Inorganic phosphate (Pi; protonation depends on pH)

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

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

evidence_span

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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

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

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

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

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

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

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

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

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

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

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

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

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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

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

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

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 a vitamin D breakdown enzyme rose.

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 1394–1404

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-cyp24a1-transcript Magnesium deprivation increased renal cyp24a1-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 a vitamin D breakdown enzyme rose. 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

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 kidney made less of the message for vitamin D activation.

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 1382–1392

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-cyp27b1-transcript Magnesium deprivation decreased renal cyp27b1-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 kidney made less of the message for vitamin D activation. 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

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

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

cross_nutrient

Magnesium -> PHOSPHO1 -> phosphate production; joins the existing calcium PHOSPHO1 records.

experimental_model

Purified recombinant phosphatase assays.

limitations

Enzyme evidence does not measure the effect of oral Mg on bone; substrate Km values are not Mg deficiency thresholds.

nutrient_topic

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

organism

Homo sapiens

plain_language

Magnesium helps a phosphate-releasing enzyme already connected to calcium mineralization.

primary_references

[mg-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

Purified recombinant human PHOSPHO1

Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1455–1465

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified recombinant phosphatase assays. · source_derived_draft · unverified_draft

### mg-phospho1-cofactor Recombinant human PHOSPHO1 showed strong Mg dependence when hydrolyzing phosphoethanolamine and phosphocholine. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Magnesium helps a phosphate-releasing enzyme already connected to calcium mineralization. organism: Homo sapiens tissue_or_cell_type: Purified recombinant human PHOSPHO1 experimental_model: Purified recombinant phosphatase assays. limitations: Enzyme evidence does not measure the effect of oral Mg on bone; substrate Km values are not Mg deficiency thresholds. cross_nutrient: Magnesium -> PHOSPHO1 -> phosphate production; joins the existing calcium PHOSPHO1 records. [mg-roberts2004] Human PHOSPHO1 exhibits high specific phosphoethanolamine and phosphocholine phosphatase activities (2004). https://pubmed.ncbi.nlm.nih.gov/15175005/ DOI: 10.1042/bj20040511

cross_nutrient

Magnesium + zinc -> ALPL; connects to calcium/phosphate mineralization.

experimental_model

Recombinant TNAP metal-reconstitution assay. Activity was measured using artificial pNPP substrate.

limitations

Not an oral supplementation synergy trial. This assay does not quantify physiological pyrophosphate turnover or mineral deposition.

nutrient_topic

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

organism

Homo sapiens

plain_language

This mineralization enzyme needs the right metals in different sites.

primary_references

[mg-hoylaerts2015] Functional significance of calcium binding to tissue-nonspecific alkaline phosphatase (2015). https://pubmed.ncbi.nlm.nih.gov/25775211/ DOI: 10.1371/journal.pone.0119874

tissue_or_cell_type

Recombinant human TNAP; cell-free p-nitrophenyl phosphate (pNPP) hydrolysis assay

Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1467–1477

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant TNAP metal-reconstitution assay. Activity was measured using artificial pNPP substrate. · source_derived_draft · unverified_draft

### mg-zinc-alpl-reconstitution Combined Mg and Zn reconstituted demetalated TNAP activity; neither metal alone restored the same activity. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: This mineralization enzyme needs the right metals in different sites. organism: Homo sapiens tissue_or_cell_type: Recombinant human TNAP; cell-free p-nitrophenyl phosphate (pNPP) hydrolysis assay experimental_model: Recombinant TNAP metal-reconstitution assay. Activity was measured using artificial pNPP substrate. limitations: Not an oral supplementation synergy trial. This assay does not quantify physiological pyrophosphate turnover or mineral deposition. cross_nutrient: Magnesium + zinc -> ALPL; connects to calcium/phosphate mineralization. [mg-hoylaerts2015] Functional significance of calcium binding to tissue-nonspecific alkaline phosphatase (2015). https://pubmed.ncbi.nlm.nih.gov/25775211/ DOI: 10.1371/journal.pone.0119874

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

magnesium -> PTH -> calcium/phosphate

experimental_model

Single-child Mg withdrawal/repletion with hormone challenge

limitations

Single case; shows PTH resistance is not obligatory. Primary hypomagnesemia was not genetically assigned in this study.

nutrient_topic

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

organism

Homo sapiens

plain_language

In this child the main failure was releasing the hormone; tissues could still respond when hormone was provided.

