feacd99776a0a1bc2b55587b371ede554ae61fbdf335de30"}
experimental_model
Randomized postoperative glucose-infusion timing study
exposure
Equal daily glucose supplied continuously versus in five-hour infusions
limitations
Acute redistribution and postoperative hypophosphatemia are not synonymous with severe whole-body phosphate depletion.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Human
plain_language
The oxygen-affinity regulator did not automatically fall with serum phosphate.
primary_references
[phosphorus-p2741619] Postoperative and glucose-induced hypophosphatemia in relation to adenosine triphosphate and 2,3-diphosphoglycerate in erythrocytes. (1989). https://pubmed.ncbi.nlm.nih.gov/2741619/
tissue_or_cell_type
Patients after elective colonic surgery; serum and red cells
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 1141–1152
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized postoperative glucose-infusion timing study · source_derived_draft · unverified_draft
### phosphorus-glucose-dpg-null The serum phosphate reductions were not accompanied by reduced red-cell 2,3-DPG. Condition category: normal nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: The oxygen-affinity regulator did not automatically fall with serum phosphate. organism: Human tissue_or_cell_type: Patients after elective colonic surgery; serum and red cells experimental_model: Randomized postoperative glucose-infusion timing study limitations: Acute redistribution and postoperative hypophosphatemia are not synonymous with severe whole-body phosphate depletion. exposure: Equal daily glucose supplied continuously versus in five-hour infusions evidence_span: {"source_cache": "artifacts/phosphorus-research/2741619.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "62051650a8db9312feacd99776a0a1bc2b55587b371ede554ae61fbdf335de30", "start_char": 0, "end_char": 1180, "text_sha256": "62051650a8db9312feacd99776a0a1bc2b55587b371ede554ae61fbdf335de30"} [phosphorus-p2741619] Postoperative and glucose-induced hypophosphatemia in relation to adenosine triphosphate and 2,3-diphosphoglycerate in erythrocytes. (1989). https://pubmed.ncbi.nlm.nih.gov/2741619/
Complete structured claim and evidence
Days alive after ICU discharge did not differ significantly: 44.8 versus 39.9 days, estimated difference 4.9 days (95% CI −2.3 to 13.6), p=0.19.
Protocolized caloric restriction during ICU refeeding-syndrome management → Days alive after ICU discharge over 60 days in the refeeding trial source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/phosphorus-research/26597128.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0324ddb02d92a61886682e682350e42356a4596c93e3ff60d23860163c6c1aa6", "start_char": 0, "end_char": 2574, "text_sha256": "0324ddb02d92a61886682e682350e42356a4596c93e3ff60d23860163c6c1aa6"}
experimental_model
Multicenter randomized clinical management trial
exposure
Protocolized caloric restriction versus continued standard feeding during electrolyte replacement; 60-day follow-up
limitations
Management-strategy trial, not isolated phosphate supplementation. Primary composite endpoint was nonsignificant; component results must retain that context.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Human
plain_language
The trial’s primary composite outcome was not statistically significant.
primary_references
[phosphorus-p26597128] Restricted versus continued standard caloric intake during the management of refeeding syndrome in critically ill adults: a randomised, parallel-group, multicentre, single-blind controlled trial. (2015). https://pubmed.ncbi.nlm.nih.gov/26597128/ DOI: 10.1016/s2213-2600(15)00418-x
tissue_or_cell_type
339 critically ill adults developing refeeding syndrome within 72 hours of nutrition
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 1154–1165
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Multicenter randomized clinical management trial · source_derived_draft · unverified_draft
### phosphorus-refeeding-primary Days alive after ICU discharge did not differ significantly: 44.8 versus 39.9 days, estimated difference 4.9 days (95% CI −2.3 to 13.6), p=0.19. Condition category: normal nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: The trial’s primary composite outcome was not statistically significant. organism: Human tissue_or_cell_type: 339 critically ill adults developing refeeding syndrome within 72 hours of nutrition experimental_model: Multicenter randomized clinical management trial limitations: Management-strategy trial, not isolated phosphate supplementation. Primary composite endpoint was nonsignificant; component results must retain that context. exposure: Protocolized caloric restriction versus continued standard feeding during electrolyte replacement; 60-day follow-up evidence_span: {"source_cache": "artifacts/phosphorus-research/26597128.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0324ddb02d92a61886682e682350e42356a4596c93e3ff60d23860163c6c1aa6", "start_char": 0, "end_char": 2574, "text_sha256": "0324ddb02d92a61886682e682350e42356a4596c93e3ff60d23860163c6c1aa6"} [phosphorus-p26597128] Restricted versus continued standard caloric intake during the management of refeeding syndrome in critically ill adults: a randomised, parallel-group, multicentre, single-blind controlled trial. (2015). https://pubmed.ncbi.nlm.nih.gov/26597128/ DOI: 10.1016/s2213-2600(15)00418-x
Complete structured claim and evidence
A component analysis found 149/164 participants alive at day 60 with restriction versus 128/163 with standard feeding, p=0.002.
Protocolized caloric restriction during ICU refeeding-syndrome management → Day-60 survival in the ICU refeeding trial source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/phosphorus-research/26597128.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0324ddb02d92a61886682e682350e42356a4596c93e3ff60d23860163c6c1aa6", "start_char": 0, "end_char": 2574, "text_sha256": "0324ddb02d92a61886682e682350e42356a4596c93e3ff60d23860163c6c1aa6"}
experimental_model
Multicenter randomized clinical management trial
exposure
Protocolized caloric restriction versus continued standard feeding during electrolyte replacement; 60-day follow-up
limitations
Management-strategy trial, not isolated phosphate supplementation. Primary composite endpoint was nonsignificant; component results must retain that context.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Human
plain_language
The survival component favored the supervised strategy, while the primary composite remained nonsignificant.
primary_references
[phosphorus-p26597128] Restricted versus continued standard caloric intake during the management of refeeding syndrome in critically ill adults: a randomised, parallel-group, multicentre, single-blind controlled trial. (2015). https://pubmed.ncbi.nlm.nih.gov/26597128/ DOI: 10.1016/s2213-2600(15)00418-x
tissue_or_cell_type
339 critically ill adults developing refeeding syndrome within 72 hours of nutrition
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 1167–1178
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Multicenter randomized clinical management trial · source_derived_draft · unverified_draft
### phosphorus-refeeding-survival A component analysis found 149/164 participants alive at day 60 with restriction versus 128/163 with standard feeding, p=0.002. Condition category: normal nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: The survival component favored the supervised strategy, while the primary composite remained nonsignificant. organism: Human tissue_or_cell_type: 339 critically ill adults developing refeeding syndrome within 72 hours of nutrition experimental_model: Multicenter randomized clinical management trial limitations: Management-strategy trial, not isolated phosphate supplementation. Primary composite endpoint was nonsignificant; component results must retain that context. exposure: Protocolized caloric restriction versus continued standard feeding during electrolyte replacement; 60-day follow-up evidence_span: {"source_cache": "artifacts/phosphorus-research/26597128.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0324ddb02d92a61886682e682350e42356a4596c93e3ff60d23860163c6c1aa6", "start_char": 0, "end_char": 2574, "text_sha256": "0324ddb02d92a61886682e682350e42356a4596c93e3ff60d23860163c6c1aa6"} [phosphorus-p26597128] Restricted versus continued standard caloric intake during the management of refeeding syndrome in critically ill adults: a randomised, parallel-group, multicentre, single-blind controlled trial. (2015). https://pubmed.ncbi.nlm.nih.gov/26597128/ DOI: 10.1016/s2213-2600(15)00418-x
Complete structured claim and evidence
Burosumab binds and inhibits FGF23, the phosphate-wasting hormone targeted in the XLH trial.
Burosumab anti-FGF23 antibody → Fibroblast growth factor 23 / FGF23 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/phosphorus-research/29947083.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c1b305f00a7b9a569ccd197728d942ebbf55f9eaa164a95086d69a34608d3c4e", "start_char": 0, "end_char": 2327, "text_sha256": "c1b305f00a7b9a569ccd197728d942ebbf55f9eaa164a95086d69a34608d3c4e"}
experimental_model
Randomized double-blind placebo-controlled phase 3 trial
exposure
Burosumab 1 mg/kg or placebo every four weeks; week-24 analysis
limitations
FGF23-mediated inherited disease, not simple nutritional deficiency. Pain and function outcomes require multiplicity-adjusted interpretation.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Human
plain_language
The treatment targets the hormone driving phosphate loss, rather than only adding phosphate.
primary_references
[phosphorus-p29947083] A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial Evaluating the Efficacy of Burosumab, an Anti-FGF23 Antibody, in Adults With X-Linked Hypophosphatemia: Week 24 Primary Analysis. (2018). https://pubmed.ncbi.nlm.nih.gov/29947083/ DOI: 10.1002/jbmr.3475
tissue_or_cell_type
134 symptomatic adults with X-linked hypophosphatemia
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 1180–1191
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized double-blind placebo-controlled phase 3 trial · source_derived_draft · unverified_draft
### phosphorus-burosumab-target Burosumab binds and inhibits FGF23, the phosphate-wasting hormone targeted in the XLH trial. Condition category: normal nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: The treatment targets the hormone driving phosphate loss, rather than only adding phosphate. organism: Human tissue_or_cell_type: 134 symptomatic adults with X-linked hypophosphatemia experimental_model: Randomized double-blind placebo-controlled phase 3 trial limitations: FGF23-mediated inherited disease, not simple nutritional deficiency. Pain and function outcomes require multiplicity-adjusted interpretation. exposure: Burosumab 1 mg/kg or placebo every four weeks; week-24 analysis evidence_span: {"source_cache": "artifacts/phosphorus-research/29947083.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c1b305f00a7b9a569ccd197728d942ebbf55f9eaa164a95086d69a34608d3c4e", "start_char": 0, "end_char": 2327, "text_sha256": "c1b305f00a7b9a569ccd197728d942ebbf55f9eaa164a95086d69a34608d3c4e"} [phosphorus-p29947083] A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial Evaluating the Efficacy of Burosumab, an Anti-FGF23 Antibody, in Adults With X-Linked Hypophosphatemia: Week 24 Primary Analysis. (2018). https://pubmed.ncbi.nlm.nih.gov/29947083/ DOI: 10.1002/jbmr.3475
Complete structured claim and evidence
Across dosing-interval midpoints, 94.1% on burosumab versus 7.6% on placebo attained mean serum phosphate above the lower limit of normal.
Burosumab anti-FGF23 antibody → Serum inorganic phosphate concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/phosphorus-research/29947083.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c1b305f00a7b9a569ccd197728d942ebbf55f9eaa164a95086d69a34608d3c4e", "start_char": 0, "end_char": 2327, "text_sha256": "c1b305f00a7b9a569ccd197728d942ebbf55f9eaa164a95086d69a34608d3c4e"}
experimental_model
Randomized double-blind placebo-controlled phase 3 trial
exposure
Burosumab 1 mg/kg or placebo every four weeks; week-24 analysis
limitations
FGF23-mediated inherited disease, not simple nutritional deficiency. Pain and function outcomes require multiplicity-adjusted interpretation.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Human
plain_language
Blocking the wasting signal substantially improved the phosphate measurement.
primary_references
[phosphorus-p29947083] A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial Evaluating the Efficacy of Burosumab, an Anti-FGF23 Antibody, in Adults With X-Linked Hypophosphatemia: Week 24 Primary Analysis. (2018). https://pubmed.ncbi.nlm.nih.gov/29947083/ DOI: 10.1002/jbmr.3475
tissue_or_cell_type
134 symptomatic adults with X-linked hypophosphatemia
trigger_kind
machinery_impairment Imported condition classification; unverified.
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 1193–1204
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized double-blind placebo-controlled phase 3 trial · source_derived_draft · unverified_draft
### phosphorus-burosumab-phosphate Across dosing-interval midpoints, 94.1% on burosumab versus 7.6% on placebo attained mean serum phosphate above the lower limit of normal. Condition category: machinery_impairment nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: Blocking the wasting signal substantially improved the phosphate measurement. organism: Human tissue_or_cell_type: 134 symptomatic adults with X-linked hypophosphatemia experimental_model: Randomized double-blind placebo-controlled phase 3 trial limitations: FGF23-mediated inherited disease, not simple nutritional deficiency. Pain and function outcomes require multiplicity-adjusted interpretation. exposure: Burosumab 1 mg/kg or placebo every four weeks; week-24 analysis evidence_span: {"source_cache": "artifacts/phosphorus-research/29947083.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c1b305f00a7b9a569ccd197728d942ebbf55f9eaa164a95086d69a34608d3c4e", "start_char": 0, "end_char": 2327, "text_sha256": "c1b305f00a7b9a569ccd197728d942ebbf55f9eaa164a95086d69a34608d3c4e"} [phosphorus-p29947083] A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial Evaluating the Efficacy of Burosumab, an Anti-FGF23 Antibody, in Adults With X-Linked Hypophosphatemia: Week 24 Primary Analysis. (2018). https://pubmed.ncbi.nlm.nih.gov/29947083/ DOI: 10.1002/jbmr.3475
Complete structured claim and evidence
At week 24, 43.1% of baseline active fractures were fully healed with burosumab versus 7.7% with placebo.
Burosumab anti-FGF23 antibody → Active fracture/pseudofracture healing in adults with XLH source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/phosphorus-research/29947083.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c1b305f00a7b9a569ccd197728d942ebbf55f9eaa164a95086d69a34608d3c4e", "start_char": 0, "end_char": 2327, "text_sha256": "c1b305f00a7b9a569ccd197728d942ebbf55f9eaa164a95086d69a34608d3c4e"}
experimental_model
Randomized double-blind placebo-controlled phase 3 trial
exposure
Burosumab 1 mg/kg or placebo every four weeks; week-24 analysis
limitations
FGF23-mediated inherited disease, not simple nutritional deficiency. Pain and function outcomes require multiplicity-adjusted interpretation.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Human
plain_language
The trial also showed a tissue-level healing benefit.
primary_references
[phosphorus-p29947083] A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial Evaluating the Efficacy of Burosumab, an Anti-FGF23 Antibody, in Adults With X-Linked Hypophosphatemia: Week 24 Primary Analysis. (2018). https://pubmed.ncbi.nlm.nih.gov/29947083/ DOI: 10.1002/jbmr.3475
tissue_or_cell_type
134 symptomatic adults with X-linked hypophosphatemia
trigger_kind
machinery_impairment Imported condition classification; unverified.
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 1206–1217
