Nutrient chapter

Inositol (stereoisomer family)

Inositol is a family of ring-shaped sugar alcohols. The body can make myo-inositol, which supplies membrane lipids and signaling molecules that connect calcium release, ion channels, phosphate handling and protein anchoring. Free inositol, its stereoisomers, and phosphorylated derivatives have different actions; clinical effects depend on the form, tissue and study context.

119 recorded mechanisms · 12 availability situations · 10 preserved sources. Draft and verified records are labeled separately.

Read recorded mechanisms Open recursive mind map

The mechanisms

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

Recombinant human ISYNA1 converted D-glucose 6-phosphate to 1D-myo-inositol 3-phosphate, an entry step in de novo inositol synthesis.
ISYNA1 (human inositol-3-phosphate synthase 1) → 1D-myo-inositol 3-phosphate source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/15024000.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5ab3a8eda77989c3e4a681b4a971fb7e969c285d3e5c8e41bc31713a7f88c9ac", "start_char": 0, "end_char": 1427, "text_sha256": "5ab3a8eda77989c3e4a681b4a971fb7e969c285d3e5c8e41bc31713a7f88c9ac"}
experimental_model
Recombinant human enzyme and complementation of yeast ino1 deletion
exposure
Substrate, NAD+, cation and valproate experiments
limitations
Purified-enzyme and yeast results do not establish supplement effects or a human dietary deficiency threshold.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Human protein expressed in bacteria and yeast
plain_language
Cells have a route to build the inositol ring from a glucose-derived molecule.
primary_references
[ino-p15024000] Human 1-D-myo-inositol-3-phosphate synthase is functional in yeast. (2004). https://pubmed.ncbi.nlm.nih.gov/15024000/ DOI: 10.1074/jbc.m312078200
tissue_or_cell_type
Purified enzyme; yeast cultures
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 171–182
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human enzyme and complementation of yeast ino1 deletion · source_derived_draft · unverified_draft
### ino-isyna-synthesis Recombinant human ISYNA1 converted D-glucose 6-phosphate to 1D-myo-inositol 3-phosphate, an entry step in de novo inositol synthesis. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: Cells have a route to build the inositol ring from a glucose-derived molecule. organism: Human protein expressed in bacteria and yeast tissue_or_cell_type: Purified enzyme; yeast cultures experimental_model: Recombinant human enzyme and complementation of yeast ino1 deletion limitations: Purified-enzyme and yeast results do not establish supplement effects or a human dietary deficiency threshold. exposure: Substrate, NAD+, cation and valproate experiments evidence_span: {"source_cache": "artifacts/inositol-research/15024000.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5ab3a8eda77989c3e4a681b4a971fb7e969c285d3e5c8e41bc31713a7f88c9ac", "start_char": 0, "end_char": 1427, "text_sha256": "5ab3a8eda77989c3e4a681b4a971fb7e969c285d3e5c8e41bc31713a7f88c9ac"} [ino-p15024000] Human 1-D-myo-inositol-3-phosphate synthase is functional in yeast. (2004). https://pubmed.ncbi.nlm.nih.gov/15024000/ DOI: 10.1074/jbc.m312078200
Complete structured claim and evidence
Human inositol monophosphatase hydrolyzes inositol monophosphates to regenerate free inositol.
IMPA1 (human inositol monophosphatase 1) → Inositol monophosphates source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/1332026.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "57cfa39b1fe68149ad3a1ea25ede4c979db0586ef14c905cbe402fe3f70ce9e5", "start_char": 0, "end_char": 1147, "text_sha256": "57cfa39b1fe68149ad3a1ea25ede4c979db0586ef14c905cbe402fe3f70ce9e5"}
experimental_model
Human enzyme crystallography and catalytic characterization
exposure
Structural analysis of the inositol recycling enzyme
limitations
Structure does not show that extra substrate bypasses a genetic enzyme defect in patients.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Homo sapiens
plain_language
A recycling step removes the last phosphate so the inositol ring can be reused.
primary_references
[ino-p1332026] Structure of inositol monophosphatase, the putative target of lithium therapy. (1992). https://pubmed.ncbi.nlm.nih.gov/1332026/ DOI: 10.1073/pnas.89.21.10031
tissue_or_cell_type
Purified inositol monophosphatase
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 236–247
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human enzyme crystallography and catalytic characterization · source_derived_draft · unverified_draft
### ino-impa-recycling Human inositol monophosphatase hydrolyzes inositol monophosphates to regenerate free inositol. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: A recycling step removes the last phosphate so the inositol ring can be reused. organism: Homo sapiens tissue_or_cell_type: Purified inositol monophosphatase experimental_model: Human enzyme crystallography and catalytic characterization limitations: Structure does not show that extra substrate bypasses a genetic enzyme defect in patients. exposure: Structural analysis of the inositol recycling enzyme evidence_span: {"source_cache": "artifacts/inositol-research/1332026.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "57cfa39b1fe68149ad3a1ea25ede4c979db0586ef14c905cbe402fe3f70ce9e5", "start_char": 0, "end_char": 1147, "text_sha256": "57cfa39b1fe68149ad3a1ea25ede4c979db0586ef14c905cbe402fe3f70ce9e5"} [ino-p1332026] Structure of inositol monophosphatase, the putative target of lithium therapy. (1992). https://pubmed.ncbi.nlm.nih.gov/1332026/ DOI: 10.1073/pnas.89.21.10031
Complete structured claim and evidence
Human placental phosphatidylinositol synthase used myo-inositol and CDP-diacylglycerol to form phosphatidylinositol.
CDIPT (human phosphatidylinositol synthase) → Phosphatidylinositol (PI) source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/8110188.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c05bb5272b443bde4f99d4af375d31988a4812150450d6c4462059a59aa8a09e", "start_char": 0, "end_char": 940, "text_sha256": "c05bb5272b443bde4f99d4af375d31988a4812150450d6c4462059a59aa8a09e"}
experimental_model
Purification and kinetics of placental PI synthase
exposure
Substrate and ion titrations
limitations
Assay optima and inhibitory concentrations are not dietary advice or proof of in vivo nutrient competition.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Homo sapiens
plain_language
This step attaches the inositol head group to a membrane lipid.
primary_references
[ino-p8110188] Purification and characterization of phosphatidylinositol synthase from human placenta. (1994). https://pubmed.ncbi.nlm.nih.gov/8110188/ DOI: 10.1042/bj2970517
tissue_or_cell_type
Placental microsomal enzyme
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 496–507
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purification and kinetics of placental PI synthase · source_derived_draft · unverified_draft
### ino-cdipt-synthesis Human placental phosphatidylinositol synthase used myo-inositol and CDP-diacylglycerol to form phosphatidylinositol. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: This step attaches the inositol head group to a membrane lipid. organism: Homo sapiens tissue_or_cell_type: Placental microsomal enzyme experimental_model: Purification and kinetics of placental PI synthase limitations: Assay optima and inhibitory concentrations are not dietary advice or proof of in vivo nutrient competition. exposure: Substrate and ion titrations evidence_span: {"source_cache": "artifacts/inositol-research/8110188.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c05bb5272b443bde4f99d4af375d31988a4812150450d6c4462059a59aa8a09e", "start_char": 0, "end_char": 940, "text_sha256": "c05bb5272b443bde4f99d4af375d31988a4812150450d6c4462059a59aa8a09e"} [ino-p8110188] Purification and characterization of phosphatidylinositol synthase from human placenta. (1994). https://pubmed.ncbi.nlm.nih.gov/8110188/ DOI: 10.1042/bj2970517
Complete structured claim and evidence
PLCB3 hydrolyzed PI(4,5)P2 to produce soluble IP3 and membrane-associated diacylglycerol.
PLCB3 (phospholipase C beta 3) → IP3 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/37991948.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "fa553185ea3f13a8af7be9a548de14cd13ebe22ff307635fb76675ddc64347d7", "start_char": 0, "end_char": 1735, "text_sha256": "fa553185ea3f13a8af7be9a548de14cd13ebe22ff307635fb76675ddc64347d7"}
experimental_model
Reconstituted lipid-bilayer kinetics and membrane-bound structural analysis
exposure
G-alpha-q and G-beta-gamma stimulation
limitations
Reconstituted biochemical regulation; not an oral inositol intervention. Product generation and lipid depletion occur in the same reaction.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Recombinant mammalian signaling proteins
plain_language
Splitting one membrane lipid creates two different signaling products.
primary_references
[ino-p37991948] The mechanism of Gαq regulation of PLCβ3-catalyzed PIP2 hydrolysis. (2023). https://pubmed.ncbi.nlm.nih.gov/37991948/ DOI: 10.1073/pnas.2315011120
tissue_or_cell_type
Defined membrane bilayers
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 626–637
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Reconstituted lipid-bilayer kinetics and membrane-bound structural analysis · source_derived_draft · unverified_draft
### ino-plc-ip3 PLCB3 hydrolyzed PI(4,5)P2 to produce soluble IP3 and membrane-associated diacylglycerol. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: Splitting one membrane lipid creates two different signaling products. organism: Recombinant mammalian signaling proteins tissue_or_cell_type: Defined membrane bilayers experimental_model: Reconstituted lipid-bilayer kinetics and membrane-bound structural analysis limitations: Reconstituted biochemical regulation; not an oral inositol intervention. Product generation and lipid depletion occur in the same reaction. exposure: G-alpha-q and G-beta-gamma stimulation evidence_span: {"source_cache": "artifacts/inositol-research/37991948.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "fa553185ea3f13a8af7be9a548de14cd13ebe22ff307635fb76675ddc64347d7", "start_char": 0, "end_char": 1735, "text_sha256": "fa553185ea3f13a8af7be9a548de14cd13ebe22ff307635fb76675ddc64347d7"} [ino-p37991948] The mechanism of Gαq regulation of PLCβ3-catalyzed PIP2 hydrolysis. (2023). https://pubmed.ncbi.nlm.nih.gov/37991948/ DOI: 10.1073/pnas.2315011120
Complete structured claim and evidence
Applied IP3 releases calcium from a nonmitochondrial intracellular store in permeabilized pancreatic acinar cells.
IP3 → ER calcium release source_derived_draftungraded
Experimental context and source evidence
compartment_description
Nonmitochondrial intracellular store to cytosol
experimental_model
Permeabilized rat pancreatic acinar cells
limitations
Permeabilized-cell application; receptor isoform and dietary status were not established.
nutrient_topic
Calcium research collection; topical membership is not evidence of a direct dietary effect. · Calcium
organism
Rattus norvegicus
plain_language
IP3 releases stored calcium inside acinar cells.
primary_references
[ca-streb1983] Release of Ca2+ from a nonmitochondrial intracellular store in pancreatic acinar cells by inositol-1,4,5-trisphosphate (1983). https://pubmed.ncbi.nlm.nih.gov/6605482/ DOI: 10.1038/306067a0
research_relationship_category
mechanism
tissue_or_cell_type
Pancreatic acinar cells
transport_or_reaction_direction
Intracellular store to cytosol
Calcium: mechanism-first literature curation (2026-09-17) · lines 464–476
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Permeabilized rat pancreatic acinar cells · source_derived_draft · unverified_draft
### ca-ip3-mobilizes-store Applied IP3 releases calcium from a nonmitochondrial intracellular store in permeabilized pancreatic acinar cells. Condition category: normal nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: IP3 releases stored calcium inside acinar cells. organism: Rattus norvegicus tissue_or_cell_type: Pancreatic acinar cells experimental_model: Permeabilized rat pancreatic acinar cells limitations: Permeabilized-cell application; receptor isoform and dietary status were not established. research_relationship_category: mechanism transport_or_reaction_direction: Intracellular store to cytosol compartment_description: Nonmitochondrial intracellular store to cytosol [ca-streb1983] Release of Ca2+ from a nonmitochondrial intracellular store in pancreatic acinar cells by inositol-1,4,5-trisphosphate (1983). https://pubmed.ncbi.nlm.nih.gov/6605482/ DOI: 10.1038/306067a0
Complete structured claim and evidence
TRPM7 currents depended on PI(4,5)P2 in the reported experiments, and PLC-mediated PIP2 hydrolysis inhibited the current.
Phosphatidylinositol 4,5-bisphosphate → TRPM7 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/11941371.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5b6343b08188b699a19591013fdcd2d9d604f8ae15adc5771b4bc677369d10b0", "start_char": 0, "end_char": 729, "text_sha256": "5b6343b08188b699a19591013fdcd2d9d604f8ae15adc5771b4bc677369d10b0"}
experimental_model
Electrophysiology and phosphoinositide manipulation
exposure
PLC activation and PIP2 depletion
limitations
PIP2 regulation is conditional; the 2007 study shows intracellular Mg and patch configuration can reverse the PLC response.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Mammalian heterologous cells and cardiac preparations
plain_language
A membrane inositol lipid helps regulate a channel that carries mineral ions; the response depends on the recording conditions.
primary_references
[ino-p11941371] The TRPM7 channel is inactivated by PIP(2) hydrolysis. (2002). https://pubmed.ncbi.nlm.nih.gov/11941371/ DOI: 10.1038/ncb781
tissue_or_cell_type
TRPM7-associated membrane currents
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 951–962
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Electrophysiology and phosphoinositide manipulation · source_derived_draft · unverified_draft
### ino-pip2-trpm7 TRPM7 currents depended on PI(4,5)P2 in the reported experiments, and PLC-mediated PIP2 hydrolysis inhibited the current. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: A membrane inositol lipid helps regulate a channel that carries mineral ions; the response depends on the recording conditions. organism: Mammalian heterologous cells and cardiac preparations tissue_or_cell_type: TRPM7-associated membrane currents experimental_model: Electrophysiology and phosphoinositide manipulation limitations: PIP2 regulation is conditional; the 2007 study shows intracellular Mg and patch configuration can reverse the PLC response. exposure: PLC activation and PIP2 depletion evidence_span: {"source_cache": "artifacts/inositol-research/11941371.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5b6343b08188b699a19591013fdcd2d9d604f8ae15adc5771b4bc677369d10b0", "start_char": 0, "end_char": 729, "text_sha256": "5b6343b08188b699a19591013fdcd2d9d604f8ae15adc5771b4bc677369d10b0"} [ino-p11941371] The TRPM7 channel is inactivated by PIP(2) hydrolysis. (2002). https://pubmed.ncbi.nlm.nih.gov/11941371/ DOI: 10.1038/ncb781
Complete structured claim and evidence
Human MIOX catalyzes oxidative cleavage of myo-inositol to D-glucuronate.
MIOX (human myo-inositol oxygenase) → Myo-inositol source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/18364358.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9992644d489f26782d7ef0a70dc13ec5ca48e2b660a011173fba8e0d4e43ae19", "start_char": 0, "end_char": 1004, "text_sha256": "9992644d489f26782d7ef0a70dc13ec5ca48e2b660a011173fba8e0d4e43ae19"}
experimental_model
Human enzyme crystallography and catalytic analysis
exposure
Diiron center and inhibitor-bound structure
limitations
Catabolism of inositol is not evidence that humans synthesize vitamin C from it; the crystal ligand was an inhibitor.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Homo sapiens
plain_language
MIOX opens the inositol ring, providing a route for its breakdown.
primary_references
[ino-p18364358] Structural and biophysical characterization of human myo-inositol oxygenase. (2008). https://pubmed.ncbi.nlm.nih.gov/18364358/ DOI: 10.1074/jbc.m800348200
tissue_or_cell_type
Purified MIOX
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 457–468
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human enzyme crystallography and catalytic analysis · source_derived_draft · unverified_draft
### ino-miox-cleavage Human MIOX catalyzes oxidative cleavage of myo-inositol to D-glucuronate. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: MIOX opens the inositol ring, providing a route for its breakdown. organism: Homo sapiens tissue_or_cell_type: Purified MIOX experimental_model: Human enzyme crystallography and catalytic analysis limitations: Catabolism of inositol is not evidence that humans synthesize vitamin C from it; the crystal ligand was an inhibitor. exposure: Diiron center and inhibitor-bound structure evidence_span: {"source_cache": "artifacts/inositol-research/18364358.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9992644d489f26782d7ef0a70dc13ec5ca48e2b660a011173fba8e0d4e43ae19", "start_char": 0, "end_char": 1004, "text_sha256": "9992644d489f26782d7ef0a70dc13ec5ca48e2b660a011173fba8e0d4e43ae19"} [ino-p18364358] Structural and biophysical characterization of human myo-inositol oxygenase. (2008). https://pubmed.ncbi.nlm.nih.gov/18364358/ DOI: 10.1074/jbc.m800348200
Complete structured claim and evidence
IP6K enzymes form 5-InsP7 from InsP6.
Inositol hexakisphosphate kinase family → 5-diphosphoinositol pentakisphosphate (5-InsP7) source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/21145457.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0de0a9c3ea11cd8ce59bccff69a41139b11e11182fd9fd66016ec72ba329a5ce", "start_char": 0, "end_char": 889, "text_sha256": "0de0a9c3ea11cd8ce59bccff69a41139b11e11182fd9fd66016ec72ba329a5ce"}
experimental_model
Biochemical Akt regulation and targeted mouse Ip6k1 deletion
exposure
5-InsP7 and Ip6k1 knockout
limitations
Whole-gene deletion is not equivalent to adding or withdrawing free myo-inositol; the reported therapeutic proposal is not established treatment.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Mammalian enzymology and Mus musculus
plain_language
Adding a phosphate onto an existing phosphate makes an inositol pyrophosphate.
primary_references
[ino-p21145457] Inositol pyrophosphates inhibit Akt signaling, thereby regulating insulin sensitivity and weight gain. (2010). https://pubmed.ncbi.nlm.nih.gov/21145457/ DOI: 10.1016/j.cell.2010.11.032
tissue_or_cell_type
Muscle, adipose tissue and liver
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 769–780
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Biochemical Akt regulation and targeted mouse Ip6k1 deletion · source_derived_draft · unverified_draft
### ino-ip6k-ip7 IP6K enzymes form 5-InsP7 from InsP6. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: Adding a phosphate onto an existing phosphate makes an inositol pyrophosphate. organism: Mammalian enzymology and Mus musculus tissue_or_cell_type: Muscle, adipose tissue and liver experimental_model: Biochemical Akt regulation and targeted mouse Ip6k1 deletion limitations: Whole-gene deletion is not equivalent to adding or withdrawing free myo-inositol; the reported therapeutic proposal is not established treatment. exposure: 5-InsP7 and Ip6k1 knockout evidence_span: {"source_cache": "artifacts/inositol-research/21145457.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0de0a9c3ea11cd8ce59bccff69a41139b11e11182fd9fd66016ec72ba329a5ce", "start_char": 0, "end_char": 889, "text_sha256": "0de0a9c3ea11cd8ce59bccff69a41139b11e11182fd9fd66016ec72ba329a5ce"} [ino-p21145457] Inositol pyrophosphates inhibit Akt signaling, thereby regulating insulin sensitivity and weight gain. (2010). https://pubmed.ncbi.nlm.nih.gov/21145457/ DOI: 10.1016/j.cell.2010.11.032
Complete structured claim and evidence
PPIP5K kinase activity converts 5-InsP7 to 1,5-InsP8.
Diphosphoinositol pentakisphosphate kinase family → 5-diphosphoinositol pentakisphosphate (5-InsP7) source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/28126903.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6f5c96ed7d02591d5fe475d0e26aa2f21dc93f0c86c12998debb417f98254d2f", "start_char": 0, "end_char": 1981, "text_sha256": "6f5c96ed7d02591d5fe475d0e26aa2f21dc93f0c86c12998debb417f98254d2f"}
experimental_model
Cellular phosphate withdrawal/repletion and bifunctional enzyme kinetics
exposure
Phosphate availability and PPIP5K kinase/phosphatase assays
limitations
Cell-culture nutrient withdrawal is not a measured human dietary threshold; PPIP5K isoforms are not identical.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Human HCT116 cells and human PPIP5K proteins
plain_language
A further phosphorylation step creates another distinct phosphate signal.
primary_references
[ino-p28126903] The Significance of the Bifunctional Kinase/Phosphatase Activities of Diphosphoinositol Pentakisphosphate Kinases (PPIP5Ks) for Coupling Inositol Pyrophosphate Cell Signaling to Cellular Phosphate Homeostasis. (2017). https://pubmed.ncbi.nlm.nih.gov/28126903/ DOI: 10.1074/jbc.m116.765743
tissue_or_cell_type
Intestinal tumor-derived cell line; purified enzymes
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 808–819
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cellular phosphate withdrawal/repletion and bifunctional enzyme kinetics · source_derived_draft · unverified_draft
### ino-ppip5k-ip8 PPIP5K kinase activity converts 5-InsP7 to 1,5-InsP8. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: A further phosphorylation step creates another distinct phosphate signal. organism: Human HCT116 cells and human PPIP5K proteins tissue_or_cell_type: Intestinal tumor-derived cell line; purified enzymes experimental_model: Cellular phosphate withdrawal/repletion and bifunctional enzyme kinetics limitations: Cell-culture nutrient withdrawal is not a measured human dietary threshold; PPIP5K isoforms are not identical. exposure: Phosphate availability and PPIP5K kinase/phosphatase assays evidence_span: {"source_cache": "artifacts/inositol-research/28126903.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6f5c96ed7d02591d5fe475d0e26aa2f21dc93f0c86c12998debb417f98254d2f", "start_char": 0, "end_char": 1981, "text_sha256": "6f5c96ed7d02591d5fe475d0e26aa2f21dc93f0c86c12998debb417f98254d2f"} [ino-p28126903] The Significance of the Bifunctional Kinase/Phosphatase Activities of Diphosphoinositol Pentakisphosphate Kinases (PPIP5Ks) for Coupling Inositol Pyrophosphate Cell Signaling to Cellular Phosphate Homeostasis. (2017). https://pubmed.ncbi.nlm.nih.gov/28126903/ DOI: 10.1074/jbc.m116.765743
Complete structured claim and evidence
InsP8 bound the XPR1 N-terminal region with a reported dissociation constant of 180 nM.
1,5-bisdiphosphoinositol tetrakisphosphate (1,5-InsP8) → XPR1 (human phosphate exporter) source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/32019887.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bb7637b9a327b1cba07716bbed5da8a3f32a3ac00c9fff70d23ada1a736d3d18", "start_char": 0, "end_char": 2004, "text_sha256": "bb7637b9a327b1cba07716bbed5da8a3f32a3ac00c9fff70d23ada1a736d3d18"}
experimental_model
Binding, knockout and rescue experiments
exposure
PPIP5K or XPR1 deletion, kinase rescue and pyrophosphate analog delivery
limitations
Cell assays establish a transport-regulation mechanism, not benefits of oral inositol or increased bone mineralization.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Human cultured cells including Saos-2 osteosarcoma cells
plain_language
A specific inositol pyrophosphate binds the phosphate-export machinery.
primary_references
[ino-p32019887] Control of XPR1-dependent cellular phosphate efflux by InsP8 is an exemplar for functionally-exclusive inositol pyrophosphate signaling. (2020). https://pubmed.ncbi.nlm.nih.gov/32019887/ DOI: 10.1073/pnas.1908830117
tissue_or_cell_type
Cellular phosphate transport
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 873–884
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Binding, knockout and rescue experiments · source_derived_draft · unverified_draft
### ino-xpr1-ip8 InsP8 bound the XPR1 N-terminal region with a reported dissociation constant of 180 nM. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: A specific inositol pyrophosphate binds the phosphate-export machinery. organism: Human cultured cells including Saos-2 osteosarcoma cells tissue_or_cell_type: Cellular phosphate transport experimental_model: Binding, knockout and rescue experiments limitations: Cell assays establish a transport-regulation mechanism, not benefits of oral inositol or increased bone mineralization. exposure: PPIP5K or XPR1 deletion, kinase rescue and pyrophosphate analog delivery evidence_span: {"source_cache": "artifacts/inositol-research/32019887.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bb7637b9a327b1cba07716bbed5da8a3f32a3ac00c9fff70d23ada1a736d3d18", "start_char": 0, "end_char": 2004, "text_sha256": "bb7637b9a327b1cba07716bbed5da8a3f32a3ac00c9fff70d23ada1a736d3d18"} [ino-p32019887] Control of XPR1-dependent cellular phosphate efflux by InsP8 is an exemplar for functionally-exclusive inositol pyrophosphate signaling. (2020). https://pubmed.ncbi.nlm.nih.gov/32019887/ DOI: 10.1073/pnas.1908830117
Complete structured claim and evidence
Human SMIT2 expression increased myo-inositol uptake 37-fold relative to vector control in rat L6 cells.
SLC5A11 (human SMIT2) → Myo-inositol source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/19032932.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4fdc565b9aa26ef5f2d083c539a1b0367403b39f0c75d3ea1b194bf6fa525242", "start_char": 0, "end_char": 1164, "text_sha256": "4fdc565b9aa26ef5f2d083c539a1b0367403b39f0c75d3ea1b194bf6fa525242"}
experimental_model
Human SMIT2 overexpression and radiotracer uptake
exposure
Overexpression, glucose competition and insulin exposure
limitations
Overexpression is not normal transporter abundance. Insulin experiments used untransfected rat cells; changes in human diabetes are proposed, not demonstrated here.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Human transporter in rat L6 myoblasts
plain_language
SMIT2 can bring free myo-inositol into cells.
primary_references
[ino-p19032932] Human sodium/inositol cotransporter 2 (SMIT2) transports inositols but not glucose in L6 cells. (2009). https://pubmed.ncbi.nlm.nih.gov/19032932/ DOI: 10.1016/j.abb.2008.11.008
tissue_or_cell_type
Skeletal-muscle cell model
transport_effect
raises Expression increased myo-inositol uptake 37-fold against vector control.
transport_pool
the expressing cell Expression increased myo-inositol uptake 37-fold against vector control.
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 288–299
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human SMIT2 overexpression and radiotracer uptake · source_derived_draft · unverified_draft
### ino-smit2-myo Human SMIT2 expression increased myo-inositol uptake 37-fold relative to vector control in rat L6 cells. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: SMIT2 can bring free myo-inositol into cells. organism: Human transporter in rat L6 myoblasts tissue_or_cell_type: Skeletal-muscle cell model experimental_model: Human SMIT2 overexpression and radiotracer uptake limitations: Overexpression is not normal transporter abundance. Insulin experiments used untransfected rat cells; changes in human diabetes are proposed, not demonstrated here. exposure: Overexpression, glucose competition and insulin exposure evidence_span: {"source_cache": "artifacts/inositol-research/19032932.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4fdc565b9aa26ef5f2d083c539a1b0367403b39f0c75d3ea1b194bf6fa525242", "start_char": 0, "end_char": 1164, "text_sha256": "4fdc565b9aa26ef5f2d083c539a1b0367403b39f0c75d3ea1b194bf6fa525242"} [ino-p19032932] Human sodium/inositol cotransporter 2 (SMIT2) transports inositols but not glucose in L6 cells. (2009). https://pubmed.ncbi.nlm.nih.gov/19032932/ DOI: 10.1016/j.abb.2008.11.008
Complete structured claim and evidence
Ovulation occurred in 19/22 D-chiro-inositol recipients versus 6/22 placebo recipients in the 1999 PCOS trial.
D-chiro-inositol → Ovulation source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/10219066.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2b70007c28cc93c6f18b457701ec8b034a3bbe888db05e85eca71d50199dc854", "start_char": 0, "end_char": 2121, "text_sha256": "2b70007c28cc93c6f18b457701ec8b034a3bbe888db05e85eca71d50199dc854"}
experimental_model
Randomized placebo-controlled trial
exposure
D-chiro-inositol 1200 mg/day for 6–8 weeks versus placebo; historical study regimen
limitations
Small short trial, not live-birth evidence. Within-group insulin improvement was stronger than the between-group comparison.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Homo sapiens
plain_language
This small trial found more ovulation with D-chiro-inositol; it did not establish improved live birth.
primary_references
[ino-p10219066] Ovulatory and metabolic effects of D-chiro-inositol in the polycystic ovary syndrome. (1999). https://pubmed.ncbi.nlm.nih.gov/10219066/ DOI: 10.1056/nejm199904293401703
tissue_or_cell_type
44 obese women with PCOS
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 1289–1300
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized placebo-controlled trial · source_derived_draft · unverified_draft
### ino-dci-trial Ovulation occurred in 19/22 D-chiro-inositol recipients versus 6/22 placebo recipients in the 1999 PCOS trial. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: This small trial found more ovulation with D-chiro-inositol; it did not establish improved live birth. organism: Homo sapiens tissue_or_cell_type: 44 obese women with PCOS experimental_model: Randomized placebo-controlled trial limitations: Small short trial, not live-birth evidence. Within-group insulin improvement was stronger than the between-group comparison. exposure: D-chiro-inositol 1200 mg/day for 6–8 weeks versus placebo; historical study regimen evidence_span: {"source_cache": "artifacts/inositol-research/10219066.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2b70007c28cc93c6f18b457701ec8b034a3bbe888db05e85eca71d50199dc854", "start_char": 0, "end_char": 2121, "text_sha256": "2b70007c28cc93c6f18b457701ec8b034a3bbe888db05e85eca71d50199dc854"} [ino-p10219066] Ovulatory and metabolic effects of D-chiro-inositol in the polycystic ovary syndrome. (1999). https://pubmed.ncbi.nlm.nih.gov/10219066/ DOI: 10.1056/nejm199904293401703
Complete structured claim and evidence
Human ISYNA1 used NAD+ in its catalytic assay, with a reported apparent Km of 8 micromolar.
NAD+ → ISYNA1 (human inositol-3-phosphate synthase 1) source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/15024000.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5ab3a8eda77989c3e4a681b4a971fb7e969c285d3e5c8e41bc31713a7f88c9ac", "start_char": 0, "end_char": 1427, "text_sha256": "5ab3a8eda77989c3e4a681b4a971fb7e969c285d3e5c8e41bc31713a7f88c9ac"}
experimental_model
Recombinant human enzyme and complementation of yeast ino1 deletion
exposure
Substrate, NAD+, cation and valproate experiments
limitations
Purified-enzyme and yeast results do not establish supplement effects or a human dietary deficiency threshold.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Human protein expressed in bacteria and yeast
plain_language
The synthesis enzyme depends on NAD+, connecting inositol chemistry to the niacin-derived cofactor network.
primary_references
[ino-p15024000] Human 1-D-myo-inositol-3-phosphate synthase is functional in yeast. (2004). https://pubmed.ncbi.nlm.nih.gov/15024000/ DOI: 10.1074/jbc.m312078200
tissue_or_cell_type
Purified enzyme; yeast cultures
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 184–195
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human enzyme and complementation of yeast ino1 deletion · source_derived_draft · unverified_draft
### ino-isyna-nad Human ISYNA1 used NAD+ in its catalytic assay, with a reported apparent Km of 8 micromolar. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: The synthesis enzyme depends on NAD+, connecting inositol chemistry to the niacin-derived cofactor network. organism: Human protein expressed in bacteria and yeast tissue_or_cell_type: Purified enzyme; yeast cultures experimental_model: Recombinant human enzyme and complementation of yeast ino1 deletion limitations: Purified-enzyme and yeast results do not establish supplement effects or a human dietary deficiency threshold. exposure: Substrate, NAD+, cation and valproate experiments evidence_span: {"source_cache": "artifacts/inositol-research/15024000.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5ab3a8eda77989c3e4a681b4a971fb7e969c285d3e5c8e41bc31713a7f88c9ac", "start_char": 0, "end_char": 1427, "text_sha256": "5ab3a8eda77989c3e4a681b4a971fb7e969c285d3e5c8e41bc31713a7f88c9ac"} [ino-p15024000] Human 1-D-myo-inositol-3-phosphate synthase is functional in yeast. (2004). https://pubmed.ncbi.nlm.nih.gov/15024000/ DOI: 10.1074/jbc.m312078200
Complete structured claim and evidence
K+ was among the stronger cation activators of purified human ISYNA1 under the tested assay conditions.