primary_references

[suh-1973-preserved-pth-response] Pathogenesis of Hypocalcemia in Primary Hypomagnesemia: Normal End-Organ Responsiveness to Parathyroid Hormone, Impaired Parathyroid Gland Function (1973). https://www.jci.org/articles/view/107159 DOI: 10.1172/JCI107159

tissue_or_cell_type

Blood and kidney

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 397–407

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Single-child Mg withdrawal/repletion with hormone challenge · source_derived_draft · unverified_draft

### primary-hypomagnesemia-can-preserve-pth-response A child with primary hypomagnesemia retained calcemic and renal phosphate/cAMP responses to parathyroid extract during Mg depletion despite impaired endogenous PTH secretion. Condition category: nutrient_deficiency nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: In this child the main failure was releasing the hormone; tissues could still respond when hormone was provided. organism: Homo sapiens tissue_or_cell_type: Blood and kidney experimental_model: Single-child Mg withdrawal/repletion with hormone challenge limitations: Single case; shows PTH resistance is not obligatory. Primary hypomagnesemia was not genetically assigned in this study. cross_nutrient: magnesium -> PTH -> calcium/phosphate [suh-1973-preserved-pth-response] Pathogenesis of Hypocalcemia in Primary Hypomagnesemia: Normal End-Organ Responsiveness to Parathyroid Hormone, Impaired Parathyroid Gland Function (1973). https://www.jci.org/articles/view/107159 DOI: 10.1172/JCI107159

evidence_span

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experimental_model

Acute-hypoxia cellular and mitochondrial experiments with ion imaging and respiratory/membrane assays

exposure

Acute hypoxia and inhibition of mitochondrial sodium/calcium exchange

limitations

Mechanistic research under hypoxia, including multiple preparations. Do not infer that dietary salt drives this chain, that every tissue responds identically, or that ROS here proves disease.

nutrient_topic

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

organism

Human and mouse cells; additional rat vascular experiments in the paper

plain_language

Calcium stored in deposits became available as free calcium.

primary_references

[sodium-p32728214] Na+ controls hypoxic signalling by the mitochondrial respiratory chain. (2020). https://pubmed.ncbi.nlm.nih.gov/32728214/ DOI: 10.1038/s41586-020-2551-y

tissue_or_cell_type

Mitochondrial matrix and inner membrane

Sodium: gradients, nutrient transport, fluid regulation and loss states (2026-09-17) · lines 759–770

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Acute-hypoxia cellular and mitochondrial experiments with ion imaging and respiratory/membrane assays · source_derived_draft · unverified_draft

### sodium-matrix-calcium Matrix acidification released free calcium from mitochondrial calcium phosphate deposits. Condition category: normal nutrient_topic: Sodium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Calcium stored in deposits became available as free calcium. organism: Human and mouse cells; additional rat vascular experiments in the paper tissue_or_cell_type: Mitochondrial matrix and inner membrane experimental_model: Acute-hypoxia cellular and mitochondrial experiments with ion imaging and respiratory/membrane assays limitations: Mechanistic research under hypoxia, including multiple preparations. Do not infer that dietary salt drives this chain, that every tissue responds identically, or that ROS here proves disease. exposure: Acute hypoxia and inhibition of mitochondrial sodium/calcium exchange evidence_span: {"source_cache": "artifacts/sodium-research/32728214.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2780431aa362c99c816f986e923fd65ed0c0324e8c8674af8ff2a2f9367762c1", "start_char": 0, "end_char": 1533, "text_sha256": "2780431aa362c99c816f986e923fd65ed0c0324e8c8674af8ff2a2f9367762c1"} [sodium-p32728214] Na+ controls hypoxic signalling by the mitochondrial respiratory chain. (2020). https://pubmed.ncbi.nlm.nih.gov/32728214/ DOI: 10.1038/s41586-020-2551-y

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

compartment_description

Bone extracellular matrix

experimental_model

Microscopy, diffraction and elemental analysis

limitations

Biological apatite is substituted and nonstoichiometric; the ideal hydroxyapatite formula is not an exact tissue composition.

nutrient_topic

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

organism

Danio rerio

plain_language

Bone contains calcium in a solid mineral phase, distinct from dissolved calcium ions.