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized double-blind placebo-controlled phase 3 trial · source_derived_draft · unverified_draft
### phosphorus-burosumab-fractures At week 24, 43.1% of baseline active fractures were fully healed with burosumab versus 7.7% with placebo. Condition category: machinery_impairment nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: The trial also showed a tissue-level healing benefit. organism: Human tissue_or_cell_type: 134 symptomatic adults with X-linked hypophosphatemia experimental_model: Randomized double-blind placebo-controlled phase 3 trial limitations: FGF23-mediated inherited disease, not simple nutritional deficiency. Pain and function outcomes require multiplicity-adjusted interpretation. exposure: Burosumab 1 mg/kg or placebo every four weeks; week-24 analysis evidence_span: {"source_cache": "artifacts/phosphorus-research/29947083.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c1b305f00a7b9a569ccd197728d942ebbf55f9eaa164a95086d69a34608d3c4e", "start_char": 0, "end_char": 2327, "text_sha256": "c1b305f00a7b9a569ccd197728d942ebbf55f9eaa164a95086d69a34608d3c4e"} [phosphorus-p29947083] A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial Evaluating the Efficacy of Burosumab, an Anti-FGF23 Antibody, in Adults With X-Linked Hypophosphatemia: Week 24 Primary Analysis. (2018). https://pubmed.ncbi.nlm.nih.gov/29947083/ DOI: 10.1002/jbmr.3475
Complete structured claim and evidence
The WOMAC stiffness endpoint significantly improved versus placebo in the week-24 analysis.
Burosumab anti-FGF23 antibody → WOMAC stiffness score in adults with XLH source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/phosphorus-research/29947083.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c1b305f00a7b9a569ccd197728d942ebbf55f9eaa164a95086d69a34608d3c4e", "start_char": 0, "end_char": 2327, "text_sha256": "c1b305f00a7b9a569ccd197728d942ebbf55f9eaa164a95086d69a34608d3c4e"}
experimental_model
Randomized double-blind placebo-controlled phase 3 trial
exposure
Burosumab 1 mg/kg or placebo every four weeks; week-24 analysis
limitations
FGF23-mediated inherited disease, not simple nutritional deficiency. Pain and function outcomes require multiplicity-adjusted interpretation.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Human
plain_language
Stiffness improved in the treated XLH group.
primary_references
[phosphorus-p29947083] A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial Evaluating the Efficacy of Burosumab, an Anti-FGF23 Antibody, in Adults With X-Linked Hypophosphatemia: Week 24 Primary Analysis. (2018). https://pubmed.ncbi.nlm.nih.gov/29947083/ DOI: 10.1002/jbmr.3475
tissue_or_cell_type
134 symptomatic adults with X-linked hypophosphatemia
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 1219–1230
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized double-blind placebo-controlled phase 3 trial · source_derived_draft · unverified_draft
### phosphorus-burosumab-stiffness The WOMAC stiffness endpoint significantly improved versus placebo in the week-24 analysis. Condition category: normal nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: Stiffness improved in the treated XLH group. organism: Human tissue_or_cell_type: 134 symptomatic adults with X-linked hypophosphatemia experimental_model: Randomized double-blind placebo-controlled phase 3 trial limitations: FGF23-mediated inherited disease, not simple nutritional deficiency. Pain and function outcomes require multiplicity-adjusted interpretation. exposure: Burosumab 1 mg/kg or placebo every four weeks; week-24 analysis evidence_span: {"source_cache": "artifacts/phosphorus-research/29947083.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c1b305f00a7b9a569ccd197728d942ebbf55f9eaa164a95086d69a34608d3c4e", "start_char": 0, "end_char": 2327, "text_sha256": "c1b305f00a7b9a569ccd197728d942ebbf55f9eaa164a95086d69a34608d3c4e"} [phosphorus-p29947083] A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial Evaluating the Efficacy of Burosumab, an Anti-FGF23 Antibody, in Adults With X-Linked Hypophosphatemia: Week 24 Primary Analysis. (2018). https://pubmed.ncbi.nlm.nih.gov/29947083/ DOI: 10.1002/jbmr.3475
Complete structured claim and evidence
Worst pain and physical function did not achieve significance after the trial’s multiplicity adjustment.
Burosumab anti-FGF23 antibody → Brief Pain Inventory worst-pain score in adults with XLH source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/phosphorus-research/29947083.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c1b305f00a7b9a569ccd197728d942ebbf55f9eaa164a95086d69a34608d3c4e", "start_char": 0, "end_char": 2327, "text_sha256": "c1b305f00a7b9a569ccd197728d942ebbf55f9eaa164a95086d69a34608d3c4e"}
experimental_model
Randomized double-blind placebo-controlled phase 3 trial
exposure
Burosumab 1 mg/kg or placebo every four weeks; week-24 analysis
limitations
FGF23-mediated inherited disease, not simple nutritional deficiency. Pain and function outcomes require multiplicity-adjusted interpretation.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Human
plain_language
Not every symptom endpoint showed a reliable benefit.
primary_references
[phosphorus-p29947083] A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial Evaluating the Efficacy of Burosumab, an Anti-FGF23 Antibody, in Adults With X-Linked Hypophosphatemia: Week 24 Primary Analysis. (2018). https://pubmed.ncbi.nlm.nih.gov/29947083/ DOI: 10.1002/jbmr.3475
tissue_or_cell_type
134 symptomatic adults with X-linked hypophosphatemia
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 1232–1243
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized double-blind placebo-controlled phase 3 trial · source_derived_draft · unverified_draft
### phosphorus-burosumab-pain-null Worst pain and physical function did not achieve significance after the trial’s multiplicity adjustment. Condition category: normal nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: Not every symptom endpoint showed a reliable benefit. organism: Human tissue_or_cell_type: 134 symptomatic adults with X-linked hypophosphatemia experimental_model: Randomized double-blind placebo-controlled phase 3 trial limitations: FGF23-mediated inherited disease, not simple nutritional deficiency. Pain and function outcomes require multiplicity-adjusted interpretation. exposure: Burosumab 1 mg/kg or placebo every four weeks; week-24 analysis evidence_span: {"source_cache": "artifacts/phosphorus-research/29947083.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c1b305f00a7b9a569ccd197728d942ebbf55f9eaa164a95086d69a34608d3c4e", "start_char": 0, "end_char": 2327, "text_sha256": "c1b305f00a7b9a569ccd197728d942ebbf55f9eaa164a95086d69a34608d3c4e"} [phosphorus-p29947083] A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial Evaluating the Efficacy of Burosumab, an Anti-FGF23 Antibody, in Adults With X-Linked Hypophosphatemia: Week 24 Primary Analysis. (2018). https://pubmed.ncbi.nlm.nih.gov/29947083/ DOI: 10.1002/jbmr.3475
Complete structured claim and evidence
Higher reported phosphate intake was associated with lower resting ATP synthesis (r=−0.62, p=0.03) in the 13-person pilot.
Dietary phosphate intake normalized to total energy intake → Human skeletal-muscle ATP synthetic flux by 31P-MRS source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/phosphorus-research/38482570.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "11f6599b477ce87228e00e4d562eb0c70615dceebb82a983188e9b0fcd8e730f", "start_char": 0, "end_char": 2164, "text_sha256": "11f6599b477ce87228e00e4d562eb0c70615dceebb82a983188e9b0fcd8e730f"}
experimental_model
Small cross-sectional diet-recall and 31P-MRS association study
exposure
24-hour dietary recall normalized to energy; calf-muscle MRS at rest/exercise
limitations
Observational pilot with n=13, not a controlled excess-phosphate intervention. The source uses a phosphocreatinine wording error; PCr is represented as phosphocreatine.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Human
plain_language
More reported dietary phosphorus did not imply better energetics; this association does not establish causation.
primary_references
[phosphorus-p38482570] Association between dietary phosphate intake and skeletal muscle energetics in adults without cardiovascular disease. (2024). https://pubmed.ncbi.nlm.nih.gov/38482570/ DOI: 10.1152/japplphysiol.00818.2023
tissue_or_cell_type
Thirteen adults without cardiopulmonary disease
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 1245–1256
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Small cross-sectional diet-recall and 31P-MRS association study · source_derived_draft · unverified_draft
### phosphorus-high-intake-atp-association Higher reported phosphate intake was associated with lower resting ATP synthesis (r=−0.62, p=0.03) in the 13-person pilot. Condition category: normal nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: More reported dietary phosphorus did not imply better energetics; this association does not establish causation. organism: Human tissue_or_cell_type: Thirteen adults without cardiopulmonary disease experimental_model: Small cross-sectional diet-recall and 31P-MRS association study limitations: Observational pilot with n=13, not a controlled excess-phosphate intervention. The source uses a phosphocreatinine wording error; PCr is represented as phosphocreatine. exposure: 24-hour dietary recall normalized to energy; calf-muscle MRS at rest/exercise evidence_span: {"source_cache": "artifacts/phosphorus-research/38482570.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "11f6599b477ce87228e00e4d562eb0c70615dceebb82a983188e9b0fcd8e730f", "start_char": 0, "end_char": 2164, "text_sha256": "11f6599b477ce87228e00e4d562eb0c70615dceebb82a983188e9b0fcd8e730f"} [phosphorus-p38482570] Association between dietary phosphate intake and skeletal muscle energetics in adults without cardiovascular disease. (2024). https://pubmed.ncbi.nlm.nih.gov/38482570/ DOI: 10.1152/japplphysiol.00818.2023
Complete structured claim and evidence
Higher reported phosphate intake was associated with greater exercise-related phosphocreatine depletion in the pilot.
Dietary phosphate intake normalized to total energy intake → Human muscle phosphocreatine depletion during exercise source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/phosphorus-research/38482570.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "11f6599b477ce87228e00e4d562eb0c70615dceebb82a983188e9b0fcd8e730f", "start_char": 0, "end_char": 2164, "text_sha256": "11f6599b477ce87228e00e4d562eb0c70615dceebb82a983188e9b0fcd8e730f"}
experimental_model
Small cross-sectional diet-recall and 31P-MRS association study
exposure
24-hour dietary recall normalized to energy; calf-muscle MRS at rest/exercise
limitations
Observational pilot with n=13, not a controlled excess-phosphate intervention. The source uses a phosphocreatinine wording error; PCr is represented as phosphocreatine.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Human
plain_language
The phosphocreatine response also differed with reported intake.
primary_references
[phosphorus-p38482570] Association between dietary phosphate intake and skeletal muscle energetics in adults without cardiovascular disease. (2024). https://pubmed.ncbi.nlm.nih.gov/38482570/ DOI: 10.1152/japplphysiol.00818.2023
tissue_or_cell_type
Thirteen adults without cardiopulmonary disease
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 1258–1269
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Small cross-sectional diet-recall and 31P-MRS association study · source_derived_draft · unverified_draft
### phosphorus-high-intake-pcr Higher reported phosphate intake was associated with greater exercise-related phosphocreatine depletion in the pilot. Condition category: normal nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: The phosphocreatine response also differed with reported intake. organism: Human tissue_or_cell_type: Thirteen adults without cardiopulmonary disease experimental_model: Small cross-sectional diet-recall and 31P-MRS association study limitations: Observational pilot with n=13, not a controlled excess-phosphate intervention. The source uses a phosphocreatinine wording error; PCr is represented as phosphocreatine. exposure: 24-hour dietary recall normalized to energy; calf-muscle MRS at rest/exercise evidence_span: {"source_cache": "artifacts/phosphorus-research/38482570.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "11f6599b477ce87228e00e4d562eb0c70615dceebb82a983188e9b0fcd8e730f", "start_char": 0, "end_char": 2164, "text_sha256": "11f6599b477ce87228e00e4d562eb0c70615dceebb82a983188e9b0fcd8e730f"} [phosphorus-p38482570] Association between dietary phosphate intake and skeletal muscle energetics in adults without cardiovascular disease. (2024). https://pubmed.ncbi.nlm.nih.gov/38482570/ DOI: 10.1152/japplphysiol.00818.2023
Complete structured claim and evidence
SLC34A3 mutations segregated with renal phosphate wasting and hypophosphatemic rickets in the studied families.
Sodium-phosphate cotransporter NaPi-IIc / SLC34A3 → Renal phosphate reabsorption source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/sodium-research/16358215.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "876374dd0624cf69b89f3f5b17e5be423d7d9a0358f135add88f2493314d2ceb", "start_char": 0, "end_char": 1515, "text_sha256": "876374dd0624cf69b89f3f5b17e5be423d7d9a0358f135add88f2493314d2ceb"}
experimental_model
Mapping and sequencing in families with hereditary hypophosphatemic rickets with hypercalciuria
exposure
SLC34A3 disease-associated mutations in five families
limitations
Genotype–phenotype evidence supports a primary renal defect; downstream calcitriol/calcium pattern is observed, not a dietary sodium intervention.
nutrient_topic
Sodium research collection; topical membership is not evidence of a direct dietary effect. · Sodium
organism
Human
plain_language
The kidney’s sodium/phosphate transporter is important for retaining phosphate.
primary_references
[sodium-p16358215] Hereditary hypophosphatemic rickets with hypercalciuria is caused by mutations in the sodium-phosphate cotransporter gene SLC34A3. (2006). https://pubmed.ncbi.nlm.nih.gov/16358215/ DOI: 10.1086/499410
tissue_or_cell_type
Renal proximal tubule and systemic mineral phenotype
trigger_kind
machinery_impairment Imported condition classification; unverified.
Sodium: gradients, nutrient transport, fluid regulation and loss states (2026-09-17) · lines 668–679
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mapping and sequencing in families with hereditary hypophosphatemic rickets with hypercalciuria · source_derived_draft · unverified_draft
### sodium-napi2c-phosphate SLC34A3 mutations segregated with renal phosphate wasting and hypophosphatemic rickets in the studied families. Condition category: machinery_impairment nutrient_topic: Sodium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The kidney’s sodium/phosphate transporter is important for retaining phosphate. organism: Human tissue_or_cell_type: Renal proximal tubule and systemic mineral phenotype experimental_model: Mapping and sequencing in families with hereditary hypophosphatemic rickets with hypercalciuria limitations: Genotype–phenotype evidence supports a primary renal defect; downstream calcitriol/calcium pattern is observed, not a dietary sodium intervention. exposure: SLC34A3 disease-associated mutations in five families evidence_span: {"source_cache": "artifacts/sodium-research/16358215.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "876374dd0624cf69b89f3f5b17e5be423d7d9a0358f135add88f2493314d2ceb", "start_char": 0, "end_char": 1515, "text_sha256": "876374dd0624cf69b89f3f5b17e5be423d7d9a0358f135add88f2493314d2ceb"} [sodium-p16358215] Hereditary hypophosphatemic rickets with hypercalciuria is caused by mutations in the sodium-phosphate cotransporter gene SLC34A3. (2006). https://pubmed.ncbi.nlm.nih.gov/16358215/ DOI: 10.1086/499410
Complete structured claim and evidence