Potassium ion → ISYNA1 (human inositol-3-phosphate synthase 1) source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/15024000.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5ab3a8eda77989c3e4a681b4a971fb7e969c285d3e5c8e41bc31713a7f88c9ac", "start_char": 0, "end_char": 1427, "text_sha256": "5ab3a8eda77989c3e4a681b4a971fb7e969c285d3e5c8e41bc31713a7f88c9ac"}
experimental_model
Recombinant human enzyme and complementation of yeast ino1 deletion
exposure
Substrate, NAD+, cation and valproate experiments
limitations
Purified-enzyme and yeast results do not establish supplement effects or a human dietary deficiency threshold.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Human protein expressed in bacteria and yeast
plain_language
Potassium can influence this enzyme in a test tube; that does not demonstrate a benefit from extra dietary potassium.
primary_references
[ino-p15024000] Human 1-D-myo-inositol-3-phosphate synthase is functional in yeast. (2004). https://pubmed.ncbi.nlm.nih.gov/15024000/ DOI: 10.1074/jbc.m312078200
tissue_or_cell_type
Purified enzyme; yeast cultures
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 197–208
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human enzyme and complementation of yeast ino1 deletion · source_derived_draft · unverified_draft
### ino-isyna-potassium K+ was among the stronger cation activators of purified human ISYNA1 under the tested assay conditions. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: Potassium can influence this enzyme in a test tube; that does not demonstrate a benefit from extra dietary potassium. organism: Human protein expressed in bacteria and yeast tissue_or_cell_type: Purified enzyme; yeast cultures experimental_model: Recombinant human enzyme and complementation of yeast ino1 deletion limitations: Purified-enzyme and yeast results do not establish supplement effects or a human dietary deficiency threshold. exposure: Substrate, NAD+, cation and valproate experiments evidence_span: {"source_cache": "artifacts/inositol-research/15024000.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5ab3a8eda77989c3e4a681b4a971fb7e969c285d3e5c8e41bc31713a7f88c9ac", "start_char": 0, "end_char": 1427, "text_sha256": "5ab3a8eda77989c3e4a681b4a971fb7e969c285d3e5c8e41bc31713a7f88c9ac"} [ino-p15024000] Human 1-D-myo-inositol-3-phosphate synthase is functional in yeast. (2004). https://pubmed.ncbi.nlm.nih.gov/15024000/ DOI: 10.1074/jbc.m312078200
Complete structured claim and evidence
Zn2+ strongly inhibited purified human ISYNA1 in the cation comparison.
Zinc(II) ion → ISYNA1 (human inositol-3-phosphate synthase 1) source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/15024000.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5ab3a8eda77989c3e4a681b4a971fb7e969c285d3e5c8e41bc31713a7f88c9ac", "start_char": 0, "end_char": 1427, "text_sha256": "5ab3a8eda77989c3e4a681b4a971fb7e969c285d3e5c8e41bc31713a7f88c9ac"}
experimental_model
Recombinant human enzyme and complementation of yeast ino1 deletion
exposure
Substrate, NAD+, cation and valproate experiments
limitations
Purified-enzyme and yeast results do not establish supplement effects or a human dietary deficiency threshold.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Human protein expressed in bacteria and yeast
plain_language
A mineral can inhibit one enzyme even while supporting many other functions.
primary_references
[ino-p15024000] Human 1-D-myo-inositol-3-phosphate synthase is functional in yeast. (2004). https://pubmed.ncbi.nlm.nih.gov/15024000/ DOI: 10.1074/jbc.m312078200
tissue_or_cell_type
Purified enzyme; yeast cultures
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 210–221
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human enzyme and complementation of yeast ino1 deletion · source_derived_draft · unverified_draft
### ino-isyna-zinc Zn2+ strongly inhibited purified human ISYNA1 in the cation comparison. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: A mineral can inhibit one enzyme even while supporting many other functions. organism: Human protein expressed in bacteria and yeast tissue_or_cell_type: Purified enzyme; yeast cultures experimental_model: Recombinant human enzyme and complementation of yeast ino1 deletion limitations: Purified-enzyme and yeast results do not establish supplement effects or a human dietary deficiency threshold. exposure: Substrate, NAD+, cation and valproate experiments evidence_span: {"source_cache": "artifacts/inositol-research/15024000.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5ab3a8eda77989c3e4a681b4a971fb7e969c285d3e5c8e41bc31713a7f88c9ac", "start_char": 0, "end_char": 1427, "text_sha256": "5ab3a8eda77989c3e4a681b4a971fb7e969c285d3e5c8e41bc31713a7f88c9ac"} [ino-p15024000] Human 1-D-myo-inositol-3-phosphate synthase is functional in yeast. (2004). https://pubmed.ncbi.nlm.nih.gov/15024000/ DOI: 10.1074/jbc.m312078200
Complete structured claim and evidence
At 0.6 mM valproate, yeast expressing human ISYNA1 had approximately 25% less intracellular inositol; purified ISYNA1 was not inhibited at that concentration.
Valproate → Intracellular myo-inositol availability source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/inositol-research/15024000.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5ab3a8eda77989c3e4a681b4a971fb7e969c285d3e5c8e41bc31713a7f88c9ac", "start_char": 0, "end_char": 1427, "text_sha256": "5ab3a8eda77989c3e4a681b4a971fb7e969c285d3e5c8e41bc31713a7f88c9ac"}
experimental_model
Recombinant human enzyme and complementation of yeast ino1 deletion
exposure
Substrate, NAD+, cation and valproate experiments
limitations
Purified-enzyme and yeast results do not establish supplement effects or a human dietary deficiency threshold.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Human protein expressed in bacteria and yeast
plain_language
The effect depended on the cellular setting rather than direct inhibition of the isolated enzyme.
primary_references
[ino-p15024000] Human 1-D-myo-inositol-3-phosphate synthase is functional in yeast. (2004). https://pubmed.ncbi.nlm.nih.gov/15024000/ DOI: 10.1074/jbc.m312078200
tissue_or_cell_type
Purified enzyme; yeast cultures
trigger_kind
machinery_impairment Imported condition classification; unverified.
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 223–234
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human enzyme and complementation of yeast ino1 deletion · source_derived_draft · unverified_draft
### ino-valproate-yeast At 0.6 mM valproate, yeast expressing human ISYNA1 had approximately 25% less intracellular inositol; purified ISYNA1 was not inhibited at that concentration. Condition category: machinery_impairment nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: The effect depended on the cellular setting rather than direct inhibition of the isolated enzyme. organism: Human protein expressed in bacteria and yeast tissue_or_cell_type: Purified enzyme; yeast cultures experimental_model: Recombinant human enzyme and complementation of yeast ino1 deletion limitations: Purified-enzyme and yeast results do not establish supplement effects or a human dietary deficiency threshold. exposure: Substrate, NAD+, cation and valproate experiments evidence_span: {"source_cache": "artifacts/inositol-research/15024000.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5ab3a8eda77989c3e4a681b4a971fb7e969c285d3e5c8e41bc31713a7f88c9ac", "start_char": 0, "end_char": 1427, "text_sha256": "5ab3a8eda77989c3e4a681b4a971fb7e969c285d3e5c8e41bc31713a7f88c9ac"} [ino-p15024000] Human 1-D-myo-inositol-3-phosphate synthase is functional in yeast. (2004). https://pubmed.ncbi.nlm.nih.gov/15024000/ DOI: 10.1074/jbc.m312078200
Complete structured claim and evidence
Mg2+ was essential for human inositol monophosphatase activity.
Mg2+ → IMPA1 (human inositol monophosphatase 1) source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/8223565.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "945d1d5166ce6410cd69984d93aebf127b635dcfcebddba31f0e8cc8b1c304a5", "start_char": 0, "end_char": 1621, "text_sha256": "945d1d5166ce6410cd69984d93aebf127b635dcfcebddba31f0e8cc8b1c304a5"}
experimental_model
Site-directed mutagenesis and enzyme kinetics
exposure
Magnesium and lithium titrations
limitations
Biochemical concentration dependence; neither lithium treatment mechanism nor magnesium supplementation response is established by this assay alone.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Human recombinant protein
plain_language
Inositol recycling needs magnesium at the enzyme level.
primary_references
[ino-p8223565] Probing the role of metal ions in the mechanism of inositol monophosphatase by site-directed mutagenesis. (1993). https://pubmed.ncbi.nlm.nih.gov/8223565/ DOI: 10.1111/j.1432-1033.1993.tb18244.x
tissue_or_cell_type
Purified IMPA1
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 249–260
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Site-directed mutagenesis and enzyme kinetics · source_derived_draft · unverified_draft
### ino-impa-magnesium Mg2+ was essential for human inositol monophosphatase activity. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: Inositol recycling needs magnesium at the enzyme level. organism: Human recombinant protein tissue_or_cell_type: Purified IMPA1 experimental_model: Site-directed mutagenesis and enzyme kinetics limitations: Biochemical concentration dependence; neither lithium treatment mechanism nor magnesium supplementation response is established by this assay alone. exposure: Magnesium and lithium titrations evidence_span: {"source_cache": "artifacts/inositol-research/8223565.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "945d1d5166ce6410cd69984d93aebf127b635dcfcebddba31f0e8cc8b1c304a5", "start_char": 0, "end_char": 1621, "text_sha256": "945d1d5166ce6410cd69984d93aebf127b635dcfcebddba31f0e8cc8b1c304a5"} [ino-p8223565] Probing the role of metal ions in the mechanism of inositol monophosphatase by site-directed mutagenesis. (1993). https://pubmed.ncbi.nlm.nih.gov/8223565/ DOI: 10.1111/j.1432-1033.1993.tb18244.x
Complete structured claim and evidence
High Mg2+ concentrations inhibited human inositol monophosphatase uncompetitively with respect to substrate.
Mg2+ → IMPA1 (human inositol monophosphatase 1) source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/8223565.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "945d1d5166ce6410cd69984d93aebf127b635dcfcebddba31f0e8cc8b1c304a5", "start_char": 0, "end_char": 1621, "text_sha256": "945d1d5166ce6410cd69984d93aebf127b635dcfcebddba31f0e8cc8b1c304a5"}
experimental_model
Site-directed mutagenesis and enzyme kinetics
exposure
Magnesium and lithium titrations
limitations
Biochemical concentration dependence; neither lithium treatment mechanism nor magnesium supplementation response is established by this assay alone.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Human recombinant protein
plain_language
An enzyme can need a mineral yet become inhibited when its concentration is too high.
primary_references
[ino-p8223565] Probing the role of metal ions in the mechanism of inositol monophosphatase by site-directed mutagenesis. (1993). https://pubmed.ncbi.nlm.nih.gov/8223565/ DOI: 10.1111/j.1432-1033.1993.tb18244.x
tissue_or_cell_type
Purified IMPA1
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 262–273
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Site-directed mutagenesis and enzyme kinetics · source_derived_draft · unverified_draft
### ino-impa-high-magnesium High Mg2+ concentrations inhibited human inositol monophosphatase uncompetitively with respect to substrate. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: An enzyme can need a mineral yet become inhibited when its concentration is too high. organism: Human recombinant protein tissue_or_cell_type: Purified IMPA1 experimental_model: Site-directed mutagenesis and enzyme kinetics limitations: Biochemical concentration dependence; neither lithium treatment mechanism nor magnesium supplementation response is established by this assay alone. exposure: Magnesium and lithium titrations evidence_span: {"source_cache": "artifacts/inositol-research/8223565.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "945d1d5166ce6410cd69984d93aebf127b635dcfcebddba31f0e8cc8b1c304a5", "start_char": 0, "end_char": 1621, "text_sha256": "945d1d5166ce6410cd69984d93aebf127b635dcfcebddba31f0e8cc8b1c304a5"} [ino-p8223565] Probing the role of metal ions in the mechanism of inositol monophosphatase by site-directed mutagenesis. (1993). https://pubmed.ncbi.nlm.nih.gov/8223565/ DOI: 10.1111/j.1432-1033.1993.tb18244.x
Complete structured claim and evidence
Li+ inhibited human inositol monophosphatase; parallel changes in Li+ and Mg2+ affinity across mutants supported a shared metal-binding site.
Lithium ion (Li+) → IMPA1 (human inositol monophosphatase 1) source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/inositol-research/8223565.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "945d1d5166ce6410cd69984d93aebf127b635dcfcebddba31f0e8cc8b1c304a5", "start_char": 0, "end_char": 1621, "text_sha256": "945d1d5166ce6410cd69984d93aebf127b635dcfcebddba31f0e8cc8b1c304a5"}
experimental_model
Site-directed mutagenesis and enzyme kinetics
exposure
Magnesium and lithium titrations
limitations
Biochemical concentration dependence; neither lithium treatment mechanism nor magnesium supplementation response is established by this assay alone.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Human recombinant protein
plain_language
Lithium can interfere with a magnesium-linked step of inositol recycling.
primary_references
[ino-p8223565] Probing the role of metal ions in the mechanism of inositol monophosphatase by site-directed mutagenesis. (1993). https://pubmed.ncbi.nlm.nih.gov/8223565/ DOI: 10.1111/j.1432-1033.1993.tb18244.x
tissue_or_cell_type
Purified IMPA1
trigger_kind
machinery_impairment Imported condition classification; unverified.
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 275–286
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Site-directed mutagenesis and enzyme kinetics · source_derived_draft · unverified_draft
### ino-impa-lithium Li+ inhibited human inositol monophosphatase; parallel changes in Li+ and Mg2+ affinity across mutants supported a shared metal-binding site. Condition category: machinery_impairment nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: Lithium can interfere with a magnesium-linked step of inositol recycling. organism: Human recombinant protein tissue_or_cell_type: Purified IMPA1 experimental_model: Site-directed mutagenesis and enzyme kinetics limitations: Biochemical concentration dependence; neither lithium treatment mechanism nor magnesium supplementation response is established by this assay alone. exposure: Magnesium and lithium titrations evidence_span: {"source_cache": "artifacts/inositol-research/8223565.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "945d1d5166ce6410cd69984d93aebf127b635dcfcebddba31f0e8cc8b1c304a5", "start_char": 0, "end_char": 1621, "text_sha256": "945d1d5166ce6410cd69984d93aebf127b635dcfcebddba31f0e8cc8b1c304a5"} [ino-p8223565] Probing the role of metal ions in the mechanism of inositol monophosphatase by site-directed mutagenesis. (1993). https://pubmed.ncbi.nlm.nih.gov/8223565/ DOI: 10.1111/j.1432-1033.1993.tb18244.x
Complete structured claim and evidence
Human SMIT2 expression increased D-chiro-inositol uptake 159-fold in rat L6 cells.
SLC5A11 (human SMIT2) → D-chiro-inositol source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/19032932.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4fdc565b9aa26ef5f2d083c539a1b0367403b39f0c75d3ea1b194bf6fa525242", "start_char": 0, "end_char": 1164, "text_sha256": "4fdc565b9aa26ef5f2d083c539a1b0367403b39f0c75d3ea1b194bf6fa525242"}
experimental_model
Human SMIT2 overexpression and radiotracer uptake
exposure
Overexpression, glucose competition and insulin exposure
limitations
Overexpression is not normal transporter abundance. Insulin experiments used untransfected rat cells; changes in human diabetes are proposed, not demonstrated here.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Human transporter in rat L6 myoblasts
plain_language
The transporter can carry a second inositol stereoisomer.
primary_references
[ino-p19032932] Human sodium/inositol cotransporter 2 (SMIT2) transports inositols but not glucose in L6 cells. (2009). https://pubmed.ncbi.nlm.nih.gov/19032932/ DOI: 10.1016/j.abb.2008.11.008
tissue_or_cell_type
Skeletal-muscle cell model
transport_effect
raises Expression increased D-chiro-inositol uptake 159-fold.
transport_pool
the expressing cell Expression increased D-chiro-inositol uptake 159-fold.
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 301–312
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human SMIT2 overexpression and radiotracer uptake · source_derived_draft · unverified_draft
### ino-smit2-dci Human SMIT2 expression increased D-chiro-inositol uptake 159-fold in rat L6 cells. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: The transporter can carry a second inositol stereoisomer. organism: Human transporter in rat L6 myoblasts tissue_or_cell_type: Skeletal-muscle cell model experimental_model: Human SMIT2 overexpression and radiotracer uptake limitations: Overexpression is not normal transporter abundance. Insulin experiments used untransfected rat cells; changes in human diabetes are proposed, not demonstrated here. exposure: Overexpression, glucose competition and insulin exposure evidence_span: {"source_cache": "artifacts/inositol-research/19032932.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4fdc565b9aa26ef5f2d083c539a1b0367403b39f0c75d3ea1b194bf6fa525242", "start_char": 0, "end_char": 1164, "text_sha256": "4fdc565b9aa26ef5f2d083c539a1b0367403b39f0c75d3ea1b194bf6fa525242"} [ino-p19032932] Human sodium/inositol cotransporter 2 (SMIT2) transports inositols but not glucose in L6 cells. (2009). https://pubmed.ncbi.nlm.nih.gov/19032932/ DOI: 10.1016/j.abb.2008.11.008
Complete structured claim and evidence
Glucose competed for D-chiro-inositol uptake with a reported Ki of 6.1 mM in the SMIT2 expression system, without evidence that SMIT2 transported glucose in those assays.
D-glucose → D-chiro-inositol uptake source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/19032932.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4fdc565b9aa26ef5f2d083c539a1b0367403b39f0c75d3ea1b194bf6fa525242", "start_char": 0, "end_char": 1164, "text_sha256": "4fdc565b9aa26ef5f2d083c539a1b0367403b39f0c75d3ea1b194bf6fa525242"}
experimental_model
Human SMIT2 overexpression and radiotracer uptake
exposure
Overexpression, glucose competition and insulin exposure
limitations
Overexpression is not normal transporter abundance. Insulin experiments used untransfected rat cells; changes in human diabetes are proposed, not demonstrated here.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Human transporter in rat L6 myoblasts
plain_language
Glucose competed for entry without itself becoming demonstrated cargo of this transporter.
primary_references
[ino-p19032932] Human sodium/inositol cotransporter 2 (SMIT2) transports inositols but not glucose in L6 cells. (2009). https://pubmed.ncbi.nlm.nih.gov/19032932/ DOI: 10.1016/j.abb.2008.11.008
tissue_or_cell_type
Skeletal-muscle cell model
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 314–325
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human SMIT2 overexpression and radiotracer uptake · source_derived_draft · unverified_draft
### ino-smit2-glucose Glucose competed for D-chiro-inositol uptake with a reported Ki of 6.1 mM in the SMIT2 expression system, without evidence that SMIT2 transported glucose in those assays. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: Glucose competed for entry without itself becoming demonstrated cargo of this transporter. organism: Human transporter in rat L6 myoblasts tissue_or_cell_type: Skeletal-muscle cell model experimental_model: Human SMIT2 overexpression and radiotracer uptake limitations: Overexpression is not normal transporter abundance. Insulin experiments used untransfected rat cells; changes in human diabetes are proposed, not demonstrated here. exposure: Overexpression, glucose competition and insulin exposure evidence_span: {"source_cache": "artifacts/inositol-research/19032932.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4fdc565b9aa26ef5f2d083c539a1b0367403b39f0c75d3ea1b194bf6fa525242", "start_char": 0, "end_char": 1164, "text_sha256": "4fdc565b9aa26ef5f2d083c539a1b0367403b39f0c75d3ea1b194bf6fa525242"} [ino-p19032932] Human sodium/inositol cotransporter 2 (SMIT2) transports inositols but not glucose in L6 cells. (2009). https://pubmed.ncbi.nlm.nih.gov/19032932/ DOI: 10.1016/j.abb.2008.11.008
Complete structured claim and evidence
Insulin exposure at 2 micromolar for 24 hours increased specific D-chiro-inositol uptake 18-fold in untransfected rat L6 cells.
Insulin → D-chiro-inositol uptake source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/19032932.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4fdc565b9aa26ef5f2d083c539a1b0367403b39f0c75d3ea1b194bf6fa525242", "start_char": 0, "end_char": 1164, "text_sha256": "4fdc565b9aa26ef5f2d083c539a1b0367403b39f0c75d3ea1b194bf6fa525242"}
experimental_model
Human SMIT2 overexpression and radiotracer uptake
exposure
Overexpression, glucose competition and insulin exposure
limitations
Overexpression is not normal transporter abundance. Insulin experiments used untransfected rat cells; changes in human diabetes are proposed, not demonstrated here.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Human transporter in rat L6 myoblasts
plain_language
The muscle-cell model adjusted its inositol uptake after insulin exposure.
primary_references
[ino-p19032932] Human sodium/inositol cotransporter 2 (SMIT2) transports inositols but not glucose in L6 cells. (2009). https://pubmed.ncbi.nlm.nih.gov/19032932/ DOI: 10.1016/j.abb.2008.11.008
tissue_or_cell_type
Skeletal-muscle cell model
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 327–338
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human SMIT2 overexpression and radiotracer uptake · source_derived_draft · unverified_draft
### ino-insulin-dci-uptake Insulin exposure at 2 micromolar for 24 hours increased specific D-chiro-inositol uptake 18-fold in untransfected rat L6 cells. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: The muscle-cell model adjusted its inositol uptake after insulin exposure. organism: Human transporter in rat L6 myoblasts tissue_or_cell_type: Skeletal-muscle cell model experimental_model: Human SMIT2 overexpression and radiotracer uptake limitations: Overexpression is not normal transporter abundance. Insulin experiments used untransfected rat cells; changes in human diabetes are proposed, not demonstrated here. exposure: Overexpression, glucose competition and insulin exposure evidence_span: {"source_cache": "artifacts/inositol-research/19032932.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4fdc565b9aa26ef5f2d083c539a1b0367403b39f0c75d3ea1b194bf6fa525242", "start_char": 0, "end_char": 1164, "text_sha256": "4fdc565b9aa26ef5f2d083c539a1b0367403b39f0c75d3ea1b194bf6fa525242"} [ino-p19032932] Human sodium/inositol cotransporter 2 (SMIT2) transports inositols but not glucose in L6 cells. (2009). https://pubmed.ncbi.nlm.nih.gov/19032932/ DOI: 10.1016/j.abb.2008.11.008
Complete structured claim and evidence
A fitted five-state model of human SMIT2 currents included cooperative Na+ binding and a likely rate-limiting return of empty transporter.
Sodium ion → SLC5A11 (human SMIT2) source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/24944204.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "12216ce12672706d91e22c9fbc1ebc5dbe77444e9869048f8a0d456f621cb41e", "start_char": 0, "end_char": 1647, "text_sha256": "12216ce12672706d91e22c9fbc1ebc5dbe77444e9869048f8a0d456f621cb41e"}
experimental_model
Voltage clamp and kinetic model fitting
exposure
Sodium and voltage manipulations
limitations
Cooperative sodium binding and turnover were model-derived; this is not a clinical sodium recommendation.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Human SMIT2 in Xenopus oocytes
plain_language
The sodium gradient is part of the transport machinery, rather than inositol moving independently of ions.
primary_references
[ino-p24944204] The transport mechanism of the human sodium/myo-inositol transporter 2 (SMIT2/SGLT6), a member of the LeuT structural family. (2014). https://pubmed.ncbi.nlm.nih.gov/24944204/ DOI: 10.1152/ajpcell.00054.2014
tissue_or_cell_type
Heterologous membrane transport
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 340–351
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Voltage clamp and kinetic model fitting · source_derived_draft · unverified_draft
### ino-smit2-sodium A fitted five-state model of human SMIT2 currents included cooperative Na+ binding and a likely rate-limiting return of empty transporter. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: The sodium gradient is part of the transport machinery, rather than inositol moving independently of ions. organism: Human SMIT2 in Xenopus oocytes tissue_or_cell_type: Heterologous membrane transport experimental_model: Voltage clamp and kinetic model fitting limitations: Cooperative sodium binding and turnover were model-derived; this is not a clinical sodium recommendation. exposure: Sodium and voltage manipulations evidence_span: {"source_cache": "artifacts/inositol-research/24944204.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "12216ce12672706d91e22c9fbc1ebc5dbe77444e9869048f8a0d456f621cb41e", "start_char": 0, "end_char": 1647, "text_sha256": "12216ce12672706d91e22c9fbc1ebc5dbe77444e9869048f8a0d456f621cb41e"} [ino-p24944204] The transport mechanism of the human sodium/myo-inositol transporter 2 (SMIT2/SGLT6), a member of the LeuT structural family. (2014). https://pubmed.ncbi.nlm.nih.gov/24944204/ DOI: 10.1152/ajpcell.00054.2014
Complete structured claim and evidence
Hypertonic MDCK culture increased sodium/myo-inositol transporter transcription, mRNA and transport activity with different time courses.
Cellular adaptation to hypertonicity → Canine SLC5A3 (SMIT1) source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/8430828.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0539c3e28460fcea154b9014b1d98f36bf5ee2b8b5a418f6951c9cf0ad92af8b", "start_char": 0, "end_char": 1156, "text_sha256": "0539c3e28460fcea154b9014b1d98f36bf5ee2b8b5a418f6951c9cf0ad92af8b"}
experimental_model
Hypertonic culture adaptation
exposure
Hypertonic exposure followed by isotonic recovery
limitations
Dog cell culture, not a human intake requirement.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Canis familiaris
plain_language
Kidney-derived cells adjust inositol uptake as part of adaptation to concentrated surroundings.
primary_references
[ino-p8430828] Hypertonicity stimulates transcription of gene for Na(+)-myo-inositol cotransporter in MDCK cells. (1993). https://pubmed.ncbi.nlm.nih.gov/8430828/ DOI: 10.1152/ajprenal.1993.264.1.f20
tissue_or_cell_type
MDCK renal epithelial cells
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 353–364
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Hypertonic culture adaptation · source_derived_draft · unverified_draft
### ino-smit1-osmotic Hypertonic MDCK culture increased sodium/myo-inositol transporter transcription, mRNA and transport activity with different time courses. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: Kidney-derived cells adjust inositol uptake as part of adaptation to concentrated surroundings. organism: Canis familiaris tissue_or_cell_type: MDCK renal epithelial cells experimental_model: Hypertonic culture adaptation limitations: Dog cell culture, not a human intake requirement. exposure: Hypertonic exposure followed by isotonic recovery evidence_span: {"source_cache": "artifacts/inositol-research/8430828.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0539c3e28460fcea154b9014b1d98f36bf5ee2b8b5a418f6951c9cf0ad92af8b", "start_char": 0, "end_char": 1156, "text_sha256": "0539c3e28460fcea154b9014b1d98f36bf5ee2b8b5a418f6951c9cf0ad92af8b"} [ino-p8430828] Hypertonicity stimulates transcription of gene for Na(+)-myo-inositol cotransporter in MDCK cells. (1993). https://pubmed.ncbi.nlm.nih.gov/8430828/ DOI: 10.1152/ajprenal.1993.264.1.f20
Complete structured claim and evidence
HMIT expressed in Xenopus oocytes mediated electrogenic proton-coupled myo-inositol uptake that increased as pH fell, with maximal tested activity near pH 5.
Rat Slc2a13 (HMIT) → Myo-inositol source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/11500374.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "fb9efd53bbc0fae1bf1ada1525cdb7d10a4e700d3309bfba4e3a598c4a9c74b9", "start_char": 0, "end_char": 1270, "text_sha256": "fb9efd53bbc0fae1bf1ada1525cdb7d10a4e700d3309bfba4e3a598c4a9c74b9"}
experimental_model
Transporter expression and electrophysiology
exposure
Extracellular pH manipulation
limitations
Transport capacity after heterologous expression does not establish a neuronal plasma-membrane role in vivo.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Rat brain transporter studied in Xenopus oocytes
plain_language
A different transporter can use a proton gradient, particularly in acidic experimental conditions.
primary_references
[ino-p11500374] Identification of a mammalian H(+)-myo-inositol symporter expressed predominantly in the brain. (2001). https://pubmed.ncbi.nlm.nih.gov/11500374/ DOI: 10.1093/emboj/20.16.4467
tissue_or_cell_type
Heterologous membranes and rat brain
transport_effect
raises Electrogenic proton-coupled myo-inositol uptake rising as pH fell.
transport_pool
the expressing cell Electrogenic proton-coupled myo-inositol uptake rising as pH fell.
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 366–377
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Transporter expression and electrophysiology · source_derived_draft · unverified_draft
### ino-hmit-acid HMIT expressed in Xenopus oocytes mediated electrogenic proton-coupled myo-inositol uptake that increased as pH fell, with maximal tested activity near pH 5. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: A different transporter can use a proton gradient, particularly in acidic experimental conditions. organism: Rat brain transporter studied in Xenopus oocytes tissue_or_cell_type: Heterologous membranes and rat brain experimental_model: Transporter expression and electrophysiology limitations: Transport capacity after heterologous expression does not establish a neuronal plasma-membrane role in vivo. exposure: Extracellular pH manipulation evidence_span: {"source_cache": "artifacts/inositol-research/11500374.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "fb9efd53bbc0fae1bf1ada1525cdb7d10a4e700d3309bfba4e3a598c4a9c74b9", "start_char": 0, "end_char": 1270, "text_sha256": "fb9efd53bbc0fae1bf1ada1525cdb7d10a4e700d3309bfba4e3a598c4a9c74b9"} [ino-p11500374] Identification of a mammalian H(+)-myo-inositol symporter expressed predominantly in the brain. (2001). https://pubmed.ncbi.nlm.nih.gov/11500374/ DOI: 10.1093/emboj/20.16.4467
Complete structured claim and evidence
HMIT localized to the Golgi apparatus in primary cultured neurons; HMIT-mediated currents were not detected in rat neurons or brain slices.
Rat Slc2a13 (HMIT) → Golgi apparatus source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/19607714.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8b8bd010f44dd8b055efc345c57791e88547114b0a2f27d782183674fc53f984", "start_char": 0, "end_char": 1332, "text_sha256": "8b8bd010f44dd8b055efc345c57791e88547114b0a2f27d782183674fc53f984"}
experimental_model
Immunolocalization, neuronal electrophysiology and knockout
exposure
Native localization and HMIT-null comparisons
limitations
Native localization qualifies earlier heterologous uptake findings; it is an explained context difference, not evidence that one experiment is false.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Rat and human brain; mouse knockout
plain_language
A transporter that works at an artificial cell surface may normally function inside the cell.
primary_references
[ino-p19607714] Evaluation of expression and function of the H+/myo-inositol transporter HMIT. (2009). https://pubmed.ncbi.nlm.nih.gov/19607714/ DOI: 10.1186/1471-2121-10-54
tissue_or_cell_type
Brain neurons and cultured neurons
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 379–390
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Immunolocalization, neuronal electrophysiology and knockout · source_derived_draft · unverified_draft
### ino-hmit-golgi HMIT localized to the Golgi apparatus in primary cultured neurons; HMIT-mediated currents were not detected in rat neurons or brain slices. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: A transporter that works at an artificial cell surface may normally function inside the cell. organism: Rat and human brain; mouse knockout tissue_or_cell_type: Brain neurons and cultured neurons experimental_model: Immunolocalization, neuronal electrophysiology and knockout limitations: Native localization qualifies earlier heterologous uptake findings; it is an explained context difference, not evidence that one experiment is false. exposure: Native localization and HMIT-null comparisons evidence_span: {"source_cache": "artifacts/inositol-research/19607714.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8b8bd010f44dd8b055efc345c57791e88547114b0a2f27d782183674fc53f984", "start_char": 0, "end_char": 1332, "text_sha256": "8b8bd010f44dd8b055efc345c57791e88547114b0a2f27d782183674fc53f984"} [ino-p19607714] Evaluation of expression and function of the H+/myo-inositol transporter HMIT. (2009). https://pubmed.ncbi.nlm.nih.gov/19607714/ DOI: 10.1186/1471-2121-10-54
Complete structured claim and evidence
HMIT-null mice did not show altered inositol transport or homeostasis in the reported analyses.