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

Fin-ray bone

Calcium: mechanism-first literature curation (2026-09-17) · lines 862–872

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Microscopy, diffraction and elemental analysis · source_derived_draft · unverified_draft

### bone-calcium-in-solid-apatite Mature zebrafish fin-ray bone contains crystalline carbonated apatite platelets embedded in an organized collagen matrix. Condition category: normal nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Bone contains calcium in a solid mineral phase, distinct from dissolved calcium ions. organism: Danio rerio tissue_or_cell_type: Fin-ray bone experimental_model: Microscopy, diffraction and elemental analysis limitations: Biological apatite is substituted and nonstoichiometric; the ideal hydroxyapatite formula is not an exact tissue composition. 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

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

compartment_description

Matrix-vesicle lumen

experimental_model

Localization and activity assays, including Alpl-deficient vesicles

limitations

Localization does not establish the sole route for vesicle phosphate or calcium entry.

nutrient_topic

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

organism

Mus musculus

plain_language

Mineralizing vesicles contain phosphate-generating machinery within their membrane.

primary_references

[roberts2007] Functional involvement of PHOSPHO1 in matrix vesicle-mediated skeletal mineralization (2007). https://pubmed.ncbi.nlm.nih.gov/17227223/ DOI: 10.1359/jbmr.070108

tissue_or_cell_type

Osteoblast-derived matrix vesicles

Calcium: mechanism-first literature curation (2026-09-17) · lines 919–929

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Localization and activity assays, including Alpl-deficient vesicles · source_derived_draft · unverified_draft

### phospho1-in-matrix-vesicles Active PHOSPHO1 was detected inside osteoblast-derived matrix vesicles; phosphoethanolamine hydrolase activity became accessible after vesicle sonication. Condition category: normal nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Mineralizing vesicles contain phosphate-generating machinery within their membrane. organism: Mus musculus tissue_or_cell_type: Osteoblast-derived matrix vesicles experimental_model: Localization and activity assays, including Alpl-deficient vesicles limitations: Localization does not establish the sole route for vesicle phosphate or calcium entry. compartment_description: Matrix-vesicle lumen [roberts2007] Functional involvement of PHOSPHO1 in matrix vesicle-mediated skeletal mineralization (2007). https://pubmed.ncbi.nlm.nih.gov/17227223/ DOI: 10.1359/jbmr.070108

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

B1 shortage -> renal electrolyte handling in case evidence.

experimental_model

Two pediatric cases.

exposure

Study-specific exposure described in the model; no regimen inferred beyond the accessed evidence.

limitations

The authors attributed the pattern to renal losses; individual electrolyte fluxes and transporter mediators are not established here.

nutrient_topic

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

organism

Homo sapiens

plain_language

B1 shortage may accompany kidney losses, which differ from minerals simply moving into cells.

primary_references

[b1-maiorana2014] Acute thiamine deficiency and refeeding syndrome: Similar findings but different pathogenesis (2014). https://pubmed.ncbi.nlm.nih.gov/24985016/ DOI: 10.1016/j.nut.2014.02.019

tissue_or_cell_type

Kidney and blood

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1758–1769

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Two pediatric cases. · source_derived_draft · unverified_draft

### b1-deficiency-renal-electrolyte-loss Two leukemia cases with acute thiamine deficiency showed proximal tubular dysfunction and electrolyte abnormalities resembling refeeding syndrome. Condition category: nutrient_deficiency nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: B1 shortage may accompany kidney losses, which differ from minerals simply moving into cells. organism: Homo sapiens tissue_or_cell_type: Kidney and blood experimental_model: Two pediatric cases. limitations: The authors attributed the pattern to renal losses; individual electrolyte fluxes and transporter mediators are not established here. cross_nutrient: B1 shortage -> renal electrolyte handling in case evidence. exposure: Study-specific exposure described in the model; no regimen inferred beyond the accessed evidence. [b1-maiorana2014] Acute thiamine deficiency and refeeding syndrome: Similar findings but different pathogenesis (2014). https://pubmed.ncbi.nlm.nih.gov/24985016/ DOI: 10.1016/j.nut.2014.02.019

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

B1 repletion and K/P/Mg management address different requirements.

experimental_model

Prospective cohort and individual case histories.

exposure

Study-specific exposure described in the model; no regimen inferred beyond the accessed evidence.

limitations

No claim that thiamine caused the syndrome, that supplementation failed biologically, or that glucose should be withheld in an emergency.

nutrient_topic

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

organism

Homo sapiens

plain_language

Providing vitamins did not by itself prevent every electrolyte and fluid complication.