The HHRH phenotype included elevated circulating 1,25-dihydroxyvitamin D with normal or low-normal FGF23.
Sodium-phosphate cotransporter NaPi-IIc / SLC34A3 → Circulating calcitriol concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/sodium-research/16358215.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "876374dd0624cf69b89f3f5b17e5be423d7d9a0358f135add88f2493314d2ceb", "start_char": 0, "end_char": 1515, "text_sha256": "876374dd0624cf69b89f3f5b17e5be423d7d9a0358f135add88f2493314d2ceb"}
experimental_model
Mapping and sequencing in families with hereditary hypophosphatemic rickets with hypercalciuria
exposure
SLC34A3 disease-associated mutations in five families
limitations
Genotype–phenotype evidence supports a primary renal defect; downstream calcitriol/calcium pattern is observed, not a dietary sodium intervention.
nutrient_topic
Sodium research collection; topical membership is not evidence of a direct dietary effect. · Sodium
organism
Human
plain_language
A phosphate-handling defect can change the vitamin D environment.
primary_references
[sodium-p16358215] Hereditary hypophosphatemic rickets with hypercalciuria is caused by mutations in the sodium-phosphate cotransporter gene SLC34A3. (2006). https://pubmed.ncbi.nlm.nih.gov/16358215/ DOI: 10.1086/499410
tissue_or_cell_type
Renal proximal tubule and systemic mineral phenotype
trigger_kind
machinery_impairment Imported condition classification; unverified.
Sodium: gradients, nutrient transport, fluid regulation and loss states (2026-09-17) · lines 681–692
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mapping and sequencing in families with hereditary hypophosphatemic rickets with hypercalciuria · source_derived_draft · unverified_draft
### sodium-napi2c-calcitriol The HHRH phenotype included elevated circulating 1,25-dihydroxyvitamin D with normal or low-normal FGF23. Condition category: machinery_impairment nutrient_topic: Sodium research collection; topical membership is not evidence of a direct dietary effect. plain_language: A phosphate-handling defect can change the vitamin D environment. organism: Human tissue_or_cell_type: Renal proximal tubule and systemic mineral phenotype experimental_model: Mapping and sequencing in families with hereditary hypophosphatemic rickets with hypercalciuria limitations: Genotype–phenotype evidence supports a primary renal defect; downstream calcitriol/calcium pattern is observed, not a dietary sodium intervention. exposure: SLC34A3 disease-associated mutations in five families evidence_span: {"source_cache": "artifacts/sodium-research/16358215.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "876374dd0624cf69b89f3f5b17e5be423d7d9a0358f135add88f2493314d2ceb", "start_char": 0, "end_char": 1515, "text_sha256": "876374dd0624cf69b89f3f5b17e5be423d7d9a0358f135add88f2493314d2ceb"} [sodium-p16358215] Hereditary hypophosphatemic rickets with hypercalciuria is caused by mutations in the sodium-phosphate cotransporter gene SLC34A3. (2006). https://pubmed.ncbi.nlm.nih.gov/16358215/ DOI: 10.1086/499410
Complete structured claim and evidence
The sodium/phosphate-transporter-associated HHRH phenotype included hypercalciuria.
Sodium-phosphate cotransporter NaPi-IIc / SLC34A3 → Urinary calcium excretion source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/sodium-research/16358215.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "876374dd0624cf69b89f3f5b17e5be423d7d9a0358f135add88f2493314d2ceb", "start_char": 0, "end_char": 1515, "text_sha256": "876374dd0624cf69b89f3f5b17e5be423d7d9a0358f135add88f2493314d2ceb"}
experimental_model
Mapping and sequencing in families with hereditary hypophosphatemic rickets with hypercalciuria
exposure
SLC34A3 disease-associated mutations in five families
limitations
Genotype–phenotype evidence supports a primary renal defect; downstream calcitriol/calcium pattern is observed, not a dietary sodium intervention.
nutrient_topic
Sodium research collection; topical membership is not evidence of a direct dietary effect. · Sodium
organism
Human
plain_language
This phosphate disorder can also increase calcium loss into urine.
primary_references
[sodium-p16358215] Hereditary hypophosphatemic rickets with hypercalciuria is caused by mutations in the sodium-phosphate cotransporter gene SLC34A3. (2006). https://pubmed.ncbi.nlm.nih.gov/16358215/ DOI: 10.1086/499410
tissue_or_cell_type
Renal proximal tubule and systemic mineral phenotype
trigger_kind
machinery_impairment Imported condition classification; unverified.
Sodium: gradients, nutrient transport, fluid regulation and loss states (2026-09-17) · lines 694–705
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mapping and sequencing in families with hereditary hypophosphatemic rickets with hypercalciuria · source_derived_draft · unverified_draft
### sodium-napi2c-calcium The sodium/phosphate-transporter-associated HHRH phenotype included hypercalciuria. Condition category: machinery_impairment nutrient_topic: Sodium research collection; topical membership is not evidence of a direct dietary effect. plain_language: This phosphate disorder can also increase calcium loss into urine. organism: Human tissue_or_cell_type: Renal proximal tubule and systemic mineral phenotype experimental_model: Mapping and sequencing in families with hereditary hypophosphatemic rickets with hypercalciuria limitations: Genotype–phenotype evidence supports a primary renal defect; downstream calcitriol/calcium pattern is observed, not a dietary sodium intervention. exposure: SLC34A3 disease-associated mutations in five families evidence_span: {"source_cache": "artifacts/sodium-research/16358215.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "876374dd0624cf69b89f3f5b17e5be423d7d9a0358f135add88f2493314d2ceb", "start_char": 0, "end_char": 1515, "text_sha256": "876374dd0624cf69b89f3f5b17e5be423d7d9a0358f135add88f2493314d2ceb"} [sodium-p16358215] Hereditary hypophosphatemic rickets with hypercalciuria is caused by mutations in the sodium-phosphate cotransporter gene SLC34A3. (2006). https://pubmed.ncbi.nlm.nih.gov/16358215/ DOI: 10.1086/499410
Complete structured claim and evidence
Two daily calcitriol injections increased active phosphate transport in wild-type mouse jejunum.
Calcitriol → Active intestinal phosphate absorption source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Vitamin D–calcium–phosphate regulation.
evidence_locator
Abstract: reported experimental results
evidence_scope
D3 active metabolite or VDR machinery experiment; not a direct D2-versus-D3 comparison.
experimental_model
Wild-type and intestinal Slc34a2-deleted mice; active versus paracellular intestinal phosphate transport assays
exposure
Intraperitoneal calcitriol once daily for 2 days; dose not specified in the retrieved abstract.
limitations
Stimulation was segment-specific: increased transporter protein in ileum did not establish the same active-flux response there. No human dietary-dose inference.
nutrient
Vitamin D2 and D3 · Vitamin D2 and D3
nutrient_topic
Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin D2 and D3
organism
Mus musculus
plain_language
Active vitamin D increased the intestine’s sodium-coupled phosphate uptake in the responsive segment.
primary_references
[vdm-hernando2021] 1,25(OH)2 vitamin D3 stimulates active phosphate transport but not paracellular phosphate absorption in mouse intestine. (2021). https://pubmed.ncbi.nlm.nih.gov/33200827/ DOI: 10.1113/jp280345
tissue_or_cell_type
Jejunum
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 665–679
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Wild-type and intestinal Slc34a2-deleted mice; active versus paracellular intestinal phosphate transport assays · source_derived_draft · unverified_draft
### vdm-calcitriol-increases-jejunal-phosphate-transport Two daily calcitriol injections increased active phosphate transport in wild-type mouse jejunum. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Active vitamin D increased the intestine’s sodium-coupled phosphate uptake in the responsive segment. organism: Mus musculus tissue_or_cell_type: Jejunum experimental_model: Wild-type and intestinal Slc34a2-deleted mice; active versus paracellular intestinal phosphate transport assays limitations: Stimulation was segment-specific: increased transporter protein in ileum did not establish the same active-flux response there. No human dietary-dose inference. exposure: Intraperitoneal calcitriol once daily for 2 days; dose not specified in the retrieved abstract. cross_nutrient: Vitamin D–calcium–phosphate regulation. evidence_locator: Abstract: reported experimental results nutrient: Vitamin D2 and D3 evidence_scope: D3 active metabolite or VDR machinery experiment; not a direct D2-versus-D3 comparison. [vdm-hernando2021] 1,25(OH)2 vitamin D3 stimulates active phosphate transport but not paracellular phosphate absorption in mouse intestine. (2021). https://pubmed.ncbi.nlm.nih.gov/33200827/ DOI: 10.1113/jp280345
Complete structured claim and evidence
The two-day calcitriol regimen did not detectably increase paracellular phosphate flux in the mouse intestine.
Calcitriol → Paracellular intestinal phosphate flux source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Vitamin D–calcium–phosphate regulation.
evidence_locator
Abstract: reported experimental results
evidence_scope
D3 active metabolite or VDR machinery experiment; not a direct D2-versus-D3 comparison.
experimental_model
Wild-type and intestinal Slc34a2-deleted mice; active versus paracellular intestinal phosphate transport assays
exposure
Intraperitoneal calcitriol once daily for 2 days; dose not specified in the retrieved abstract.
limitations
A negative result for this assay and regimen does not exclude other doses, durations, species or intestinal segments.
nutrient
Vitamin D2 and D3 · Vitamin D2 and D3
nutrient_topic
Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin D2 and D3
organism
Mus musculus
plain_language
The measured phosphate response involved transport through cells; the route between cells did not show the same increase.
primary_references
[vdm-hernando2021] 1,25(OH)2 vitamin D3 stimulates active phosphate transport but not paracellular phosphate absorption in mouse intestine. (2021). https://pubmed.ncbi.nlm.nih.gov/33200827/ DOI: 10.1113/jp280345
tissue_or_cell_type
Intestinal epithelium
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 681–695
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Wild-type and intestinal Slc34a2-deleted mice; active versus paracellular intestinal phosphate transport assays · source_derived_draft · unverified_draft
### vdm-calcitriol-no-detected-paracellular-phosphate-response The two-day calcitriol regimen did not detectably increase paracellular phosphate flux in the mouse intestine. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The measured phosphate response involved transport through cells; the route between cells did not show the same increase. organism: Mus musculus tissue_or_cell_type: Intestinal epithelium experimental_model: Wild-type and intestinal Slc34a2-deleted mice; active versus paracellular intestinal phosphate transport assays limitations: A negative result for this assay and regimen does not exclude other doses, durations, species or intestinal segments. exposure: Intraperitoneal calcitriol once daily for 2 days; dose not specified in the retrieved abstract. cross_nutrient: Vitamin D–calcium–phosphate regulation. evidence_locator: Abstract: reported experimental results nutrient: Vitamin D2 and D3 evidence_scope: D3 active metabolite or VDR machinery experiment; not a direct D2-versus-D3 comparison. [vdm-hernando2021] 1,25(OH)2 vitamin D3 stimulates active phosphate transport but not paracellular phosphate absorption in mouse intestine. (2021). https://pubmed.ncbi.nlm.nih.gov/33200827/ DOI: 10.1113/jp280345
Complete structured claim and evidence
Recombinant FGF23 reduced renal NaPi-IIa mRNA and protein abundance in the acute rodent injection study.
Fibroblast growth factor 23 / FGF23 → Sodium-phosphate cotransporter NaPi-IIa / SLC34A1 source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Vitamin D–calcium–phosphate regulation.
evidence_locator
Abstract: reported experimental results
evidence_scope
D3 active metabolite or VDR machinery experiment; not a direct D2-versus-D3 comparison.
experimental_model
Single recombinant FGF23 injection in rodents; renal transcript/protein and serum phosphate measurements
exposure
Single recombinant FGF23 injection; serum phosphate reduction was first observed at 9 hours; dose not recovered in the primary abstract.
limitations
Transporter abundance is not itself a flux measurement. Lack of a PTH rise and parathyroidectomized-rat responses support a PTH-independent action in this experiment.
nutrient
Vitamin D2 and D3 · Vitamin D2 and D3
nutrient_topic
Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin D2 and D3
organism
Mus musculus; Rattus norvegicus
plain_language
FGF23 reduced a kidney transporter that normally helps retain phosphate.
primary_references
[vdm-shimada2004] FGF-23 is a potent regulator of vitamin D metabolism and phosphate homeostasis. (2004). https://pubmed.ncbi.nlm.nih.gov/15040831/ DOI: 10.1359/jbmr.0301264
tissue_or_cell_type
Kidney
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 745–759
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Single recombinant FGF23 injection in rodents; renal transcript/protein and serum phosphate measurements · source_derived_draft · unverified_draft
### vdm-fgf23-reduces-renal-napi2a Recombinant FGF23 reduced renal NaPi-IIa mRNA and protein abundance in the acute rodent injection study. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: FGF23 reduced a kidney transporter that normally helps retain phosphate. organism: Mus musculus; Rattus norvegicus tissue_or_cell_type: Kidney experimental_model: Single recombinant FGF23 injection in rodents; renal transcript/protein and serum phosphate measurements limitations: Transporter abundance is not itself a flux measurement. Lack of a PTH rise and parathyroidectomized-rat responses support a PTH-independent action in this experiment. exposure: Single recombinant FGF23 injection; serum phosphate reduction was first observed at 9 hours; dose not recovered in the primary abstract. cross_nutrient: Vitamin D–calcium–phosphate regulation. evidence_locator: Abstract: reported experimental results nutrient: Vitamin D2 and D3 evidence_scope: D3 active metabolite or VDR machinery experiment; not a direct D2-versus-D3 comparison. [vdm-shimada2004] FGF-23 is a potent regulator of vitamin D metabolism and phosphate homeostasis. (2004). https://pubmed.ncbi.nlm.nih.gov/15040831/ DOI: 10.1359/jbmr.0301264
Complete structured claim and evidence
Recombinant FGF23 raises renal CYP24A1 mRNA as circulating calcitriol declines.
Fibroblast growth factor 23 / FGF23 → Vitamin D 24-hydroxylase / CYP24A1 source_derived_draftungraded
Experimental context and source evidence
experimental_model
Recombinant FGF23 injections in normal and parathyroidectomized rodents
limitations
Acute rodent transcript response; does not quantify human calcium balance.
nutrient_topic
Calcium research collection; topical membership is not evidence of a direct dietary effect. · Calcium
organism
Mus musculus; Rattus norvegicus
plain_language
FGF23 increases vitamin D inactivation machinery.
primary_references
[shimada2004injection] FGF-23 is a potent regulator of vitamin D metabolism and phosphate homeostasis (2004). https://pubmed.ncbi.nlm.nih.gov/15040831/ DOI: 10.1359/JBMR.0301264
tissue_or_cell_type
Kidney
Calcium: mechanism-first literature curation (2026-09-17) · lines 102–111
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant FGF23 injections in normal and parathyroidectomized rodents · source_derived_draft · unverified_draft