Mouse Slc2a13 (HMIT) → Intracellular myo-inositol availability source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/inositol-research/19607714.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8b8bd010f44dd8b055efc345c57791e88547114b0a2f27d782183674fc53f984", "start_char": 0, "end_char": 1332, "text_sha256": "8b8bd010f44dd8b055efc345c57791e88547114b0a2f27d782183674fc53f984"}
experimental_model
Immunolocalization, neuronal electrophysiology and knockout
exposure
Native localization and HMIT-null comparisons
limitations
Native localization qualifies earlier heterologous uptake findings; it is an explained context difference, not evidence that one experiment is false.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Rat and human brain; mouse knockout
plain_language
Removing this one candidate transporter did not produce the predicted general uptake failure.
primary_references
[ino-p19607714] Evaluation of expression and function of the H+/myo-inositol transporter HMIT. (2009). https://pubmed.ncbi.nlm.nih.gov/19607714/ DOI: 10.1186/1471-2121-10-54
tissue_or_cell_type
Brain neurons and cultured neurons
trigger_kind
machinery_impairment Imported condition classification; unverified.
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 392–403
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Immunolocalization, neuronal electrophysiology and knockout · source_derived_draft · unverified_draft
### ino-hmit-null HMIT-null mice did not show altered inositol transport or homeostasis in the reported analyses. Condition category: machinery_impairment nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: Removing this one candidate transporter did not produce the predicted general uptake failure. organism: Rat and human brain; mouse knockout tissue_or_cell_type: Brain neurons and cultured neurons experimental_model: Immunolocalization, neuronal electrophysiology and knockout limitations: Native localization qualifies earlier heterologous uptake findings; it is an explained context difference, not evidence that one experiment is false. exposure: Native localization and HMIT-null comparisons evidence_span: {"source_cache": "artifacts/inositol-research/19607714.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8b8bd010f44dd8b055efc345c57791e88547114b0a2f27d782183674fc53f984", "start_char": 0, "end_char": 1332, "text_sha256": "8b8bd010f44dd8b055efc345c57791e88547114b0a2f27d782183674fc53f984"} [ino-p19607714] Evaluation of expression and function of the H+/myo-inositol transporter HMIT. (2009). https://pubmed.ncbi.nlm.nih.gov/19607714/ DOI: 10.1186/1471-2121-10-54
Complete structured claim and evidence
ISYNA1 transcriptional silencing characterized SLC5A3-dependent AML lines and produced an inositol auxotrophy.
ISYNA1 transcriptional silencing → SLC5A3 (human SMIT1) source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/inositol-research/34531253.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e709021b8916a9b38a3a52f092732c2b587c55247c0bd9bd3f96438e74ad4b27", "start_char": 0, "end_char": 1431, "text_sha256": "e709021b8916a9b38a3a52f092732c2b587c55247c0bd9bd3f96438e74ad4b27"}
experimental_model
Genetic screening, gain/loss of function and patient sample profiling
exposure
SLC5A3/ISYNA1 perturbation
limitations
Restricted to an epigenetically defined subset; no evidence that dietary inositol restriction treats leukemia.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Human AML cells and in vivo leukemia models
plain_language
When a cell loses its synthesis route, the import route can become essential.
primary_references
[ino-p34531253] SLC5A3-Dependent Myo-inositol Auxotrophy in Acute Myeloid Leukemia. (2022). https://pubmed.ncbi.nlm.nih.gov/34531253/ DOI: 10.1158/2159-8290.cd-20-1849
tissue_or_cell_type
Acute myeloid leukemia
trigger_kind
machinery_impairment Imported condition classification; unverified.
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 405–416
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Genetic screening, gain/loss of function and patient sample profiling · source_derived_draft · unverified_draft
### ino-aml-silencing ISYNA1 transcriptional silencing characterized SLC5A3-dependent AML lines and produced an inositol auxotrophy. Condition category: machinery_impairment nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: When a cell loses its synthesis route, the import route can become essential. organism: Human AML cells and in vivo leukemia models tissue_or_cell_type: Acute myeloid leukemia experimental_model: Genetic screening, gain/loss of function and patient sample profiling limitations: Restricted to an epigenetically defined subset; no evidence that dietary inositol restriction treats leukemia. exposure: SLC5A3/ISYNA1 perturbation evidence_span: {"source_cache": "artifacts/inositol-research/34531253.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e709021b8916a9b38a3a52f092732c2b587c55247c0bd9bd3f96438e74ad4b27", "start_char": 0, "end_char": 1431, "text_sha256": "e709021b8916a9b38a3a52f092732c2b587c55247c0bd9bd3f96438e74ad4b27"} [ino-p34531253] SLC5A3-Dependent Myo-inositol Auxotrophy in Acute Myeloid Leukemia. (2022). https://pubmed.ncbi.nlm.nih.gov/34531253/ DOI: 10.1158/2159-8290.cd-20-1849
Complete structured claim and evidence
Gain- and loss-of-function experiments supported redundant contributions of ISYNA1 synthesis and SLC5A3 transport to intracellular inositol and AML-cell fitness.
ISYNA1 (human inositol-3-phosphate synthase 1) → SLC5A3 (human SMIT1) source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/inositol-research/34531253.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e709021b8916a9b38a3a52f092732c2b587c55247c0bd9bd3f96438e74ad4b27", "start_char": 0, "end_char": 1431, "text_sha256": "e709021b8916a9b38a3a52f092732c2b587c55247c0bd9bd3f96438e74ad4b27"}
experimental_model
Genetic screening, gain/loss of function and patient sample profiling
exposure
SLC5A3/ISYNA1 perturbation
limitations
Restricted to an epigenetically defined subset; no evidence that dietary inositol restriction treats leukemia.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Human AML cells and in vivo leukemia models
plain_language
Restoring synthesis can remove dependence on the same import route.
primary_references
[ino-p34531253] SLC5A3-Dependent Myo-inositol Auxotrophy in Acute Myeloid Leukemia. (2022). https://pubmed.ncbi.nlm.nih.gov/34531253/ DOI: 10.1158/2159-8290.cd-20-1849
tissue_or_cell_type
Acute myeloid leukemia
trigger_kind
machinery_impairment Imported condition classification; unverified.
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 418–429
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Genetic screening, gain/loss of function and patient sample profiling · source_derived_draft · unverified_draft
### ino-aml-redundancy Gain- and loss-of-function experiments supported redundant contributions of ISYNA1 synthesis and SLC5A3 transport to intracellular inositol and AML-cell fitness. Condition category: machinery_impairment nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: Restoring synthesis can remove dependence on the same import route. organism: Human AML cells and in vivo leukemia models tissue_or_cell_type: Acute myeloid leukemia experimental_model: Genetic screening, gain/loss of function and patient sample profiling limitations: Restricted to an epigenetically defined subset; no evidence that dietary inositol restriction treats leukemia. exposure: SLC5A3/ISYNA1 perturbation evidence_span: {"source_cache": "artifacts/inositol-research/34531253.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e709021b8916a9b38a3a52f092732c2b587c55247c0bd9bd3f96438e74ad4b27", "start_char": 0, "end_char": 1431, "text_sha256": "e709021b8916a9b38a3a52f092732c2b587c55247c0bd9bd3f96438e74ad4b27"} [ino-p34531253] SLC5A3-Dependent Myo-inositol Auxotrophy in Acute Myeloid Leukemia. (2022). https://pubmed.ncbi.nlm.nih.gov/34531253/ DOI: 10.1158/2159-8290.cd-20-1849
Complete structured claim and evidence
The original report described profound brain myo-inositol deficiency in its lethal mouse transport-loss model.
Mouse Slc5a3 (SMIT1) → Brain myo-inositol pool source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/inositol-research/15110328.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "efa2c78237254c73512bf946f2600f4ead3f1e510cda84a06327906d4663d3ee", "start_char": 0, "end_char": 1202, "text_sha256": "efa2c78237254c73512bf946f2600f4ead3f1e510cda84a06327906d4663d3ee"}
experimental_model
Transporter knockout and brain chemical analysis
exposure
SMIT1-null mice
limitations
Severe genetic transport failure is not dietary deficiency. Unchanged total PI does not rule out local phosphoinositide abnormalities. An indexed erratum exists (10.1016/j.ymgme.2004.06.012); its content was not retrievable during this curation, so these findings remain provisional reports from the indexed original abstract.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Mus musculus
plain_language
Loss of a transport route caused a major free-inositol deficit in this reported model.
primary_references
[ino-p15110328] Phosphoinositide deficiency due to inositol depletion is not a mechanism of lithium action in brain. (2004). https://pubmed.ncbi.nlm.nih.gov/15110328/ DOI: 10.1016/j.ymgme.2004.02.002
tissue_or_cell_type
Brain
trigger_kind
machinery_impairment Imported condition classification; unverified.
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 431–442
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Transporter knockout and brain chemical analysis · source_derived_draft · unverified_draft
### ino-smit1-low-pool The original report described profound brain myo-inositol deficiency in its lethal mouse transport-loss model. Condition category: machinery_impairment nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: Loss of a transport route caused a major free-inositol deficit in this reported model. organism: Mus musculus tissue_or_cell_type: Brain experimental_model: Transporter knockout and brain chemical analysis limitations: Severe genetic transport failure is not dietary deficiency. Unchanged total PI does not rule out local phosphoinositide abnormalities. An indexed erratum exists (10.1016/j.ymgme.2004.06.012); its content was not retrievable during this curation, so these findings remain provisional reports from the indexed original abstract. exposure: SMIT1-null mice evidence_span: {"source_cache": "artifacts/inositol-research/15110328.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "efa2c78237254c73512bf946f2600f4ead3f1e510cda84a06327906d4663d3ee", "start_char": 0, "end_char": 1202, "text_sha256": "efa2c78237254c73512bf946f2600f4ead3f1e510cda84a06327906d4663d3ee"} [ino-p15110328] Phosphoinositide deficiency due to inositol depletion is not a mechanism of lithium action in brain. (2004). https://pubmed.ncbi.nlm.nih.gov/15110328/ DOI: 10.1016/j.ymgme.2004.02.002
Complete structured claim and evidence
Despite severely reduced brain myo-inositol, measured brain phosphatidylinositol was not decreased in SMIT1-null mice.
Mouse Slc5a3 (SMIT1) → Phosphatidylinositol (PI) source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/inositol-research/15110328.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "efa2c78237254c73512bf946f2600f4ead3f1e510cda84a06327906d4663d3ee", "start_char": 0, "end_char": 1202, "text_sha256": "efa2c78237254c73512bf946f2600f4ead3f1e510cda84a06327906d4663d3ee"}
experimental_model
Transporter knockout and brain chemical analysis
exposure
SMIT1-null mice
limitations
Severe genetic transport failure is not dietary deficiency. Unchanged total PI does not rule out local phosphoinositide abnormalities. An indexed erratum exists (10.1016/j.ymgme.2004.06.012); its content was not retrievable during this curation, so these findings remain provisional reports from the indexed original abstract.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Mus musculus
plain_language
The free pool and the total membrane-lipid pool did not fall together.
primary_references
[ino-p15110328] Phosphoinositide deficiency due to inositol depletion is not a mechanism of lithium action in brain. (2004). https://pubmed.ncbi.nlm.nih.gov/15110328/ DOI: 10.1016/j.ymgme.2004.02.002
tissue_or_cell_type
Brain
trigger_kind
machinery_impairment Imported condition classification; unverified.
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 444–455
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Transporter knockout and brain chemical analysis · source_derived_draft · unverified_draft
### ino-smit1-pi-preserved Despite severely reduced brain myo-inositol, measured brain phosphatidylinositol was not decreased in SMIT1-null mice. Condition category: machinery_impairment nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: The free pool and the total membrane-lipid pool did not fall together. organism: Mus musculus tissue_or_cell_type: Brain experimental_model: Transporter knockout and brain chemical analysis limitations: Severe genetic transport failure is not dietary deficiency. Unchanged total PI does not rule out local phosphoinositide abnormalities. An indexed erratum exists (10.1016/j.ymgme.2004.06.012); its content was not retrievable during this curation, so these findings remain provisional reports from the indexed original abstract. exposure: SMIT1-null mice evidence_span: {"source_cache": "artifacts/inositol-research/15110328.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "efa2c78237254c73512bf946f2600f4ead3f1e510cda84a06327906d4663d3ee", "start_char": 0, "end_char": 1202, "text_sha256": "efa2c78237254c73512bf946f2600f4ead3f1e510cda84a06327906d4663d3ee"} [ino-p15110328] Phosphoinositide deficiency due to inositol depletion is not a mechanism of lithium action in brain. (2004). https://pubmed.ncbi.nlm.nih.gov/15110328/ DOI: 10.1016/j.ymgme.2004.02.002
Complete structured claim and evidence
Human MIOX contains a diiron catalytic center involved in oxygen-dependent inositol cleavage.
Diiron catalytic center → MIOX (human myo-inositol oxygenase) source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/18364358.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9992644d489f26782d7ef0a70dc13ec5ca48e2b660a011173fba8e0d4e43ae19", "start_char": 0, "end_char": 1004, "text_sha256": "9992644d489f26782d7ef0a70dc13ec5ca48e2b660a011173fba8e0d4e43ae19"}
experimental_model
Human enzyme crystallography and catalytic analysis
exposure
Diiron center and inhibitor-bound structure
limitations
Catabolism of inositol is not evidence that humans synthesize vitamin C from it; the crystal ligand was an inhibitor.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Homo sapiens
plain_language
Two iron atoms are part of this breakdown enzyme, linking inositol metabolism to iron chemistry.
primary_references
[ino-p18364358] Structural and biophysical characterization of human myo-inositol oxygenase. (2008). https://pubmed.ncbi.nlm.nih.gov/18364358/ DOI: 10.1074/jbc.m800348200
tissue_or_cell_type
Purified MIOX
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 470–481
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human enzyme crystallography and catalytic analysis · source_derived_draft · unverified_draft
### ino-miox-iron Human MIOX contains a diiron catalytic center involved in oxygen-dependent inositol cleavage. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: Two iron atoms are part of this breakdown enzyme, linking inositol metabolism to iron chemistry. organism: Homo sapiens tissue_or_cell_type: Purified MIOX experimental_model: Human enzyme crystallography and catalytic analysis limitations: Catabolism of inositol is not evidence that humans synthesize vitamin C from it; the crystal ligand was an inhibitor. exposure: Diiron center and inhibitor-bound structure evidence_span: {"source_cache": "artifacts/inositol-research/18364358.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9992644d489f26782d7ef0a70dc13ec5ca48e2b660a011173fba8e0d4e43ae19", "start_char": 0, "end_char": 1004, "text_sha256": "9992644d489f26782d7ef0a70dc13ec5ca48e2b660a011173fba8e0d4e43ae19"} [ino-p18364358] Structural and biophysical characterization of human myo-inositol oxygenase. (2008). https://pubmed.ncbi.nlm.nih.gov/18364358/ DOI: 10.1074/jbc.m800348200
Complete structured claim and evidence
The human MIOX structure contained bound myo-inosose-1, an inhibitor rather than the normal myo-inositol substrate.
Myo-inosose-1 → MIOX (human myo-inositol oxygenase) source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/18364358.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9992644d489f26782d7ef0a70dc13ec5ca48e2b660a011173fba8e0d4e43ae19", "start_char": 0, "end_char": 1004, "text_sha256": "9992644d489f26782d7ef0a70dc13ec5ca48e2b660a011173fba8e0d4e43ae19"}
experimental_model
Human enzyme crystallography and catalytic analysis
exposure
Diiron center and inhibitor-bound structure
limitations
Catabolism of inositol is not evidence that humans synthesize vitamin C from it; the crystal ligand was an inhibitor.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Homo sapiens
plain_language
A bound look-alike helped reveal the active site; it must not be mislabeled as the substrate.
primary_references
[ino-p18364358] Structural and biophysical characterization of human myo-inositol oxygenase. (2008). https://pubmed.ncbi.nlm.nih.gov/18364358/ DOI: 10.1074/jbc.m800348200
tissue_or_cell_type
Purified MIOX
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 483–494
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human enzyme crystallography and catalytic analysis · source_derived_draft · unverified_draft
### ino-miox-inhibitor The human MIOX structure contained bound myo-inosose-1, an inhibitor rather than the normal myo-inositol substrate. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: A bound look-alike helped reveal the active site; it must not be mislabeled as the substrate. organism: Homo sapiens tissue_or_cell_type: Purified MIOX experimental_model: Human enzyme crystallography and catalytic analysis limitations: Catabolism of inositol is not evidence that humans synthesize vitamin C from it; the crystal ligand was an inhibitor. exposure: Diiron center and inhibitor-bound structure evidence_span: {"source_cache": "artifacts/inositol-research/18364358.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9992644d489f26782d7ef0a70dc13ec5ca48e2b660a011173fba8e0d4e43ae19", "start_char": 0, "end_char": 1004, "text_sha256": "9992644d489f26782d7ef0a70dc13ec5ca48e2b660a011173fba8e0d4e43ae19"} [ino-p18364358] Structural and biophysical characterization of human myo-inositol oxygenase. (2008). https://pubmed.ncbi.nlm.nih.gov/18364358/ DOI: 10.1074/jbc.m800348200
Complete structured claim and evidence
Purified human placental PI synthase required Mn2+ or Mg2+ for activity.
Mg2+ → CDIPT (human phosphatidylinositol synthase) source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/8110188.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c05bb5272b443bde4f99d4af375d31988a4812150450d6c4462059a59aa8a09e", "start_char": 0, "end_char": 940, "text_sha256": "c05bb5272b443bde4f99d4af375d31988a4812150450d6c4462059a59aa8a09e"}
experimental_model
Purification and kinetics of placental PI synthase
exposure
Substrate and ion titrations
limitations
Assay optima and inhibitory concentrations are not dietary advice or proof of in vivo nutrient competition.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Homo sapiens
plain_language
Magnesium can support the enzyme that builds PI.
primary_references
[ino-p8110188] Purification and characterization of phosphatidylinositol synthase from human placenta. (1994). https://pubmed.ncbi.nlm.nih.gov/8110188/ DOI: 10.1042/bj2970517
tissue_or_cell_type
Placental microsomal enzyme
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 509–520
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purification and kinetics of placental PI synthase · source_derived_draft · unverified_draft
### ino-cdipt-magnesium Purified human placental PI synthase required Mn2+ or Mg2+ for activity. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: Magnesium can support the enzyme that builds PI. organism: Homo sapiens tissue_or_cell_type: Placental microsomal enzyme experimental_model: Purification and kinetics of placental PI synthase limitations: Assay optima and inhibitory concentrations are not dietary advice or proof of in vivo nutrient competition. exposure: Substrate and ion titrations evidence_span: {"source_cache": "artifacts/inositol-research/8110188.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c05bb5272b443bde4f99d4af375d31988a4812150450d6c4462059a59aa8a09e", "start_char": 0, "end_char": 940, "text_sha256": "c05bb5272b443bde4f99d4af375d31988a4812150450d6c4462059a59aa8a09e"} [ino-p8110188] Purification and characterization of phosphatidylinositol synthase from human placenta. (1994). https://pubmed.ncbi.nlm.nih.gov/8110188/ DOI: 10.1042/bj2970517
Complete structured claim and evidence
Mn2+ supported purified human placental PI synthase as an alternative activating divalent cation to Mg2+.
Mn2+ → CDIPT (human phosphatidylinositol synthase) source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/8110188.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c05bb5272b443bde4f99d4af375d31988a4812150450d6c4462059a59aa8a09e", "start_char": 0, "end_char": 940, "text_sha256": "c05bb5272b443bde4f99d4af375d31988a4812150450d6c4462059a59aa8a09e"}
experimental_model
Purification and kinetics of placental PI synthase
exposure
Substrate and ion titrations
limitations
Assay optima and inhibitory concentrations are not dietary advice or proof of in vivo nutrient competition.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Homo sapiens
plain_language
Manganese was another supporting ion in the assay; this is not evidence that extra manganese is needed.
primary_references
[ino-p8110188] Purification and characterization of phosphatidylinositol synthase from human placenta. (1994). https://pubmed.ncbi.nlm.nih.gov/8110188/ DOI: 10.1042/bj2970517
tissue_or_cell_type
Placental microsomal enzyme
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 522–533
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purification and kinetics of placental PI synthase · source_derived_draft · unverified_draft
### ino-cdipt-manganese Mn2+ supported purified human placental PI synthase as an alternative activating divalent cation to Mg2+. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: Manganese was another supporting ion in the assay; this is not evidence that extra manganese is needed. organism: Homo sapiens tissue_or_cell_type: Placental microsomal enzyme experimental_model: Purification and kinetics of placental PI synthase limitations: Assay optima and inhibitory concentrations are not dietary advice or proof of in vivo nutrient competition. exposure: Substrate and ion titrations evidence_span: {"source_cache": "artifacts/inositol-research/8110188.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c05bb5272b443bde4f99d4af375d31988a4812150450d6c4462059a59aa8a09e", "start_char": 0, "end_char": 940, "text_sha256": "c05bb5272b443bde4f99d4af375d31988a4812150450d6c4462059a59aa8a09e"} [ino-p8110188] Purification and characterization of phosphatidylinositol synthase from human placenta. (1994). https://pubmed.ncbi.nlm.nih.gov/8110188/ DOI: 10.1042/bj2970517
Complete structured claim and evidence
Ca2+ inhibited purified human placental PI synthase in the tested conditions.
Calcium ion → CDIPT (human phosphatidylinositol synthase) source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/8110188.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c05bb5272b443bde4f99d4af375d31988a4812150450d6c4462059a59aa8a09e", "start_char": 0, "end_char": 940, "text_sha256": "c05bb5272b443bde4f99d4af375d31988a4812150450d6c4462059a59aa8a09e"}
experimental_model
Purification and kinetics of placental PI synthase
exposure
Substrate and ion titrations
limitations
Assay optima and inhibitory concentrations are not dietary advice or proof of in vivo nutrient competition.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Homo sapiens
plain_language
Calcium can restrain this isolated lipid-synthesis reaction.
primary_references
[ino-p8110188] Purification and characterization of phosphatidylinositol synthase from human placenta. (1994). https://pubmed.ncbi.nlm.nih.gov/8110188/ DOI: 10.1042/bj2970517
tissue_or_cell_type
Placental microsomal enzyme
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 535–546
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purification and kinetics of placental PI synthase · source_derived_draft · unverified_draft
### ino-cdipt-calcium Ca2+ inhibited purified human placental PI synthase in the tested conditions. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: Calcium can restrain this isolated lipid-synthesis reaction. organism: Homo sapiens tissue_or_cell_type: Placental microsomal enzyme experimental_model: Purification and kinetics of placental PI synthase limitations: Assay optima and inhibitory concentrations are not dietary advice or proof of in vivo nutrient competition. exposure: Substrate and ion titrations evidence_span: {"source_cache": "artifacts/inositol-research/8110188.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c05bb5272b443bde4f99d4af375d31988a4812150450d6c4462059a59aa8a09e", "start_char": 0, "end_char": 940, "text_sha256": "c05bb5272b443bde4f99d4af375d31988a4812150450d6c4462059a59aa8a09e"} [ino-p8110188] Purification and characterization of phosphatidylinositol synthase from human placenta. (1994). https://pubmed.ncbi.nlm.nih.gov/8110188/ DOI: 10.1042/bj2970517
Complete structured claim and evidence
Zn2+ inhibited purified human placental PI synthase in the tested conditions.
Zinc(II) ion → CDIPT (human phosphatidylinositol synthase) source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/8110188.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c05bb5272b443bde4f99d4af375d31988a4812150450d6c4462059a59aa8a09e", "start_char": 0, "end_char": 940, "text_sha256": "c05bb5272b443bde4f99d4af375d31988a4812150450d6c4462059a59aa8a09e"}
experimental_model
Purification and kinetics of placental PI synthase
exposure
Substrate and ion titrations
limitations
Assay optima and inhibitory concentrations are not dietary advice or proof of in vivo nutrient competition.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Homo sapiens
plain_language
The same mineral can have different effects on different enzymes.
primary_references
[ino-p8110188] Purification and characterization of phosphatidylinositol synthase from human placenta. (1994). https://pubmed.ncbi.nlm.nih.gov/8110188/ DOI: 10.1042/bj2970517
tissue_or_cell_type
Placental microsomal enzyme
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 548–559
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purification and kinetics of placental PI synthase · source_derived_draft · unverified_draft
### ino-cdipt-zinc Zn2+ inhibited purified human placental PI synthase in the tested conditions. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: The same mineral can have different effects on different enzymes. organism: Homo sapiens tissue_or_cell_type: Placental microsomal enzyme experimental_model: Purification and kinetics of placental PI synthase limitations: Assay optima and inhibitory concentrations are not dietary advice or proof of in vivo nutrient competition. exposure: Substrate and ion titrations evidence_span: {"source_cache": "artifacts/inositol-research/8110188.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c05bb5272b443bde4f99d4af375d31988a4812150450d6c4462059a59aa8a09e", "start_char": 0, "end_char": 940, "text_sha256": "c05bb5272b443bde4f99d4af375d31988a4812150450d6c4462059a59aa8a09e"} [ino-p8110188] Purification and characterization of phosphatidylinositol synthase from human placenta. (1994). https://pubmed.ncbi.nlm.nih.gov/8110188/ DOI: 10.1042/bj2970517
Complete structured claim and evidence
Recombinant human PI4K230, now designated PI4KA, showed phosphatidylinositol 4-kinase activity.
PI4KA (human phosphatidylinositol 4-kinase alpha) → Phosphatidylinositol (PI) source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/10101268.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "fa5bbd801387ed6401fcba3b21ddc260a21a089c33818db5abcfea346b3db5d0", "start_char": 0, "end_char": 1101, "text_sha256": "fa5bbd801387ed6401fcba3b21ddc260a21a089c33818db5abcfea346b3db5d0"}
experimental_model
Recombinant human PI4K230 enzyme characterization
exposure
ATP-dependent kinase assays
limitations
An enzyme reaction does not establish that free inositol supplementation increases signaling.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Human protein expressed in Sf9 cells
plain_language
An enzyme adds a phosphate at position 4 of the PI head group.
primary_references
[ino-p10101268] Functional expression and characterisation of a new human phosphatidylinositol 4-kinase PI4K230. (1999). https://pubmed.ncbi.nlm.nih.gov/10101268/ DOI: 10.1016/s1388-1981(99)00029-3
tissue_or_cell_type
Recombinant PI4KA
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 561–572
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human PI4K230 enzyme characterization · source_derived_draft · unverified_draft
### ino-pi4ka-pi4p Recombinant human PI4K230, now designated PI4KA, showed phosphatidylinositol 4-kinase activity. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: An enzyme adds a phosphate at position 4 of the PI head group. organism: Human protein expressed in Sf9 cells tissue_or_cell_type: Recombinant PI4KA experimental_model: Recombinant human PI4K230 enzyme characterization limitations: An enzyme reaction does not establish that free inositol supplementation increases signaling. exposure: ATP-dependent kinase assays evidence_span: {"source_cache": "artifacts/inositol-research/10101268.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "fa5bbd801387ed6401fcba3b21ddc260a21a089c33818db5abcfea346b3db5d0", "start_char": 0, "end_char": 1101, "text_sha256": "fa5bbd801387ed6401fcba3b21ddc260a21a089c33818db5abcfea346b3db5d0"} [ino-p10101268] Functional expression and characterisation of a new human phosphatidylinositol 4-kinase PI4K230. (1999). https://pubmed.ncbi.nlm.nih.gov/10101268/ DOI: 10.1016/s1388-1981(99)00029-3
Complete structured claim and evidence
Human PIP5K1C_i4 displayed PI4P 5-kinase activity in vitro.
Human PIP5K1C_i4 isoform (700 amino acids) → Phosphatidylinositol 4-phosphate (PI4P) source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/19548880.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5ae150d47bf139d7352c8a5a128e0d6b071340f8c47d78700d5f398a549d3cd8", "start_char": 0, "end_char": 1766, "text_sha256": "5ae150d47bf139d7352c8a5a128e0d6b071340f8c47d78700d5f398a549d3cd8"}
experimental_model
Human splice-isoform expression, localization and kinase assay
exposure
PIP5K1C_i4 and i5 characterization
limitations
Isoforms have different localizations; a bulk lipid concentration cannot describe every local pool.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Human proteins in cellular expression assays
plain_language
This isoform can make PI(4,5)P2 from PI4P.
primary_references
[ino-p19548880] Two novel phosphatidylinositol-4-phosphate 5-kinase type Igamma splice variants expressed in human cells display distinctive cellular targeting. (2009). https://pubmed.ncbi.nlm.nih.gov/19548880/ DOI: 10.1042/bj20090638
tissue_or_cell_type
Nuclear and vesicular compartments
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 574–585
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human splice-isoform expression, localization and kinase assay · source_derived_draft · unverified_draft
### ino-pip5k-i4 Human PIP5K1C_i4 displayed PI4P 5-kinase activity in vitro. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: This isoform can make PI(4,5)P2 from PI4P. organism: Human proteins in cellular expression assays tissue_or_cell_type: Nuclear and vesicular compartments experimental_model: Human splice-isoform expression, localization and kinase assay limitations: Isoforms have different localizations; a bulk lipid concentration cannot describe every local pool. exposure: PIP5K1C_i4 and i5 characterization evidence_span: {"source_cache": "artifacts/inositol-research/19548880.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5ae150d47bf139d7352c8a5a128e0d6b071340f8c47d78700d5f398a549d3cd8", "start_char": 0, "end_char": 1766, "text_sha256": "5ae150d47bf139d7352c8a5a128e0d6b071340f8c47d78700d5f398a549d3cd8"} [ino-p19548880] Two novel phosphatidylinositol-4-phosphate 5-kinase type Igamma splice variants expressed in human cells display distinctive cellular targeting. (2009). https://pubmed.ncbi.nlm.nih.gov/19548880/ DOI: 10.1042/bj20090638
Complete structured claim and evidence
Human PIP5K1C_i5 also displayed PI4P 5-kinase activity in vitro.