primary_references

[b1-rio2013] Occurrence of refeeding syndrome in adults started on artificial nutrition support: prospective cohort study (2013). https://pubmed.ncbi.nlm.nih.gov/23315514/ DOI: 10.1136/bmjopen-2012-002173

tissue_or_cell_type

Whole-body clinical nutrition

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1733–1744

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Prospective cohort and individual case histories. · source_derived_draft · unverified_draft

### b1-refeeding-vitamins-not-complete-rescue Refeeding syndrome occurred in three cohort participants; two had received vitamin B/C preparations before nutrition support. Condition category: nutrient_deficiency nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Providing vitamins did not by itself prevent every electrolyte and fluid complication. organism: Homo sapiens tissue_or_cell_type: Whole-body clinical nutrition experimental_model: Prospective cohort and individual case histories. limitations: No claim that thiamine caused the syndrome, that supplementation failed biologically, or that glucose should be withheld in an emergency. cross_nutrient: B1 repletion and K/P/Mg management address different requirements. exposure: Study-specific exposure described in the model; no regimen inferred beyond the accessed evidence. [b1-rio2013] Occurrence of refeeding syndrome in adults started on artificial nutrition support: prospective cohort study (2013). https://pubmed.ncbi.nlm.nih.gov/23315514/ DOI: 10.1136/bmjopen-2012-002173

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/chloride-research/11099045.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4929ed9da0f3702bbd28bf679f79c2dfb13b4e81d23e44327b27bebdcf3a7cca", "start_char": 0, "end_char": 1218, "text_sha256": "4929ed9da0f3702bbd28bf679f79c2dfb13b4e81d23e44327b27bebdcf3a7cca"}

experimental_model

Clcn5 knockout and uptake measurements

exposure

Clcn5 disruption

limitations

The PTH/vitamin-D/hypercalciuria explanation includes proposed downstream steps; do not treat every link as demonstrated.

nutrient_topic

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

organism

Mouse

plain_language

An endosomal defect changed where the phosphate transporter was located.

primary_references

[chloride-p11099045] ClC-5 Cl- -channel disruption impairs endocytosis in a mouse model for Dent's disease. (2000). https://pubmed.ncbi.nlm.nih.gov/11099045/ DOI: 10.1038/35042597

tissue_or_cell_type

Proximal renal tubule

trigger_kind

machinery_impairment Imported condition classification; unverified.

Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 718–729

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Clcn5 knockout and uptake measurements · source_derived_draft · unverified_draft

### chloride-clc5-napi NaPi-2 redistributed toward intracellular vesicles at steady state despite slower internalization. Condition category: machinery_impairment nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: An endosomal defect changed where the phosphate transporter was located. organism: Mouse tissue_or_cell_type: Proximal renal tubule experimental_model: Clcn5 knockout and uptake measurements limitations: The PTH/vitamin-D/hypercalciuria explanation includes proposed downstream steps; do not treat every link as demonstrated. exposure: Clcn5 disruption evidence_span: {"source_cache": "artifacts/chloride-research/11099045.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4929ed9da0f3702bbd28bf679f79c2dfb13b4e81d23e44327b27bebdcf3a7cca", "start_char": 0, "end_char": 1218, "text_sha256": "4929ed9da0f3702bbd28bf679f79c2dfb13b4e81d23e44327b27bebdcf3a7cca"} [chloride-p11099045] ClC-5 Cl- -channel disruption impairs endocytosis in a mouse model for Dent's disease. (2000). https://pubmed.ncbi.nlm.nih.gov/11099045/ DOI: 10.1038/35042597

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/chloride-research/11207362.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5e10ae61257fa402ab9e10d55af44013139462a9d85236b75f5b52bdea0c7b5a", "start_char": 0, "end_char": 821, "text_sha256": "5e10ae61257fa402ab9e10d55af44013139462a9d85236b75f5b52bdea0c7b5a"}

experimental_model

Clcn7 knockout and human mutation identification

exposure

ClC-7 loss

limitations

Historical title calls ClC-7 a channel; current exchanger classification does not change the reported knockout phenotype. Not a dietary chloride study.

nutrient_topic

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

organism

Mouse; human infantile osteopetrosis patient

plain_language

Having bone-resorbing cells is insufficient when their transport machinery fails.

primary_references

[chloride-p11207362] Loss of the ClC-7 chloride channel leads to osteopetrosis in mice and man. (2001). https://pubmed.ncbi.nlm.nih.gov/11207362/ DOI: 10.1016/s0092-8674(01)00206-9

tissue_or_cell_type

Osteoclast ruffled border

trigger_kind

machinery_impairment Imported condition classification; unverified.