### fgf23-increases-cyp24a1-expression Recombinant FGF23 raises renal CYP24A1 mRNA as circulating calcitriol declines. Condition category: normal nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: FGF23 increases vitamin D inactivation machinery. organism: Mus musculus; Rattus norvegicus tissue_or_cell_type: Kidney experimental_model: Recombinant FGF23 injections in normal and parathyroidectomized rodents limitations: Acute rodent transcript response; does not quantify human calcium balance. [shimada2004injection] FGF-23 is a potent regulator of vitamin D metabolism and phosphate homeostasis (2004). https://pubmed.ncbi.nlm.nih.gov/15040831/ DOI: 10.1359/JBMR.0301264
Complete structured claim and evidence
Recombinant FGF23 lowers renal CYP27B1 mRNA before the fall in serum phosphate.
Fibroblast growth factor 23 / FGF23 → Vitamin D 1-alpha-hydroxylase / CYP27B1 source_derived_draftungraded
Experimental context and source evidence
experimental_model
Recombinant FGF23 injections in normal and parathyroidectomized rodents
limitations
Injection study; transcript change is not direct enzyme inhibition.
nutrient_topic
Calcium research collection; topical membership is not evidence of a direct dietary effect. · Calcium
organism
Mus musculus; Rattus norvegicus
plain_language
FGF23 restrains a vitamin D activation enzyme.
primary_references
[shimada2004injection] FGF-23 is a potent regulator of vitamin D metabolism and phosphate homeostasis (2004). https://pubmed.ncbi.nlm.nih.gov/15040831/ DOI: 10.1359/JBMR.0301264
tissue_or_cell_type
Kidney
Calcium: mechanism-first literature curation (2026-09-17) · lines 91–100
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant FGF23 injections in normal and parathyroidectomized rodents · source_derived_draft · unverified_draft
### fgf23-reduces-cyp27b1-expression Recombinant FGF23 lowers renal CYP27B1 mRNA before the fall in serum phosphate. Condition category: normal nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: FGF23 restrains a vitamin D activation enzyme. organism: Mus musculus; Rattus norvegicus tissue_or_cell_type: Kidney experimental_model: Recombinant FGF23 injections in normal and parathyroidectomized rodents limitations: Injection study; transcript change is not direct enzyme inhibition. [shimada2004injection] FGF-23 is a potent regulator of vitamin D metabolism and phosphate homeostasis (2004). https://pubmed.ncbi.nlm.nih.gov/15040831/ DOI: 10.1359/JBMR.0301264
Complete structured claim and evidence
Alpha-Klotho cooperates with FGFR1(IIIc) to confer high-affinity binding and signaling by FGF23.
Alpha-Klotho / KL → Fibroblast growth factor receptor 1 / FGFR1 source_derived_draftungraded
Experimental context and source evidence
experimental_model
Renal homogenates, receptor-reconstitution cell assays and anti-Klotho antibody in mice
limitations
Specifically FGFR1(IIIc) reconstitution; not all FGFR1 splice forms are equivalent.
nutrient_topic
Calcium research collection; topical membership is not evidence of a direct dietary effect. · Calcium
organism
Mammalian cell systems; Mus musculus
plain_language
FGF23 needs a suitable receptor partnership.
primary_references
[urakawa2006] Klotho converts canonical FGF receptor into a specific receptor for FGF23 (2006). https://pubmed.ncbi.nlm.nih.gov/17086194/ DOI: 10.1038/nature05315
tissue_or_cell_type
Kidney receptor system
Calcium: mechanism-first literature curation (2026-09-17) · lines 113–122
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Renal homogenates, receptor-reconstitution cell assays and anti-Klotho antibody in mice · source_derived_draft · unverified_draft
### klotho-fgfr1-fgf23-receptor Alpha-Klotho cooperates with FGFR1(IIIc) to confer high-affinity binding and signaling by FGF23. Condition category: normal nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: FGF23 needs a suitable receptor partnership. organism: Mammalian cell systems; Mus musculus tissue_or_cell_type: Kidney receptor system experimental_model: Renal homogenates, receptor-reconstitution cell assays and anti-Klotho antibody in mice limitations: Specifically FGFR1(IIIc) reconstitution; not all FGFR1 splice forms are equivalent. [urakawa2006] Klotho converts canonical FGF receptor into a specific receptor for FGF23 (2006). https://pubmed.ncbi.nlm.nih.gov/17086194/ DOI: 10.1038/nature05315
Complete structured claim and evidence
Human PHOSPHO1 also hydrolyzes phosphocholine, producing inorganic phosphate and choline.
Phosphocholine → Inorganic phosphate (Pi; protonation depends on pH) source_derived_draftungraded
Experimental context and source evidence
experimental_model
Purified-enzyme substrate assay
limitations
This reaction uses magnesium-dependent machinery; calcium is the eventual mineral constituent, not the demonstrated phosphatase cofactor.
nutrient_topic
Calcium research collection; topical membership is not evidence of a direct dietary effect. · Calcium
organism
Homo sapiens
plain_language
A second phospholipid-headgroup metabolite can supply phosphate.
primary_references
[roberts2004] Human PHOSPHO1 exhibits high specific phosphoethanolamine and phosphocholine phosphatase activities (2004). https://pubmed.ncbi.nlm.nih.gov/15175005/ DOI: 10.1042/BJ20040511
tissue_or_cell_type
Recombinant enzyme
Calcium: mechanism-first literature curation (2026-09-17) · lines 908–917
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified-enzyme substrate assay · source_derived_draft · unverified_draft
### phospho1-phosphocholine-hydrolysis Human PHOSPHO1 also hydrolyzes phosphocholine, producing inorganic phosphate and choline. Condition category: normal nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: A second phospholipid-headgroup metabolite can supply phosphate. organism: Homo sapiens tissue_or_cell_type: Recombinant enzyme experimental_model: Purified-enzyme substrate assay limitations: This reaction uses magnesium-dependent machinery; calcium is the eventual mineral constituent, not the demonstrated phosphatase cofactor. [roberts2004] Human PHOSPHO1 exhibits high specific phosphoethanolamine and phosphocholine phosphatase activities (2004). https://pubmed.ncbi.nlm.nih.gov/15175005/ DOI: 10.1042/BJ20040511
Complete structured claim and evidence
Human PHOSPHO1 hydrolyzes phosphoethanolamine, releasing inorganic phosphate and ethanolamine; the enzyme requires Mg2+ in the assay.
Phosphoethanolamine → Inorganic phosphate (Pi; protonation depends on pH) source_derived_draftungraded
Experimental context and source evidence
experimental_model
Purified-enzyme substrate assay
limitations
Catalytic capacity does not quantify phosphate supply in vivo; Pi denotes pH-dependent protonation states.
nutrient_topic
Calcium research collection; topical membership is not evidence of a direct dietary effect. · Calcium
organism
Homo sapiens
plain_language
PHOSPHO1 can release phosphate from a membrane-headgroup metabolite.
primary_references
[roberts2004] Human PHOSPHO1 exhibits high specific phosphoethanolamine and phosphocholine phosphatase activities (2004). https://pubmed.ncbi.nlm.nih.gov/15175005/ DOI: 10.1042/BJ20040511
tissue_or_cell_type
Recombinant enzyme; mineralizing-cell context
Calcium: mechanism-first literature curation (2026-09-17) · lines 897–906
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified-enzyme substrate assay · source_derived_draft · unverified_draft
### phospho1-phosphoethanolamine-hydrolysis Human PHOSPHO1 hydrolyzes phosphoethanolamine, releasing inorganic phosphate and ethanolamine; the enzyme requires Mg2+ in the assay. Condition category: normal nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: PHOSPHO1 can release phosphate from a membrane-headgroup metabolite. organism: Homo sapiens tissue_or_cell_type: Recombinant enzyme; mineralizing-cell context experimental_model: Purified-enzyme substrate assay limitations: Catalytic capacity does not quantify phosphate supply in vivo; Pi denotes pH-dependent protonation states. [roberts2004] Human PHOSPHO1 exhibits high specific phosphoethanolamine and phosphocholine phosphatase activities (2004). https://pubmed.ncbi.nlm.nih.gov/15175005/ DOI: 10.1042/BJ20040511
Complete structured claim and evidence
ALPL/TNAP hydrolyzes extracellular pyrophosphate to inorganic phosphate, reducing an inhibitor of matrix mineralization.
Inorganic pyrophosphate → Inorganic phosphate (Pi; protonation depends on pH) source_derived_draftungraded
Experimental context and source evidence
compartment_description
Extracellular matrix and vesicle surface
experimental_model
Genetic and ex vivo pyrophosphate/mineralization experiments
limitations
Pi and PPi labels pool protonation states; this is not evidence that calcium activates TNAP.
nutrient_topic
Calcium research collection; topical membership is not evidence of a direct dietary effect. · Calcium
organism
Mus musculus
plain_language
TNAP removes a local brake on calcium phosphate crystal growth.
primary_references
[hessle2002] Tissue-nonspecific alkaline phosphatase and plasma cell membrane glycoprotein-1 are central antagonistic regulators of bone mineralization (2002). https://pmc.ncbi.nlm.nih.gov/articles/PMC123160/ DOI: 10.1073/pnas.142063399
tissue_or_cell_type
Osteoblast matrix and matrix vesicles
Calcium: mechanism-first literature curation (2026-09-17) · lines 931–941
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Genetic and ex vivo pyrophosphate/mineralization experiments · source_derived_draft · unverified_draft
### alpl-pyrophosphate-hydrolysis ALPL/TNAP hydrolyzes extracellular pyrophosphate to inorganic phosphate, reducing an inhibitor of matrix mineralization. Condition category: normal nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: TNAP removes a local brake on calcium phosphate crystal growth. organism: Mus musculus tissue_or_cell_type: Osteoblast matrix and matrix vesicles experimental_model: Genetic and ex vivo pyrophosphate/mineralization experiments limitations: Pi and PPi labels pool protonation states; this is not evidence that calcium activates TNAP. compartment_description: Extracellular matrix and vesicle surface [hessle2002] Tissue-nonspecific alkaline phosphatase and plasma cell membrane glycoprotein-1 are central antagonistic regulators of bone mineralization (2002). https://pmc.ncbi.nlm.nih.gov/articles/PMC123160/ DOI: 10.1073/pnas.142063399
Complete structured claim and evidence
ENPP1 converts extracellular ATP into AMP and PPi; ANKH-expressing cells lacking ENPP1 released ATP without the accompanying PPi accumulation.
ATP → Inorganic pyrophosphate source_derived_draftungraded
Experimental context and source evidence
compartment_description
Extracellular space
experimental_model
ENPP1-proficient versus deficient cells
limitations
Other ectonucleotidases compete for ATP; PPi is not synonymous with orthophosphate.
nutrient_topic
Calcium research collection; topical membership is not evidence of a direct dietary effect. · Calcium
organism
Homo sapiens
plain_language
An extracellular enzyme converts exported ATP into a mineralization inhibitor.
primary_references
[szeri2022] The mineralization regulator ANKH mediates cellular efflux of ATP, not pyrophosphate (2022). https://pmc.ncbi.nlm.nih.gov/articles/PMC9098669/ DOI: 10.1002/jbmr.4528
tissue_or_cell_type
HEK293 extracellular medium
Calcium: mechanism-first literature curation (2026-09-17) · lines 1012–1022
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · ENPP1-proficient versus deficient cells · source_derived_draft · unverified_draft
### enpp1-atp-to-pyrophosphate ENPP1 converts extracellular ATP into AMP and PPi; ANKH-expressing cells lacking ENPP1 released ATP without the accompanying PPi accumulation. Condition category: normal nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: An extracellular enzyme converts exported ATP into a mineralization inhibitor. organism: Homo sapiens tissue_or_cell_type: HEK293 extracellular medium experimental_model: ENPP1-proficient versus deficient cells limitations: Other ectonucleotidases compete for ATP; PPi is not synonymous with orthophosphate. compartment_description: Extracellular space [szeri2022] The mineralization regulator ANKH mediates cellular efflux of ATP, not pyrophosphate (2022). https://pmc.ncbi.nlm.nih.gov/articles/PMC9098669/ DOI: 10.1002/jbmr.4528
Complete structured claim and evidence
In Alpl-deficient mice and osteoblast preparations, excess pyrophosphate accompanied poor mineralization; removing Enpp1 normalized pyrophosphate and improved mineral deposition.
Inorganic pyrophosphate → Skeletal matrix mineralization source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
experimental_model
Single versus combined Alpl/Enpp1 knockout
limitations
The genetic rescue supports local PPi control; it is not a calcium-supplement experiment.
nutrient_topic
Calcium research collection; topical membership is not evidence of a direct dietary effect. · Calcium
organism
Mus musculus
plain_language
Mineral formation depends on controlling an inhibitor as well as supplying calcium.
primary_references
[hessle2002] Tissue-nonspecific alkaline phosphatase and plasma cell membrane glycoprotein-1 are central antagonistic regulators of bone mineralization (2002). https://pmc.ncbi.nlm.nih.gov/articles/PMC123160/ DOI: 10.1073/pnas.142063399
tissue_or_cell_type
Bone and cultured osteoblast matrix
trigger_kind
machinery_impairment Imported condition classification; unverified.
Calcium: mechanism-first literature curation (2026-09-17) · lines 943–952
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Single versus combined Alpl/Enpp1 knockout · source_derived_draft · unverified_draft
### pyrophosphate-restrains-mineral-deposition In Alpl-deficient mice and osteoblast preparations, excess pyrophosphate accompanied poor mineralization; removing Enpp1 normalized pyrophosphate and improved mineral deposition. Condition category: machinery_impairment nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Mineral formation depends on controlling an inhibitor as well as supplying calcium. organism: Mus musculus tissue_or_cell_type: Bone and cultured osteoblast matrix experimental_model: Single versus combined Alpl/Enpp1 knockout limitations: The genetic rescue supports local PPi control; it is not a calcium-supplement experiment. [hessle2002] Tissue-nonspecific alkaline phosphatase and plasma cell membrane glycoprotein-1 are central antagonistic regulators of bone mineralization (2002). https://pmc.ncbi.nlm.nih.gov/articles/PMC123160/ DOI: 10.1073/pnas.142063399
Complete structured claim and evidence
Human enamel crystallites have an apatite lattice containing calcium and phosphate, with heterogeneous magnesium, sodium, fluoride and carbonate substitutions.
Hydroxyapatite / biological substituted apatite → Tooth enamel source_derived_draftungraded
Experimental context and source evidence
experimental_model
Atomic-scale imaging and correlative spectroscopy
limitations
A structural tissue study; it does not test dietary calcium intake or enamel regeneration.
nutrient_topic
Calcium research collection; topical membership is not evidence of a direct dietary effect. · Calcium
organism
Homo sapiens
plain_language
Tooth enamel is built from chemically varied calcium phosphate crystals.
primary_references
[derocher2020] Chemical gradients in human enamel crystallites (2020). https://pmc.ncbi.nlm.nih.gov/articles/PMC8290891/ DOI: 10.1038/s41586-020-2433-3
tissue_or_cell_type
Dental enamel
Calcium: mechanism-first literature curation (2026-09-17) · lines 886–895
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Atomic-scale imaging and correlative spectroscopy · source_derived_draft · unverified_draft
### enamel-calcium-in-substituted-apatite Human enamel crystallites have an apatite lattice containing calcium and phosphate, with heterogeneous magnesium, sodium, fluoride and carbonate substitutions. Condition category: normal nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Tooth enamel is built from chemically varied calcium phosphate crystals. organism: Homo sapiens tissue_or_cell_type: Dental enamel experimental_model: Atomic-scale imaging and correlative spectroscopy limitations: A structural tissue study; it does not test dietary calcium intake or enamel regeneration. [derocher2020] Chemical gradients in human enamel crystallites (2020). https://pmc.ncbi.nlm.nih.gov/articles/PMC8290891/ DOI: 10.1038/s41586-020-2433-3
Complete structured claim and evidence