Human PIP5K1C_i5 isoform (707 amino acids) → Phosphatidylinositol 4-phosphate (PI4P) source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/19548880.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5ae150d47bf139d7352c8a5a128e0d6b071340f8c47d78700d5f398a549d3cd8", "start_char": 0, "end_char": 1766, "text_sha256": "5ae150d47bf139d7352c8a5a128e0d6b071340f8c47d78700d5f398a549d3cd8"}
experimental_model
Human splice-isoform expression, localization and kinase assay
exposure
PIP5K1C_i4 and i5 characterization
limitations
Isoforms have different localizations; a bulk lipid concentration cannot describe every local pool.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Human proteins in cellular expression assays
plain_language
A separately identified isoform can carry out the same chemical step.
primary_references
[ino-p19548880] Two novel phosphatidylinositol-4-phosphate 5-kinase type Igamma splice variants expressed in human cells display distinctive cellular targeting. (2009). https://pubmed.ncbi.nlm.nih.gov/19548880/ DOI: 10.1042/bj20090638
tissue_or_cell_type
Nuclear and vesicular compartments
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 587–598
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human splice-isoform expression, localization and kinase assay · source_derived_draft · unverified_draft
### ino-pip5k-i5 Human PIP5K1C_i5 also displayed PI4P 5-kinase activity in vitro. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: A separately identified isoform can carry out the same chemical step. organism: Human proteins in cellular expression assays tissue_or_cell_type: Nuclear and vesicular compartments experimental_model: Human splice-isoform expression, localization and kinase assay limitations: Isoforms have different localizations; a bulk lipid concentration cannot describe every local pool. exposure: PIP5K1C_i4 and i5 characterization evidence_span: {"source_cache": "artifacts/inositol-research/19548880.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5ae150d47bf139d7352c8a5a128e0d6b071340f8c47d78700d5f398a549d3cd8", "start_char": 0, "end_char": 1766, "text_sha256": "5ae150d47bf139d7352c8a5a128e0d6b071340f8c47d78700d5f398a549d3cd8"} [ino-p19548880] Two novel phosphatidylinositol-4-phosphate 5-kinase type Igamma splice variants expressed in human cells display distinctive cellular targeting. (2009). https://pubmed.ncbi.nlm.nih.gov/19548880/ DOI: 10.1042/bj20090638
Complete structured claim and evidence
The newly characterized 700-amino-acid PIP5K1C_i4 isoform localized to the nucleus.
Human PIP5K1C_i4 isoform (700 amino acids) → Nucleus source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/19548880.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5ae150d47bf139d7352c8a5a128e0d6b071340f8c47d78700d5f398a549d3cd8", "start_char": 0, "end_char": 1766, "text_sha256": "5ae150d47bf139d7352c8a5a128e0d6b071340f8c47d78700d5f398a549d3cd8"}
experimental_model
Human splice-isoform expression, localization and kinase assay
exposure
PIP5K1C_i4 and i5 characterization
limitations
Isoforms have different localizations; a bulk lipid concentration cannot describe every local pool.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Human proteins in cellular expression assays
plain_language
Where an enzyme works can matter as much as its reaction.
primary_references
[ino-p19548880] Two novel phosphatidylinositol-4-phosphate 5-kinase type Igamma splice variants expressed in human cells display distinctive cellular targeting. (2009). https://pubmed.ncbi.nlm.nih.gov/19548880/ DOI: 10.1042/bj20090638
tissue_or_cell_type
Nuclear and vesicular compartments
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 600–611
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human splice-isoform expression, localization and kinase assay · source_derived_draft · unverified_draft
### ino-pip5k-i4-location The newly characterized 700-amino-acid PIP5K1C_i4 isoform localized to the nucleus. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: Where an enzyme works can matter as much as its reaction. organism: Human proteins in cellular expression assays tissue_or_cell_type: Nuclear and vesicular compartments experimental_model: Human splice-isoform expression, localization and kinase assay limitations: Isoforms have different localizations; a bulk lipid concentration cannot describe every local pool. exposure: PIP5K1C_i4 and i5 characterization evidence_span: {"source_cache": "artifacts/inositol-research/19548880.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5ae150d47bf139d7352c8a5a128e0d6b071340f8c47d78700d5f398a549d3cd8", "start_char": 0, "end_char": 1766, "text_sha256": "5ae150d47bf139d7352c8a5a128e0d6b071340f8c47d78700d5f398a549d3cd8"} [ino-p19548880] Two novel phosphatidylinositol-4-phosphate 5-kinase type Igamma splice variants expressed in human cells display distinctive cellular targeting. (2009). https://pubmed.ncbi.nlm.nih.gov/19548880/ DOI: 10.1042/bj20090638
Complete structured claim and evidence
The 707-amino-acid PIP5K1C_i5 isoform localized to vesicular structures.
Human PIP5K1C_i5 isoform (707 amino acids) → Cytoplasmic vesicles source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/19548880.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5ae150d47bf139d7352c8a5a128e0d6b071340f8c47d78700d5f398a549d3cd8", "start_char": 0, "end_char": 1766, "text_sha256": "5ae150d47bf139d7352c8a5a128e0d6b071340f8c47d78700d5f398a549d3cd8"}
experimental_model
Human splice-isoform expression, localization and kinase assay
exposure
PIP5K1C_i4 and i5 characterization
limitations
Isoforms have different localizations; a bulk lipid concentration cannot describe every local pool.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Human proteins in cellular expression assays
plain_language
This isoform supplies a different cellular neighborhood.
primary_references
[ino-p19548880] Two novel phosphatidylinositol-4-phosphate 5-kinase type Igamma splice variants expressed in human cells display distinctive cellular targeting. (2009). https://pubmed.ncbi.nlm.nih.gov/19548880/ DOI: 10.1042/bj20090638
tissue_or_cell_type
Nuclear and vesicular compartments
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 613–624
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human splice-isoform expression, localization and kinase assay · source_derived_draft · unverified_draft
### ino-pip5k-i5-location The 707-amino-acid PIP5K1C_i5 isoform localized to vesicular structures. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: This isoform supplies a different cellular neighborhood. organism: Human proteins in cellular expression assays tissue_or_cell_type: Nuclear and vesicular compartments experimental_model: Human splice-isoform expression, localization and kinase assay limitations: Isoforms have different localizations; a bulk lipid concentration cannot describe every local pool. exposure: PIP5K1C_i4 and i5 characterization evidence_span: {"source_cache": "artifacts/inositol-research/19548880.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5ae150d47bf139d7352c8a5a128e0d6b071340f8c47d78700d5f398a549d3cd8", "start_char": 0, "end_char": 1766, "text_sha256": "5ae150d47bf139d7352c8a5a128e0d6b071340f8c47d78700d5f398a549d3cd8"} [ino-p19548880] Two novel phosphatidylinositol-4-phosphate 5-kinase type Igamma splice variants expressed in human cells display distinctive cellular targeting. (2009). https://pubmed.ncbi.nlm.nih.gov/19548880/ DOI: 10.1042/bj20090638
Complete structured claim and evidence
Diacylglycerol was the lipid product of PLCB3-catalyzed PI(4,5)P2 hydrolysis.
PLCB3 (phospholipase C beta 3) → DAG source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/37991948.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "fa553185ea3f13a8af7be9a548de14cd13ebe22ff307635fb76675ddc64347d7", "start_char": 0, "end_char": 1735, "text_sha256": "fa553185ea3f13a8af7be9a548de14cd13ebe22ff307635fb76675ddc64347d7"}
experimental_model
Reconstituted lipid-bilayer kinetics and membrane-bound structural analysis
exposure
G-alpha-q and G-beta-gamma stimulation
limitations
Reconstituted biochemical regulation; not an oral inositol intervention. Product generation and lipid depletion occur in the same reaction.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Recombinant mammalian signaling proteins
plain_language
The second product stays in the membrane rather than becoming soluble IP3.
primary_references
[ino-p37991948] The mechanism of Gαq regulation of PLCβ3-catalyzed PIP2 hydrolysis. (2023). https://pubmed.ncbi.nlm.nih.gov/37991948/ DOI: 10.1073/pnas.2315011120
tissue_or_cell_type
Defined membrane bilayers
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 639–650
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Reconstituted lipid-bilayer kinetics and membrane-bound structural analysis · source_derived_draft · unverified_draft
### ino-plc-dag Diacylglycerol was the lipid product of PLCB3-catalyzed PI(4,5)P2 hydrolysis. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: The second product stays in the membrane rather than becoming soluble IP3. organism: Recombinant mammalian signaling proteins tissue_or_cell_type: Defined membrane bilayers experimental_model: Reconstituted lipid-bilayer kinetics and membrane-bound structural analysis limitations: Reconstituted biochemical regulation; not an oral inositol intervention. Product generation and lipid depletion occur in the same reaction. exposure: G-alpha-q and G-beta-gamma stimulation evidence_span: {"source_cache": "artifacts/inositol-research/37991948.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "fa553185ea3f13a8af7be9a548de14cd13ebe22ff307635fb76675ddc64347d7", "start_char": 0, "end_char": 1735, "text_sha256": "fa553185ea3f13a8af7be9a548de14cd13ebe22ff307635fb76675ddc64347d7"} [ino-p37991948] The mechanism of Gαq regulation of PLCβ3-catalyzed PIP2 hydrolysis. (2023). https://pubmed.ncbi.nlm.nih.gov/37991948/ DOI: 10.1073/pnas.2315011120
Complete structured claim and evidence
G-alpha-q increased PLCB3 catalytic turnover in the membrane assay; relief of X-Y-linker autoinhibition was proposed as the mechanism.
GNAQ (G protein alpha q) → PLCB3 (phospholipase C beta 3) source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/37991948.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "fa553185ea3f13a8af7be9a548de14cd13ebe22ff307635fb76675ddc64347d7", "start_char": 0, "end_char": 1735, "text_sha256": "fa553185ea3f13a8af7be9a548de14cd13ebe22ff307635fb76675ddc64347d7"}
experimental_model
Reconstituted lipid-bilayer kinetics and membrane-bound structural analysis
exposure
G-alpha-q and G-beta-gamma stimulation
limitations
Reconstituted biochemical regulation; not an oral inositol intervention. Product generation and lipid depletion occur in the same reaction.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Recombinant mammalian signaling proteins
plain_language
A receptor-linked G protein can speed up the enzyme; the detailed allosteric explanation remains an interpretation.
primary_references
[ino-p37991948] The mechanism of Gαq regulation of PLCβ3-catalyzed PIP2 hydrolysis. (2023). https://pubmed.ncbi.nlm.nih.gov/37991948/ DOI: 10.1073/pnas.2315011120
tissue_or_cell_type
Defined membrane bilayers
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 652–663
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Reconstituted lipid-bilayer kinetics and membrane-bound structural analysis · source_derived_draft · unverified_draft
### ino-gq-plc G-alpha-q increased PLCB3 catalytic turnover in the membrane assay; relief of X-Y-linker autoinhibition was proposed as the mechanism. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: A receptor-linked G protein can speed up the enzyme; the detailed allosteric explanation remains an interpretation. organism: Recombinant mammalian signaling proteins tissue_or_cell_type: Defined membrane bilayers experimental_model: Reconstituted lipid-bilayer kinetics and membrane-bound structural analysis limitations: Reconstituted biochemical regulation; not an oral inositol intervention. Product generation and lipid depletion occur in the same reaction. exposure: G-alpha-q and G-beta-gamma stimulation evidence_span: {"source_cache": "artifacts/inositol-research/37991948.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "fa553185ea3f13a8af7be9a548de14cd13ebe22ff307635fb76675ddc64347d7", "start_char": 0, "end_char": 1735, "text_sha256": "fa553185ea3f13a8af7be9a548de14cd13ebe22ff307635fb76675ddc64347d7"} [ino-p37991948] The mechanism of Gαq regulation of PLCβ3-catalyzed PIP2 hydrolysis. (2023). https://pubmed.ncbi.nlm.nih.gov/37991948/ DOI: 10.1073/pnas.2315011120
Complete structured claim and evidence
G-beta-gamma and G-alpha-q could bind PLCB3 simultaneously, with dual stimulation following the product of their independent effects.
G protein beta-gamma complex → GNAQ (G protein alpha q) source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/37991948.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "fa553185ea3f13a8af7be9a548de14cd13ebe22ff307635fb76675ddc64347d7", "start_char": 0, "end_char": 1735, "text_sha256": "fa553185ea3f13a8af7be9a548de14cd13ebe22ff307635fb76675ddc64347d7"}
experimental_model
Reconstituted lipid-bilayer kinetics and membrane-bound structural analysis
exposure
G-alpha-q and G-beta-gamma stimulation
limitations
Reconstituted biochemical regulation; not an oral inositol intervention. Product generation and lipid depletion occur in the same reaction.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Recombinant mammalian signaling proteins
plain_language
Recruiting an enzyme to a membrane and increasing its catalytic rate can cooperate.
primary_references
[ino-p37991948] The mechanism of Gαq regulation of PLCβ3-catalyzed PIP2 hydrolysis. (2023). https://pubmed.ncbi.nlm.nih.gov/37991948/ DOI: 10.1073/pnas.2315011120
tissue_or_cell_type
Defined membrane bilayers
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 665–676
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Reconstituted lipid-bilayer kinetics and membrane-bound structural analysis · source_derived_draft · unverified_draft
### ino-g-protein-dual G-beta-gamma and G-alpha-q could bind PLCB3 simultaneously, with dual stimulation following the product of their independent effects. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: Recruiting an enzyme to a membrane and increasing its catalytic rate can cooperate. organism: Recombinant mammalian signaling proteins tissue_or_cell_type: Defined membrane bilayers experimental_model: Reconstituted lipid-bilayer kinetics and membrane-bound structural analysis limitations: Reconstituted biochemical regulation; not an oral inositol intervention. Product generation and lipid depletion occur in the same reaction. exposure: G-alpha-q and G-beta-gamma stimulation evidence_span: {"source_cache": "artifacts/inositol-research/37991948.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "fa553185ea3f13a8af7be9a548de14cd13ebe22ff307635fb76675ddc64347d7", "start_char": 0, "end_char": 1735, "text_sha256": "fa553185ea3f13a8af7be9a548de14cd13ebe22ff307635fb76675ddc64347d7"} [ino-p37991948] The mechanism of Gαq regulation of PLCβ3-catalyzed PIP2 hydrolysis. (2023). https://pubmed.ncbi.nlm.nih.gov/37991948/ DOI: 10.1073/pnas.2315011120
Complete structured claim and evidence
Human IPMK has IP3 3-kinase activity, producing inositol 1,3,4,5-tetrakisphosphate.
IPMK (human inositol phosphate multikinase) → IP3 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/28882892.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "39494635d8bd1a8a8df3ac71f8aa6c5f6440bd3c6fa7cb4756e52d572a8f16db", "start_char": 0, "end_char": 1781, "text_sha256": "39494635d8bd1a8a8df3ac71f8aa6c5f6440bd3c6fa7cb4756e52d572a8f16db"}
experimental_model
Crystal structures and targeted human IPMK mutants
exposure
IP3 and PI(4,5)P2 substrate binding and phosphorylation
limitations
Human substrate specificity differs from yeast and plant orthologs; do not merge their regioselectivity.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Human protein
plain_language
Soluble IP3 can be redirected into a more highly phosphorylated molecule.
primary_references
[ino-p28882892] Structural features of human inositol phosphate multikinase rationalize its inositol phosphate kinase and phosphoinositide 3-kinase activities. (2017). https://pubmed.ncbi.nlm.nih.gov/28882892/ DOI: 10.1074/jbc.m117.801845
tissue_or_cell_type
Purified IPMK
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 678–689
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Crystal structures and targeted human IPMK mutants · source_derived_draft · unverified_draft
### ino-ipmk-ip4 Human IPMK has IP3 3-kinase activity, producing inositol 1,3,4,5-tetrakisphosphate. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: Soluble IP3 can be redirected into a more highly phosphorylated molecule. organism: Human protein tissue_or_cell_type: Purified IPMK experimental_model: Crystal structures and targeted human IPMK mutants limitations: Human substrate specificity differs from yeast and plant orthologs; do not merge their regioselectivity. exposure: IP3 and PI(4,5)P2 substrate binding and phosphorylation evidence_span: {"source_cache": "artifacts/inositol-research/28882892.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "39494635d8bd1a8a8df3ac71f8aa6c5f6440bd3c6fa7cb4756e52d572a8f16db", "start_char": 0, "end_char": 1781, "text_sha256": "39494635d8bd1a8a8df3ac71f8aa6c5f6440bd3c6fa7cb4756e52d572a8f16db"} [ino-p28882892] Structural features of human inositol phosphate multikinase rationalize its inositol phosphate kinase and phosphoinositide 3-kinase activities. (2017). https://pubmed.ncbi.nlm.nih.gov/28882892/ DOI: 10.1074/jbc.m117.801845
Complete structured claim and evidence
Human IPMK also has PI(4,5)P2 3-kinase activity, producing PI(3,4,5)P3.
IPMK (human inositol phosphate multikinase) → Phosphatidylinositol 4,5-bisphosphate source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/28882892.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "39494635d8bd1a8a8df3ac71f8aa6c5f6440bd3c6fa7cb4756e52d572a8f16db", "start_char": 0, "end_char": 1781, "text_sha256": "39494635d8bd1a8a8df3ac71f8aa6c5f6440bd3c6fa7cb4756e52d572a8f16db"}
experimental_model
Crystal structures and targeted human IPMK mutants
exposure
IP3 and PI(4,5)P2 substrate binding and phosphorylation
limitations
Human substrate specificity differs from yeast and plant orthologs; do not merge their regioselectivity.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Human protein
plain_language
One enzyme acts on both soluble inositol phosphates and a membrane lipid.
primary_references
[ino-p28882892] Structural features of human inositol phosphate multikinase rationalize its inositol phosphate kinase and phosphoinositide 3-kinase activities. (2017). https://pubmed.ncbi.nlm.nih.gov/28882892/ DOI: 10.1074/jbc.m117.801845
tissue_or_cell_type
Purified IPMK
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 691–702
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Crystal structures and targeted human IPMK mutants · source_derived_draft · unverified_draft
### ino-ipmk-pip3 Human IPMK also has PI(4,5)P2 3-kinase activity, producing PI(3,4,5)P3. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: One enzyme acts on both soluble inositol phosphates and a membrane lipid. organism: Human protein tissue_or_cell_type: Purified IPMK experimental_model: Crystal structures and targeted human IPMK mutants limitations: Human substrate specificity differs from yeast and plant orthologs; do not merge their regioselectivity. exposure: IP3 and PI(4,5)P2 substrate binding and phosphorylation evidence_span: {"source_cache": "artifacts/inositol-research/28882892.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "39494635d8bd1a8a8df3ac71f8aa6c5f6440bd3c6fa7cb4756e52d572a8f16db", "start_char": 0, "end_char": 1781, "text_sha256": "39494635d8bd1a8a8df3ac71f8aa6c5f6440bd3c6fa7cb4756e52d572a8f16db"} [ino-p28882892] Structural features of human inositol phosphate multikinase rationalize its inositol phosphate kinase and phosphoinositide 3-kinase activities. (2017). https://pubmed.ncbi.nlm.nih.gov/28882892/ DOI: 10.1074/jbc.m117.801845
Complete structured claim and evidence
Recombinant human IPMK phosphorylated IP3 at positions 3 and 6, reaching inositol 1,3,4,5,6-pentakisphosphate.
IPMK (human inositol phosphate multikinase) → Inositol 1,3,4,5,6-pentakisphosphate source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/12027805.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d015b4f1e5198aceb869411c91fd2ab00da093fb573c1b195305fe8adfe66b26", "start_char": 0, "end_char": 1282, "text_sha256": "d015b4f1e5198aceb869411c91fd2ab00da093fb573c1b195305fe8adfe66b26"}
experimental_model
Human cDNA cloning and recombinant kinase characterization
exposure
IP3 phosphorylation and product analysis
limitations
Enzyme activity and expression-system localization do not establish dietary effects or a single obligatory route for all cells.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Human protein expressed in bacteria and mammalian cells
plain_language
The multikinase supplies a route from IP3 toward the five-phosphate precursor of InsP6.
primary_references
[ino-p12027805] The human homologue of yeast ArgRIII protein is an inositol phosphate multikinase with predominantly nuclear localization. (2002). https://pubmed.ncbi.nlm.nih.gov/12027805/ DOI: 10.1042/bj20020327
tissue_or_cell_type
Recombinant enzyme and tagged-protein localization
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 704–715
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human cDNA cloning and recombinant kinase characterization · source_derived_draft · unverified_draft
### ino-ipmk-ip5 Recombinant human IPMK phosphorylated IP3 at positions 3 and 6, reaching inositol 1,3,4,5,6-pentakisphosphate. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: The multikinase supplies a route from IP3 toward the five-phosphate precursor of InsP6. organism: Human protein expressed in bacteria and mammalian cells tissue_or_cell_type: Recombinant enzyme and tagged-protein localization experimental_model: Human cDNA cloning and recombinant kinase characterization limitations: Enzyme activity and expression-system localization do not establish dietary effects or a single obligatory route for all cells. exposure: IP3 phosphorylation and product analysis evidence_span: {"source_cache": "artifacts/inositol-research/12027805.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d015b4f1e5198aceb869411c91fd2ab00da093fb573c1b195305fe8adfe66b26", "start_char": 0, "end_char": 1282, "text_sha256": "d015b4f1e5198aceb869411c91fd2ab00da093fb573c1b195305fe8adfe66b26"} [ino-p12027805] The human homologue of yeast ArgRIII protein is an inositol phosphate multikinase with predominantly nuclear localization. (2002). https://pubmed.ncbi.nlm.nih.gov/12027805/ DOI: 10.1042/bj20020327
Complete structured claim and evidence
Human PTEN removed the 3-phosphate from PI(3,4,5)P3, forming PI(4,5)P2.
PTEN (human phosphatase and tensin homolog) → Phosphatidylinositol 3,4,5-trisphosphate (PIP3) source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/9593664.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "118dd3dacb2fa7be09cb0258dd0f6de1193cf2553142c94a5750d82c5f00a248", "start_char": 0, "end_char": 1012, "text_sha256": "118dd3dacb2fa7be09cb0258dd0f6de1193cf2553142c94a5750d82c5f00a248"}
experimental_model
Phosphatase assays and human cell expression
exposure
Wild-type versus catalytic-mutant PTEN
limitations
Cellular overexpression and enzymology do not imply that inositol supplements activate PTEN.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Human protein and HEK293 cells
plain_language
A phosphatase reverses a signaling-lipid phosphorylation step.
primary_references
[ino-p9593664] The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate. (1998). https://pubmed.ncbi.nlm.nih.gov/9593664/ DOI: 10.1074/jbc.273.22.13375
tissue_or_cell_type
Purified enzyme and cultured cells
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 717–728
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Phosphatase assays and human cell expression · source_derived_draft · unverified_draft
### ino-pten-pip3 Human PTEN removed the 3-phosphate from PI(3,4,5)P3, forming PI(4,5)P2. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: A phosphatase reverses a signaling-lipid phosphorylation step. organism: Human protein and HEK293 cells tissue_or_cell_type: Purified enzyme and cultured cells experimental_model: Phosphatase assays and human cell expression limitations: Cellular overexpression and enzymology do not imply that inositol supplements activate PTEN. exposure: Wild-type versus catalytic-mutant PTEN evidence_span: {"source_cache": "artifacts/inositol-research/9593664.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "118dd3dacb2fa7be09cb0258dd0f6de1193cf2553142c94a5750d82c5f00a248", "start_char": 0, "end_char": 1012, "text_sha256": "118dd3dacb2fa7be09cb0258dd0f6de1193cf2553142c94a5750d82c5f00a248"} [ino-p9593664] The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate. (1998). https://pubmed.ncbi.nlm.nih.gov/9593664/ DOI: 10.1074/jbc.273.22.13375
Complete structured claim and evidence
PTEN also showed 3-phosphatase activity toward soluble inositol 1,3,4,5-tetrakisphosphate.
PTEN (human phosphatase and tensin homolog) → Inositol 1,3,4,5-tetrakisphosphate source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/9593664.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "118dd3dacb2fa7be09cb0258dd0f6de1193cf2553142c94a5750d82c5f00a248", "start_char": 0, "end_char": 1012, "text_sha256": "118dd3dacb2fa7be09cb0258dd0f6de1193cf2553142c94a5750d82c5f00a248"}
experimental_model
Phosphatase assays and human cell expression
exposure
Wild-type versus catalytic-mutant PTEN
limitations
Cellular overexpression and enzymology do not imply that inositol supplements activate PTEN.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Human protein and HEK293 cells
plain_language
A related phosphate-removal reaction was observed on a soluble molecule.
primary_references
[ino-p9593664] The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate. (1998). https://pubmed.ncbi.nlm.nih.gov/9593664/ DOI: 10.1074/jbc.273.22.13375
tissue_or_cell_type
Purified enzyme and cultured cells
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 730–741
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Phosphatase assays and human cell expression · source_derived_draft · unverified_draft
### ino-pten-soluble PTEN also showed 3-phosphatase activity toward soluble inositol 1,3,4,5-tetrakisphosphate. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: A related phosphate-removal reaction was observed on a soluble molecule. organism: Human protein and HEK293 cells tissue_or_cell_type: Purified enzyme and cultured cells experimental_model: Phosphatase assays and human cell expression limitations: Cellular overexpression and enzymology do not imply that inositol supplements activate PTEN. exposure: Wild-type versus catalytic-mutant PTEN evidence_span: {"source_cache": "artifacts/inositol-research/9593664.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "118dd3dacb2fa7be09cb0258dd0f6de1193cf2553142c94a5750d82c5f00a248", "start_char": 0, "end_char": 1012, "text_sha256": "118dd3dacb2fa7be09cb0258dd0f6de1193cf2553142c94a5750d82c5f00a248"} [ino-p9593664] The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate. (1998). https://pubmed.ncbi.nlm.nih.gov/9593664/ DOI: 10.1074/jbc.273.22.13375
Complete structured claim and evidence
Human IPPK used ATP to phosphorylate inositol 1,3,4,5,6-pentakisphosphate at position 2, producing InsP6.
IPPK (human inositol-pentakisphosphate 2-kinase) → Inositol 1,3,4,5,6-pentakisphosphate source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/12084730.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7e44dbc7039048a53bffd92fd69dfa1f35f1dc762389c8d810f913ea70e10c80", "start_char": 0, "end_char": 1407, "text_sha256": "7e44dbc7039048a53bffd92fd69dfa1f35f1dc762389c8d810f913ea70e10c80"}
experimental_model
Recombinant kinase and yeast complementation
exposure
Inositol pentakisphosphate and ATP assays
limitations
Human enzyme activity; yeast rescue is not a clinical supplementation trial.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Human IPPK expressed in Sf21 cells
plain_language
The cell can make the six-phosphate inositol molecule inside itself.
primary_references
[ino-p12084730] The synthesis of inositol hexakisphosphate. Characterization of human inositol 1,3,4,5,6-pentakisphosphate 2-kinase. (2002). https://pubmed.ncbi.nlm.nih.gov/12084730/ DOI: 10.1074/jbc.m205682200
tissue_or_cell_type
Purified kinase
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 743–754
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant kinase and yeast complementation · source_derived_draft · unverified_draft
### ino-ippk-ip6 Human IPPK used ATP to phosphorylate inositol 1,3,4,5,6-pentakisphosphate at position 2, producing InsP6. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: The cell can make the six-phosphate inositol molecule inside itself. organism: Human IPPK expressed in Sf21 cells tissue_or_cell_type: Purified kinase experimental_model: Recombinant kinase and yeast complementation limitations: Human enzyme activity; yeast rescue is not a clinical supplementation trial. exposure: Inositol pentakisphosphate and ATP assays evidence_span: {"source_cache": "artifacts/inositol-research/12084730.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7e44dbc7039048a53bffd92fd69dfa1f35f1dc762389c8d810f913ea70e10c80", "start_char": 0, "end_char": 1407, "text_sha256": "7e44dbc7039048a53bffd92fd69dfa1f35f1dc762389c8d810f913ea70e10c80"} [ino-p12084730] The synthesis of inositol hexakisphosphate. Characterization of human inositol 1,3,4,5,6-pentakisphosphate 2-kinase. (2002). https://pubmed.ncbi.nlm.nih.gov/12084730/ DOI: 10.1074/jbc.m205682200
Complete structured claim and evidence
The mouse Ippk structure identified a zinc-binding site involved in maintaining the enzyme’s structural organization.
Zinc(II) ion → Mouse Ippk (inositol-pentakisphosphate 2-kinase) source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/28450399.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a7b18249458f30cd8f1147710856a6bf7f87ca1b045e97290a04ce7c7cbfbb78", "start_char": 0, "end_char": 1555, "text_sha256": "a7b18249458f30cd8f1147710856a6bf7f87ca1b045e97290a04ce7c7cbfbb78"}
experimental_model
Mouse enzyme crystallography and functional analysis
exposure
Structure with substrates and zinc-site characterization
limitations
Mouse protein; intracellular InsP6 synthesis is distinct from intestinal exposure to dietary phytate.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Mus musculus protein
plain_language
Zinc is part of the architecture of this mouse inositol-phosphate enzyme; dietary benefit was not tested.
primary_references
[ino-p28450399] The crystal structure of mammalian inositol 1,3,4,5,6-pentakisphosphate 2-kinase reveals a new zinc-binding site and key features for protein function. (2017). https://pubmed.ncbi.nlm.nih.gov/28450399/ DOI: 10.1074/jbc.m117.780395
tissue_or_cell_type
Purified Ippk
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 756–767
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mouse enzyme crystallography and functional analysis · source_derived_draft · unverified_draft
### ino-ippk-zinc The mouse Ippk structure identified a zinc-binding site involved in maintaining the enzyme’s structural organization. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: Zinc is part of the architecture of this mouse inositol-phosphate enzyme; dietary benefit was not tested. organism: Mus musculus protein tissue_or_cell_type: Purified Ippk experimental_model: Mouse enzyme crystallography and functional analysis limitations: Mouse protein; intracellular InsP6 synthesis is distinct from intestinal exposure to dietary phytate. exposure: Structure with substrates and zinc-site characterization evidence_span: {"source_cache": "artifacts/inositol-research/28450399.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a7b18249458f30cd8f1147710856a6bf7f87ca1b045e97290a04ce7c7cbfbb78", "start_char": 0, "end_char": 1555, "text_sha256": "a7b18249458f30cd8f1147710856a6bf7f87ca1b045e97290a04ce7c7cbfbb78"} [ino-p28450399] The crystal structure of mammalian inositol 1,3,4,5,6-pentakisphosphate 2-kinase reveals a new zinc-binding site and key features for protein function. (2017). https://pubmed.ncbi.nlm.nih.gov/28450399/ DOI: 10.1074/jbc.m117.780395
Complete structured claim and evidence
5-InsP7 inhibited PDK1-dependent Akt phosphorylation and activation in the reported biochemical pathway.