Chloride: transport, acid-base balance, nutrient interactions and loss states (2026-09-17) · lines 783–794

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Clcn7 knockout and human mutation identification · source_derived_draft · unverified_draft

### chloride-clc7-bone Clcn7-null mice had severe osteopetrosis despite normal osteoclast numbers. Condition category: machinery_impairment nutrient_topic: Chloride research collection; topical membership is not evidence of a direct dietary effect. plain_language: Having bone-resorbing cells is insufficient when their transport machinery fails. organism: Mouse; human infantile osteopetrosis patient tissue_or_cell_type: Osteoclast ruffled border experimental_model: Clcn7 knockout and human mutation identification limitations: Historical title calls ClC-7 a channel; current exchanger classification does not change the reported knockout phenotype. Not a dietary chloride study. exposure: ClC-7 loss evidence_span: {"source_cache": "artifacts/chloride-research/11207362.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5e10ae61257fa402ab9e10d55af44013139462a9d85236b75f5b52bdea0c7b5a", "start_char": 0, "end_char": 821, "text_sha256": "5e10ae61257fa402ab9e10d55af44013139462a9d85236b75f5b52bdea0c7b5a"} [chloride-p11207362] Loss of the ClC-7 chloride channel leads to osteopetrosis in mice and man. (2001). https://pubmed.ncbi.nlm.nih.gov/11207362/ DOI: 10.1016/s0092-8674(01)00206-9

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Potassium deficiency changes sodium-phosphate transport machinery in an isoform-specific manner.

endpoint

Potassium deficiency increased brush-border NaPi-IIa abundance in the studied rat experiments despite reduced total sodium-dependent phosphate transport.

experimental-exposure

Potassium-deficient rats and mice; renal brush-border membrane protein, transcript, immunofluorescence and electron-microscopy analyses.

experimental_model

Potassium-deficient rats and mice; renal brush-border membrane protein, transcript, immunofluorescence and electron-microscopy analyses.

limitations

Isoform abundance and localization do not apportion total phosphate flux; transporter-specific contributions and initiating signal remain unresolved.

nutrient_topic

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

organism

Rattus norvegicus; Mus musculus where specified

plain_language

More of one transporter did not mean greater overall phosphate recovery.

primary_references

[breusegem-2009-phosphate] Differential regulation of the renal sodium-phosphate cotransporters NaPi-IIa, NaPi-IIc, and PiT-2 in dietary potassium deficiency (2009). https://pubmed.ncbi.nlm.nih.gov/19493963/ DOI: 10.1152/ajprenal.90765.2008

tissue_or_cell_type

renal proximal-tubule brush border

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1372–1384

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Potassium-deficient rats and mice; renal brush-border membrane protein, transcript, immunofluorescence and electron-microscopy analyses. · source_derived_draft · unverified_draft

### k-deficiency-napi2a-abundance Potassium deficiency increased brush-border NaPi-IIa abundance in the studied rat experiments despite reduced total sodium-dependent phosphate transport. Condition category: nutrient_deficiency nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: More of one transporter did not mean greater overall phosphate recovery. organism: Rattus norvegicus; Mus musculus where specified tissue_or_cell_type: renal proximal-tubule brush border experimental_model: Potassium-deficient rats and mice; renal brush-border membrane protein, transcript, immunofluorescence and electron-microscopy analyses. limitations: Isoform abundance and localization do not apportion total phosphate flux; transporter-specific contributions and initiating signal remain unresolved. cross_nutrient: Potassium deficiency changes sodium-phosphate transport machinery in an isoform-specific manner. experimental-exposure: Potassium-deficient rats and mice; renal brush-border membrane protein, transcript, immunofluorescence and electron-microscopy analyses. endpoint: Potassium deficiency increased brush-border NaPi-IIa abundance in the studied rat experiments despite reduced total sodium-dependent phosphate transport. [breusegem-2009-phosphate] Differential regulation of the renal sodium-phosphate cotransporters NaPi-IIa, NaPi-IIc, and PiT-2 in dietary potassium deficiency (2009). https://pubmed.ncbi.nlm.nih.gov/19493963/ DOI: 10.1152/ajprenal.90765.2008

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Potassium deficiency changes sodium-phosphate transport machinery in an isoform-specific manner.

endpoint

Dietary potassium deficiency decreased proximal-tubule brush-border NaPi-IIc protein abundance in rats and mice.