Amorphous calcium phosphate in newly forming zebrafish fin bone and increasing crystallinity with maturation support an amorphous-precursor model.
Amorphous calcium phosphate → Hydroxyapatite / biological substituted apatite source_derived_draftungraded
Experimental context and source evidence
compartment_description
Bone extracellular matrix
experimental_model
Spatial maturation series and extracted-particle crystallization
limitations
The proposed sequence is not direct tracking of every mineral particle in living human bone.
nutrient_topic
Calcium research collection; topical membership is not evidence of a direct dietary effect. · Calcium
organism
Danio rerio
plain_language
A disordered calcium phosphate phase may precede organized bone crystals.
primary_references
[mahamid2008] Amorphous calcium phosphate is a major component of the forming fin bones of zebrafish: Indications for an amorphous precursor phase (2008). https://pmc.ncbi.nlm.nih.gov/articles/PMC2529085/ DOI: 10.1073/pnas.0803354105
tissue_or_cell_type
Growing fin-ray bone
Calcium: mechanism-first literature curation (2026-09-17) · lines 874–884
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Spatial maturation series and extracted-particle crystallization · source_derived_draft · unverified_draft
### bone-amorphous-mineral-precursor-hypothesis Amorphous calcium phosphate in newly forming zebrafish fin bone and increasing crystallinity with maturation support an amorphous-precursor model. Condition category: normal nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: A disordered calcium phosphate phase may precede organized bone crystals. organism: Danio rerio tissue_or_cell_type: Growing fin-ray bone experimental_model: Spatial maturation series and extracted-particle crystallization limitations: The proposed sequence is not direct tracking of every mineral particle in living human bone. compartment_description: Bone extracellular matrix [mahamid2008] Amorphous calcium phosphate is a major component of the forming fin bones of zebrafish: Indications for an amorphous precursor phase (2008). https://pmc.ncbi.nlm.nih.gov/articles/PMC2529085/ DOI: 10.1073/pnas.0803354105
Complete structured claim and evidence
Magnesium deprivation decreased renal slc34a1-mrna abundance in the 21-day rat experiment.
Magnesium → SLC34A1 mRNA source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Magnesium -> vitamin D/phosphate handling; transcript-level evidence.
experimental_model
Mg-free versus 0.05% Mg diet.
limitations
mRNA endpoint; no transporter flux or obligatory enzyme-bound Mg inference.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Rattus norvegicus
plain_language
The message for one phosphate-reabsorbing transporter fell.
primary_references
[mg-matsuzaki2013] Magnesium deficiency regulates vitamin D metabolizing enzymes and type II sodium-phosphate cotransporter mRNA expression in rats (2013). https://pubmed.ncbi.nlm.nih.gov/23816829/ DOI: 10.1684/mrh.2013.0341
tissue_or_cell_type
Rat kidney
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1406–1416
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mg-free versus 0.05% Mg diet. · source_derived_draft · unverified_draft
### mg-deficiency-napi2a-transcript Magnesium deprivation decreased renal slc34a1-mrna abundance in the 21-day rat experiment. Condition category: nutrient_deficiency nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The message for one phosphate-reabsorbing transporter fell. organism: Rattus norvegicus tissue_or_cell_type: Rat kidney experimental_model: Mg-free versus 0.05% Mg diet. limitations: mRNA endpoint; no transporter flux or obligatory enzyme-bound Mg inference. cross_nutrient: Magnesium -> vitamin D/phosphate handling; transcript-level evidence. [mg-matsuzaki2013] Magnesium deficiency regulates vitamin D metabolizing enzymes and type II sodium-phosphate cotransporter mRNA expression in rats (2013). https://pubmed.ncbi.nlm.nih.gov/23816829/ DOI: 10.1684/mrh.2013.0341
Complete structured claim and evidence
Magnesium deprivation decreased renal slc34a3-mrna abundance in the 21-day rat experiment.
Magnesium → SLC34A3 mRNA source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Magnesium -> vitamin D/phosphate handling; transcript-level evidence.
experimental_model
Mg-free versus 0.05% Mg diet.
limitations
mRNA endpoint; no transporter flux or obligatory enzyme-bound Mg inference.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Rattus norvegicus
plain_language
A second phosphate-transporter message also fell.
primary_references
[mg-matsuzaki2013] Magnesium deficiency regulates vitamin D metabolizing enzymes and type II sodium-phosphate cotransporter mRNA expression in rats (2013). https://pubmed.ncbi.nlm.nih.gov/23816829/ DOI: 10.1684/mrh.2013.0341
tissue_or_cell_type
Rat kidney
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1418–1428
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mg-free versus 0.05% Mg diet. · source_derived_draft · unverified_draft
### mg-deficiency-napi2c-transcript Magnesium deprivation decreased renal slc34a3-mrna abundance in the 21-day rat experiment. Condition category: nutrient_deficiency nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: A second phosphate-transporter message also fell. organism: Rattus norvegicus tissue_or_cell_type: Rat kidney experimental_model: Mg-free versus 0.05% Mg diet. limitations: mRNA endpoint; no transporter flux or obligatory enzyme-bound Mg inference. cross_nutrient: Magnesium -> vitamin D/phosphate handling; transcript-level evidence. [mg-matsuzaki2013] Magnesium deficiency regulates vitamin D metabolizing enzymes and type II sodium-phosphate cotransporter mRNA expression in rats (2013). https://pubmed.ncbi.nlm.nih.gov/23816829/ DOI: 10.1684/mrh.2013.0341
Complete structured claim and evidence
Recombinant human TPK1 catalyzes thiamine diphosphorylation with ATP and Mg2+.
Thiamine (vitamin B1) → Thiamine diphosphate source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Magnesium availability supports vitamin B1 activation or cofactor use in the specified preparation; this does not establish a dietary threshold or universal treatment failure.
experimental_model
Purified His-tagged recombinant human TPK1, steady-state kinetics and mutations.
limitations
Assay chemistry; no clinical response measured.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Homo sapiens
plain_language
The enzyme uses ATP to convert vitamin B1 into its diphosphate cofactor.
primary_references
[onozuka-2003-tpk1] Steady-state kinetics and mutational studies of recombinant human thiamin pyrophosphokinase (2003). https://pubmed.ncbi.nlm.nih.gov/12953792/ DOI: 10.3177/jnsv.49.156
tissue_or_cell_type
Purified recombinant enzyme
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 481–491
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified His-tagged recombinant human TPK1, steady-state kinetics and mutations. · source_derived_draft · unverified_draft
### mg-tpk1-thiamine-to-thdp Recombinant human TPK1 catalyzes thiamine diphosphorylation with ATP and Mg2+. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The enzyme uses ATP to convert vitamin B1 into its diphosphate cofactor. organism: Homo sapiens tissue_or_cell_type: Purified recombinant enzyme experimental_model: Purified His-tagged recombinant human TPK1, steady-state kinetics and mutations. limitations: Assay chemistry; no clinical response measured. cross_nutrient: Magnesium availability supports vitamin B1 activation or cofactor use in the specified preparation; this does not establish a dietary threshold or universal treatment failure. [onozuka-2003-tpk1] Steady-state kinetics and mutational studies of recombinant human thiamin pyrophosphokinase (2003). https://pubmed.ncbi.nlm.nih.gov/12953792/ DOI: 10.3177/jnsv.49.156
Complete structured claim and evidence
Kinase kinetic experiments identified MgATP as the preferred phosphate-donor complex under the reported physiological assay conditions.
Magnesium-ATP complex → Pyridoxal kinase / PDXK source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Magnesium-B6 activation chemistry.
evidence_location
Indexed abstract and publisher abstract; human enzyme findings only
experimental_model
Purified recombinant human and E. coli pyridoxal kinases.
exposure
MgATP versus ZnATP kinetic comparisons.
limitations
Metal preference depends on assay conditions and does not prove magnesium supplementation improves B6 status.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
Magnesium helps supply ATP to B6 activation.
primary_references
[disalvo2004] Expression, purification, and kinetic constants for human and Escherichia coli pyridoxal kinases. (2004). https://pubmed.ncbi.nlm.nih.gov/15249053/ DOI: 10.1016/j.pep.2004.04.021
tissue_or_cell_type
Purified human enzyme
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 189–201
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified recombinant human and E. coli pyridoxal kinases. · source_derived_draft · unverified_draft
### b6-transport-pdxk-mgatp Kinase kinetic experiments identified MgATP as the preferred phosphate-donor complex under the reported physiological assay conditions. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Magnesium helps supply ATP to B6 activation. organism: Homo sapiens tissue_or_cell_type: Purified human enzyme experimental_model: Purified recombinant human and E. coli pyridoxal kinases. limitations: Metal preference depends on assay conditions and does not prove magnesium supplementation improves B6 status. exposure: MgATP versus ZnATP kinetic comparisons. evidence_location: Indexed abstract and publisher abstract; human enzyme findings only cross_nutrient: Magnesium-B6 activation chemistry. [disalvo2004] Expression, purification, and kinetic constants for human and Escherichia coli pyridoxal kinases. (2004). https://pubmed.ncbi.nlm.nih.gov/15249053/ DOI: 10.1016/j.pep.2004.04.021
Complete structured claim and evidence
The NAD+-dependent rat MTHFD2L assay also requires phosphate in the presence of magnesium.
Inorganic phosphate (Pi; protonation depends on pH) → Rat mitochondrial MTHFD2L source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Direct magnesium/phosphate requirement in folate oxidation.
experimental_model
Cofactor omission/addition assays
exposure
Assay conditions described in the linked primary study.
limitations
No dietary magnesium threshold follows from these assays.
nutrient_topic
Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. · Folate (vitamin B9)
organism
Rattus norvegicus
plain_language
Phosphate is another required partner in the NAD-linked reaction.
primary_references
[shin-2014] Mitochondrial MTHFD2L is a dual redox cofactor-specific methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase expressed in both adult and embryonic tissues (2014). https://pubmed.ncbi.nlm.nih.gov/24733394/ DOI: 10.1074/jbc.m114.555573
tissue_or_cell_type
Cell-free
Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1321–1332
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cofactor omission/addition assays · source_derived_draft · unverified_draft
### rat-mthfd2l-phosphate-nad-requirement The NAD+-dependent rat MTHFD2L assay also requires phosphate in the presence of magnesium. Condition category: normal nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Phosphate is another required partner in the NAD-linked reaction. organism: Rattus norvegicus tissue_or_cell_type: Cell-free experimental_model: Cofactor omission/addition assays limitations: No dietary magnesium threshold follows from these assays. exposure: Assay conditions described in the linked primary study. cross_nutrient: Direct magnesium/phosphate requirement in folate oxidation. [shin-2014] Mitochondrial MTHFD2L is a dual redox cofactor-specific methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase expressed in both adult and embryonic tissues (2014). https://pubmed.ncbi.nlm.nih.gov/24733394/ DOI: 10.1074/jbc.m114.555573
Complete structured claim and evidence
Inorganic phosphate inhibits the NADP+-dependent dehydrogenase activity of rat MTHFD2L.
Inorganic phosphate (Pi; protonation depends on pH) → Rat mitochondrial MTHFD2L source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Direct magnesium/phosphate requirement in folate oxidation.
experimental_model
Cofactor omission/addition assays
exposure
Assay conditions described in the linked primary study.
limitations
No dietary magnesium threshold follows from these assays.
nutrient_topic
Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. · Folate (vitamin B9)
organism
Rattus norvegicus
plain_language
The same phosphate has the opposite effect with the alternative electron carrier.
primary_references
[shin-2014] Mitochondrial MTHFD2L is a dual redox cofactor-specific methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase expressed in both adult and embryonic tissues (2014). https://pubmed.ncbi.nlm.nih.gov/24733394/ DOI: 10.1074/jbc.m114.555573
tissue_or_cell_type
Cell-free
Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1334–1345
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cofactor omission/addition assays · source_derived_draft · unverified_draft
### rat-mthfd2l-phosphate-nadp-inhibition Inorganic phosphate inhibits the NADP+-dependent dehydrogenase activity of rat MTHFD2L. Condition category: normal nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The same phosphate has the opposite effect with the alternative electron carrier. organism: Rattus norvegicus tissue_or_cell_type: Cell-free experimental_model: Cofactor omission/addition assays limitations: No dietary magnesium threshold follows from these assays. exposure: Assay conditions described in the linked primary study. cross_nutrient: Direct magnesium/phosphate requirement in folate oxidation. [shin-2014] Mitochondrial MTHFD2L is a dual redox cofactor-specific methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase expressed in both adult and embryonic tissues (2014). https://pubmed.ncbi.nlm.nih.gov/24733394/ DOI: 10.1074/jbc.m114.555573
Complete structured claim and evidence
Creatine kinase catalyzes reversible phosphoryl transfer between ATP and creatine to form ADP and phosphocreatine.
Torpedo californica creatine kinase → Creatine source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/creatine-research/12437342.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "291edd82015566452fe1b1321454a1df644a4c6da705fda90e8e369ea6ab53a1", "start_char": 0, "end_char": 1625, "text_sha256": "291edd82015566452fe1b1321454a1df644a4c6da705fda90e8e369ea6ab53a1"}
experimental_model
X-ray structure of a creatine kinase transition-state analogue complex
exposure
ADP, magnesium, nitrate and creatine complex at 2.1 angstrom resolution
limitations
Nitrate models the transferring phosphoryl group; it is not declared a physiological substrate. Structural magnesium dependence does not establish benefit from extra oral magnesium.
nutrient_topic
Creatine research collection; topical membership is not evidence of a direct dietary effect. · Creatine
organism
Torpedo californica enzyme
plain_language
Creatine can temporarily hold a phosphate group and return it to ADP when ATP must be regenerated.
primary_references
[creatine-p12437342] The 2.1 A structure of Torpedo californica creatine kinase complexed with the ADP-Mg(2+)-NO(3)(-)-creatine transition-state analogue complex. (2002). https://pubmed.ncbi.nlm.nih.gov/12437342/ DOI: 10.1021/bi026655p
tissue_or_cell_type
Purified creatine kinase
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17) · lines 334–345
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · X-ray structure of a creatine kinase transition-state analogue complex · source_derived_draft · unverified_draft