5-diphosphoinositol pentakisphosphate (5-InsP7) → AKT serine/threonine kinase family source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/21145457.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0de0a9c3ea11cd8ce59bccff69a41139b11e11182fd9fd66016ec72ba329a5ce", "start_char": 0, "end_char": 889, "text_sha256": "0de0a9c3ea11cd8ce59bccff69a41139b11e11182fd9fd66016ec72ba329a5ce"}
experimental_model
Biochemical Akt regulation and targeted mouse Ip6k1 deletion
exposure
5-InsP7 and Ip6k1 knockout
limitations
Whole-gene deletion is not equivalent to adding or withdrawing free myo-inositol; the reported therapeutic proposal is not established treatment.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Mammalian enzymology and Mus musculus
plain_language
An inositol-derived signal can restrain insulin-pathway signaling rather than always increasing it.
primary_references
[ino-p21145457] Inositol pyrophosphates inhibit Akt signaling, thereby regulating insulin sensitivity and weight gain. (2010). https://pubmed.ncbi.nlm.nih.gov/21145457/ DOI: 10.1016/j.cell.2010.11.032
tissue_or_cell_type
Muscle, adipose tissue and liver
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 782–793
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Biochemical Akt regulation and targeted mouse Ip6k1 deletion · source_derived_draft · unverified_draft
### ino-ip7-akt 5-InsP7 inhibited PDK1-dependent Akt phosphorylation and activation in the reported biochemical pathway. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: An inositol-derived signal can restrain insulin-pathway signaling rather than always increasing it. organism: Mammalian enzymology and Mus musculus tissue_or_cell_type: Muscle, adipose tissue and liver experimental_model: Biochemical Akt regulation and targeted mouse Ip6k1 deletion limitations: Whole-gene deletion is not equivalent to adding or withdrawing free myo-inositol; the reported therapeutic proposal is not established treatment. exposure: 5-InsP7 and Ip6k1 knockout evidence_span: {"source_cache": "artifacts/inositol-research/21145457.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0de0a9c3ea11cd8ce59bccff69a41139b11e11182fd9fd66016ec72ba329a5ce", "start_char": 0, "end_char": 889, "text_sha256": "0de0a9c3ea11cd8ce59bccff69a41139b11e11182fd9fd66016ec72ba329a5ce"} [ino-p21145457] Inositol pyrophosphates inhibit Akt signaling, thereby regulating insulin sensitivity and weight gain. (2010). https://pubmed.ncbi.nlm.nih.gov/21145457/ DOI: 10.1016/j.cell.2010.11.032
Complete structured claim and evidence
Ip6k1-null mice showed increased insulin sensitivity and resistance to diet- or age-associated obesity.
Mouse Ip6k1 → Insulin sensitivity source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/inositol-research/21145457.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0de0a9c3ea11cd8ce59bccff69a41139b11e11182fd9fd66016ec72ba329a5ce", "start_char": 0, "end_char": 889, "text_sha256": "0de0a9c3ea11cd8ce59bccff69a41139b11e11182fd9fd66016ec72ba329a5ce"}
experimental_model
Biochemical Akt regulation and targeted mouse Ip6k1 deletion
exposure
5-InsP7 and Ip6k1 knockout
limitations
Whole-gene deletion is not equivalent to adding or withdrawing free myo-inositol; the reported therapeutic proposal is not established treatment.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Mammalian enzymology and Mus musculus
plain_language
Removing a specific signaling enzyme improved these metabolic outcomes in mice.
primary_references
[ino-p21145457] Inositol pyrophosphates inhibit Akt signaling, thereby regulating insulin sensitivity and weight gain. (2010). https://pubmed.ncbi.nlm.nih.gov/21145457/ DOI: 10.1016/j.cell.2010.11.032
tissue_or_cell_type
Muscle, adipose tissue and liver
trigger_kind
machinery_impairment Imported condition classification; unverified.
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 795–806
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Biochemical Akt regulation and targeted mouse Ip6k1 deletion · source_derived_draft · unverified_draft
### ino-ip6k1-insulin Ip6k1-null mice showed increased insulin sensitivity and resistance to diet- or age-associated obesity. Condition category: machinery_impairment nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: Removing a specific signaling enzyme improved these metabolic outcomes in mice. organism: Mammalian enzymology and Mus musculus tissue_or_cell_type: Muscle, adipose tissue and liver experimental_model: Biochemical Akt regulation and targeted mouse Ip6k1 deletion limitations: Whole-gene deletion is not equivalent to adding or withdrawing free myo-inositol; the reported therapeutic proposal is not established treatment. exposure: 5-InsP7 and Ip6k1 knockout evidence_span: {"source_cache": "artifacts/inositol-research/21145457.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0de0a9c3ea11cd8ce59bccff69a41139b11e11182fd9fd66016ec72ba329a5ce", "start_char": 0, "end_char": 889, "text_sha256": "0de0a9c3ea11cd8ce59bccff69a41139b11e11182fd9fd66016ec72ba329a5ce"} [ino-p21145457] Inositol pyrophosphates inhibit Akt signaling, thereby regulating insulin sensitivity and weight gain. (2010). https://pubmed.ncbi.nlm.nih.gov/21145457/ DOI: 10.1016/j.cell.2010.11.032
Complete structured claim and evidence
PPIP5K proteins also possess InsP8 phosphatase activity, opposing their kinase reaction.
Diphosphoinositol pentakisphosphate kinase family → 1,5-bisdiphosphoinositol tetrakisphosphate (1,5-InsP8) source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/28126903.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6f5c96ed7d02591d5fe475d0e26aa2f21dc93f0c86c12998debb417f98254d2f", "start_char": 0, "end_char": 1981, "text_sha256": "6f5c96ed7d02591d5fe475d0e26aa2f21dc93f0c86c12998debb417f98254d2f"}
experimental_model
Cellular phosphate withdrawal/repletion and bifunctional enzyme kinetics
exposure
Phosphate availability and PPIP5K kinase/phosphatase assays
limitations
Cell-culture nutrient withdrawal is not a measured human dietary threshold; PPIP5K isoforms are not identical.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Human HCT116 cells and human PPIP5K proteins
plain_language
The same protein family can build and break down the signal.
primary_references
[ino-p28126903] The Significance of the Bifunctional Kinase/Phosphatase Activities of Diphosphoinositol Pentakisphosphate Kinases (PPIP5Ks) for Coupling Inositol Pyrophosphate Cell Signaling to Cellular Phosphate Homeostasis. (2017). https://pubmed.ncbi.nlm.nih.gov/28126903/ DOI: 10.1074/jbc.m116.765743
tissue_or_cell_type
Intestinal tumor-derived cell line; purified enzymes
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 821–832
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cellular phosphate withdrawal/repletion and bifunctional enzyme kinetics · source_derived_draft · unverified_draft
### ino-ppip5k-reverse PPIP5K proteins also possess InsP8 phosphatase activity, opposing their kinase reaction. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: The same protein family can build and break down the signal. organism: Human HCT116 cells and human PPIP5K proteins tissue_or_cell_type: Intestinal tumor-derived cell line; purified enzymes experimental_model: Cellular phosphate withdrawal/repletion and bifunctional enzyme kinetics limitations: Cell-culture nutrient withdrawal is not a measured human dietary threshold; PPIP5K isoforms are not identical. exposure: Phosphate availability and PPIP5K kinase/phosphatase assays evidence_span: {"source_cache": "artifacts/inositol-research/28126903.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6f5c96ed7d02591d5fe475d0e26aa2f21dc93f0c86c12998debb417f98254d2f", "start_char": 0, "end_char": 1981, "text_sha256": "6f5c96ed7d02591d5fe475d0e26aa2f21dc93f0c86c12998debb417f98254d2f"} [ino-p28126903] The Significance of the Bifunctional Kinase/Phosphatase Activities of Diphosphoinositol Pentakisphosphate Kinases (PPIP5Ks) for Coupling Inositol Pyrophosphate Cell Signaling to Cellular Phosphate Homeostasis. (2017). https://pubmed.ncbi.nlm.nih.gov/28126903/ DOI: 10.1074/jbc.m116.765743
Complete structured claim and evidence
Inorganic phosphate inhibited PPIP5K InsP8 phosphatase activities by approximately 40–90% across 0–1 mM in the reported assays.
Inorganic phosphate → Diphosphoinositol pentakisphosphate kinase family source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/28126903.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6f5c96ed7d02591d5fe475d0e26aa2f21dc93f0c86c12998debb417f98254d2f", "start_char": 0, "end_char": 1981, "text_sha256": "6f5c96ed7d02591d5fe475d0e26aa2f21dc93f0c86c12998debb417f98254d2f"}
experimental_model
Cellular phosphate withdrawal/repletion and bifunctional enzyme kinetics
exposure
Phosphate availability and PPIP5K kinase/phosphatase assays
limitations
Cell-culture nutrient withdrawal is not a measured human dietary threshold; PPIP5K isoforms are not identical.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Human HCT116 cells and human PPIP5K proteins
plain_language
Phosphate availability can slow destruction of the inositol-pyrophosphate signal.
primary_references
[ino-p28126903] The Significance of the Bifunctional Kinase/Phosphatase Activities of Diphosphoinositol Pentakisphosphate Kinases (PPIP5Ks) for Coupling Inositol Pyrophosphate Cell Signaling to Cellular Phosphate Homeostasis. (2017). https://pubmed.ncbi.nlm.nih.gov/28126903/ DOI: 10.1074/jbc.m116.765743
tissue_or_cell_type
Intestinal tumor-derived cell line; purified enzymes
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 834–845
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cellular phosphate withdrawal/repletion and bifunctional enzyme kinetics · source_derived_draft · unverified_draft
### ino-pi-ppip-phosphatase Inorganic phosphate inhibited PPIP5K InsP8 phosphatase activities by approximately 40–90% across 0–1 mM in the reported assays. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: Phosphate availability can slow destruction of the inositol-pyrophosphate signal. organism: Human HCT116 cells and human PPIP5K proteins tissue_or_cell_type: Intestinal tumor-derived cell line; purified enzymes experimental_model: Cellular phosphate withdrawal/repletion and bifunctional enzyme kinetics limitations: Cell-culture nutrient withdrawal is not a measured human dietary threshold; PPIP5K isoforms are not identical. exposure: Phosphate availability and PPIP5K kinase/phosphatase assays evidence_span: {"source_cache": "artifacts/inositol-research/28126903.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6f5c96ed7d02591d5fe475d0e26aa2f21dc93f0c86c12998debb417f98254d2f", "start_char": 0, "end_char": 1981, "text_sha256": "6f5c96ed7d02591d5fe475d0e26aa2f21dc93f0c86c12998debb417f98254d2f"} [ino-p28126903] The Significance of the Bifunctional Kinase/Phosphatase Activities of Diphosphoinositol Pentakisphosphate Kinases (PPIP5Ks) for Coupling Inositol Pyrophosphate Cell Signaling to Cellular Phosphate Homeostasis. (2017). https://pubmed.ncbi.nlm.nih.gov/28126903/ DOI: 10.1074/jbc.m116.765743
Complete structured claim and evidence
Phosphate increased PPIP5K2 5-InsP7 kinase activity approximately twofold across 0–5 mM.
Inorganic phosphate → PPIP5K2 (human diphosphoinositol pentakisphosphate kinase 2) source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/28126903.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6f5c96ed7d02591d5fe475d0e26aa2f21dc93f0c86c12998debb417f98254d2f", "start_char": 0, "end_char": 1981, "text_sha256": "6f5c96ed7d02591d5fe475d0e26aa2f21dc93f0c86c12998debb417f98254d2f"}
experimental_model
Cellular phosphate withdrawal/repletion and bifunctional enzyme kinetics
exposure
Phosphate availability and PPIP5K kinase/phosphatase assays
limitations
Cell-culture nutrient withdrawal is not a measured human dietary threshold; PPIP5K isoforms are not identical.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Human HCT116 cells and human PPIP5K proteins
plain_language
For this isoform, phosphate also increased the signal-building reaction.
primary_references
[ino-p28126903] The Significance of the Bifunctional Kinase/Phosphatase Activities of Diphosphoinositol Pentakisphosphate Kinases (PPIP5Ks) for Coupling Inositol Pyrophosphate Cell Signaling to Cellular Phosphate Homeostasis. (2017). https://pubmed.ncbi.nlm.nih.gov/28126903/ DOI: 10.1074/jbc.m116.765743
tissue_or_cell_type
Intestinal tumor-derived cell line; purified enzymes
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 847–858
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cellular phosphate withdrawal/repletion and bifunctional enzyme kinetics · source_derived_draft · unverified_draft
### ino-pi-ppip5k2-kinase Phosphate increased PPIP5K2 5-InsP7 kinase activity approximately twofold across 0–5 mM. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: For this isoform, phosphate also increased the signal-building reaction. organism: Human HCT116 cells and human PPIP5K proteins tissue_or_cell_type: Intestinal tumor-derived cell line; purified enzymes experimental_model: Cellular phosphate withdrawal/repletion and bifunctional enzyme kinetics limitations: Cell-culture nutrient withdrawal is not a measured human dietary threshold; PPIP5K isoforms are not identical. exposure: Phosphate availability and PPIP5K kinase/phosphatase assays evidence_span: {"source_cache": "artifacts/inositol-research/28126903.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6f5c96ed7d02591d5fe475d0e26aa2f21dc93f0c86c12998debb417f98254d2f", "start_char": 0, "end_char": 1981, "text_sha256": "6f5c96ed7d02591d5fe475d0e26aa2f21dc93f0c86c12998debb417f98254d2f"} [ino-p28126903] The Significance of the Bifunctional Kinase/Phosphatase Activities of Diphosphoinositol Pentakisphosphate Kinases (PPIP5Ks) for Coupling Inositol Pyrophosphate Cell Signaling to Cellular Phosphate Homeostasis. (2017). https://pubmed.ncbi.nlm.nih.gov/28126903/ DOI: 10.1074/jbc.m116.765743
Complete structured claim and evidence
Phosphate starvation lowered ATP and 5-InsP7, while InsP8 showed a larger and more sensitive response; levels recovered with phosphate replenishment.
Inorganic phosphate → 1,5-bisdiphosphoinositol tetrakisphosphate (1,5-InsP8) source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/inositol-research/28126903.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6f5c96ed7d02591d5fe475d0e26aa2f21dc93f0c86c12998debb417f98254d2f", "start_char": 0, "end_char": 1981, "text_sha256": "6f5c96ed7d02591d5fe475d0e26aa2f21dc93f0c86c12998debb417f98254d2f"}
experimental_model
Cellular phosphate withdrawal/repletion and bifunctional enzyme kinetics
exposure
Phosphate availability and PPIP5K kinase/phosphatase assays
limitations
Cell-culture nutrient withdrawal is not a measured human dietary threshold; PPIP5K isoforms are not identical.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Human HCT116 cells and human PPIP5K proteins
plain_language
The signaling network detects phosphate supply instead of depending only on the amount of free inositol.
primary_references
[ino-p28126903] The Significance of the Bifunctional Kinase/Phosphatase Activities of Diphosphoinositol Pentakisphosphate Kinases (PPIP5Ks) for Coupling Inositol Pyrophosphate Cell Signaling to Cellular Phosphate Homeostasis. (2017). https://pubmed.ncbi.nlm.nih.gov/28126903/ DOI: 10.1074/jbc.m116.765743
tissue_or_cell_type
Intestinal tumor-derived cell line; purified enzymes
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 860–871
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cellular phosphate withdrawal/repletion and bifunctional enzyme kinetics · source_derived_draft · unverified_draft
### ino-phosphate-ip8 Phosphate starvation lowered ATP and 5-InsP7, while InsP8 showed a larger and more sensitive response; levels recovered with phosphate replenishment. Condition category: nutrient_deficiency nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: The signaling network detects phosphate supply instead of depending only on the amount of free inositol. organism: Human HCT116 cells and human PPIP5K proteins tissue_or_cell_type: Intestinal tumor-derived cell line; purified enzymes experimental_model: Cellular phosphate withdrawal/repletion and bifunctional enzyme kinetics limitations: Cell-culture nutrient withdrawal is not a measured human dietary threshold; PPIP5K isoforms are not identical. exposure: Phosphate availability and PPIP5K kinase/phosphatase assays evidence_span: {"source_cache": "artifacts/inositol-research/28126903.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6f5c96ed7d02591d5fe475d0e26aa2f21dc93f0c86c12998debb417f98254d2f", "start_char": 0, "end_char": 1981, "text_sha256": "6f5c96ed7d02591d5fe475d0e26aa2f21dc93f0c86c12998debb417f98254d2f"} [ino-p28126903] The Significance of the Bifunctional Kinase/Phosphatase Activities of Diphosphoinositol Pentakisphosphate Kinases (PPIP5Ks) for Coupling Inositol Pyrophosphate Cell Signaling to Cellular Phosphate Homeostasis. (2017). https://pubmed.ncbi.nlm.nih.gov/28126903/ DOI: 10.1074/jbc.m116.765743
Complete structured claim and evidence
PPIP5K knockout reduced XPR1-dependent phosphate efflux; wild-type PPIP5K1 rescued efflux whereas kinase-dead PPIP5K1 did not.
Diphosphoinositol pentakisphosphate kinase family → Cellular inorganic phosphate export source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/inositol-research/32019887.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bb7637b9a327b1cba07716bbed5da8a3f32a3ac00c9fff70d23ada1a736d3d18", "start_char": 0, "end_char": 2004, "text_sha256": "bb7637b9a327b1cba07716bbed5da8a3f32a3ac00c9fff70d23ada1a736d3d18"}
experimental_model
Binding, knockout and rescue experiments
exposure
PPIP5K or XPR1 deletion, kinase rescue and pyrophosphate analog delivery
limitations
Cell assays establish a transport-regulation mechanism, not benefits of oral inositol or increased bone mineralization.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Human cultured cells including Saos-2 osteosarcoma cells
plain_language
The exporter needed the signal-generating activity, not simply the presence of the protein.
primary_references
[ino-p32019887] Control of XPR1-dependent cellular phosphate efflux by InsP8 is an exemplar for functionally-exclusive inositol pyrophosphate signaling. (2020). https://pubmed.ncbi.nlm.nih.gov/32019887/ DOI: 10.1073/pnas.1908830117
tissue_or_cell_type
Cellular phosphate transport
trigger_kind
machinery_impairment Imported condition classification; unverified.
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 886–897
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Binding, knockout and rescue experiments · source_derived_draft · unverified_draft
### ino-ppip5k-export PPIP5K knockout reduced XPR1-dependent phosphate efflux; wild-type PPIP5K1 rescued efflux whereas kinase-dead PPIP5K1 did not. Condition category: machinery_impairment nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: The exporter needed the signal-generating activity, not simply the presence of the protein. organism: Human cultured cells including Saos-2 osteosarcoma cells tissue_or_cell_type: Cellular phosphate transport experimental_model: Binding, knockout and rescue experiments limitations: Cell assays establish a transport-regulation mechanism, not benefits of oral inositol or increased bone mineralization. exposure: PPIP5K or XPR1 deletion, kinase rescue and pyrophosphate analog delivery evidence_span: {"source_cache": "artifacts/inositol-research/32019887.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bb7637b9a327b1cba07716bbed5da8a3f32a3ac00c9fff70d23ada1a736d3d18", "start_char": 0, "end_char": 2004, "text_sha256": "bb7637b9a327b1cba07716bbed5da8a3f32a3ac00c9fff70d23ada1a736d3d18"} [ino-p32019887] Control of XPR1-dependent cellular phosphate efflux by InsP8 is an exemplar for functionally-exclusive inositol pyrophosphate signaling. (2020). https://pubmed.ncbi.nlm.nih.gov/32019887/ DOI: 10.1073/pnas.1908830117
Complete structured claim and evidence
Liposomal delivery of a metabolically resistant InsP8 analog rescued phosphate efflux in PPIP5K-null cells; tested analogs of other inositol pyrophosphates did not.
1,5-bisdiphosphoinositol tetrakisphosphate (1,5-InsP8) → Cellular inorganic phosphate export source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/inositol-research/32019887.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bb7637b9a327b1cba07716bbed5da8a3f32a3ac00c9fff70d23ada1a736d3d18", "start_char": 0, "end_char": 2004, "text_sha256": "bb7637b9a327b1cba07716bbed5da8a3f32a3ac00c9fff70d23ada1a736d3d18"}
experimental_model
Binding, knockout and rescue experiments
exposure
PPIP5K or XPR1 deletion, kinase rescue and pyrophosphate analog delivery
limitations
Cell assays establish a transport-regulation mechanism, not benefits of oral inositol or increased bone mineralization.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Human cultured cells including Saos-2 osteosarcoma cells
plain_language
The rescue was chemically selective, rather than an effect of any inositol compound.
primary_references
[ino-p32019887] Control of XPR1-dependent cellular phosphate efflux by InsP8 is an exemplar for functionally-exclusive inositol pyrophosphate signaling. (2020). https://pubmed.ncbi.nlm.nih.gov/32019887/ DOI: 10.1073/pnas.1908830117
tissue_or_cell_type
Cellular phosphate transport
trigger_kind
machinery_impairment Imported condition classification; unverified.
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 899–910
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Binding, knockout and rescue experiments · source_derived_draft · unverified_draft
### ino-ip8-specific-rescue Liposomal delivery of a metabolically resistant InsP8 analog rescued phosphate efflux in PPIP5K-null cells; tested analogs of other inositol pyrophosphates did not. Condition category: machinery_impairment nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: The rescue was chemically selective, rather than an effect of any inositol compound. organism: Human cultured cells including Saos-2 osteosarcoma cells tissue_or_cell_type: Cellular phosphate transport experimental_model: Binding, knockout and rescue experiments limitations: Cell assays establish a transport-regulation mechanism, not benefits of oral inositol or increased bone mineralization. exposure: PPIP5K or XPR1 deletion, kinase rescue and pyrophosphate analog delivery evidence_span: {"source_cache": "artifacts/inositol-research/32019887.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bb7637b9a327b1cba07716bbed5da8a3f32a3ac00c9fff70d23ada1a736d3d18", "start_char": 0, "end_char": 2004, "text_sha256": "bb7637b9a327b1cba07716bbed5da8a3f32a3ac00c9fff70d23ada1a736d3d18"} [ino-p32019887] Control of XPR1-dependent cellular phosphate efflux by InsP8 is an exemplar for functionally-exclusive inositol pyrophosphate signaling. (2020). https://pubmed.ncbi.nlm.nih.gov/32019887/ DOI: 10.1073/pnas.1908830117
Complete structured claim and evidence
XPR1 or PPIP5K knockout reduced phosphate export and accelerated the mineralization endpoint in Saos-2 cells.
XPR1 (human phosphate exporter) → Saos-2 cell mineralization source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/inositol-research/32019887.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bb7637b9a327b1cba07716bbed5da8a3f32a3ac00c9fff70d23ada1a736d3d18", "start_char": 0, "end_char": 2004, "text_sha256": "bb7637b9a327b1cba07716bbed5da8a3f32a3ac00c9fff70d23ada1a736d3d18"}
experimental_model
Binding, knockout and rescue experiments
exposure
PPIP5K or XPR1 deletion, kinase rescue and pyrophosphate analog delivery
limitations
Cell assays establish a transport-regulation mechanism, not benefits of oral inositol or increased bone mineralization.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Human cultured cells including Saos-2 osteosarcoma cells
plain_language
Retaining phosphate changed mineral deposition in a bone-tumor cell model.
primary_references
[ino-p32019887] Control of XPR1-dependent cellular phosphate efflux by InsP8 is an exemplar for functionally-exclusive inositol pyrophosphate signaling. (2020). https://pubmed.ncbi.nlm.nih.gov/32019887/ DOI: 10.1073/pnas.1908830117
tissue_or_cell_type
Cellular phosphate transport
trigger_kind
machinery_impairment Imported condition classification; unverified.
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 912–923
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Binding, knockout and rescue experiments · source_derived_draft · unverified_draft
### ino-xpr1-mineralization XPR1 or PPIP5K knockout reduced phosphate export and accelerated the mineralization endpoint in Saos-2 cells. Condition category: machinery_impairment nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: Retaining phosphate changed mineral deposition in a bone-tumor cell model. organism: Human cultured cells including Saos-2 osteosarcoma cells tissue_or_cell_type: Cellular phosphate transport experimental_model: Binding, knockout and rescue experiments limitations: Cell assays establish a transport-regulation mechanism, not benefits of oral inositol or increased bone mineralization. exposure: PPIP5K or XPR1 deletion, kinase rescue and pyrophosphate analog delivery evidence_span: {"source_cache": "artifacts/inositol-research/32019887.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bb7637b9a327b1cba07716bbed5da8a3f32a3ac00c9fff70d23ada1a736d3d18", "start_char": 0, "end_char": 2004, "text_sha256": "bb7637b9a327b1cba07716bbed5da8a3f32a3ac00c9fff70d23ada1a736d3d18"} [ino-p32019887] Control of XPR1-dependent cellular phosphate efflux by InsP8 is an exemplar for functionally-exclusive inositol pyrophosphate signaling. (2020). https://pubmed.ncbi.nlm.nih.gov/32019887/ DOI: 10.1073/pnas.1908830117
Complete structured claim and evidence
In the presence of InsP6 and phosphate, human XPR1-KIDINS220 adopted an outward-open structure; InsP6 occupied SPX and juxtamembrane regions.
Phytic acid / phytate → Human XPR1-KIDINS220 complex source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/40128258.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4765253840f684d5dafa834980e3fea9edc5d7419379b4a27ccf1090f081ce00", "start_char": 0, "end_char": 1071, "text_sha256": "4765253840f684d5dafa834980e3fea9edc5d7419379b4a27ccf1090f081ce00"}
experimental_model
Cryo-EM and functional mutagenesis
exposure
InsP6 and phosphate binding
limitations
This paper tests InsP6 despite pyrophosphate wording in its title. It does not establish that dietary phytate reaches this intracellular site or overrides InsP8 selectivity in other assays.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Human proteins
plain_language
An intracellular inositol phosphate helped stabilize an open exporter complex.
primary_references
[ino-p40128258] Synergistic activation of the human phosphate exporter XPR1 by KIDINS220 and inositol pyrophosphate. (2025). https://pubmed.ncbi.nlm.nih.gov/40128258/ DOI: 10.1038/s41467-025-58200-y
tissue_or_cell_type
XPR1-KIDINS220 transport complex
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 925–936
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cryo-EM and functional mutagenesis · source_derived_draft · unverified_draft
### ino-xpr1-ins-p6 In the presence of InsP6 and phosphate, human XPR1-KIDINS220 adopted an outward-open structure; InsP6 occupied SPX and juxtamembrane regions. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: An intracellular inositol phosphate helped stabilize an open exporter complex. organism: Human proteins tissue_or_cell_type: XPR1-KIDINS220 transport complex experimental_model: Cryo-EM and functional mutagenesis limitations: This paper tests InsP6 despite pyrophosphate wording in its title. It does not establish that dietary phytate reaches this intracellular site or overrides InsP8 selectivity in other assays. exposure: InsP6 and phosphate binding evidence_span: {"source_cache": "artifacts/inositol-research/40128258.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4765253840f684d5dafa834980e3fea9edc5d7419379b4a27ccf1090f081ce00", "start_char": 0, "end_char": 1071, "text_sha256": "4765253840f684d5dafa834980e3fea9edc5d7419379b4a27ccf1090f081ce00"} [ino-p40128258] Synergistic activation of the human phosphate exporter XPR1 by KIDINS220 and inositol pyrophosphate. (2025). https://pubmed.ncbi.nlm.nih.gov/40128258/ DOI: 10.1038/s41467-025-58200-y
Complete structured claim and evidence
XPR1 alone remained closed even with InsP6 and phosphate in the tested structures, whereas the KIDINS220-containing complex could open.
KIDINS220 (human kinase D-interacting substrate 220) → XPR1 (human phosphate exporter) source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/40128258.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4765253840f684d5dafa834980e3fea9edc5d7419379b4a27ccf1090f081ce00", "start_char": 0, "end_char": 1071, "text_sha256": "4765253840f684d5dafa834980e3fea9edc5d7419379b4a27ccf1090f081ce00"}
experimental_model
Cryo-EM and functional mutagenesis
exposure
InsP6 and phosphate binding
limitations
This paper tests InsP6 despite pyrophosphate wording in its title. It does not establish that dietary phytate reaches this intracellular site or overrides InsP8 selectivity in other assays.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Human proteins
plain_language
A partner protein mattered as well as the chemical signal.
primary_references
[ino-p40128258] Synergistic activation of the human phosphate exporter XPR1 by KIDINS220 and inositol pyrophosphate. (2025). https://pubmed.ncbi.nlm.nih.gov/40128258/ DOI: 10.1038/s41467-025-58200-y
tissue_or_cell_type
XPR1-KIDINS220 transport complex
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 938–949
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cryo-EM and functional mutagenesis · source_derived_draft · unverified_draft
### ino-kidins-xpr1 XPR1 alone remained closed even with InsP6 and phosphate in the tested structures, whereas the KIDINS220-containing complex could open. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: A partner protein mattered as well as the chemical signal. organism: Human proteins tissue_or_cell_type: XPR1-KIDINS220 transport complex experimental_model: Cryo-EM and functional mutagenesis limitations: This paper tests InsP6 despite pyrophosphate wording in its title. It does not establish that dietary phytate reaches this intracellular site or overrides InsP8 selectivity in other assays. exposure: InsP6 and phosphate binding evidence_span: {"source_cache": "artifacts/inositol-research/40128258.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4765253840f684d5dafa834980e3fea9edc5d7419379b4a27ccf1090f081ce00", "start_char": 0, "end_char": 1071, "text_sha256": "4765253840f684d5dafa834980e3fea9edc5d7419379b4a27ccf1090f081ce00"} [ino-p40128258] Synergistic activation of the human phosphate exporter XPR1 by KIDINS220 and inositol pyrophosphate. (2025). https://pubmed.ncbi.nlm.nih.gov/40128258/ DOI: 10.1038/s41467-025-58200-y
Complete structured claim and evidence
PLC-dependent TRPM7 inhibition under whole-cell recording was observed only when intracellular Mg2+ was reduced below physiological levels.
Mg2+ → TRPM7-mediated membrane current source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/inositol-research/17095511.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "28346917b1f99a6c832092a0ff4d39cb2906a680e5e18257412a19ba289d6c83", "start_char": 0, "end_char": 1403, "text_sha256": "28346917b1f99a6c832092a0ff4d39cb2906a680e5e18257412a19ba289d6c83"}
experimental_model
Perforated versus whole-cell patch clamp and FRET
exposure
PLC-coupled agonists with different intracellular magnesium conditions
limitations
The opposite current responses are explicitly explained by experimental ionic conditions; they are not an unresolved scientific contradiction.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Mouse N1E-115 neuroblastoma cells
plain_language
Changing magnesium inside the recorded cell changed how the channel responded.
primary_references
[ino-p17095511] Activation of TRPM7 channels by phospholipase C-coupled receptor agonists. (2007). https://pubmed.ncbi.nlm.nih.gov/17095511/ DOI: 10.1074/jbc.m605300200
tissue_or_cell_type
TRPM7-expressing cells
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 964–975
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Perforated versus whole-cell patch clamp and FRET · source_derived_draft · unverified_draft
### ino-trpm7-low-mg PLC-dependent TRPM7 inhibition under whole-cell recording was observed only when intracellular Mg2+ was reduced below physiological levels. Condition category: nutrient_deficiency nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: Changing magnesium inside the recorded cell changed how the channel responded. organism: Mouse N1E-115 neuroblastoma cells tissue_or_cell_type: TRPM7-expressing cells experimental_model: Perforated versus whole-cell patch clamp and FRET limitations: The opposite current responses are explicitly explained by experimental ionic conditions; they are not an unresolved scientific contradiction. exposure: PLC-coupled agonists with different intracellular magnesium conditions evidence_span: {"source_cache": "artifacts/inositol-research/17095511.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "28346917b1f99a6c832092a0ff4d39cb2906a680e5e18257412a19ba289d6c83", "start_char": 0, "end_char": 1403, "text_sha256": "28346917b1f99a6c832092a0ff4d39cb2906a680e5e18257412a19ba289d6c83"} [ino-p17095511] Activation of TRPM7 channels by phospholipase C-coupled receptor agonists. (2007). https://pubmed.ncbi.nlm.nih.gov/17095511/ DOI: 10.1074/jbc.m605300200
Complete structured claim and evidence
PLC-coupled agonists activated TRPM7 currents under perforated-patch conditions that preserved physiological intracellular ions.