experimental-exposure

Potassium-deficient rats and mice; renal brush-border membrane protein, transcript, immunofluorescence and electron-microscopy analyses.

experimental_model

Potassium-deficient rats and mice; renal brush-border membrane protein, transcript, immunofluorescence and electron-microscopy analyses.

limitations

Isoform abundance and localization do not apportion total phosphate flux; transporter-specific contributions and initiating signal remain unresolved.

nutrient_topic

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

organism

Rattus norvegicus; Mus musculus where specified

plain_language

A sodium-phosphate uptake protein was depleted from the membrane.

primary_references

[breusegem-2009-phosphate] Differential regulation of the renal sodium-phosphate cotransporters NaPi-IIa, NaPi-IIc, and PiT-2 in dietary potassium deficiency (2009). https://pubmed.ncbi.nlm.nih.gov/19493963/ DOI: 10.1152/ajprenal.90765.2008

tissue_or_cell_type

renal proximal-tubule brush border

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1344–1356

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Potassium-deficient rats and mice; renal brush-border membrane protein, transcript, immunofluorescence and electron-microscopy analyses. · source_derived_draft · unverified_draft

### k-deficiency-napi2c-abundance Dietary potassium deficiency decreased proximal-tubule brush-border NaPi-IIc protein abundance in rats and mice. Condition category: nutrient_deficiency nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: A sodium-phosphate uptake protein was depleted from the membrane. organism: Rattus norvegicus; Mus musculus where specified tissue_or_cell_type: renal proximal-tubule brush border experimental_model: Potassium-deficient rats and mice; renal brush-border membrane protein, transcript, immunofluorescence and electron-microscopy analyses. limitations: Isoform abundance and localization do not apportion total phosphate flux; transporter-specific contributions and initiating signal remain unresolved. cross_nutrient: Potassium deficiency changes sodium-phosphate transport machinery in an isoform-specific manner. experimental-exposure: Potassium-deficient rats and mice; renal brush-border membrane protein, transcript, immunofluorescence and electron-microscopy analyses. endpoint: Dietary potassium deficiency decreased proximal-tubule brush-border NaPi-IIc protein abundance in rats and mice. [breusegem-2009-phosphate] Differential regulation of the renal sodium-phosphate cotransporters NaPi-IIa, NaPi-IIc, and PiT-2 in dietary potassium deficiency (2009). https://pubmed.ncbi.nlm.nih.gov/19493963/ DOI: 10.1152/ajprenal.90765.2008

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Potassium deficiency changes sodium-phosphate transport machinery in an isoform-specific manner.

endpoint

Dietary potassium deficiency decreased proximal-tubule brush-border PiT-2 abundance in rats and mice.

experimental-exposure

Potassium-deficient rats and mice; renal brush-border membrane protein, transcript, immunofluorescence and electron-microscopy analyses.

experimental_model

Potassium-deficient rats and mice; renal brush-border membrane protein, transcript, immunofluorescence and electron-microscopy analyses.

limitations

Isoform abundance and localization do not apportion total phosphate flux; transporter-specific contributions and initiating signal remain unresolved.

nutrient_topic

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

organism

Rattus norvegicus; Mus musculus where specified

plain_language

A second, distinct sodium-phosphate transporter declined.

primary_references

[breusegem-2009-phosphate] Differential regulation of the renal sodium-phosphate cotransporters NaPi-IIa, NaPi-IIc, and PiT-2 in dietary potassium deficiency (2009). https://pubmed.ncbi.nlm.nih.gov/19493963/ DOI: 10.1152/ajprenal.90765.2008

tissue_or_cell_type

renal proximal-tubule brush border

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1358–1370

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Potassium-deficient rats and mice; renal brush-border membrane protein, transcript, immunofluorescence and electron-microscopy analyses. · source_derived_draft · unverified_draft

### k-deficiency-pit2-abundance Dietary potassium deficiency decreased proximal-tubule brush-border PiT-2 abundance in rats and mice. Condition category: nutrient_deficiency nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: A second, distinct sodium-phosphate transporter declined. organism: Rattus norvegicus; Mus musculus where specified tissue_or_cell_type: renal proximal-tubule brush border experimental_model: Potassium-deficient rats and mice; renal brush-border membrane protein, transcript, immunofluorescence and electron-microscopy analyses. limitations: Isoform abundance and localization do not apportion total phosphate flux; transporter-specific contributions and initiating signal remain unresolved. cross_nutrient: Potassium deficiency changes sodium-phosphate transport machinery in an isoform-specific manner. experimental-exposure: Potassium-deficient rats and mice; renal brush-border membrane protein, transcript, immunofluorescence and electron-microscopy analyses. endpoint: Dietary potassium deficiency decreased proximal-tubule brush-border PiT-2 abundance in rats and mice. [breusegem-2009-phosphate] Differential regulation of the renal sodium-phosphate cotransporters NaPi-IIa, NaPi-IIc, and PiT-2 in dietary potassium deficiency (2009). https://pubmed.ncbi.nlm.nih.gov/19493963/ DOI: 10.1152/ajprenal.90765.2008