### creatine-ck-reversible-phosphate Creatine kinase catalyzes reversible phosphoryl transfer between ATP and creatine to form ADP and phosphocreatine. Condition category: normal nutrient_topic: Creatine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Creatine can temporarily hold a phosphate group and return it to ADP when ATP must be regenerated. organism: Torpedo californica enzyme tissue_or_cell_type: Purified creatine kinase experimental_model: X-ray structure of a creatine kinase transition-state analogue complex limitations: Nitrate models the transferring phosphoryl group; it is not declared a physiological substrate. Structural magnesium dependence does not establish benefit from extra oral magnesium. exposure: ADP, magnesium, nitrate and creatine complex at 2.1 angstrom resolution evidence_span: {"source_cache": "artifacts/creatine-research/12437342.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "291edd82015566452fe1b1321454a1df644a4c6da705fda90e8e369ea6ab53a1", "start_char": 0, "end_char": 1625, "text_sha256": "291edd82015566452fe1b1321454a1df644a4c6da705fda90e8e369ea6ab53a1"} [creatine-p12437342] The 2.1 A structure of Torpedo californica creatine kinase complexed with the ADP-Mg(2+)-NO(3)(-)-creatine transition-state analogue complex. (2002). https://pubmed.ncbi.nlm.nih.gov/12437342/ DOI: 10.1021/bi026655p
Complete structured claim and evidence
SLC25A3 supported copper transport in heterologous assays and reconstituted liposomes.
Human mitochondrial phosphate/copper carrier SLC25A3 → Copper source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/copper-research/29237729.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d4dd7c6b3cafb3923a0baab088fd82b08e087b7ec8f5fd26ee8b2bad114d54c1", "start_char": 0, "end_char": 1292, "text_sha256": "d4dd7c6b3cafb3923a0baab088fd82b08e087b7ec8f5fd26ee8b2bad114d54c1"}
experimental_model
Carrier perturbation, yeast complementation, bacterial transport and reconstituted liposomes
exposure
SLC25A3 loss or reconstitution; extracellular copper addition
limitations
The study established copper transport and COX dependence; later export findings extend rather than negate this work. Rescue conditions differ between experiments.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Human and mouse cells; heterologous yeast and Lactococcus assays
plain_language
The mitochondrial phosphate carrier also moves copper.
primary_references
[copper-p29237729] The mammalian phosphate carrier SLC25A3 is a mitochondrial copper transporter required for cytochrome c oxidase biogenesis. (2018). https://pubmed.ncbi.nlm.nih.gov/29237729/ DOI: 10.1074/jbc.ra117.000265
tissue_or_cell_type
Inner mitochondrial membrane
transport_effect
depends Transport supported in heterologous assays and liposomes, with no direction recorded.
transport_pool
the mitochondrial matrix Transport supported in heterologous assays and liposomes, with no direction recorded.
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 520–531
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Carrier perturbation, yeast complementation, bacterial transport and reconstituted liposomes · source_derived_draft · unverified_draft
### copper-slc25a3-copper-carrier SLC25A3 supported copper transport in heterologous assays and reconstituted liposomes. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: The mitochondrial phosphate carrier also moves copper. organism: Human and mouse cells; heterologous yeast and Lactococcus assays tissue_or_cell_type: Inner mitochondrial membrane experimental_model: Carrier perturbation, yeast complementation, bacterial transport and reconstituted liposomes limitations: The study established copper transport and COX dependence; later export findings extend rather than negate this work. Rescue conditions differ between experiments. exposure: SLC25A3 loss or reconstitution; extracellular copper addition evidence_span: {"source_cache": "artifacts/copper-research/29237729.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d4dd7c6b3cafb3923a0baab088fd82b08e087b7ec8f5fd26ee8b2bad114d54c1", "start_char": 0, "end_char": 1292, "text_sha256": "d4dd7c6b3cafb3923a0baab088fd82b08e087b7ec8f5fd26ee8b2bad114d54c1"} [copper-p29237729] The mammalian phosphate carrier SLC25A3 is a mitochondrial copper transporter required for cytochrome c oxidase biogenesis. (2018). https://pubmed.ncbi.nlm.nih.gov/29237729/ DOI: 10.1074/jbc.ra117.000265
Complete structured claim and evidence
Ferric carboxymaltose increased biologically active FGF23 in the substudy; the mean within-person increase at the week-two peak was approximately 303%, versus 10% with ferumoxytol.
Ferric carboxymaltose → Circulating biologically active intact FGF23 source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/iron-research/30518682.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "489945718bb05c0630fd563dc5a6da0874e80685717ab06ceedfefc38d172257", "start_char": 0, "end_char": 2371, "text_sha256": "489945718bb05c0630fd563dc5a6da0874e80685717ab06ceedfefc38d172257"}
experimental_model
Double-blind randomized comparison with physiological substudy
exposure
One treatment course of ferric carboxymaltose versus ferumoxytol; five-week follow-up
limitations
Formulation-specific pharmacological effect, not dietary iron or all intravenous iron. Trial funded by ferumoxytol manufacturer; mineral associations support but do not individually prove every causal arrow.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
1997 adults with iron-deficiency anemia; 185 in substudy
plain_language
The treatment changed a hormone that controls phosphate handling.
primary_references
[iron-p30518682] Randomized trial of intravenous iron-induced hypophosphatemia. (2018). https://pubmed.ncbi.nlm.nih.gov/30518682/ DOI: 10.1172/jci.insight.124486
tissue_or_cell_type
Blood and renal phosphate handling
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 953–964
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Double-blind randomized comparison with physiological substudy · source_derived_draft · unverified_draft
### iron-fcm-intact-fgf23 Ferric carboxymaltose increased biologically active FGF23 in the substudy; the mean within-person increase at the week-two peak was approximately 303%, versus 10% with ferumoxytol. Condition category: nutrient_deficiency nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: The treatment changed a hormone that controls phosphate handling. organism: 1997 adults with iron-deficiency anemia; 185 in substudy tissue_or_cell_type: Blood and renal phosphate handling experimental_model: Double-blind randomized comparison with physiological substudy limitations: Formulation-specific pharmacological effect, not dietary iron or all intravenous iron. Trial funded by ferumoxytol manufacturer; mineral associations support but do not individually prove every causal arrow. exposure: One treatment course of ferric carboxymaltose versus ferumoxytol; five-week follow-up evidence_span: {"source_cache": "artifacts/iron-research/30518682.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "489945718bb05c0630fd563dc5a6da0874e80685717ab06ceedfefc38d172257", "start_char": 0, "end_char": 2371, "text_sha256": "489945718bb05c0630fd563dc5a6da0874e80685717ab06ceedfefc38d172257"} [iron-p30518682] Randomized trial of intravenous iron-induced hypophosphatemia. (2018). https://pubmed.ncbi.nlm.nih.gov/30518682/ DOI: 10.1172/jci.insight.124486
Complete structured claim and evidence
Phosphate below 2.0 mg/dL occurred in 50.8% with ferric carboxymaltose versus 0.9% with ferumoxytol; low phosphate persisted at five weeks in 29.1% versus none.
Ferric carboxymaltose → Hypophosphatemia after intravenous iron source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/iron-research/30518682.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "489945718bb05c0630fd563dc5a6da0874e80685717ab06ceedfefc38d172257", "start_char": 0, "end_char": 2371, "text_sha256": "489945718bb05c0630fd563dc5a6da0874e80685717ab06ceedfefc38d172257"}
experimental_model
Double-blind randomized comparison with physiological substudy
exposure
One treatment course of ferric carboxymaltose versus ferumoxytol; five-week follow-up
limitations
Formulation-specific pharmacological effect, not dietary iron or all intravenous iron. Trial funded by ferumoxytol manufacturer; mineral associations support but do not individually prove every causal arrow.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
1997 adults with iron-deficiency anemia; 185 in substudy
plain_language
The phosphate risk depended strongly on the iron formulation.
primary_references
[iron-p30518682] Randomized trial of intravenous iron-induced hypophosphatemia. (2018). https://pubmed.ncbi.nlm.nih.gov/30518682/ DOI: 10.1172/jci.insight.124486
tissue_or_cell_type
Blood and renal phosphate handling
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 940–951
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Double-blind randomized comparison with physiological substudy · source_derived_draft · unverified_draft
### iron-fcm-phosphate-frequency Phosphate below 2.0 mg/dL occurred in 50.8% with ferric carboxymaltose versus 0.9% with ferumoxytol; low phosphate persisted at five weeks in 29.1% versus none. Condition category: nutrient_deficiency nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: The phosphate risk depended strongly on the iron formulation. organism: 1997 adults with iron-deficiency anemia; 185 in substudy tissue_or_cell_type: Blood and renal phosphate handling experimental_model: Double-blind randomized comparison with physiological substudy limitations: Formulation-specific pharmacological effect, not dietary iron or all intravenous iron. Trial funded by ferumoxytol manufacturer; mineral associations support but do not individually prove every causal arrow. exposure: One treatment course of ferric carboxymaltose versus ferumoxytol; five-week follow-up evidence_span: {"source_cache": "artifacts/iron-research/30518682.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "489945718bb05c0630fd563dc5a6da0874e80685717ab06ceedfefc38d172257", "start_char": 0, "end_char": 2371, "text_sha256": "489945718bb05c0630fd563dc5a6da0874e80685717ab06ceedfefc38d172257"} [iron-p30518682] Randomized trial of intravenous iron-induced hypophosphatemia. (2018). https://pubmed.ncbi.nlm.nih.gov/30518682/ DOI: 10.1172/jci.insight.124486
Complete structured claim and evidence
The rise in active FGF23 was associated with increased renal phosphate wasting and hypophosphatemia.
Circulating biologically active intact FGF23 → Renal phosphate wasting source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/iron-research/30518682.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "489945718bb05c0630fd563dc5a6da0874e80685717ab06ceedfefc38d172257", "start_char": 0, "end_char": 2371, "text_sha256": "489945718bb05c0630fd563dc5a6da0874e80685717ab06ceedfefc38d172257"}
experimental_model
Double-blind randomized comparison with physiological substudy
exposure
One treatment course of ferric carboxymaltose versus ferumoxytol; five-week follow-up
limitations
Formulation-specific pharmacological effect, not dietary iron or all intravenous iron. Trial funded by ferumoxytol manufacturer; mineral associations support but do not individually prove every causal arrow.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
1997 adults with iron-deficiency anemia; 185 in substudy
plain_language
More phosphate was being lost through the kidneys as the hormone rose.
primary_references
[iron-p30518682] Randomized trial of intravenous iron-induced hypophosphatemia. (2018). https://pubmed.ncbi.nlm.nih.gov/30518682/ DOI: 10.1172/jci.insight.124486
tissue_or_cell_type
Blood and renal phosphate handling
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 966–977
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Double-blind randomized comparison with physiological substudy · source_derived_draft · unverified_draft
### iron-fgf23-phosphate-loss The rise in active FGF23 was associated with increased renal phosphate wasting and hypophosphatemia. Condition category: nutrient_deficiency nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: More phosphate was being lost through the kidneys as the hormone rose. organism: 1997 adults with iron-deficiency anemia; 185 in substudy tissue_or_cell_type: Blood and renal phosphate handling experimental_model: Double-blind randomized comparison with physiological substudy limitations: Formulation-specific pharmacological effect, not dietary iron or all intravenous iron. Trial funded by ferumoxytol manufacturer; mineral associations support but do not individually prove every causal arrow. exposure: One treatment course of ferric carboxymaltose versus ferumoxytol; five-week follow-up evidence_span: {"source_cache": "artifacts/iron-research/30518682.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "489945718bb05c0630fd563dc5a6da0874e80685717ab06ceedfefc38d172257", "start_char": 0, "end_char": 2371, "text_sha256": "489945718bb05c0630fd563dc5a6da0874e80685717ab06ceedfefc38d172257"} [iron-p30518682] Randomized trial of intravenous iron-induced hypophosphatemia. (2018). https://pubmed.ncbi.nlm.nih.gov/30518682/ DOI: 10.1172/jci.insight.124486
Complete structured claim and evidence
Hypophosphatemia occurred in 7.9% versus 75.0% in trial A and 8.1% versus 73.7% in trial B with derisomaltose versus carboxymaltose.
Ferric derisomaltose / iron isomaltoside → Hypophosphatemia after intravenous iron source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/iron-research/32016310.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "883aac76c40012cb98ac88924e33b33f4985d356302929b8b26931c1869e2f0a", "start_char": 0, "end_char": 2731, "text_sha256": "883aac76c40012cb98ac88924e33b33f4985d356302929b8b26931c1869e2f0a"}
experimental_model
Two open-label randomized trials
exposure
Ferric derisomaltose 1000 mg once versus ferric carboxymaltose 750 mg twice; 35 days
limitations
Formulation and total regimen differed; no fracture endpoint or identical risk in all populations is inferred.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
245 adults, predominantly women, without reduced kidney function
plain_language
A second pair of trials also found that iron formulations differed in their phosphate effects.
primary_references
[iron-p32016310] Effects of Iron Isomaltoside vs Ferric Carboxymaltose on Hypophosphatemia in Iron-Deficiency Anemia: Two Randomized Clinical Trials. (2020). https://pubmed.ncbi.nlm.nih.gov/32016310/ DOI: 10.1001/jama.2019.22450
tissue_or_cell_type
Serum phosphate
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 992–1003
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Two open-label randomized trials · source_derived_draft · unverified_draft
### iron-fdi-fcm-comparison Hypophosphatemia occurred in 7.9% versus 75.0% in trial A and 8.1% versus 73.7% in trial B with derisomaltose versus carboxymaltose. Condition category: nutrient_deficiency nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: A second pair of trials also found that iron formulations differed in their phosphate effects. organism: 245 adults, predominantly women, without reduced kidney function tissue_or_cell_type: Serum phosphate experimental_model: Two open-label randomized trials limitations: Formulation and total regimen differed; no fracture endpoint or identical risk in all populations is inferred. exposure: Ferric derisomaltose 1000 mg once versus ferric carboxymaltose 750 mg twice; 35 days evidence_span: {"source_cache": "artifacts/iron-research/32016310.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "883aac76c40012cb98ac88924e33b33f4985d356302929b8b26931c1869e2f0a", "start_char": 0, "end_char": 2731, "text_sha256": "883aac76c40012cb98ac88924e33b33f4985d356302929b8b26931c1869e2f0a"} [iron-p32016310] Effects of Iron Isomaltoside vs Ferric Carboxymaltose on Hypophosphatemia in Iron-Deficiency Anemia: Two Randomized Clinical Trials. (2020). https://pubmed.ncbi.nlm.nih.gov/32016310/ DOI: 10.1001/jama.2019.22450
Complete structured claim and evidence