Mouse Trpm7 channel → TRPM7-mediated membrane current source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/17095511.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "28346917b1f99a6c832092a0ff4d39cb2906a680e5e18257412a19ba289d6c83", "start_char": 0, "end_char": 1403, "text_sha256": "28346917b1f99a6c832092a0ff4d39cb2906a680e5e18257412a19ba289d6c83"}
experimental_model
Perforated versus whole-cell patch clamp and FRET
exposure
PLC-coupled agonists with different intracellular magnesium conditions
limitations
The opposite current responses are explicitly explained by experimental ionic conditions; they are not an unresolved scientific contradiction.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Mouse N1E-115 neuroblastoma cells
plain_language
The channel response reversed when the cell’s internal environment was better preserved.
primary_references
[ino-p17095511] Activation of TRPM7 channels by phospholipase C-coupled receptor agonists. (2007). https://pubmed.ncbi.nlm.nih.gov/17095511/ DOI: 10.1074/jbc.m605300200
tissue_or_cell_type
TRPM7-expressing cells
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 977–988
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Perforated versus whole-cell patch clamp and FRET · source_derived_draft · unverified_draft
### ino-trpm7-physiologic PLC-coupled agonists activated TRPM7 currents under perforated-patch conditions that preserved physiological intracellular ions. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: The channel response reversed when the cell’s internal environment was better preserved. organism: Mouse N1E-115 neuroblastoma cells tissue_or_cell_type: TRPM7-expressing cells experimental_model: Perforated versus whole-cell patch clamp and FRET limitations: The opposite current responses are explicitly explained by experimental ionic conditions; they are not an unresolved scientific contradiction. exposure: PLC-coupled agonists with different intracellular magnesium conditions evidence_span: {"source_cache": "artifacts/inositol-research/17095511.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "28346917b1f99a6c832092a0ff4d39cb2906a680e5e18257412a19ba289d6c83", "start_char": 0, "end_char": 1403, "text_sha256": "28346917b1f99a6c832092a0ff4d39cb2906a680e5e18257412a19ba289d6c83"} [ino-p17095511] Activation of TRPM7 channels by phospholipase C-coupled receptor agonists. (2007). https://pubmed.ncbi.nlm.nih.gov/17095511/ DOI: 10.1074/jbc.m605300200
Complete structured claim and evidence
Hydrolyzable ATP supported maintenance of cardiac magnesium-inhibited cation current, whereas a nonhydrolyzable ATP analog did not substitute.
ATP → Cardiac magnesium-inhibited cation current source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/inositol-research/16707555.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b411ec23aa4b3ee2a861a8a9a99811acb039a03c18015a5954a1f90971d175ef", "start_char": 0, "end_char": 1640, "text_sha256": "b411ec23aa4b3ee2a861a8a9a99811acb039a03c18015a5954a1f90971d175ef"}
experimental_model
Cardiac patch clamp and lipid/ATP manipulation
exposure
ATP withdrawal, analogs and exogenous PIP2
limitations
The current was described as TRPM7-like; this experiment alone does not establish its molecular identity.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Pig, rat and guinea pig cardiac cells
plain_language
ATP had to support a chemical reaction, rather than merely occupy a binding site.
primary_references
[ino-p16707555] ATP and PIP2 dependence of the magnesium-inhibited, TRPM7-like cation channel in cardiac myocytes. (2006). https://pubmed.ncbi.nlm.nih.gov/16707555/ DOI: 10.1152/ajpcell.00074.2006
tissue_or_cell_type
Cardiac magnesium-inhibited current
trigger_kind
machinery_impairment Imported condition classification; unverified.
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 990–1001
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cardiac patch clamp and lipid/ATP manipulation · source_derived_draft · unverified_draft
### ino-mic-atp Hydrolyzable ATP supported maintenance of cardiac magnesium-inhibited cation current, whereas a nonhydrolyzable ATP analog did not substitute. Condition category: machinery_impairment nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: ATP had to support a chemical reaction, rather than merely occupy a binding site. organism: Pig, rat and guinea pig cardiac cells tissue_or_cell_type: Cardiac magnesium-inhibited current experimental_model: Cardiac patch clamp and lipid/ATP manipulation limitations: The current was described as TRPM7-like; this experiment alone does not establish its molecular identity. exposure: ATP withdrawal, analogs and exogenous PIP2 evidence_span: {"source_cache": "artifacts/inositol-research/16707555.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b411ec23aa4b3ee2a861a8a9a99811acb039a03c18015a5954a1f90971d175ef", "start_char": 0, "end_char": 1640, "text_sha256": "b411ec23aa4b3ee2a861a8a9a99811acb039a03c18015a5954a1f90971d175ef"} [ino-p16707555] ATP and PIP2 dependence of the magnesium-inhibited, TRPM7-like cation channel in cardiac myocytes. (2006). https://pubmed.ncbi.nlm.nih.gov/16707555/ DOI: 10.1152/ajpcell.00074.2006
Complete structured claim and evidence
Exogenous PIP2 restored cardiac MIC current after rundown in ATP-depleted conditions.
Phosphatidylinositol 4,5-bisphosphate → Cardiac magnesium-inhibited cation current source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/inositol-research/16707555.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b411ec23aa4b3ee2a861a8a9a99811acb039a03c18015a5954a1f90971d175ef", "start_char": 0, "end_char": 1640, "text_sha256": "b411ec23aa4b3ee2a861a8a9a99811acb039a03c18015a5954a1f90971d175ef"}
experimental_model
Cardiac patch clamp and lipid/ATP manipulation
exposure
ATP withdrawal, analogs and exogenous PIP2
limitations
The current was described as TRPM7-like; this experiment alone does not establish its molecular identity.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Pig, rat and guinea pig cardiac cells
plain_language
Restoring the membrane signal bypassed one consequence of ATP depletion in this assay.
primary_references
[ino-p16707555] ATP and PIP2 dependence of the magnesium-inhibited, TRPM7-like cation channel in cardiac myocytes. (2006). https://pubmed.ncbi.nlm.nih.gov/16707555/ DOI: 10.1152/ajpcell.00074.2006
tissue_or_cell_type
Cardiac magnesium-inhibited current
trigger_kind
machinery_impairment Imported condition classification; unverified.
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 1003–1014
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cardiac patch clamp and lipid/ATP manipulation · source_derived_draft · unverified_draft
### ino-mic-pip2-rescue Exogenous PIP2 restored cardiac MIC current after rundown in ATP-depleted conditions. Condition category: machinery_impairment nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: Restoring the membrane signal bypassed one consequence of ATP depletion in this assay. organism: Pig, rat and guinea pig cardiac cells tissue_or_cell_type: Cardiac magnesium-inhibited current experimental_model: Cardiac patch clamp and lipid/ATP manipulation limitations: The current was described as TRPM7-like; this experiment alone does not establish its molecular identity. exposure: ATP withdrawal, analogs and exogenous PIP2 evidence_span: {"source_cache": "artifacts/inositol-research/16707555.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b411ec23aa4b3ee2a861a8a9a99811acb039a03c18015a5954a1f90971d175ef", "start_char": 0, "end_char": 1640, "text_sha256": "b411ec23aa4b3ee2a861a8a9a99811acb039a03c18015a5954a1f90971d175ef"} [ino-p16707555] ATP and PIP2 dependence of the magnesium-inhibited, TRPM7-like cation channel in cardiac myocytes. (2006). https://pubmed.ncbi.nlm.nih.gov/16707555/ DOI: 10.1152/ajpcell.00074.2006
Complete structured claim and evidence
PIP2 depletion in the studied mouse small-vessel disease model impaired endothelial Kir2.1 activity.
Phosphatidylinositol 4,5-bisphosphate → Mouse Kcnj2 (Kir2.1) source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/inositol-research/33875602.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "139eeba386e63329898f8e36ebe93ad741eed904819bbebe7fc2b1808130a19d", "start_char": 0, "end_char": 1108, "text_sha256": "139eeba386e63329898f8e36ebe93ad741eed904819bbebe7fc2b1808130a19d"}
experimental_model
Genetic small-vessel disease mouse model and lipid rescue
exposure
PIP2 depletion and soluble PIP2 administration
limitations
Mouse disease model; not evidence that oral inositol treats human cerebrovascular disease.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Mus musculus
plain_language
The potassium channel can fail because its supporting lipid is missing, even though the channel protein remains.
primary_references
[ino-p33875602] PIP2 corrects cerebral blood flow deficits in small vessel disease by rescuing capillary Kir2.1 activity. (2021). https://pubmed.ncbi.nlm.nih.gov/33875602/ DOI: 10.1073/pnas.2025998118
tissue_or_cell_type
Brain capillary endothelium and cerebral circulation
trigger_kind
machinery_impairment Imported condition classification; unverified.
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 1016–1027
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Genetic small-vessel disease mouse model and lipid rescue · source_derived_draft · unverified_draft
### ino-kir-pip2 PIP2 depletion in the studied mouse small-vessel disease model impaired endothelial Kir2.1 activity. Condition category: machinery_impairment nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: The potassium channel can fail because its supporting lipid is missing, even though the channel protein remains. organism: Mus musculus tissue_or_cell_type: Brain capillary endothelium and cerebral circulation experimental_model: Genetic small-vessel disease mouse model and lipid rescue limitations: Mouse disease model; not evidence that oral inositol treats human cerebrovascular disease. exposure: PIP2 depletion and soluble PIP2 administration evidence_span: {"source_cache": "artifacts/inositol-research/33875602.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "139eeba386e63329898f8e36ebe93ad741eed904819bbebe7fc2b1808130a19d", "start_char": 0, "end_char": 1108, "text_sha256": "139eeba386e63329898f8e36ebe93ad741eed904819bbebe7fc2b1808130a19d"} [ino-p33875602] PIP2 corrects cerebral blood flow deficits in small vessel disease by rescuing capillary Kir2.1 activity. (2021). https://pubmed.ncbi.nlm.nih.gov/33875602/ DOI: 10.1073/pnas.2025998118
Complete structured claim and evidence
Soluble PIP2 administration restored Kir2.1-dependent neurovascular responses in the studied mouse model.
Phosphatidylinositol 4,5-bisphosphate → Neural-activity-evoked cerebral blood flow source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/inositol-research/33875602.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "139eeba386e63329898f8e36ebe93ad741eed904819bbebe7fc2b1808130a19d", "start_char": 0, "end_char": 1108, "text_sha256": "139eeba386e63329898f8e36ebe93ad741eed904819bbebe7fc2b1808130a19d"}
experimental_model
Genetic small-vessel disease mouse model and lipid rescue
exposure
PIP2 depletion and soluble PIP2 administration
limitations
Mouse disease model; not evidence that oral inositol treats human cerebrovascular disease.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Mus musculus
plain_language
Replacing the deficient lipid signal restored a blood-flow response in these mice.
primary_references
[ino-p33875602] PIP2 corrects cerebral blood flow deficits in small vessel disease by rescuing capillary Kir2.1 activity. (2021). https://pubmed.ncbi.nlm.nih.gov/33875602/ DOI: 10.1073/pnas.2025998118
tissue_or_cell_type
Brain capillary endothelium and cerebral circulation
trigger_kind
machinery_impairment Imported condition classification; unverified.
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 1029–1040
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Genetic small-vessel disease mouse model and lipid rescue · source_derived_draft · unverified_draft
### ino-kir-flow-rescue Soluble PIP2 administration restored Kir2.1-dependent neurovascular responses in the studied mouse model. Condition category: machinery_impairment nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: Replacing the deficient lipid signal restored a blood-flow response in these mice. organism: Mus musculus tissue_or_cell_type: Brain capillary endothelium and cerebral circulation experimental_model: Genetic small-vessel disease mouse model and lipid rescue limitations: Mouse disease model; not evidence that oral inositol treats human cerebrovascular disease. exposure: PIP2 depletion and soluble PIP2 administration evidence_span: {"source_cache": "artifacts/inositol-research/33875602.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "139eeba386e63329898f8e36ebe93ad741eed904819bbebe7fc2b1808130a19d", "start_char": 0, "end_char": 1108, "text_sha256": "139eeba386e63329898f8e36ebe93ad741eed904819bbebe7fc2b1808130a19d"} [ino-p33875602] PIP2 corrects cerebral blood flow deficits in small vessel disease by rescuing capillary Kir2.1 activity. (2021). https://pubmed.ncbi.nlm.nih.gov/33875602/ DOI: 10.1073/pnas.2025998118
Complete structured claim and evidence
Rat arterial SMIT1 associated with Kv7.4/Kv7.5 channels in the reported interaction experiments.
Rat Slc5a3 (SMIT1) → Rat Kv7.4/Kv7.5 channel complex source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/32787517.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5581d37bc8ebfa221d5d351a107a7fa9a76a8b1e7476599e469648779622b3c3", "start_char": 0, "end_char": 1875, "text_sha256": "5581d37bc8ebfa221d5d351a107a7fa9a76a8b1e7476599e469648779622b3c3"}
experimental_model
Arterial physiology, protein interactions and knockdown
exposure
SMIT1 manipulation, myo-inositol/raffinose and Kv7 blockade
limitations
Rat ex vivo arteries; not proof of a blood-pressure benefit from human inositol supplements.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Rattus norvegicus
plain_language
An inositol transporter can physically interact with a potassium-channel complex.
primary_references
[ino-p32787517] SMIT (Sodium-Myo-Inositol Transporter) 1 Regulates Arterial Contractility Through the Modulation of Vascular Kv7 Channels. (2020). https://pubmed.ncbi.nlm.nih.gov/32787517/ DOI: 10.1161/atvbaha.120.315096
tissue_or_cell_type
Renal and mesenteric arteries
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 1042–1053
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Arterial physiology, protein interactions and knockdown · source_derived_draft · unverified_draft
### ino-smit1-kv7 Rat arterial SMIT1 associated with Kv7.4/Kv7.5 channels in the reported interaction experiments. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: An inositol transporter can physically interact with a potassium-channel complex. organism: Rattus norvegicus tissue_or_cell_type: Renal and mesenteric arteries experimental_model: Arterial physiology, protein interactions and knockdown limitations: Rat ex vivo arteries; not proof of a blood-pressure benefit from human inositol supplements. exposure: SMIT1 manipulation, myo-inositol/raffinose and Kv7 blockade evidence_span: {"source_cache": "artifacts/inositol-research/32787517.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5581d37bc8ebfa221d5d351a107a7fa9a76a8b1e7476599e469648779622b3c3", "start_char": 0, "end_char": 1875, "text_sha256": "5581d37bc8ebfa221d5d351a107a7fa9a76a8b1e7476599e469648779622b3c3"} [ino-p32787517] SMIT (Sodium-Myo-Inositol Transporter) 1 Regulates Arterial Contractility Through the Modulation of Vascular Kv7 Channels. (2020). https://pubmed.ncbi.nlm.nih.gov/32787517/ DOI: 10.1161/atvbaha.120.315096
Complete structured claim and evidence
Myo-inositol plus raffinose reduced methoxamine-induced contraction in rat arteries; Kv7 inhibition or knockdown prevented the effect.
Myo-inositol → Arterial smooth-muscle contraction source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/32787517.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5581d37bc8ebfa221d5d351a107a7fa9a76a8b1e7476599e469648779622b3c3", "start_char": 0, "end_char": 1875, "text_sha256": "5581d37bc8ebfa221d5d351a107a7fa9a76a8b1e7476599e469648779622b3c3"}
experimental_model
Arterial physiology, protein interactions and knockdown
exposure
SMIT1 manipulation, myo-inositol/raffinose and Kv7 blockade
limitations
Rat ex vivo arteries; not proof of a blood-pressure benefit from human inositol supplements.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Rattus norvegicus
plain_language
A combined experimental exposure changed contraction through a potassium-channel-dependent route.
primary_references
[ino-p32787517] SMIT (Sodium-Myo-Inositol Transporter) 1 Regulates Arterial Contractility Through the Modulation of Vascular Kv7 Channels. (2020). https://pubmed.ncbi.nlm.nih.gov/32787517/ DOI: 10.1161/atvbaha.120.315096
tissue_or_cell_type
Renal and mesenteric arteries
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 1055–1066
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Arterial physiology, protein interactions and knockdown · source_derived_draft · unverified_draft
### ino-smit1-artery Myo-inositol plus raffinose reduced methoxamine-induced contraction in rat arteries; Kv7 inhibition or knockdown prevented the effect. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: A combined experimental exposure changed contraction through a potassium-channel-dependent route. organism: Rattus norvegicus tissue_or_cell_type: Renal and mesenteric arteries experimental_model: Arterial physiology, protein interactions and knockdown limitations: Rat ex vivo arteries; not proof of a blood-pressure benefit from human inositol supplements. exposure: SMIT1 manipulation, myo-inositol/raffinose and Kv7 blockade evidence_span: {"source_cache": "artifacts/inositol-research/32787517.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5581d37bc8ebfa221d5d351a107a7fa9a76a8b1e7476599e469648779622b3c3", "start_char": 0, "end_char": 1875, "text_sha256": "5581d37bc8ebfa221d5d351a107a7fa9a76a8b1e7476599e469648779622b3c3"} [ino-p32787517] SMIT (Sodium-Myo-Inositol Transporter) 1 Regulates Arterial Contractility Through the Modulation of Vascular Kv7 Channels. (2020). https://pubmed.ncbi.nlm.nih.gov/32787517/ DOI: 10.1161/atvbaha.120.315096
Complete structured claim and evidence
Low-selenium culture conditions were associated with defective IP3R palmitoylation and reduced receptor expression in the SELENOK study.
Selenium → IP3 receptor palmitoylation source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/inositol-research/25368151.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "84452ee9a1f04bf54aba8030e5384d46a1dafdbb460281fd99c244e57d6644d9", "start_char": 0, "end_char": 1873, "text_sha256": "84452ee9a1f04bf54aba8030e5384d46a1dafdbb460281fd99c244e57d6644d9"}
experimental_model
Immune-cell perturbation, co-immunoprecipitation and palmitoylation assays
exposure
Selk deletion, low-selenium media, DHHC6 knockdown and IP3R cysteine mutants
limitations
Selenium limitation and genetic deletion are distinct. This does not establish that inositol supplements repair selenium-dependent receptor failure.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Mouse immune cells and mammalian cell models
plain_language
The cell may still make the message but lose a properly maintained receptor.
primary_references
[ino-p25368151] Stable expression and function of the inositol 1,4,5-triphosphate receptor requires palmitoylation by a DHHC6/selenoprotein K complex. (2014). https://pubmed.ncbi.nlm.nih.gov/25368151/ DOI: 10.1073/pnas.1417176111
tissue_or_cell_type
ER-associated IP3 receptor machinery
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 1068–1079
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Immune-cell perturbation, co-immunoprecipitation and palmitoylation assays · source_derived_draft · unverified_draft
### ino-selenium-receptor Low-selenium culture conditions were associated with defective IP3R palmitoylation and reduced receptor expression in the SELENOK study. Condition category: nutrient_deficiency nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: The cell may still make the message but lose a properly maintained receptor. organism: Mouse immune cells and mammalian cell models tissue_or_cell_type: ER-associated IP3 receptor machinery experimental_model: Immune-cell perturbation, co-immunoprecipitation and palmitoylation assays limitations: Selenium limitation and genetic deletion are distinct. This does not establish that inositol supplements repair selenium-dependent receptor failure. exposure: Selk deletion, low-selenium media, DHHC6 knockdown and IP3R cysteine mutants evidence_span: {"source_cache": "artifacts/inositol-research/25368151.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "84452ee9a1f04bf54aba8030e5384d46a1dafdbb460281fd99c244e57d6644d9", "start_char": 0, "end_char": 1873, "text_sha256": "84452ee9a1f04bf54aba8030e5384d46a1dafdbb460281fd99c244e57d6644d9"} [ino-p25368151] Stable expression and function of the inositol 1,4,5-triphosphate receptor requires palmitoylation by a DHHC6/selenoprotein K complex. (2014). https://pubmed.ncbi.nlm.nih.gov/25368151/ DOI: 10.1073/pnas.1417176111
Complete structured claim and evidence
SELENOK deficiency did not impair receptor-induced IP3 production in the reported experiments.
SELENOK → Receptor-evoked IP3 production source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/inositol-research/25368151.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "84452ee9a1f04bf54aba8030e5384d46a1dafdbb460281fd99c244e57d6644d9", "start_char": 0, "end_char": 1873, "text_sha256": "84452ee9a1f04bf54aba8030e5384d46a1dafdbb460281fd99c244e57d6644d9"}
experimental_model
Immune-cell perturbation, co-immunoprecipitation and palmitoylation assays
exposure
Selk deletion, low-selenium media, DHHC6 knockdown and IP3R cysteine mutants
limitations
Selenium limitation and genetic deletion are distinct. This does not establish that inositol supplements repair selenium-dependent receptor failure.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Mouse immune cells and mammalian cell models
plain_language
Failure downstream of IP3 does not automatically mean too little inositol or too little IP3.
primary_references
[ino-p25368151] Stable expression and function of the inositol 1,4,5-triphosphate receptor requires palmitoylation by a DHHC6/selenoprotein K complex. (2014). https://pubmed.ncbi.nlm.nih.gov/25368151/ DOI: 10.1073/pnas.1417176111
tissue_or_cell_type
ER-associated IP3 receptor machinery
trigger_kind
machinery_impairment Imported condition classification; unverified.
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 1081–1092
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Immune-cell perturbation, co-immunoprecipitation and palmitoylation assays · source_derived_draft · unverified_draft
### ino-selk-message-intact SELENOK deficiency did not impair receptor-induced IP3 production in the reported experiments. Condition category: machinery_impairment nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: Failure downstream of IP3 does not automatically mean too little inositol or too little IP3. organism: Mouse immune cells and mammalian cell models tissue_or_cell_type: ER-associated IP3 receptor machinery experimental_model: Immune-cell perturbation, co-immunoprecipitation and palmitoylation assays limitations: Selenium limitation and genetic deletion are distinct. This does not establish that inositol supplements repair selenium-dependent receptor failure. exposure: Selk deletion, low-selenium media, DHHC6 knockdown and IP3R cysteine mutants evidence_span: {"source_cache": "artifacts/inositol-research/25368151.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "84452ee9a1f04bf54aba8030e5384d46a1dafdbb460281fd99c244e57d6644d9", "start_char": 0, "end_char": 1873, "text_sha256": "84452ee9a1f04bf54aba8030e5384d46a1dafdbb460281fd99c244e57d6644d9"} [ino-p25368151] Stable expression and function of the inositol 1,4,5-triphosphate receptor requires palmitoylation by a DHHC6/selenoprotein K complex. (2014). https://pubmed.ncbi.nlm.nih.gov/25368151/ DOI: 10.1073/pnas.1417176111
Complete structured claim and evidence
SELENOK and DHHC6 interacted at the ER membrane through SH3-related binding interactions.
SELENOK → ZDHHC6 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/25368151.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "84452ee9a1f04bf54aba8030e5384d46a1dafdbb460281fd99c244e57d6644d9", "start_char": 0, "end_char": 1873, "text_sha256": "84452ee9a1f04bf54aba8030e5384d46a1dafdbb460281fd99c244e57d6644d9"}
experimental_model
Immune-cell perturbation, co-immunoprecipitation and palmitoylation assays
exposure
Selk deletion, low-selenium media, DHHC6 knockdown and IP3R cysteine mutants
limitations
Selenium limitation and genetic deletion are distinct. This does not establish that inositol supplements repair selenium-dependent receptor failure.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Mouse immune cells and mammalian cell models
plain_language
Two separately identifiable proteins cooperate in maintaining the receptor.
primary_references
[ino-p25368151] Stable expression and function of the inositol 1,4,5-triphosphate receptor requires palmitoylation by a DHHC6/selenoprotein K complex. (2014). https://pubmed.ncbi.nlm.nih.gov/25368151/ DOI: 10.1073/pnas.1417176111
tissue_or_cell_type
ER-associated IP3 receptor machinery
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 1094–1105
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Immune-cell perturbation, co-immunoprecipitation and palmitoylation assays · source_derived_draft · unverified_draft
### ino-selk-dhhc6 SELENOK and DHHC6 interacted at the ER membrane through SH3-related binding interactions. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: Two separately identifiable proteins cooperate in maintaining the receptor. organism: Mouse immune cells and mammalian cell models tissue_or_cell_type: ER-associated IP3 receptor machinery experimental_model: Immune-cell perturbation, co-immunoprecipitation and palmitoylation assays limitations: Selenium limitation and genetic deletion are distinct. This does not establish that inositol supplements repair selenium-dependent receptor failure. exposure: Selk deletion, low-selenium media, DHHC6 knockdown and IP3R cysteine mutants evidence_span: {"source_cache": "artifacts/inositol-research/25368151.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "84452ee9a1f04bf54aba8030e5384d46a1dafdbb460281fd99c244e57d6644d9", "start_char": 0, "end_char": 1873, "text_sha256": "84452ee9a1f04bf54aba8030e5384d46a1dafdbb460281fd99c244e57d6644d9"} [ino-p25368151] Stable expression and function of the inositol 1,4,5-triphosphate receptor requires palmitoylation by a DHHC6/selenoprotein K complex. (2014). https://pubmed.ncbi.nlm.nih.gov/25368151/ DOI: 10.1073/pnas.1417176111
Complete structured claim and evidence
DHHC6 knockdown reduced IP3R expression and IP3R-dependent calcium flux.
ZDHHC6 → IP3 receptor-dependent calcium release source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/inositol-research/25368151.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "84452ee9a1f04bf54aba8030e5384d46a1dafdbb460281fd99c244e57d6644d9", "start_char": 0, "end_char": 1873, "text_sha256": "84452ee9a1f04bf54aba8030e5384d46a1dafdbb460281fd99c244e57d6644d9"}
experimental_model
Immune-cell perturbation, co-immunoprecipitation and palmitoylation assays
exposure
Selk deletion, low-selenium media, DHHC6 knockdown and IP3R cysteine mutants
limitations
Selenium limitation and genetic deletion are distinct. This does not establish that inositol supplements repair selenium-dependent receptor failure.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Mouse immune cells and mammalian cell models
plain_language
Impairing the modification enzyme weakened the calcium-release response.
primary_references
[ino-p25368151] Stable expression and function of the inositol 1,4,5-triphosphate receptor requires palmitoylation by a DHHC6/selenoprotein K complex. (2014). https://pubmed.ncbi.nlm.nih.gov/25368151/ DOI: 10.1073/pnas.1417176111
tissue_or_cell_type
ER-associated IP3 receptor machinery
trigger_kind
machinery_impairment Imported condition classification; unverified.
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 1107–1118
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Immune-cell perturbation, co-immunoprecipitation and palmitoylation assays · source_derived_draft · unverified_draft
### ino-dhhc6-flux DHHC6 knockdown reduced IP3R expression and IP3R-dependent calcium flux. Condition category: machinery_impairment nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: Impairing the modification enzyme weakened the calcium-release response. organism: Mouse immune cells and mammalian cell models tissue_or_cell_type: ER-associated IP3 receptor machinery experimental_model: Immune-cell perturbation, co-immunoprecipitation and palmitoylation assays limitations: Selenium limitation and genetic deletion are distinct. This does not establish that inositol supplements repair selenium-dependent receptor failure. exposure: Selk deletion, low-selenium media, DHHC6 knockdown and IP3R cysteine mutants evidence_span: {"source_cache": "artifacts/inositol-research/25368151.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "84452ee9a1f04bf54aba8030e5384d46a1dafdbb460281fd99c244e57d6644d9", "start_char": 0, "end_char": 1873, "text_sha256": "84452ee9a1f04bf54aba8030e5384d46a1dafdbb460281fd99c244e57d6644d9"} [ino-p25368151] Stable expression and function of the inositol 1,4,5-triphosphate receptor requires palmitoylation by a DHHC6/selenoprotein K complex. (2014). https://pubmed.ncbi.nlm.nih.gov/25368151/ DOI: 10.1073/pnas.1417176111
Complete structured claim and evidence
GPI N-acetylglucosaminyltransferase initiates anchor biosynthesis by transferring GlcNAc from UDP-GlcNAc to PI.
Human GPI N-acetylglucosaminyltransferase complex → N-acetylglucosaminyl-phosphatidylinositol (GlcNAc-PI) source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/40378954.fulltext.txt", "locator": "Exact primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3cc2c3ec38a92b3f125ade893ea74380cd41dab129c560dcca339f6f9dae1ed8", "start_char": 602, "end_char": 1102, "text_sha256": "efb80e58245431f0e571ea2fbf380914ac09fe0c07c148fd9a062f5e744166e4"}
experimental_model
Human-cell gene perturbation and isolated-complex activity
exposure
ARV1/PIGQ association and PI utilization
limitations
The ring-shaped assembly was AlphaFold-predicted, not an experimentally resolved structure. Effects on GPI-anchored proteins varied by cell and protein.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Homo sapiens
plain_language
Inositol-containing membrane lipid is a starting material for anchors that hold proteins at the cell surface.
primary_references
[ino-p40378954] ARV1 is a component of the enzyme initiating glycosylphosphatidylinositol biosynthesis. (2025). https://pubmed.ncbi.nlm.nih.gov/40378954/ DOI: 10.1016/j.jbc.2025.110236
tissue_or_cell_type
Fibroblasts, HEK293 cells and ER enzyme complex
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 1120–1131
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human-cell gene perturbation and isolated-complex activity · source_derived_draft · unverified_draft
### ino-gpi-initiation GPI N-acetylglucosaminyltransferase initiates anchor biosynthesis by transferring GlcNAc from UDP-GlcNAc to PI. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: Inositol-containing membrane lipid is a starting material for anchors that hold proteins at the cell surface. organism: Homo sapiens tissue_or_cell_type: Fibroblasts, HEK293 cells and ER enzyme complex experimental_model: Human-cell gene perturbation and isolated-complex activity limitations: The ring-shaped assembly was AlphaFold-predicted, not an experimentally resolved structure. Effects on GPI-anchored proteins varied by cell and protein. exposure: ARV1/PIGQ association and PI utilization evidence_span: {"source_cache": "artifacts/inositol-research/40378954.fulltext.txt", "locator": "Exact primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3cc2c3ec38a92b3f125ade893ea74380cd41dab129c560dcca339f6f9dae1ed8", "start_char": 602, "end_char": 1102, "text_sha256": "efb80e58245431f0e571ea2fbf380914ac09fe0c07c148fd9a062f5e744166e4"} [ino-p40378954] ARV1 is a component of the enzyme initiating glycosylphosphatidylinositol biosynthesis. (2025). https://pubmed.ncbi.nlm.nih.gov/40378954/ DOI: 10.1016/j.jbc.2025.110236
Complete structured claim and evidence
Human ARV1 associated with PIGQ; disrupting that association removed ARV1-mediated enhancement of GPI-GnT activity.