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Potassium -> calcium/phosphate/PTH observations.

experimental_model

Concurrent mineral and hormone measurements.

limitations

Co-occurrence does not establish that PTH caused every excretion change.

nutrient_topic

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

organism

Homo sapiens

plain_language

Potassium depletion affected calcium-phosphate regulation alongside sodium handling.

primary_references

[k-krishna1991] Potassium depletion exacerbates essential hypertension (1991). https://pubmed.ncbi.nlm.nih.gov/2058867/ DOI: 10.7326/0003-4819-115-2-77

tissue_or_cell_type

Plasma and urine

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Potassium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1534–1544

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Concurrent mineral and hormone measurements. · source_derived_draft · unverified_draft

### k-depletion-human-mineral-pth-response The depletion period also increased urinary calcium and phosphate and plasma immunoreactive PTH. Condition category: nutrient_deficiency nutrient_topic: Potassium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Potassium depletion affected calcium-phosphate regulation alongside sodium handling. organism: Homo sapiens tissue_or_cell_type: Plasma and urine experimental_model: Concurrent mineral and hormone measurements. limitations: Co-occurrence does not establish that PTH caused every excretion change. cross_nutrient: Potassium -> calcium/phosphate/PTH observations. [k-krishna1991] Potassium depletion exacerbates essential hypertension (1991). https://pubmed.ncbi.nlm.nih.gov/2058867/ DOI: 10.7326/0003-4819-115-2-77

cross_nutrient

Inorganic phosphate (Pi; protonation depends on pH) (tested_addition); L-Ascorbate (tested_addition); Manganese (measured_nutrient)

evidence_span

{"source_cache": "artifacts/manganese-clinical-sources/davidsson1991.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "7570e2285532eac2292b252a3813f1be97b46d68529a4d4150a88b4f9038676a", "start_char": 0, "end_char": 912, "text_sha256": "7570e2285532eac2292b252a3813f1be97b46d68529a4d4150a88b4f9038676a", "text_characters": 912}

experimental_model

Paired radiotracer test-meal study in adults

exposure

Human milk, infant formula and wheat bread used as adult test meals; individual mineral and dietary-component additions.

limitations

These were adult experiments even when milk or infant formula was the matrix. Added amounts were not independently verified from the indexed abstract; no universal interaction or spacing rule follows.

nutrient_topic

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

organism

Homo sapiens

plain_language

The tested additions had no detectable effect in this formula matrix.

primary_references

[mn-clin-davidsson1991] The effect of individual dietary components on manganese absorption in humans. (1991). https://pubmed.ncbi.nlm.nih.gov/1957822/ DOI: 10.1093/ajcn/54.6.1065

tissue_or_cell_type

Intestinal absorption

Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17) · lines 1062–1074

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Paired radiotracer test-meal study in adults · source_derived_draft · unverified_draft

### mn-clin-meal-formula-additions Adding phytate, phosphate or ascorbic acid to the formula test meals did not significantly alter manganese absorption in adults. Condition category: normal nutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect. plain_language: The tested additions had no detectable effect in this formula matrix. organism: Homo sapiens tissue_or_cell_type: Intestinal absorption experimental_model: Paired radiotracer test-meal study in adults limitations: These were adult experiments even when milk or infant formula was the matrix. Added amounts were not independently verified from the indexed abstract; no universal interaction or spacing rule follows. exposure: Human milk, infant formula and wheat bread used as adult test meals; individual mineral and dietary-component additions. cross_nutrient: Inorganic phosphate (Pi; protonation depends on pH) (tested_addition); L-Ascorbate (tested_addition); Manganese (measured_nutrient) evidence_span: {"source_cache": "artifacts/manganese-clinical-sources/davidsson1991.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "7570e2285532eac2292b252a3813f1be97b46d68529a4d4150a88b4f9038676a", "start_char": 0, "end_char": 912, "text_sha256": "7570e2285532eac2292b252a3813f1be97b46d68529a4d4150a88b4f9038676a", "text_characters": 912} [mn-clin-davidsson1991] The effect of individual dietary components on manganese absorption in humans. (1991). https://pubmed.ncbi.nlm.nih.gov/1957822/ DOI: 10.1093/ajcn/54.6.1065

dose

Fructose 250 mg/kg bolus

duration

Early 5 min changes; sugar-phosphate recovery within about 20 min

evidence_access

Primary abstract/metadata; unrecovered methods explicitly retained.