InsP8 bound the XPR1 N-terminal region with a reported dissociation constant of 180 nM.
1,5-bisdiphosphoinositol tetrakisphosphate (1,5-InsP8) → XPR1 (human phosphate exporter) source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/32019887.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bb7637b9a327b1cba07716bbed5da8a3f32a3ac00c9fff70d23ada1a736d3d18", "start_char": 0, "end_char": 2004, "text_sha256": "bb7637b9a327b1cba07716bbed5da8a3f32a3ac00c9fff70d23ada1a736d3d18"}
experimental_model
Binding, knockout and rescue experiments
exposure
PPIP5K or XPR1 deletion, kinase rescue and pyrophosphate analog delivery
limitations
Cell assays establish a transport-regulation mechanism, not benefits of oral inositol or increased bone mineralization.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Human cultured cells including Saos-2 osteosarcoma cells
plain_language
A specific inositol pyrophosphate binds the phosphate-export machinery.
primary_references
[ino-p32019887] Control of XPR1-dependent cellular phosphate efflux by InsP8 is an exemplar for functionally-exclusive inositol pyrophosphate signaling. (2020). https://pubmed.ncbi.nlm.nih.gov/32019887/ DOI: 10.1073/pnas.1908830117
tissue_or_cell_type
Cellular phosphate transport
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 873–884
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Binding, knockout and rescue experiments · source_derived_draft · unverified_draft
### ino-xpr1-ip8 InsP8 bound the XPR1 N-terminal region with a reported dissociation constant of 180 nM. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: A specific inositol pyrophosphate binds the phosphate-export machinery. organism: Human cultured cells including Saos-2 osteosarcoma cells tissue_or_cell_type: Cellular phosphate transport experimental_model: Binding, knockout and rescue experiments limitations: Cell assays establish a transport-regulation mechanism, not benefits of oral inositol or increased bone mineralization. exposure: PPIP5K or XPR1 deletion, kinase rescue and pyrophosphate analog delivery evidence_span: {"source_cache": "artifacts/inositol-research/32019887.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bb7637b9a327b1cba07716bbed5da8a3f32a3ac00c9fff70d23ada1a736d3d18", "start_char": 0, "end_char": 2004, "text_sha256": "bb7637b9a327b1cba07716bbed5da8a3f32a3ac00c9fff70d23ada1a736d3d18"} [ino-p32019887] Control of XPR1-dependent cellular phosphate efflux by InsP8 is an exemplar for functionally-exclusive inositol pyrophosphate signaling. (2020). https://pubmed.ncbi.nlm.nih.gov/32019887/ DOI: 10.1073/pnas.1908830117
Complete structured claim and evidence
PPIP5K knockout reduced XPR1-dependent phosphate efflux; wild-type PPIP5K1 rescued efflux whereas kinase-dead PPIP5K1 did not.
Diphosphoinositol pentakisphosphate kinase family → Cellular inorganic phosphate export source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/inositol-research/32019887.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bb7637b9a327b1cba07716bbed5da8a3f32a3ac00c9fff70d23ada1a736d3d18", "start_char": 0, "end_char": 2004, "text_sha256": "bb7637b9a327b1cba07716bbed5da8a3f32a3ac00c9fff70d23ada1a736d3d18"}
experimental_model
Binding, knockout and rescue experiments
exposure
PPIP5K or XPR1 deletion, kinase rescue and pyrophosphate analog delivery
limitations
Cell assays establish a transport-regulation mechanism, not benefits of oral inositol or increased bone mineralization.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Human cultured cells including Saos-2 osteosarcoma cells
plain_language
The exporter needed the signal-generating activity, not simply the presence of the protein.
primary_references
[ino-p32019887] Control of XPR1-dependent cellular phosphate efflux by InsP8 is an exemplar for functionally-exclusive inositol pyrophosphate signaling. (2020). https://pubmed.ncbi.nlm.nih.gov/32019887/ DOI: 10.1073/pnas.1908830117
tissue_or_cell_type
Cellular phosphate transport
trigger_kind
machinery_impairment Imported condition classification; unverified.
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 886–897
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Binding, knockout and rescue experiments · source_derived_draft · unverified_draft
### ino-ppip5k-export PPIP5K knockout reduced XPR1-dependent phosphate efflux; wild-type PPIP5K1 rescued efflux whereas kinase-dead PPIP5K1 did not. Condition category: machinery_impairment nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: The exporter needed the signal-generating activity, not simply the presence of the protein. organism: Human cultured cells including Saos-2 osteosarcoma cells tissue_or_cell_type: Cellular phosphate transport experimental_model: Binding, knockout and rescue experiments limitations: Cell assays establish a transport-regulation mechanism, not benefits of oral inositol or increased bone mineralization. exposure: PPIP5K or XPR1 deletion, kinase rescue and pyrophosphate analog delivery evidence_span: {"source_cache": "artifacts/inositol-research/32019887.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bb7637b9a327b1cba07716bbed5da8a3f32a3ac00c9fff70d23ada1a736d3d18", "start_char": 0, "end_char": 2004, "text_sha256": "bb7637b9a327b1cba07716bbed5da8a3f32a3ac00c9fff70d23ada1a736d3d18"} [ino-p32019887] Control of XPR1-dependent cellular phosphate efflux by InsP8 is an exemplar for functionally-exclusive inositol pyrophosphate signaling. (2020). https://pubmed.ncbi.nlm.nih.gov/32019887/ DOI: 10.1073/pnas.1908830117
Complete structured claim and evidence
In the presence of InsP6 and phosphate, human XPR1-KIDINS220 adopted an outward-open structure; InsP6 occupied SPX and juxtamembrane regions.
Phytic acid / phytate → Human XPR1-KIDINS220 complex source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/40128258.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4765253840f684d5dafa834980e3fea9edc5d7419379b4a27ccf1090f081ce00", "start_char": 0, "end_char": 1071, "text_sha256": "4765253840f684d5dafa834980e3fea9edc5d7419379b4a27ccf1090f081ce00"}
experimental_model
Cryo-EM and functional mutagenesis
exposure
InsP6 and phosphate binding
limitations
This paper tests InsP6 despite pyrophosphate wording in its title. It does not establish that dietary phytate reaches this intracellular site or overrides InsP8 selectivity in other assays.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Human proteins
plain_language
An intracellular inositol phosphate helped stabilize an open exporter complex.
primary_references
[ino-p40128258] Synergistic activation of the human phosphate exporter XPR1 by KIDINS220 and inositol pyrophosphate. (2025). https://pubmed.ncbi.nlm.nih.gov/40128258/ DOI: 10.1038/s41467-025-58200-y
tissue_or_cell_type
XPR1-KIDINS220 transport complex
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 925–936
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cryo-EM and functional mutagenesis · source_derived_draft · unverified_draft
### ino-xpr1-ins-p6 In the presence of InsP6 and phosphate, human XPR1-KIDINS220 adopted an outward-open structure; InsP6 occupied SPX and juxtamembrane regions. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: An intracellular inositol phosphate helped stabilize an open exporter complex. organism: Human proteins tissue_or_cell_type: XPR1-KIDINS220 transport complex experimental_model: Cryo-EM and functional mutagenesis limitations: This paper tests InsP6 despite pyrophosphate wording in its title. It does not establish that dietary phytate reaches this intracellular site or overrides InsP8 selectivity in other assays. exposure: InsP6 and phosphate binding evidence_span: {"source_cache": "artifacts/inositol-research/40128258.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4765253840f684d5dafa834980e3fea9edc5d7419379b4a27ccf1090f081ce00", "start_char": 0, "end_char": 1071, "text_sha256": "4765253840f684d5dafa834980e3fea9edc5d7419379b4a27ccf1090f081ce00"} [ino-p40128258] Synergistic activation of the human phosphate exporter XPR1 by KIDINS220 and inositol pyrophosphate. (2025). https://pubmed.ncbi.nlm.nih.gov/40128258/ DOI: 10.1038/s41467-025-58200-y
Complete structured claim and evidence
Adding phytate to matched-Mg bread meals reduced fractional apparent Mg absorption in a dose-dependent pattern.
Phytic acid / phytate → Intestinal magnesium absorption source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Dietary phytate -> magnesium uptake; mineral content and fractional absorption are distinct.
experimental_model
Two human crossover stable-isotope studies, 8-9 adults each.
exposure
1.49 mmol phytate: 32.5% to 13.0%; 0.75 mmol: 32.2% to 24.0%; 3.6 mmol Mg per meal.
limitations
Absorption is measured; mineral complexation was not isolated. Does not show that whole grains are net Mg-poor.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Homo sapiens
plain_language
A food component can reduce how much magnesium reaches the body from a meal.
primary_references
[mg-bohn2004] Phytic acid added to white-wheat bread inhibits fractional apparent magnesium absorption in humans (2004). https://pubmed.ncbi.nlm.nih.gov/14985216/ DOI: 10.1093/ajcn/79.3.418
tissue_or_cell_type
Human intestinal absorption estimated by fecal isotope recovery
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1602–1613
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Two human crossover stable-isotope studies, 8-9 adults each. · source_derived_draft · unverified_draft
### mg-phytate-lowers-absorption Adding phytate to matched-Mg bread meals reduced fractional apparent Mg absorption in a dose-dependent pattern. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: A food component can reduce how much magnesium reaches the body from a meal. organism: Homo sapiens tissue_or_cell_type: Human intestinal absorption estimated by fecal isotope recovery experimental_model: Two human crossover stable-isotope studies, 8-9 adults each. limitations: Absorption is measured; mineral complexation was not isolated. Does not show that whole grains are net Mg-poor. cross_nutrient: Dietary phytate -> magnesium uptake; mineral content and fractional absorption are distinct. exposure: 1.49 mmol phytate: 32.5% to 13.0%; 0.75 mmol: 32.2% to 24.0%; 3.6 mmol Mg per meal. [mg-bohn2004] Phytic acid added to white-wheat bread inhibits fractional apparent magnesium absorption in humans (2004). https://pubmed.ncbi.nlm.nih.gov/14985216/ DOI: 10.1093/ajcn/79.3.418
Complete structured claim and evidence
At added phytate-P levels of 0, 25, 50, 75, 100, 140, 175 and 250 mg, mean zinc absorption was 22%, 16%, 14%, 11%, 7%, 7%, 7% and 6%. Reductions were significant from 50 mg phytate-P in these meals.
Phytic acid / phytate → Intestinal zinc absorption source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Zinc (absorbed_nutrient); Calcium (meal_context)
evidence_location
Indexed primary abstract.
evidence_span
{"source_cache": "artifacts/zinc-clinical-sources/hallberg2006.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "3a8556f5e4076009ed9adbf018205c8a3b2d0aaae43cccc866dc6be0271451d4", "utf8_bytes": 1603}
experimental_model
Human dual-radioisotope meal study: 40 subjects, 105 meals
exposure
Wheat-roll meals contained 3.1 mg zinc and 266 mg calcium; added sodium phytate supplied 0–250 mg phytate phosphorus.
limitations
Phytate-P mass is phosphorus mass, not total phytate mass. Seven-day calcium retention and zinc absorption are distinct endpoints; meal-specific significance levels are not universal thresholds.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Homo sapiens
plain_language
Increasing phytate progressively reduced zinc uptake in the test meal.
primary_references
[zn-clin-hallberg2006] Absorption of zinc and retention of calcium: dose-dependent inhibition by phytate. (2006). https://pubmed.ncbi.nlm.nih.gov/16632176/ DOI: 10.1016/j.jtemb.2006.01.003
tissue_or_cell_type
Intestinal zinc absorption and whole-body calcium retention
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 1287–1300
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human dual-radioisotope meal study: 40 subjects, 105 meals · source_derived_draft · unverified_draft
### zn-clin-phytate-gradient At added phytate-P levels of 0, 25, 50, 75, 100, 140, 175 and 250 mg, mean zinc absorption was 22%, 16%, 14%, 11%, 7%, 7%, 7% and 6%. Reductions were significant from 50 mg phytate-P in these meals. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: Increasing phytate progressively reduced zinc uptake in the test meal. organism: Homo sapiens tissue_or_cell_type: Intestinal zinc absorption and whole-body calcium retention experimental_model: Human dual-radioisotope meal study: 40 subjects, 105 meals limitations: Phytate-P mass is phosphorus mass, not total phytate mass. Seven-day calcium retention and zinc absorption are distinct endpoints; meal-specific significance levels are not universal thresholds. exposure: Wheat-roll meals contained 3.1 mg zinc and 266 mg calcium; added sodium phytate supplied 0–250 mg phytate phosphorus. cross_nutrient: Zinc (absorbed_nutrient); Calcium (meal_context) evidence_location: Indexed primary abstract. evidence_span: {"source_cache": "artifacts/zinc-clinical-sources/hallberg2006.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "3a8556f5e4076009ed9adbf018205c8a3b2d0aaae43cccc866dc6be0271451d4", "utf8_bytes": 1603} [zn-clin-hallberg2006] Absorption of zinc and retention of calcium: dose-dependent inhibition by phytate. (2006). https://pubmed.ncbi.nlm.nih.gov/16632176/ DOI: 10.1016/j.jtemb.2006.01.003
Complete structured claim and evidence
Adding sodium phytate to otherwise phytate-free wheat rolls inhibited iron absorption in a dose-dependent manner.
Phytic acid / phytate → Nonheme iron absorption source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/2911999.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a5b0473a7a412eec5479259c7214b462fa6cfcc5948a6dae68db636de4e76f24", "start_char": 0, "end_char": 943, "text_sha256": "a5b0473a7a412eec5479259c7214b462fa6cfcc5948a6dae68db636de4e76f24"}
experimental_model
Paired radioisotope meal-absorption study
exposure
Wheat rolls with increasing sodium phytate
limitations
Luminal phytate/InsP6 exposure is distinct from free myo-inositol and intracellular InsP6 signaling.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Homo sapiens
plain_language
The six-phosphate form in food can reduce absorption of iron from that meal.
primary_references
[ino-p2911999] Iron absorption in man: ascorbic acid and dose-dependent inhibition by phytate. (1989). https://pubmed.ncbi.nlm.nih.gov/2911999/ DOI: 10.1093/ajcn/49.1.140
tissue_or_cell_type
Intestinal iron absorption
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 1159–1170
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Paired radioisotope meal-absorption study · source_derived_draft · unverified_draft
### ino-phytate-iron Adding sodium phytate to otherwise phytate-free wheat rolls inhibited iron absorption in a dose-dependent manner. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: The six-phosphate form in food can reduce absorption of iron from that meal. organism: Homo sapiens tissue_or_cell_type: Intestinal iron absorption experimental_model: Paired radioisotope meal-absorption study limitations: Luminal phytate/InsP6 exposure is distinct from free myo-inositol and intracellular InsP6 signaling. exposure: Wheat rolls with increasing sodium phytate evidence_span: {"source_cache": "artifacts/inositol-research/2911999.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a5b0473a7a412eec5479259c7214b462fa6cfcc5948a6dae68db636de4e76f24", "start_char": 0, "end_char": 943, "text_sha256": "a5b0473a7a412eec5479259c7214b462fa6cfcc5948a6dae68db636de4e76f24"} [ino-p2911999] Iron absorption in man: ascorbic acid and dose-dependent inhibition by phytate. (1989). https://pubmed.ncbi.nlm.nih.gov/2911999/ DOI: 10.1093/ajcn/49.1.140
Complete structured claim and evidence