ARV1 (human ER membrane protein) → PIGQ (human GPI biosynthesis subunit) source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/40378954.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "858f4bd2342d09239e21945d3d83aab06d84f33da26cb788e3ac091b713a1917", "start_char": 0, "end_char": 1260, "text_sha256": "858f4bd2342d09239e21945d3d83aab06d84f33da26cb788e3ac091b713a1917"}
experimental_model
Human-cell gene perturbation and isolated-complex activity
exposure
ARV1/PIGQ association and PI utilization
limitations
The ring-shaped assembly was AlphaFold-predicted, not an experimentally resolved structure. Effects on GPI-anchored proteins varied by cell and protein.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Homo sapiens
plain_language
A partner protein helps the anchor-building enzyme work efficiently.
primary_references
[ino-p40378954] ARV1 is a component of the enzyme initiating glycosylphosphatidylinositol biosynthesis. (2025). https://pubmed.ncbi.nlm.nih.gov/40378954/ DOI: 10.1016/j.jbc.2025.110236
tissue_or_cell_type
Fibroblasts, HEK293 cells and ER enzyme complex
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 1133–1144
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human-cell gene perturbation and isolated-complex activity · source_derived_draft · unverified_draft
### ino-arv1-pigq Human ARV1 associated with PIGQ; disrupting that association removed ARV1-mediated enhancement of GPI-GnT activity. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: A partner protein helps the anchor-building enzyme work efficiently. organism: Homo sapiens tissue_or_cell_type: Fibroblasts, HEK293 cells and ER enzyme complex experimental_model: Human-cell gene perturbation and isolated-complex activity limitations: The ring-shaped assembly was AlphaFold-predicted, not an experimentally resolved structure. Effects on GPI-anchored proteins varied by cell and protein. exposure: ARV1/PIGQ association and PI utilization evidence_span: {"source_cache": "artifacts/inositol-research/40378954.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "858f4bd2342d09239e21945d3d83aab06d84f33da26cb788e3ac091b713a1917", "start_char": 0, "end_char": 1260, "text_sha256": "858f4bd2342d09239e21945d3d83aab06d84f33da26cb788e3ac091b713a1917"} [ino-p40378954] ARV1 is a component of the enzyme initiating glycosylphosphatidylinositol biosynthesis. (2025). https://pubmed.ncbi.nlm.nih.gov/40378954/ DOI: 10.1016/j.jbc.2025.110236
Complete structured claim and evidence
ARV1-containing GPI-GnT used PI more efficiently than the ARV1-less complex in vitro.
ARV1 (human ER membrane protein) → Human GPI N-acetylglucosaminyltransferase complex source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/40378954.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "858f4bd2342d09239e21945d3d83aab06d84f33da26cb788e3ac091b713a1917", "start_char": 0, "end_char": 1260, "text_sha256": "858f4bd2342d09239e21945d3d83aab06d84f33da26cb788e3ac091b713a1917"}
experimental_model
Human-cell gene perturbation and isolated-complex activity
exposure
ARV1/PIGQ association and PI utilization
limitations
The ring-shaped assembly was AlphaFold-predicted, not an experimentally resolved structure. Effects on GPI-anchored proteins varied by cell and protein.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Homo sapiens
plain_language
The anchor pathway depends on substrate handling, not only the total amount of inositol.
primary_references
[ino-p40378954] ARV1 is a component of the enzyme initiating glycosylphosphatidylinositol biosynthesis. (2025). https://pubmed.ncbi.nlm.nih.gov/40378954/ DOI: 10.1016/j.jbc.2025.110236
tissue_or_cell_type
Fibroblasts, HEK293 cells and ER enzyme complex
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 1146–1157
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human-cell gene perturbation and isolated-complex activity · source_derived_draft · unverified_draft
### ino-arv1-pi ARV1-containing GPI-GnT used PI more efficiently than the ARV1-less complex in vitro. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: The anchor pathway depends on substrate handling, not only the total amount of inositol. organism: Homo sapiens tissue_or_cell_type: Fibroblasts, HEK293 cells and ER enzyme complex experimental_model: Human-cell gene perturbation and isolated-complex activity limitations: The ring-shaped assembly was AlphaFold-predicted, not an experimentally resolved structure. Effects on GPI-anchored proteins varied by cell and protein. exposure: ARV1/PIGQ association and PI utilization evidence_span: {"source_cache": "artifacts/inositol-research/40378954.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "858f4bd2342d09239e21945d3d83aab06d84f33da26cb788e3ac091b713a1917", "start_char": 0, "end_char": 1260, "text_sha256": "858f4bd2342d09239e21945d3d83aab06d84f33da26cb788e3ac091b713a1917"} [ino-p40378954] ARV1 is a component of the enzyme initiating glycosylphosphatidylinositol biosynthesis. (2025). https://pubmed.ncbi.nlm.nih.gov/40378954/ DOI: 10.1016/j.jbc.2025.110236
Complete structured claim and evidence
Adding sodium phytate to otherwise phytate-free wheat rolls inhibited iron absorption in a dose-dependent manner.
Phytic acid / phytate → Nonheme iron absorption source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/2911999.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a5b0473a7a412eec5479259c7214b462fa6cfcc5948a6dae68db636de4e76f24", "start_char": 0, "end_char": 943, "text_sha256": "a5b0473a7a412eec5479259c7214b462fa6cfcc5948a6dae68db636de4e76f24"}
experimental_model
Paired radioisotope meal-absorption study
exposure
Wheat rolls with increasing sodium phytate
limitations
Luminal phytate/InsP6 exposure is distinct from free myo-inositol and intracellular InsP6 signaling.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Homo sapiens
plain_language
The six-phosphate form in food can reduce absorption of iron from that meal.
primary_references
[ino-p2911999] Iron absorption in man: ascorbic acid and dose-dependent inhibition by phytate. (1989). https://pubmed.ncbi.nlm.nih.gov/2911999/ DOI: 10.1093/ajcn/49.1.140
tissue_or_cell_type
Intestinal iron absorption
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 1159–1170
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Paired radioisotope meal-absorption study · source_derived_draft · unverified_draft
### ino-phytate-iron Adding sodium phytate to otherwise phytate-free wheat rolls inhibited iron absorption in a dose-dependent manner. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: The six-phosphate form in food can reduce absorption of iron from that meal. organism: Homo sapiens tissue_or_cell_type: Intestinal iron absorption experimental_model: Paired radioisotope meal-absorption study limitations: Luminal phytate/InsP6 exposure is distinct from free myo-inositol and intracellular InsP6 signaling. exposure: Wheat rolls with increasing sodium phytate evidence_span: {"source_cache": "artifacts/inositol-research/2911999.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a5b0473a7a412eec5479259c7214b462fa6cfcc5948a6dae68db636de4e76f24", "start_char": 0, "end_char": 943, "text_sha256": "a5b0473a7a412eec5479259c7214b462fa6cfcc5948a6dae68db636de4e76f24"} [ino-p2911999] Iron absorption in man: ascorbic acid and dose-dependent inhibition by phytate. (1989). https://pubmed.ncbi.nlm.nih.gov/2911999/ DOI: 10.1093/ajcn/49.1.140
Complete structured claim and evidence
Rat liver cytosol contained activity converting myo-inositol to D-chiro-inositol.
Myo-to-D-chiro-inositol epimerase activity in rat cytosol → Myo-inositol source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/12051772.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "28ae1225b489898738997d2376ab09857f017314086979032d3ad907299a1154", "start_char": 0, "end_char": 2218, "text_sha256": "28ae1225b489898738997d2376ab09857f017314086979032d3ad907299a1154"}
experimental_model
Radiotracer conversion and cytosolic enzyme assays
exposure
Diabetic rat versus controls; reduced pyridine-nucleotide cofactors
limitations
The molecular identity of the activity was not established here. A later mouse stable-isotope study found no myo-to-D-chiro conversion; the research disagreement is recorded separately. Do not invent a human epimerase gene or infer a universal supplement ratio.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Goto-Kakizaki and Wistar rats
plain_language
One stereoisomer can be converted into another in this rat tissue preparation.
primary_references
[ino-p12051772] Both myo-inositol to chiro-inositol epimerase activities and chiro-inositol to myo-inositol ratios are decreased in tissues of GK type 2 diabetic rats compared to Wistar controls. (2002). https://pubmed.ncbi.nlm.nih.gov/12051772/ DOI: 10.1016/s0006-291x(02)00313-3
tissue_or_cell_type
Liver, muscle, kidney and adipose preparations
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 1172–1183
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Radiotracer conversion and cytosolic enzyme assays · source_derived_draft · unverified_draft
### ino-rat-epimerase Rat liver cytosol contained activity converting myo-inositol to D-chiro-inositol. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: One stereoisomer can be converted into another in this rat tissue preparation. organism: Goto-Kakizaki and Wistar rats tissue_or_cell_type: Liver, muscle, kidney and adipose preparations experimental_model: Radiotracer conversion and cytosolic enzyme assays limitations: The molecular identity of the activity was not established here. A later mouse stable-isotope study found no myo-to-D-chiro conversion; the research disagreement is recorded separately. Do not invent a human epimerase gene or infer a universal supplement ratio. exposure: Diabetic rat versus controls; reduced pyridine-nucleotide cofactors evidence_span: {"source_cache": "artifacts/inositol-research/12051772.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "28ae1225b489898738997d2376ab09857f017314086979032d3ad907299a1154", "start_char": 0, "end_char": 2218, "text_sha256": "28ae1225b489898738997d2376ab09857f017314086979032d3ad907299a1154"} [ino-p12051772] Both myo-inositol to chiro-inositol epimerase activities and chiro-inositol to myo-inositol ratios are decreased in tissues of GK type 2 diabetic rats compared to Wistar controls. (2002). https://pubmed.ncbi.nlm.nih.gov/12051772/ DOI: 10.1016/s0006-291x(02)00313-3
Complete structured claim and evidence
The rat cytosolic epimerase assay required NADH and NADPH for full activity.
NADH → Myo-to-D-chiro-inositol epimerase activity in rat cytosol source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/12051772.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "28ae1225b489898738997d2376ab09857f017314086979032d3ad907299a1154", "start_char": 0, "end_char": 2218, "text_sha256": "28ae1225b489898738997d2376ab09857f017314086979032d3ad907299a1154"}
experimental_model
Radiotracer conversion and cytosolic enzyme assays
exposure
Diabetic rat versus controls; reduced pyridine-nucleotide cofactors
limitations
The molecular identity of the activity was not established here. A later mouse stable-isotope study found no myo-to-D-chiro conversion; the research disagreement is recorded separately. Do not invent a human epimerase gene or infer a universal supplement ratio.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Goto-Kakizaki and Wistar rats
plain_language
Reduced niacin-derived cofactors supported the observed conversion.
primary_references
[ino-p12051772] Both myo-inositol to chiro-inositol epimerase activities and chiro-inositol to myo-inositol ratios are decreased in tissues of GK type 2 diabetic rats compared to Wistar controls. (2002). https://pubmed.ncbi.nlm.nih.gov/12051772/ DOI: 10.1016/s0006-291x(02)00313-3
tissue_or_cell_type
Liver, muscle, kidney and adipose preparations
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 1185–1196
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Radiotracer conversion and cytosolic enzyme assays · source_derived_draft · unverified_draft
### ino-epimerase-nadh The rat cytosolic epimerase assay required NADH and NADPH for full activity. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: Reduced niacin-derived cofactors supported the observed conversion. organism: Goto-Kakizaki and Wistar rats tissue_or_cell_type: Liver, muscle, kidney and adipose preparations experimental_model: Radiotracer conversion and cytosolic enzyme assays limitations: The molecular identity of the activity was not established here. A later mouse stable-isotope study found no myo-to-D-chiro conversion; the research disagreement is recorded separately. Do not invent a human epimerase gene or infer a universal supplement ratio. exposure: Diabetic rat versus controls; reduced pyridine-nucleotide cofactors evidence_span: {"source_cache": "artifacts/inositol-research/12051772.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "28ae1225b489898738997d2376ab09857f017314086979032d3ad907299a1154", "start_char": 0, "end_char": 2218, "text_sha256": "28ae1225b489898738997d2376ab09857f017314086979032d3ad907299a1154"} [ino-p12051772] Both myo-inositol to chiro-inositol epimerase activities and chiro-inositol to myo-inositol ratios are decreased in tissues of GK type 2 diabetic rats compared to Wistar controls. (2002). https://pubmed.ncbi.nlm.nih.gov/12051772/ DOI: 10.1016/s0006-291x(02)00313-3
Complete structured claim and evidence
Myo-to-chiro epimerase activity was lower in liver, muscle and fat cytosol from diabetic GK rats than Wistar controls.
Myo-to-D-chiro-inositol epimerase activity in rat cytosol → Diabetic state in Goto-Kakizaki rats source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/12051772.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "28ae1225b489898738997d2376ab09857f017314086979032d3ad907299a1154", "start_char": 0, "end_char": 2218, "text_sha256": "28ae1225b489898738997d2376ab09857f017314086979032d3ad907299a1154"}
experimental_model
Radiotracer conversion and cytosolic enzyme assays
exposure
Diabetic rat versus controls; reduced pyridine-nucleotide cofactors
limitations
The molecular identity of the activity was not established here. A later mouse stable-isotope study found no myo-to-D-chiro conversion; the research disagreement is recorded separately. Do not invent a human epimerase gene or infer a universal supplement ratio.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Goto-Kakizaki and Wistar rats
plain_language
Reduced conversion accompanied insulin resistance in these rat tissues; causation was not settled.
primary_references
[ino-p12051772] Both myo-inositol to chiro-inositol epimerase activities and chiro-inositol to myo-inositol ratios are decreased in tissues of GK type 2 diabetic rats compared to Wistar controls. (2002). https://pubmed.ncbi.nlm.nih.gov/12051772/ DOI: 10.1016/s0006-291x(02)00313-3
tissue_or_cell_type
Liver, muscle, kidney and adipose preparations
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 1198–1209
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Radiotracer conversion and cytosolic enzyme assays · source_derived_draft · unverified_draft
### ino-rat-epimerase-low Myo-to-chiro epimerase activity was lower in liver, muscle and fat cytosol from diabetic GK rats than Wistar controls. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: Reduced conversion accompanied insulin resistance in these rat tissues; causation was not settled. organism: Goto-Kakizaki and Wistar rats tissue_or_cell_type: Liver, muscle, kidney and adipose preparations experimental_model: Radiotracer conversion and cytosolic enzyme assays limitations: The molecular identity of the activity was not established here. A later mouse stable-isotope study found no myo-to-D-chiro conversion; the research disagreement is recorded separately. Do not invent a human epimerase gene or infer a universal supplement ratio. exposure: Diabetic rat versus controls; reduced pyridine-nucleotide cofactors evidence_span: {"source_cache": "artifacts/inositol-research/12051772.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "28ae1225b489898738997d2376ab09857f017314086979032d3ad907299a1154", "start_char": 0, "end_char": 2218, "text_sha256": "28ae1225b489898738997d2376ab09857f017314086979032d3ad907299a1154"} [ino-p12051772] Both myo-inositol to chiro-inositol epimerase activities and chiro-inositol to myo-inositol ratios are decreased in tissues of GK type 2 diabetic rats compared to Wistar controls. (2002). https://pubmed.ncbi.nlm.nih.gov/12051772/ DOI: 10.1016/s0006-291x(02)00313-3
Complete structured claim and evidence
PCOS theca cells had increased epimerase activity and a lower myo-inositol:D-chiro-inositol ratio than control theca cells.
Myo-to-D-chiro-inositol epimerase activity in human theca cells → Tissue myo-inositol:D-chiro-inositol ratio source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/24189751.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "908458aee805858d7e4d050e42256d81a0010564d86afe89d6a04656e856f219", "start_char": 0, "end_char": 1243, "text_sha256": "908458aee805858d7e4d050e42256d81a0010564d86afe89d6a04656e856f219"}
experimental_model
Cultured human ovarian theca-cell comparison
exposure
PCOS versus control-derived cells
limitations
Opposite direction to insulin-resistant peripheral tissues is tissue/context dependence, not a universal contradiction or proof of an optimal supplement ratio.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Homo sapiens
plain_language
The ovarian cell pattern differed from insulin-resistant peripheral tissues.
primary_references
[ino-p24189751] Decreased myo-inositol to chiro-inositol (M/C) ratios and increased M/C epimerase activity in PCOS theca cells demonstrate increased insulin sensitivity compared to controls. (2014). https://pubmed.ncbi.nlm.nih.gov/24189751/ DOI: 10.1507/endocrj.ej13-0423
tissue_or_cell_type
Ovarian theca cells
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 1211–1222
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cultured human ovarian theca-cell comparison · source_derived_draft · unverified_draft
### ino-theca-epimerase PCOS theca cells had increased epimerase activity and a lower myo-inositol:D-chiro-inositol ratio than control theca cells. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: The ovarian cell pattern differed from insulin-resistant peripheral tissues. organism: Homo sapiens tissue_or_cell_type: Ovarian theca cells experimental_model: Cultured human ovarian theca-cell comparison limitations: Opposite direction to insulin-resistant peripheral tissues is tissue/context dependence, not a universal contradiction or proof of an optimal supplement ratio. exposure: PCOS versus control-derived cells evidence_span: {"source_cache": "artifacts/inositol-research/24189751.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "908458aee805858d7e4d050e42256d81a0010564d86afe89d6a04656e856f219", "start_char": 0, "end_char": 1243, "text_sha256": "908458aee805858d7e4d050e42256d81a0010564d86afe89d6a04656e856f219"} [ino-p24189751] Decreased myo-inositol to chiro-inositol (M/C) ratios and increased M/C epimerase activity in PCOS theca cells demonstrate increased insulin sensitivity compared to controls. (2014). https://pubmed.ncbi.nlm.nih.gov/24189751/ DOI: 10.1507/endocrj.ej13-0423
Complete structured claim and evidence
In the mouse tracer experiments, labeled D-chiro-inositol was not detected after heavy-water exposure or deuterated myo-inositol administration.
Myo-inositol → D-chiro-inositol source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/19586572.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7c6e57e631fef5921afd04f75718024d5b14ca525460e2c96275a4fc320c3b26", "start_char": 0, "end_char": 1544, "text_sha256": "7c6e57e631fef5921afd04f75718024d5b14ca525460e2c96275a4fc320c3b26"}
experimental_model
Dietary balance, GC-MS and stable-isotope tracing
exposure
Defined diets, heavy water and deuterated myo-inositol/DCI
limitations
Failure to detect conversion in mice does not exclude all human or isolated-tissue activity. Isotope strategy, chemical identification, species and dietary DCI contamination may contribute to disagreement with earlier radiotracer reports.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Rats and mice; conversion tracing in mice
plain_language
This study did not reproduce the proposed endogenous conversion route in its mouse experiments.
primary_references
[ino-p19586572] d- chiro-Inositol is absorbed but not synthesised in rodents. (2009). https://pubmed.ncbi.nlm.nih.gov/19586572/ DOI: 10.1017/s0007114509990456
tissue_or_cell_type
Gastrointestinal absorption, plasma and excreta
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 1224–1235
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Dietary balance, GC-MS and stable-isotope tracing · source_derived_draft · unverified_draft
### ino-dci-no-conversion In the mouse tracer experiments, labeled D-chiro-inositol was not detected after heavy-water exposure or deuterated myo-inositol administration. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: This study did not reproduce the proposed endogenous conversion route in its mouse experiments. organism: Rats and mice; conversion tracing in mice tissue_or_cell_type: Gastrointestinal absorption, plasma and excreta experimental_model: Dietary balance, GC-MS and stable-isotope tracing limitations: Failure to detect conversion in mice does not exclude all human or isolated-tissue activity. Isotope strategy, chemical identification, species and dietary DCI contamination may contribute to disagreement with earlier radiotracer reports. exposure: Defined diets, heavy water and deuterated myo-inositol/DCI evidence_span: {"source_cache": "artifacts/inositol-research/19586572.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7c6e57e631fef5921afd04f75718024d5b14ca525460e2c96275a4fc320c3b26", "start_char": 0, "end_char": 1544, "text_sha256": "7c6e57e631fef5921afd04f75718024d5b14ca525460e2c96275a4fc320c3b26"} [ino-p19586572] d- chiro-Inositol is absorbed but not synthesised in rodents. (2009). https://pubmed.ncbi.nlm.nih.gov/19586572/ DOI: 10.1017/s0007114509990456
Complete structured claim and evidence
More than 98% of dietary D-chiro-inositol equivalents from the tested rodent diet, purified pinitol or labeled D-chiro-inositol were absorbed in rat balance experiments.
D-chiro-inositol → D-chiro-inositol uptake source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/19586572.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7c6e57e631fef5921afd04f75718024d5b14ca525460e2c96275a4fc320c3b26", "start_char": 0, "end_char": 1544, "text_sha256": "7c6e57e631fef5921afd04f75718024d5b14ca525460e2c96275a4fc320c3b26"}
experimental_model
Dietary balance, GC-MS and stable-isotope tracing
exposure
Defined diets, heavy water and deuterated myo-inositol/DCI
limitations
Failure to detect conversion in mice does not exclude all human or isolated-tissue activity. Isotope strategy, chemical identification, species and dietary DCI contamination may contribute to disagreement with earlier radiotracer reports.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Rats and mice; conversion tracing in mice
plain_language
Diet itself can supply substantial D-chiro-inositol and confound attempts to measure its synthesis.
primary_references
[ino-p19586572] d- chiro-Inositol is absorbed but not synthesised in rodents. (2009). https://pubmed.ncbi.nlm.nih.gov/19586572/ DOI: 10.1017/s0007114509990456
tissue_or_cell_type
Gastrointestinal absorption, plasma and excreta
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 1237–1248
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Dietary balance, GC-MS and stable-isotope tracing · source_derived_draft · unverified_draft
### ino-dci-absorption More than 98% of dietary D-chiro-inositol equivalents from the tested rodent diet, purified pinitol or labeled D-chiro-inositol were absorbed in rat balance experiments. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: Diet itself can supply substantial D-chiro-inositol and confound attempts to measure its synthesis. organism: Rats and mice; conversion tracing in mice tissue_or_cell_type: Gastrointestinal absorption, plasma and excreta experimental_model: Dietary balance, GC-MS and stable-isotope tracing limitations: Failure to detect conversion in mice does not exclude all human or isolated-tissue activity. Isotope strategy, chemical identification, species and dietary DCI contamination may contribute to disagreement with earlier radiotracer reports. exposure: Defined diets, heavy water and deuterated myo-inositol/DCI evidence_span: {"source_cache": "artifacts/inositol-research/19586572.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7c6e57e631fef5921afd04f75718024d5b14ca525460e2c96275a4fc320c3b26", "start_char": 0, "end_char": 1544, "text_sha256": "7c6e57e631fef5921afd04f75718024d5b14ca525460e2c96275a4fc320c3b26"} [ino-p19586572] d- chiro-Inositol is absorbed but not synthesised in rodents. (2009). https://pubmed.ncbi.nlm.nih.gov/19586572/ DOI: 10.1017/s0007114509990456
Complete structured claim and evidence
DCI in mouse plasma, stool and urine fell to very low levels on the pinitol/DCI-depleted diet, whereas levels remained stable on standard chow.
D-chiro-inositol → Measured D-chiro-inositol pool source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/inositol-research/19586572.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7c6e57e631fef5921afd04f75718024d5b14ca525460e2c96275a4fc320c3b26", "start_char": 0, "end_char": 1544, "text_sha256": "7c6e57e631fef5921afd04f75718024d5b14ca525460e2c96275a4fc320c3b26"}
experimental_model
Dietary balance, GC-MS and stable-isotope tracing
exposure
Defined diets, heavy water and deuterated myo-inositol/DCI
limitations
Failure to detect conversion in mice does not exclude all human or isolated-tissue activity. Isotope strategy, chemical identification, species and dietary DCI contamination may contribute to disagreement with earlier radiotracer reports.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Rats and mice; conversion tracing in mice
plain_language
The measured pool depended strongly on dietary input in this experiment.
primary_references
[ino-p19586572] d- chiro-Inositol is absorbed but not synthesised in rodents. (2009). https://pubmed.ncbi.nlm.nih.gov/19586572/ DOI: 10.1017/s0007114509990456
tissue_or_cell_type
Gastrointestinal absorption, plasma and excreta
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 1250–1261
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Dietary balance, GC-MS and stable-isotope tracing · source_derived_draft · unverified_draft
### ino-dci-diet-depletion DCI in mouse plasma, stool and urine fell to very low levels on the pinitol/DCI-depleted diet, whereas levels remained stable on standard chow. Condition category: nutrient_deficiency nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: The measured pool depended strongly on dietary input in this experiment. organism: Rats and mice; conversion tracing in mice tissue_or_cell_type: Gastrointestinal absorption, plasma and excreta experimental_model: Dietary balance, GC-MS and stable-isotope tracing limitations: Failure to detect conversion in mice does not exclude all human or isolated-tissue activity. Isotope strategy, chemical identification, species and dietary DCI contamination may contribute to disagreement with earlier radiotracer reports. exposure: Defined diets, heavy water and deuterated myo-inositol/DCI evidence_span: {"source_cache": "artifacts/inositol-research/19586572.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7c6e57e631fef5921afd04f75718024d5b14ca525460e2c96275a4fc320c3b26", "start_char": 0, "end_char": 1544, "text_sha256": "7c6e57e631fef5921afd04f75718024d5b14ca525460e2c96275a4fc320c3b26"} [ino-p19586572] d- chiro-Inositol is absorbed but not synthesised in rodents. (2009). https://pubmed.ncbi.nlm.nih.gov/19586572/ DOI: 10.1017/s0007114509990456
Complete structured claim and evidence
IMPA1-deficient patient-derived neuronal progenitors showed impaired proliferation, cell-cycle arrest, apoptosis and reduced neuronal differentiation.
IMPA1 (human inositol monophosphatase 1) → Neural progenitor survival and neurogenesis source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/inositol-research/32839513.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5ca10517672cac78ad8cdb0c593f14f73f1989e55977432d979690eebc3eefed", "start_char": 0, "end_char": 1711, "text_sha256": "5ca10517672cac78ad8cdb0c593f14f73f1989e55977432d979690eebc3eefed"}
experimental_model
Patient-derived iPSC differentiation and rescue
exposure
Biallelic IMPA1 defect and myo-inositol-supplemented medium
limitations
Cellular rescue is not demonstrated neurological benefit in treated patients; effects were lineage-specific.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Homo sapiens
plain_language
Failure of the inositol-processing machinery affected developing nerve cells.
primary_references
[ino-p32839513] Inositol monophosphatase 1 (IMPA1) mutation in intellectual disability patients impairs neurogenesis but not gliogenesis. (2021). https://pubmed.ncbi.nlm.nih.gov/32839513/ DOI: 10.1038/s41380-020-00862-9
tissue_or_cell_type
Hippocampal dentate-gyrus-like neuronal progenitors
trigger_kind
machinery_impairment Imported condition classification; unverified.
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 1263–1274
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Patient-derived iPSC differentiation and rescue · source_derived_draft · unverified_draft
### ino-impa1-progenitors IMPA1-deficient patient-derived neuronal progenitors showed impaired proliferation, cell-cycle arrest, apoptosis and reduced neuronal differentiation. Condition category: machinery_impairment nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: Failure of the inositol-processing machinery affected developing nerve cells. organism: Homo sapiens tissue_or_cell_type: Hippocampal dentate-gyrus-like neuronal progenitors experimental_model: Patient-derived iPSC differentiation and rescue limitations: Cellular rescue is not demonstrated neurological benefit in treated patients; effects were lineage-specific. exposure: Biallelic IMPA1 defect and myo-inositol-supplemented medium evidence_span: {"source_cache": "artifacts/inositol-research/32839513.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5ca10517672cac78ad8cdb0c593f14f73f1989e55977432d979690eebc3eefed", "start_char": 0, "end_char": 1711, "text_sha256": "5ca10517672cac78ad8cdb0c593f14f73f1989e55977432d979690eebc3eefed"} [ino-p32839513] Inositol monophosphatase 1 (IMPA1) mutation in intellectual disability patients impairs neurogenesis but not gliogenesis. (2021). https://pubmed.ncbi.nlm.nih.gov/32839513/ DOI: 10.1038/s41380-020-00862-9
Complete structured claim and evidence
Myo-inositol supplementation of differentiation medium rescued the reported neuronal-progenitor phenotype in IMPA1-deficient patient-derived cultures.
Myo-inositol → Neural progenitor survival and neurogenesis source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/inositol-research/32839513.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5ca10517672cac78ad8cdb0c593f14f73f1989e55977432d979690eebc3eefed", "start_char": 0, "end_char": 1711, "text_sha256": "5ca10517672cac78ad8cdb0c593f14f73f1989e55977432d979690eebc3eefed"}
experimental_model
Patient-derived iPSC differentiation and rescue
exposure
Biallelic IMPA1 defect and myo-inositol-supplemented medium
limitations
Cellular rescue is not demonstrated neurological benefit in treated patients; effects were lineage-specific.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Homo sapiens
plain_language
Providing the missing downstream molecule helped cells in culture; clinical benefit remains untested here.
primary_references
[ino-p32839513] Inositol monophosphatase 1 (IMPA1) mutation in intellectual disability patients impairs neurogenesis but not gliogenesis. (2021). https://pubmed.ncbi.nlm.nih.gov/32839513/ DOI: 10.1038/s41380-020-00862-9
tissue_or_cell_type
Hippocampal dentate-gyrus-like neuronal progenitors
trigger_kind
machinery_impairment Imported condition classification; unverified.
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 1276–1287
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Patient-derived iPSC differentiation and rescue · source_derived_draft · unverified_draft
### ino-impa1-myo-rescue Myo-inositol supplementation of differentiation medium rescued the reported neuronal-progenitor phenotype in IMPA1-deficient patient-derived cultures. Condition category: machinery_impairment nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: Providing the missing downstream molecule helped cells in culture; clinical benefit remains untested here. organism: Homo sapiens tissue_or_cell_type: Hippocampal dentate-gyrus-like neuronal progenitors experimental_model: Patient-derived iPSC differentiation and rescue limitations: Cellular rescue is not demonstrated neurological benefit in treated patients; effects were lineage-specific. exposure: Biallelic IMPA1 defect and myo-inositol-supplemented medium evidence_span: {"source_cache": "artifacts/inositol-research/32839513.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5ca10517672cac78ad8cdb0c593f14f73f1989e55977432d979690eebc3eefed", "start_char": 0, "end_char": 1711, "text_sha256": "5ca10517672cac78ad8cdb0c593f14f73f1989e55977432d979690eebc3eefed"} [ino-p32839513] Inositol monophosphatase 1 (IMPA1) mutation in intellectual disability patients impairs neurogenesis but not gliogenesis. (2021). https://pubmed.ncbi.nlm.nih.gov/32839513/ DOI: 10.1038/s41380-020-00862-9
Complete structured claim and evidence
Insulin-area reduction was significant within the D-chiro-inositol group, but the difference in change versus placebo had P=0.07.