evidence_scope

literature_reviewed; source-specific curation

experimental_model

Seven healthy human volunteers

exposure_scope

Isolated fructose, intravenous

limitations

Injection bypasses the intestine. Magnitude cannot be assigned to a normal oral HFCS serving or to dietary phosphate deficiency.

nutrient_topic

HFCS chapter: actual formulation studies, component biochemistry and interventions are explicitly distinguished. · High-Fructose Corn Syrup / HFCS

organism

Seven healthy human volunteers

plain_language

The intravenous fructose bolus acutely lowered hepatic inorganic phosphate as sugar phosphates accumulated.

primary_references

Assessment of human liver metabolism by phosphorus-31 magnetic resonance spectroscopy. (1986). https://pubmed.ncbi.nlm.nih.gov/3730768/ DOI: 10.1259/0007-1285-59-703-695

route

Intravenous injection

tissue

Liver phosphorus-31 MRS

High-Fructose Corn Syrup: mechanism of action and metabolic impact (2026-09-20) · lines 245–255

Original AI-assisted curation of twenty primary studies and official FDA composition information, with one reused canonical glucose-transport claim. Study-specific citations, negative findings and limitations retained. Not publisher full text. · supports · Seven healthy human volunteers · source_derived_draft · unverified_draft

## hfcs-iv-phosphate The intravenous fructose bolus acutely lowered hepatic inorganic phosphate as sugar phosphates accumulated. Model/species: Seven healthy human volunteers Tissue: Liver phosphorus-31 MRS Exposure: Fructose 250 mg/kg bolus Route: Intravenous injection Duration: Early 5 min changes; sugar-phosphate recovery within about 20 min Exposure scope: Isolated fructose, intravenous Limits: Injection bypasses the intestine. Magnitude cannot be assigned to a normal oral HFCS serving or to dietary phosphate deficiency. Reference: Assessment of human liver metabolism by phosphorus-31 magnetic resonance spectroscopy. (1986). https://pubmed.ncbi.nlm.nih.gov/3730768/ DOI: 10.1259/0007-1285-59-703-695 Access: Primary abstract/metadata; unrecovered methods explicitly retained.

cross_nutrient

Retinoid signaling -> calcium/phosphate mineralization.

experimental_model

Primary human osteoblasts and MC3T3-E1 cells.

limitations

Pharmacology and culture exposure do not define a safe dietary threshold.

nutrient_topic

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

organism

Homo sapiens; Mus musculus

plain_language

Too much local retinoid signaling can impair mineral deposition in these models.

primary_references

[va-lind2013] Vitamin a is a negative regulator of osteoblast mineralization (2013). https://pubmed.ncbi.nlm.nih.gov/24340023/ DOI: 10.1371/journal.pone.0082388

tissue_or_cell_type

Osteoblasts

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1650–1660

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Primary human osteoblasts and MC3T3-E1 cells. · source_derived_draft · unverified_draft

### va-retinoic-acid-mineralization Retinoic acid reduced mineralization in human and murine osteoblast models through RAR-linked effects. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: Too much local retinoid signaling can impair mineral deposition in these models. organism: Homo sapiens; Mus musculus tissue_or_cell_type: Osteoblasts experimental_model: Primary human osteoblasts and MC3T3-E1 cells. limitations: Pharmacology and culture exposure do not define a safe dietary threshold. cross_nutrient: Retinoid signaling -> calcium/phosphate mineralization. [va-lind2013] Vitamin a is a negative regulator of osteoblast mineralization (2013). https://pubmed.ncbi.nlm.nih.gov/24340023/ DOI: 10.1371/journal.pone.0082388

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

Magnesium supports this NAD-linked folate 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 862–873

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-magnesium-phosphate The NAD+-dependent rat MTHFD2L dehydrogenase assay requires magnesium in the presence of phosphate. Condition category: normal nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Magnesium supports this NAD-linked folate 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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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