Availability and dependencies

Each situation shows the normal role first, then what the sources report under a specific condition. A shortfall in the diet, a fault in the machinery, and a low blood reading are kept separate because they are not the same thing.

When intestinal phosphate transport is reduced

Condition: machinery_impairment · Experimental inducible Slc34a2 deletion.

Normal role: NaPi-IIb contributes to active intestinal phosphate uptake.

Recorded consequence: Intestinal absorption falls while renal conservation can preserve serum phosphate.

Scope: Mouse intestinal and renal physiology

When the drug target NHE3 is absent

Condition: machinery_impairment · NHE3-deficient enteroid monolayers.

Normal role: NHE3 inhibition alters epithelial resistance and phosphate flux.

Recorded consequence: Tenapanor adds no further effect on TEER or phosphate flux.

Scope: Human intestinal enteroid model

When an apical PTH signal loses its scaffold

Condition: machinery_impairment · Experimental Nherf1 deletion.

Normal role: Apical PTH receptors can couple through NHERF1 to PLC and transporter internalization.

Recorded consequence: Apically selective PTH signaling is impaired, while other stimulation routes can still internalize NaPi-IIa.

Scope: Mouse renal proximal tubule

When CaSR phosphate sensing is disrupted

Condition: machinery_impairment · R62 mutation in the receptor or experimental Casr loss in mouse glands.

Normal role: Phosphate inhibits CaSR activity and increases PTH secretion in the tested system.

Recorded consequence: The phosphate-induced receptor inhibition or glandular secretory response is lost.

Scope: Receptor constructs and isolated mouse glands

When mitochondrial phosphate entry fails

Condition: machinery_impairment · Homozygous Gly72Glu in the muscle-expressed exon-3A isoform.

Normal role: SLC25A3 supplies matrix phosphate for ATP synthesis.

Recorded consequence: Muscle mitochondrial ATP synthesis was deficient, whereas fibroblast ATP synthesis was preserved.

Scope: Two affected human siblings; tissue assays

When dietary phosphate restriction lowers muscle ATP flux

Condition: nutrient_deficiency · Experimentally induced dietary hypophosphatemia.

Normal role: Adequate phosphate availability supports muscle ATP synthetic flux.

Recorded consequence: Measured muscle ATP synthetic flux fell and normalized after phosphate restoration.

Scope: Mouse low-phosphate feeding study

When renal phosphate wasting limits muscle energetics

Condition: machinery_impairment · NaPi-IIa knockout in mice or SLC34A3-associated renal wasting in one human.

Normal role: Renal reabsorption helps maintain phosphate available to muscle.

Recorded consequence: Low phosphate and low ATP synthetic flux improved after phosphate repletion.

Scope: Mouse genetics and one human clinical investigation

When one phosphate transporter compensates for another

Condition: machinery_impairment · Smooth-muscle Slc20a1 deletion, with or without PiT2 suppression.

Normal role: PiT-family transport supports phosphate uptake in vascular smooth muscle.

Recorded consequence: PiT2 can preserve phosphate uptake and calcification; removing the backup reduces both.

Scope: Mouse vascular smooth muscle and human cell rescue

When iron treatment increases phosphate loss

Condition: machinery_impairment · Ferric carboxymaltose-associated rise in intact FGF23.

Normal role: Renal conservation and calcitriol help maintain phosphate balance.

Recorded consequence: Renal phosphate wasting occurs alongside lower calcitriol/calcium and higher PTH.

Scope: Human randomized trial and physiological substudy

When hypophosphatemia accompanies weak diaphragm contraction

Condition: biomarker_context · Low measured serum phosphorus during acute respiratory failure.

Normal role: Diaphragm contraction depends on adequate cellular energetics and excitation.

Recorded consequence: Stimulated diaphragm pressure improved after phosphate correction in the study.

Scope: Eight ventilated patients

When very low phosphate accompanies red-cell ATP depletion

Condition: biomarker_context · Very low plasma and erythrocyte inorganic phosphate in ICU samples.

Normal role: Red cells regulate ATP and organic phosphate pools.

Recorded consequence: Marked ATP depletion was confined to the low-Pi samples in this observational dataset.

Scope: Human ICU erythrocytes

When excess FGF23 drives phosphate loss

Condition: machinery_impairment · PHEX-associated XLH with excess FGF23.

Normal role: Renal handling maintains circulating phosphate for tissue use.

Recorded consequence: FGF23 blockade improves the serum phosphate endpoint and fracture healing in the trial.

Scope: Adults with XLH

The sources

Every document behind this chapter is preserved word for word. Open one to read it in full with its recorded conflicts marked in place.

Calcium: mechanism-first literature curation (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Creatine: synthesis, transport, phosphocreatine energetics and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Sodium: gradients, nutrient transport, fluid regulation and loss states (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source

Recorded disagreements

Where two sources say different things, both are kept and the difference is explained. You can discuss a disagreement or propose a mechanism that might account for it.

ANKH-associated PPi: earlier transport interpretation versus extracellular ATP conversionEarly cellular PPi redistribution and oocyte PPi uptake supported direct-transport interpretations; later ENPP1 deletion separated ATP release from PPi appearance. Research comparison category: mechanism_and_model_difference.Read the recorded disagreement

Open questions in this collection

Questions the curators could not answer from the sources in front of them, kept here with the reason each one is still open. These are gaps in this collection, not findings or proof that no one has studied them.

How much phosphate moves by each intestinal route at a particular human intake?Active-transporter contributions depend on species, intake and method; a mouse active-flux percentage is not a universal human total-absorption percentage.
What dietary phosphate exposure optimizes long-term outcomes across different kidney-function states?Small diet studies and cell experiments cannot provide one universal intake target; the 13-person energy study was observational.
When does an acute low serum phosphate result indicate harmful intracellular depletion rather than transient redistribution?The postoperative and ICU red-cell studies show that ATP and 2,3-DPG do not invariably track serum phosphate.
How do InsP6 and InsP8 contributions to XPR1 differ across native tissues and preparation conditions?Keep the respective binding, cell-rescue and KIDINS220 structure evidence without inventing an exclusive ligand assignment.
What explains the formulation-specific FGF23 effect of intravenous iron in every patient?The randomized outcomes and downstream cascade are documented; one unifying upstream processing mechanism is not established by these trials.
How broadly does the 2026 phosphate–mitochondrial peroxide–FGFR1 mechanism apply outside the tested tumor systems?This new mechanism does not establish a dietary phosphorus–cancer causal effect in humans.
Which human intracellular phosphate measurements best identify a tissue energy limitation?Serum phosphate, ATP concentration, ATP synthetic flux and compartmental transport can diverge.
Does nutritional phosphate repletion materially alter thiamine, B6 or folate enzyme function in phosphate-depleted humans?The shared enzymology is real, but linked experiments do not demonstrate a universal failure or rescue of vitamin repletion.

Chapters are assembled from supplied drafts and curated literature summaries. Statements remain unverified against the primary studies, and the ledger is not medical advice.

Evidence, AI assistance and curation standards

Phosphorus

The mechanisms

Raising extracellular phosphate inhibited CaSR activity through noncompetitive antagonism in the experimental system.

Human MAT2A formed S-adenosylmethionine before rapid triphosphate hydrolysis and product release in the kinetic study.

Reported serum FGF23 decreased during low-phosphate feeding and increased after oral phosphate loading in healthy men.

Marked erythrocyte ATP depletion below 1 mmol/L cells was observed only when cellular Pi was below 0.3 mmol/L cells and plasma Pi below 0.35 mmol/L in this dataset.

After low-phosphate feeding and an acute phosphate bolus, Slc34a2-null mice absorbed approximately 50% less phosphate than wild type.

Slc34a2-null mice excreted more phosphate in feces.

Slc34a2-null mice excreted less phosphate in urine.

Serum phosphate remained unchanged in the Slc34a2-null mice despite altered intestinal and urinary handling.

The Slc34a2-null phenotype included reduced circulating FGF23.

Renal NaPi-IIa protein expression increased in Slc34a2-null mice.

NaPi-IIb accounted for more than 90% of measured active phosphate absorption in isolated mouse ileum segments.

Tenapanor inhibits intestinal NHE3, the sodium/hydrogen exchanger targeted in the phosphate-absorption study.

Tenapanor increased transepithelial electrical resistance in the human intestinal enteroid model.

Tenapanor reduced paracellular phosphate permeability in the human intestinal enteroid model.

NHE3-deficient monolayers mimicked the phosphate phenotype and showed no further tenapanor effect on phosphate flux or TEER.

Tenapanor increased stool phosphorus in the four-day healthy-volunteer study.

Tenapanor decreased urinary phosphorus in the four-day healthy-volunteer study.

PTH-(1–34) induced NaPi-IIa internalization in both wild-type and Nherf1-deficient mice.

Apical PTH-receptor stimulation of PLC was impaired in Nherf1-deficient mice.

PTH-(3–34), used to stimulate apical receptors, failed to induce NaPi-IIa internalization in Nherf1-deficient mice.

Pathophysiologic phosphate concentrations rapidly and reversibly increased PTH secretion from freshly isolated human parathyroid cells.

The R62A CaSR construct lost the phosphate-induced receptor inhibition observed with wild-type receptor.

The phosphate-induced PTH increase seen in wild-type mouse parathyroid glands was absent in Casr-knockout glands.

FAM20C directly phosphorylated FGF23 at Ser180 within its proteolytic processing motif.

Ser180 phosphorylation inhibited GalNAc-T3-mediated O-glycosylation of FGF23.

FAM20C-dependent FGF23 phosphorylation promoted furin cleavage and hormone inactivation.

SLC25A3 supplies inorganic phosphate to the mitochondrial matrix for aerobic ATP synthesis; the family study localized the defect to the muscle-expressed isoform.

Intact muscle mitochondria from the affected siblings showed deficient ATP synthesis.

Fibroblast mitochondrial ATP synthesis was preserved, correlating with use of the alternative exon-3B isoform.

Diet-induced hypophosphatemic mice had approximately 50% lower basal and insulin-stimulated muscle ATP synthetic flux.

NaPi-IIa-knockout mice had approximately 50% lower plasma phosphate and muscle ATP synthetic flux than controls.

Restoring plasma phosphate normalized muscle ATP synthetic flux in both mouse hypophosphatemia models.

The patient with SLC34A3-associated chronic hypophosphatemia had approximately 50% lower serum phosphate and muscle ATP synthetic flux.

After oral phosphate repletion normalized serum phosphate, measured muscle ATP synthetic flux normalized in the single patient.

After SAM formation, MAT2A rapidly hydrolyzed the beta–gamma bond of triphosphate and released phosphate and pyrophosphate.

Two Mg2+ ions chelated the alpha- and gamma-phosphoryl groups of PNPNP in the human MAT2A structure.

The beta-phosphoryl oxygen of the MAT2A-bound PNPNP ligand contacted the essential potassium ion.

Changing pyrophosphate-mimicking nucleotide leaving groups altered POLB chemical-step kinetics in a base-pair-dependent manner.

Human CCTbeta expression increased CCT activity and cellular CDP-choline accumulation in COS-7 cells.

Human CCTbeta expression enhanced radiolabeling of phosphatidylcholine in COS-7 cells.

XPR1 was identified as a binding partner of the phosphate-uptake transporter PiT1.

XPR1 localized to a subset of intracellular LAMP1-positive puncta designated XLPVs.

In the challenge model, InsP8-dependent XPR1 regulation first adjusted phosphate efflux.

The study reported later XPR1-dependent modulation of PiT1 turnover, resetting phosphate uptake after the earlier efflux response.

Elevated extracellular phosphate induced concentration-dependent mineral deposition in human aortic smooth-muscle cultures; 1.4 mmol/L control cultures did not mineralize.

Elevated phosphate increased osteocalcin and Cbfa1/RUNX2 expression in cultured human aortic smooth-muscle cells.

Aortic medial PiT2 mRNA increased approximately twofold after smooth-muscle PiT1 deletion.

PiT1 deletion did not reduce aortic calcification in the mouse CKD/phosphate-loading model.

PiT2 knockdown reduced phosphate uptake in PiT1-deficient mouse vascular smooth-muscle cells.

PiT2 knockdown reduced phosphate-induced calcification in PiT1-deficient mouse vascular smooth-muscle cells.

PiT2 overexpression restored phosphate uptake and phosphate-induced calcification in human PiT1-deficient vascular smooth-muscle cells.

The study linked phosphate entry into mitochondria to increased hydrogen-peroxide production in the FGFR1 activation pathway.

The phosphate-associated hydrogen-peroxide burst oxidized critical cysteine and methionine residues of FGFR1.

FGFR1 oxidation promoted receptor activation and downstream signaling in the phosphate-sensing tumor-model experiments.

Diet-related FGF23 changes correlated inversely with maximal tubular phosphate reabsorption and calcitriol, and positively with urinary phosphate excretion.

Serum phosphate rose from 1.11 to 1.32 mmol/L during the higher-phosphate/calcium regimen.

Intact FGF23 rose from 33 to 37 ng/L during the higher-phosphate/calcium regimen.

Urinary phosphate rose from 21.6 to 28.8 mmol/day during the higher-phosphate/calcium regimen.

PTH declined during the higher-phosphate/calcium regimen even while FGF23 increased.

The vegetarian diet produced lower serum phosphorus than the meat diet after one week.

The vegetarian diet produced lower FGF23 than the meat diet after one week.

Ferric carboxymaltose-associated intact-FGF23 elevation accompanied lower circulating calcitriol in the substudy.

The ferric-carboxymaltose substudy found lower calcium accompanying the intact-FGF23 rise.

PTH increased in the ferric-carboxymaltose-associated phosphate-wasting cascade.

After serum phosphorus rose from 0.55 to 1.33 mmol/L, mean stimulated transdiaphragmatic pressure increased from 9.75 to 17.25 cm H2O.

No dependence of erythrocyte 2,3-DPG concentration on cellular Pi was detected in the ICU dataset.

Raising incubation Pi from 1 to 5 mmol/L increased normal-donor erythrocyte lactate production from 2.09 to 3.11 mmol/hour/L cells.

The 1-versus-5 mmol/L Pi incubation changed erythrocyte glycolytic output without a significant ATP-concentration change.

Serum phosphate fell after surgery and during glucose infusion, particularly with continuous glucose administration.

The postoperative and glucose-associated serum phosphate reductions were not accompanied by reduced red-cell ATP.

The serum phosphate reductions were not accompanied by reduced red-cell 2,3-DPG.

Days alive after ICU discharge did not differ significantly: 44.8 versus 39.9 days, estimated difference 4.9 days (95% CI −2.3 to 13.6), p=0.19.

A component analysis found 149/164 participants alive at day 60 with restriction versus 128/163 with standard feeding, p=0.002.

Burosumab binds and inhibits FGF23, the phosphate-wasting hormone targeted in the XLH trial.

Across dosing-interval midpoints, 94.1% on burosumab versus 7.6% on placebo attained mean serum phosphate above the lower limit of normal.

At week 24, 43.1% of baseline active fractures were fully healed with burosumab versus 7.7% with placebo.

The WOMAC stiffness endpoint significantly improved versus placebo in the week-24 analysis.

Worst pain and physical function did not achieve significance after the trial’s multiplicity adjustment.