D-chiro-inositol → Plasma insulin response to glucose challenge source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/10219066.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2b70007c28cc93c6f18b457701ec8b034a3bbe888db05e85eca71d50199dc854", "start_char": 0, "end_char": 2121, "text_sha256": "2b70007c28cc93c6f18b457701ec8b034a3bbe888db05e85eca71d50199dc854"}
experimental_model
Randomized placebo-controlled trial
exposure
D-chiro-inositol 1200 mg/day for 6–8 weeks versus placebo; historical study regimen
limitations
Small short trial, not live-birth evidence. Within-group insulin improvement was stronger than the between-group comparison.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Homo sapiens
plain_language
Improvement within one group alone was not a conventionally significant between-group result.
primary_references
[ino-p10219066] Ovulatory and metabolic effects of D-chiro-inositol in the polycystic ovary syndrome. (1999). https://pubmed.ncbi.nlm.nih.gov/10219066/ DOI: 10.1056/nejm199904293401703
tissue_or_cell_type
44 obese women with PCOS
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 1302–1313
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized placebo-controlled trial · source_derived_draft · unverified_draft
### ino-dci-insulin-uncertain Insulin-area reduction was significant within the D-chiro-inositol group, but the difference in change versus placebo had P=0.07. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: Improvement within one group alone was not a conventionally significant between-group result. organism: Homo sapiens tissue_or_cell_type: 44 obese women with PCOS experimental_model: Randomized placebo-controlled trial limitations: Small short trial, not live-birth evidence. Within-group insulin improvement was stronger than the between-group comparison. exposure: D-chiro-inositol 1200 mg/day for 6–8 weeks versus placebo; historical study regimen evidence_span: {"source_cache": "artifacts/inositol-research/10219066.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2b70007c28cc93c6f18b457701ec8b034a3bbe888db05e85eca71d50199dc854", "start_char": 0, "end_char": 2121, "text_sha256": "2b70007c28cc93c6f18b457701ec8b034a3bbe888db05e85eca71d50199dc854"} [ino-p10219066] Ovulatory and metabolic effects of D-chiro-inositol in the polycystic ovary syndrome. (1999). https://pubmed.ncbi.nlm.nih.gov/10219066/ DOI: 10.1056/nejm199904293401703
Complete structured claim and evidence
The reduction in free testosterone differed from placebo in the small D-chiro-inositol trial (P=0.006).
D-chiro-inositol → Circulating free testosterone concentration source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/10219066.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2b70007c28cc93c6f18b457701ec8b034a3bbe888db05e85eca71d50199dc854", "start_char": 0, "end_char": 2121, "text_sha256": "2b70007c28cc93c6f18b457701ec8b034a3bbe888db05e85eca71d50199dc854"}
experimental_model
Randomized placebo-controlled trial
exposure
D-chiro-inositol 1200 mg/day for 6–8 weeks versus placebo; historical study regimen
limitations
Small short trial, not live-birth evidence. Within-group insulin improvement was stronger than the between-group comparison.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Homo sapiens
plain_language
One androgen measure improved in this specific study.
primary_references
[ino-p10219066] Ovulatory and metabolic effects of D-chiro-inositol in the polycystic ovary syndrome. (1999). https://pubmed.ncbi.nlm.nih.gov/10219066/ DOI: 10.1056/nejm199904293401703
tissue_or_cell_type
44 obese women with PCOS
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 1315–1326
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized placebo-controlled trial · source_derived_draft · unverified_draft
### ino-dci-testosterone The reduction in free testosterone differed from placebo in the small D-chiro-inositol trial (P=0.006). Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: One androgen measure improved in this specific study. organism: Homo sapiens tissue_or_cell_type: 44 obese women with PCOS experimental_model: Randomized placebo-controlled trial limitations: Small short trial, not live-birth evidence. Within-group insulin improvement was stronger than the between-group comparison. exposure: D-chiro-inositol 1200 mg/day for 6–8 weeks versus placebo; historical study regimen evidence_span: {"source_cache": "artifacts/inositol-research/10219066.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2b70007c28cc93c6f18b457701ec8b034a3bbe888db05e85eca71d50199dc854", "start_char": 0, "end_char": 2121, "text_sha256": "2b70007c28cc93c6f18b457701ec8b034a3bbe888db05e85eca71d50199dc854"} [ino-p10219066] Ovulatory and metabolic effects of D-chiro-inositol in the polycystic ovary syndrome. (1999). https://pubmed.ncbi.nlm.nih.gov/10219066/ DOI: 10.1056/nejm199904293401703
Complete structured claim and evidence
The 2013 trial reported gestational diabetes in 6% of the myo-inositol-plus-folic-acid group versus 15.3% with folic acid alone.
Myo-inositol → Gestational diabetes incidence source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/23340885.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "384eb5d40ed312af297e2ecdd98b1c3f804fda5555db8984de47dc08c3cdf336", "start_char": 0, "end_char": 1685, "text_sha256": "384eb5d40ed312af297e2ecdd98b1c3f804fda5555db8984de47dc08c3cdf336"}
experimental_model
Prospective randomized open-label pregnancy trial
exposure
Myo-inositol plus folic acid versus folic acid alone
limitations
Open-label design and selected risk group; this is neither an inositol-versus-folate comparison nor proof of a nutrient interaction.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Homo sapiens
plain_language
An early trial suggested benefit in one risk group, with folic acid present in both groups.
primary_references
[ino-p23340885] myo-Inositol supplementation and onset of gestational diabetes mellitus in pregnant women with a family history of type 2 diabetes: a prospective, randomized, placebo-controlled study. (2013). https://pubmed.ncbi.nlm.nih.gov/23340885/ DOI: 10.2337/dc12-1371
tissue_or_cell_type
Pregnant women with a family history of type 2 diabetes
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 1328–1339
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Prospective randomized open-label pregnancy trial · source_derived_draft · unverified_draft
### ino-gdm-2013 The 2013 trial reported gestational diabetes in 6% of the myo-inositol-plus-folic-acid group versus 15.3% with folic acid alone. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: An early trial suggested benefit in one risk group, with folic acid present in both groups. organism: Homo sapiens tissue_or_cell_type: Pregnant women with a family history of type 2 diabetes experimental_model: Prospective randomized open-label pregnancy trial limitations: Open-label design and selected risk group; this is neither an inositol-versus-folate comparison nor proof of a nutrient interaction. exposure: Myo-inositol plus folic acid versus folic acid alone evidence_span: {"source_cache": "artifacts/inositol-research/23340885.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "384eb5d40ed312af297e2ecdd98b1c3f804fda5555db8984de47dc08c3cdf336", "start_char": 0, "end_char": 1685, "text_sha256": "384eb5d40ed312af297e2ecdd98b1c3f804fda5555db8984de47dc08c3cdf336"} [ino-p23340885] myo-Inositol supplementation and onset of gestational diabetes mellitus in pregnant women with a family history of type 2 diabetes: a prospective, randomized, placebo-controlled study. (2013). https://pubmed.ncbi.nlm.nih.gov/23340885/ DOI: 10.2337/dc12-1371
Complete structured claim and evidence
In MYPP, the gestational-diabetes/preeclampsia/preterm-birth composite occurred in 25.0% versus 26.8% (RR 0.93, 95% CI 0.68–1.28; P=0.67).
Myo-inositol → Gestational diabetes, preeclampsia or preterm birth composite source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/40920401.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f72221b219fbb1cae0af2c44b123ab1e95c74e0ba9c10f75ed601720b96248a0", "start_char": 0, "end_char": 1949, "text_sha256": "f72221b219fbb1cae0af2c44b123ab1e95c74e0ba9c10f75ed601720b96248a0"}
experimental_model
MYPP double-blind multicenter randomized trial
exposure
Myo-inositol 2 g plus folic acid 0.2 mg twice daily versus matching folic acid control until delivery
limitations
A larger null result for a prespecified composite in PCOS pregnancy; not the same population or endpoint as the 2013 trial. Confidence limits permit benefit or harm of varying sizes.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Homo sapiens
plain_language
The larger blinded PCOS-pregnancy trial did not demonstrate a reduction in its main complication outcome.
primary_references
[ino-p40920401] Myo-inositol Supplementation to Prevent Pregnancy Complications in Polycystic Ovary Syndrome: A Randomized Clinical Trial. (2025). https://pubmed.ncbi.nlm.nih.gov/40920401/ DOI: 10.1001/jama.2025.13668
tissue_or_cell_type
464 pregnant individuals with PCOS at 13 Dutch hospitals
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 1341–1352
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · MYPP double-blind multicenter randomized trial · source_derived_draft · unverified_draft
### ino-gdm-2025 In MYPP, the gestational-diabetes/preeclampsia/preterm-birth composite occurred in 25.0% versus 26.8% (RR 0.93, 95% CI 0.68–1.28; P=0.67). Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: The larger blinded PCOS-pregnancy trial did not demonstrate a reduction in its main complication outcome. organism: Homo sapiens tissue_or_cell_type: 464 pregnant individuals with PCOS at 13 Dutch hospitals experimental_model: MYPP double-blind multicenter randomized trial limitations: A larger null result for a prespecified composite in PCOS pregnancy; not the same population or endpoint as the 2013 trial. Confidence limits permit benefit or harm of varying sizes. exposure: Myo-inositol 2 g plus folic acid 0.2 mg twice daily versus matching folic acid control until delivery evidence_span: {"source_cache": "artifacts/inositol-research/40920401.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f72221b219fbb1cae0af2c44b123ab1e95c74e0ba9c10f75ed601720b96248a0", "start_char": 0, "end_char": 1949, "text_sha256": "f72221b219fbb1cae0af2c44b123ab1e95c74e0ba9c10f75ed601720b96248a0"} [ino-p40920401] Myo-inositol Supplementation to Prevent Pregnancy Complications in Polycystic Ovary Syndrome: A Randomized Clinical Trial. (2025). https://pubmed.ncbi.nlm.nih.gov/40920401/ DOI: 10.1001/jama.2025.13668
Complete structured claim and evidence
MiGDM found no significant GDM difference among 43 completers, but early funding-related termination prevented a definitive efficacy test.
Myo-inositol → Gestational diabetes incidence source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/41742988.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3b78fed7bce4eedabdbeae7d6e7e562bee8153fa1d0d805b5e96a52004344b29", "start_char": 0, "end_char": 3433, "text_sha256": "3b78fed7bce4eedabdbeae7d6e7e562bee8153fa1d0d805b5e96a52004344b29"}
experimental_model
MiGDM double-blind randomized pilot
exposure
Myo-inositol 2 g twice daily versus placebo; stopped early for funding
limitations
Only 67 enrolled and 43 completed versus 640 planned. Severe underpowering makes the result inconclusive, not proof of equivalence.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Homo sapiens
plain_language
This small unfinished trial cannot settle whether the supplement works.
primary_references
[ino-p41742988] The Effect of Myo-Inositol Supplementation During Pregnancy on Fetal and Maternal Outcomes: Results of the Myo-Inositol for the Prevention of Gestational Diabetes Mellitus (MiGDM) Randomized Double-Blind, Placebo-Controlled Pilot Trial. (2026). https://pubmed.ncbi.nlm.nih.gov/41742988/ DOI: 10.7759/cureus.102259
tissue_or_cell_type
Pregnant women in Qatar
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 1354–1365
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · MiGDM double-blind randomized pilot · source_derived_draft · unverified_draft
### ino-gdm-2026 MiGDM found no significant GDM difference among 43 completers, but early funding-related termination prevented a definitive efficacy test. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: This small unfinished trial cannot settle whether the supplement works. organism: Homo sapiens tissue_or_cell_type: Pregnant women in Qatar experimental_model: MiGDM double-blind randomized pilot limitations: Only 67 enrolled and 43 completed versus 640 planned. Severe underpowering makes the result inconclusive, not proof of equivalence. exposure: Myo-inositol 2 g twice daily versus placebo; stopped early for funding evidence_span: {"source_cache": "artifacts/inositol-research/41742988.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3b78fed7bce4eedabdbeae7d6e7e562bee8153fa1d0d805b5e96a52004344b29", "start_char": 0, "end_char": 3433, "text_sha256": "3b78fed7bce4eedabdbeae7d6e7e562bee8153fa1d0d805b5e96a52004344b29"} [ino-p41742988] The Effect of Myo-Inositol Supplementation During Pregnancy on Fetal and Maternal Outcomes: Results of the Myo-Inositol for the Prevention of Gestational Diabetes Mellitus (MiGDM) Randomized Double-Blind, Placebo-Controlled Pilot Trial. (2026). https://pubmed.ncbi.nlm.nih.gov/41742988/ DOI: 10.7759/cureus.102259
Complete structured claim and evidence
Blocking PKC beta I prevented the inositol-mediated reduction of neural tube defects in curly-tail mouse embryos.
Mouse PKC beta I isoform → Embryonic neural tube closure source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/inositol-research/14613966.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "670b8f0a36bfbecfb417fe28f8748e65994ac47b153ffcf66c42c21e7489f9cc", "start_char": 0, "end_char": 1735, "text_sha256": "670b8f0a36bfbecfb417fe28f8748e65994ac47b153ffcf66c42c21e7489f9cc"}
experimental_model
Embryo culture with selective PKC inhibition
exposure
Inositol exposure in a folate-resistant neural-tube-defect model
limitations
Mechanistic mouse prevention does not establish human efficacy or permit replacing folic acid.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Curly-tail mutant mice
plain_language
Adding inositol could not overcome failure of this downstream signaling step.
primary_references
[ino-p14613966] Specific isoforms of protein kinase C are essential for prevention of folate-resistant neural tube defects by inositol. (2004). https://pubmed.ncbi.nlm.nih.gov/14613966/ DOI: 10.1093/hmg/ddh003
tissue_or_cell_type
Neurulation-stage embryos and hindgut
trigger_kind
machinery_impairment Imported condition classification; unverified.
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 1367–1378
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Embryo culture with selective PKC inhibition · source_derived_draft · unverified_draft
### ino-ntd-pkc-beta Blocking PKC beta I prevented the inositol-mediated reduction of neural tube defects in curly-tail mouse embryos. Condition category: machinery_impairment nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: Adding inositol could not overcome failure of this downstream signaling step. organism: Curly-tail mutant mice tissue_or_cell_type: Neurulation-stage embryos and hindgut experimental_model: Embryo culture with selective PKC inhibition limitations: Mechanistic mouse prevention does not establish human efficacy or permit replacing folic acid. exposure: Inositol exposure in a folate-resistant neural-tube-defect model evidence_span: {"source_cache": "artifacts/inositol-research/14613966.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "670b8f0a36bfbecfb417fe28f8748e65994ac47b153ffcf66c42c21e7489f9cc", "start_char": 0, "end_char": 1735, "text_sha256": "670b8f0a36bfbecfb417fe28f8748e65994ac47b153ffcf66c42c21e7489f9cc"} [ino-p14613966] Specific isoforms of protein kinase C are essential for prevention of folate-resistant neural tube defects by inositol. (2004). https://pubmed.ncbi.nlm.nih.gov/14613966/ DOI: 10.1093/hmg/ddh003
Complete structured claim and evidence
PKC gamma activity was also required for inositol prevention of neural tube defects in this mouse model.
Mouse PKC gamma → Embryonic neural tube closure source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/inositol-research/14613966.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "670b8f0a36bfbecfb417fe28f8748e65994ac47b153ffcf66c42c21e7489f9cc", "start_char": 0, "end_char": 1735, "text_sha256": "670b8f0a36bfbecfb417fe28f8748e65994ac47b153ffcf66c42c21e7489f9cc"}
experimental_model
Embryo culture with selective PKC inhibition
exposure
Inositol exposure in a folate-resistant neural-tube-defect model
limitations
Mechanistic mouse prevention does not establish human efficacy or permit replacing folic acid.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Curly-tail mutant mice
plain_language
A second PKC isoform was separately required.
primary_references
[ino-p14613966] Specific isoforms of protein kinase C are essential for prevention of folate-resistant neural tube defects by inositol. (2004). https://pubmed.ncbi.nlm.nih.gov/14613966/ DOI: 10.1093/hmg/ddh003
tissue_or_cell_type
Neurulation-stage embryos and hindgut
trigger_kind
machinery_impairment Imported condition classification; unverified.
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 1380–1391
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Embryo culture with selective PKC inhibition · source_derived_draft · unverified_draft
### ino-ntd-pkc-gamma PKC gamma activity was also required for inositol prevention of neural tube defects in this mouse model. Condition category: machinery_impairment nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: A second PKC isoform was separately required. organism: Curly-tail mutant mice tissue_or_cell_type: Neurulation-stage embryos and hindgut experimental_model: Embryo culture with selective PKC inhibition limitations: Mechanistic mouse prevention does not establish human efficacy or permit replacing folic acid. exposure: Inositol exposure in a folate-resistant neural-tube-defect model evidence_span: {"source_cache": "artifacts/inositol-research/14613966.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "670b8f0a36bfbecfb417fe28f8748e65994ac47b153ffcf66c42c21e7489f9cc", "start_char": 0, "end_char": 1735, "text_sha256": "670b8f0a36bfbecfb417fe28f8748e65994ac47b153ffcf66c42c21e7489f9cc"} [ino-p14613966] Specific isoforms of protein kinase C are essential for prevention of folate-resistant neural tube defects by inositol. (2004). https://pubmed.ncbi.nlm.nih.gov/14613966/ DOI: 10.1093/hmg/ddh003
Complete structured claim and evidence
Inositol stimulated hindgut-cell proliferation in curly-tail embryos, and this effect required PKC beta I.
Myo-inositol → Embryonic hindgut cell proliferation source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/14613966.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "670b8f0a36bfbecfb417fe28f8748e65994ac47b153ffcf66c42c21e7489f9cc", "start_char": 0, "end_char": 1735, "text_sha256": "670b8f0a36bfbecfb417fe28f8748e65994ac47b153ffcf66c42c21e7489f9cc"}
experimental_model
Embryo culture with selective PKC inhibition
exposure
Inositol exposure in a folate-resistant neural-tube-defect model
limitations
Mechanistic mouse prevention does not establish human efficacy or permit replacing folic acid.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Curly-tail mutant mice
plain_language
The rescue involved growth of a particular embryonic tissue, not just a general vitamin effect.
primary_references
[ino-p14613966] Specific isoforms of protein kinase C are essential for prevention of folate-resistant neural tube defects by inositol. (2004). https://pubmed.ncbi.nlm.nih.gov/14613966/ DOI: 10.1093/hmg/ddh003
tissue_or_cell_type
Neurulation-stage embryos and hindgut
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 1393–1404
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Embryo culture with selective PKC inhibition · source_derived_draft · unverified_draft
### ino-ntd-hindgut Inositol stimulated hindgut-cell proliferation in curly-tail embryos, and this effect required PKC beta I. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: The rescue involved growth of a particular embryonic tissue, not just a general vitamin effect. organism: Curly-tail mutant mice tissue_or_cell_type: Neurulation-stage embryos and hindgut experimental_model: Embryo culture with selective PKC inhibition limitations: Mechanistic mouse prevention does not establish human efficacy or permit replacing folic acid. exposure: Inositol exposure in a folate-resistant neural-tube-defect model evidence_span: {"source_cache": "artifacts/inositol-research/14613966.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "670b8f0a36bfbecfb417fe28f8748e65994ac47b153ffcf66c42c21e7489f9cc", "start_char": 0, "end_char": 1735, "text_sha256": "670b8f0a36bfbecfb417fe28f8748e65994ac47b153ffcf66c42c21e7489f9cc"} [ino-p14613966] Specific isoforms of protein kinase C are essential for prevention of folate-resistant neural tube defects by inositol. (2004). https://pubmed.ncbi.nlm.nih.gov/14613966/ DOI: 10.1093/hmg/ddh003
Complete structured claim and evidence
Among randomized PONTI pregnancies, NTD recurrence occurred in 0/14 with inositol plus folic acid versus 1/19 with placebo plus folic acid.
Myo-inositol → Neural tube defect recurrence source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/26847388.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a7617d160ca71553f41ce2a7346478950ed9580a4bc9cca9688d3b710ec0cf82", "start_char": 0, "end_char": 1680, "text_sha256": "a7617d160ca71553f41ce2a7346478950ed9580a4bc9cca9688d3b710ec0cf82"}
experimental_model
PONTI double-blind randomized pilot with separately described nonrandomized pregnancies
exposure
Periconceptional inositol plus folic acid versus folic acid plus placebo
limitations
47 women randomized; only 33 randomized pregnancies. The pilot was not powered to establish prevention. Corrigendum PMID 26917444 corrects the separate nonrandomized pregnancy count from 22 to 24; randomized counts used here are unchanged. Nonrandomized outcomes must not be pooled as randomized evidence.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Homo sapiens
plain_language
The pilot supported further study but was far too small to establish efficacy or replace folic acid.
primary_references
[ino-p26847388] Inositol for the prevention of neural tube defects: a pilot randomised controlled trial. (2016). https://pubmed.ncbi.nlm.nih.gov/26847388/ DOI: 10.1017/s0007114515005322
tissue_or_cell_type
Women with a prior neural-tube-defect pregnancy
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 1406–1417
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · PONTI double-blind randomized pilot with separately described nonrandomized pregnancies · source_derived_draft · unverified_draft
### ino-ponti Among randomized PONTI pregnancies, NTD recurrence occurred in 0/14 with inositol plus folic acid versus 1/19 with placebo plus folic acid. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: The pilot supported further study but was far too small to establish efficacy or replace folic acid. organism: Homo sapiens tissue_or_cell_type: Women with a prior neural-tube-defect pregnancy experimental_model: PONTI double-blind randomized pilot with separately described nonrandomized pregnancies limitations: 47 women randomized; only 33 randomized pregnancies. The pilot was not powered to establish prevention. Corrigendum PMID 26917444 corrects the separate nonrandomized pregnancy count from 22 to 24; randomized counts used here are unchanged. Nonrandomized outcomes must not be pooled as randomized evidence. exposure: Periconceptional inositol plus folic acid versus folic acid plus placebo evidence_span: {"source_cache": "artifacts/inositol-research/26847388.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a7617d160ca71553f41ce2a7346478950ed9580a4bc9cca9688d3b710ec0cf82", "start_char": 0, "end_char": 1680, "text_sha256": "a7617d160ca71553f41ce2a7346478950ed9580a4bc9cca9688d3b710ec0cf82"} [ino-p26847388] Inositol for the prevention of neural tube defects: a pilot randomised controlled trial. (2016). https://pubmed.ncbi.nlm.nih.gov/26847388/ DOI: 10.1017/s0007114515005322
Complete structured claim and evidence
TSH fell from baseline in the myo-inositol-plus-selenomethionine arm, while no TSH change was reported in the selenomethionine-only arm; the reported TSH P value was a within-group comparison.
Myo-inositol → Serum TSH concentration source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/24224112.fulltext.txt", "locator": "Exact primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b9b55ed122a2f26149680eb0f4bfab9ea981927754bcbb40305d4697c5d32412", "start_char": 7984, "end_char": 8184, "text_sha256": "34e1c5b3fe451ea1278c2adfb27f4977a40d100b82946252ecad03a7879592dc"}
experimental_model
Double-blind randomized combination trial
exposure
Myo-inositol plus selenomethionine versus selenomethionine
limitations
Small combination trial without a myo-inositol-only arm. A significant within-group change versus a nonsignificant change in the other arm is not by itself a significant between-group difference or nutrient synergy.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Homo sapiens
plain_language
A thyroid blood marker improved in the combined-treatment group, but these comparisons do not establish a statistical interaction between nutrients.
primary_references
[ino-p24224112] Combined treatment with Myo-inositol and selenium ensures euthyroidism in subclinical hypothyroidism patients with autoimmune thyroiditis. (2013). https://pubmed.ncbi.nlm.nih.gov/24224112/ DOI: 10.1155/2013/424163
tissue_or_cell_type
Women with autoimmune subclinical hypothyroidism
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 1419–1430
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Double-blind randomized combination trial · source_derived_draft · unverified_draft
### ino-thyroid-combination TSH fell from baseline in the myo-inositol-plus-selenomethionine arm, while no TSH change was reported in the selenomethionine-only arm; the reported TSH P value was a within-group comparison. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: A thyroid blood marker improved in the combined-treatment group, but these comparisons do not establish a statistical interaction between nutrients. organism: Homo sapiens tissue_or_cell_type: Women with autoimmune subclinical hypothyroidism experimental_model: Double-blind randomized combination trial limitations: Small combination trial without a myo-inositol-only arm. A significant within-group change versus a nonsignificant change in the other arm is not by itself a significant between-group difference or nutrient synergy. exposure: Myo-inositol plus selenomethionine versus selenomethionine evidence_span: {"source_cache": "artifacts/inositol-research/24224112.fulltext.txt", "locator": "Exact primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b9b55ed122a2f26149680eb0f4bfab9ea981927754bcbb40305d4697c5d32412", "start_char": 7984, "end_char": 8184, "text_sha256": "34e1c5b3fe451ea1278c2adfb27f4977a40d100b82946252ecad03a7879592dc"} [ino-p24224112] Combined treatment with Myo-inositol and selenium ensures euthyroidism in subclinical hypothyroidism patients with autoimmune thyroiditis. (2013). https://pubmed.ncbi.nlm.nih.gov/24224112/ DOI: 10.1155/2013/424163
Complete structured claim and evidence
The 1992 trial reported ROP in 13% of inositol-treated infants versus 26% of placebo recipients, and stage 4 ROP in 0% versus 9%.
Myo-inositol → Retinopathy of prematurity incidence source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/1560798.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6ece5de763b822dca6ca1a93b5f7a61a2d94be9af29755ffd9379f16a983027e", "start_char": 0, "end_char": 2123, "text_sha256": "6ece5de763b822dca6ca1a93b5f7a61a2d94be9af29755ffd9379f16a983027e"}
experimental_model
Randomized double-blind neonatal trial
exposure
Inositol 80 mg/kg/day for the first five days during parenteral nutrition
limitations
Early-era neonatal care and short exposure. The indexed abstract has inconsistent BPD count/percentage arithmetic; that endpoint is not numerically reproduced here. ROP findings are retained with the later adverse trial.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Homo sapiens
plain_language
An early neonatal trial reported fewer severe eye complications.
primary_references
[ino-p1560798] Inositol supplementation in premature infants with respiratory distress syndrome. (1992). https://pubmed.ncbi.nlm.nih.gov/1560798/ DOI: 10.1056/nejm199205073261901
tissue_or_cell_type
221 infants at 24–32 weeks gestation with respiratory distress
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 1432–1443
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized double-blind neonatal trial · source_derived_draft · unverified_draft
### ino-preterm-1992-rop The 1992 trial reported ROP in 13% of inositol-treated infants versus 26% of placebo recipients, and stage 4 ROP in 0% versus 9%. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: An early neonatal trial reported fewer severe eye complications. organism: Homo sapiens tissue_or_cell_type: 221 infants at 24–32 weeks gestation with respiratory distress experimental_model: Randomized double-blind neonatal trial limitations: Early-era neonatal care and short exposure. The indexed abstract has inconsistent BPD count/percentage arithmetic; that endpoint is not numerically reproduced here. ROP findings are retained with the later adverse trial. exposure: Inositol 80 mg/kg/day for the first five days during parenteral nutrition evidence_span: {"source_cache": "artifacts/inositol-research/1560798.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6ece5de763b822dca6ca1a93b5f7a61a2d94be9af29755ffd9379f16a983027e", "start_char": 0, "end_char": 2123, "text_sha256": "6ece5de763b822dca6ca1a93b5f7a61a2d94be9af29755ffd9379f16a983027e"} [ino-p1560798] Inositol supplementation in premature infants with respiratory distress syndrome. (1992). https://pubmed.ncbi.nlm.nih.gov/1560798/ DOI: 10.1056/nejm199205073261901
Complete structured claim and evidence
Death or type 1 ROP occurred in 29% with myo-inositol versus 21% with placebo (adjusted RR 1.41, 95% CI 1.08–1.83).
Myo-inositol → Death or type 1 retinopathy of prematurity composite source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/30357297.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b3301c8c680b4b3c6424dfb6677ae55839221db1d3cd51d9df4724b9cf35d57f", "start_char": 0, "end_char": 2589, "text_sha256": "b3301c8c680b4b3c6424dfb6677ae55839221db1d3cd51d9df4724b9cf35d57f"}
experimental_model
Multicenter randomized neonatal trial stopped early
exposure
Myo-inositol 40 mg/kg every 12 hours, initially IV then enteral, for up to 10 weeks versus placebo
limitations
Early termination limits estimates but does not remove the mortality signal. Different era, gestational ages, treatment duration and endpoints may contribute to divergence from early trials; the explanation remains unresolved.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Homo sapiens
plain_language
The later larger neonatal trial did not reproduce the expected overall benefit.
primary_references
[ino-p30357297] Effects of Myo-inositol on Type 1 Retinopathy of Prematurity Among Preterm Infants <28 Weeks' Gestational Age: A Randomized Clinical Trial. (2018). https://pubmed.ncbi.nlm.nih.gov/30357297/ DOI: 10.1001/jama.2018.14996
tissue_or_cell_type
638 infants born before 28 weeks at 18 US centers
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 1445–1456
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Multicenter randomized neonatal trial stopped early · source_derived_draft · unverified_draft
### ino-preterm-2018-composite Death or type 1 ROP occurred in 29% with myo-inositol versus 21% with placebo (adjusted RR 1.41, 95% CI 1.08–1.83). Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: The later larger neonatal trial did not reproduce the expected overall benefit. organism: Homo sapiens tissue_or_cell_type: 638 infants born before 28 weeks at 18 US centers experimental_model: Multicenter randomized neonatal trial stopped early limitations: Early termination limits estimates but does not remove the mortality signal. Different era, gestational ages, treatment duration and endpoints may contribute to divergence from early trials; the explanation remains unresolved. exposure: Myo-inositol 40 mg/kg every 12 hours, initially IV then enteral, for up to 10 weeks versus placebo evidence_span: {"source_cache": "artifacts/inositol-research/30357297.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b3301c8c680b4b3c6424dfb6677ae55839221db1d3cd51d9df4724b9cf35d57f", "start_char": 0, "end_char": 2589, "text_sha256": "b3301c8c680b4b3c6424dfb6677ae55839221db1d3cd51d9df4724b9cf35d57f"} [ino-p30357297] Effects of Myo-inositol on Type 1 Retinopathy of Prematurity Among Preterm Infants <28 Weeks' Gestational Age: A Randomized Clinical Trial. (2018). https://pubmed.ncbi.nlm.nih.gov/30357297/ DOI: 10.1001/jama.2018.14996
Complete structured claim and evidence
Mortality before 55 weeks postmenstrual age was 18% versus 11% (adjusted RR 1.66, 95% CI 1.14–2.43), prompting early trial termination.
Myo-inositol → Mortality in very preterm infants source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/30357297.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b3301c8c680b4b3c6424dfb6677ae55839221db1d3cd51d9df4724b9cf35d57f", "start_char": 0, "end_char": 2589, "text_sha256": "b3301c8c680b4b3c6424dfb6677ae55839221db1d3cd51d9df4724b9cf35d57f"}
experimental_model
Multicenter randomized neonatal trial stopped early
exposure
Myo-inositol 40 mg/kg every 12 hours, initially IV then enteral, for up to 10 weeks versus placebo
limitations
Early termination limits estimates but does not remove the mortality signal. Different era, gestational ages, treatment duration and endpoints may contribute to divergence from early trials; the explanation remains unresolved.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Homo sapiens
plain_language
The increased deaths are essential evidence and cannot be hidden behind the earlier positive findings.
primary_references
[ino-p30357297] Effects of Myo-inositol on Type 1 Retinopathy of Prematurity Among Preterm Infants <28 Weeks' Gestational Age: A Randomized Clinical Trial. (2018). https://pubmed.ncbi.nlm.nih.gov/30357297/ DOI: 10.1001/jama.2018.14996
tissue_or_cell_type
638 infants born before 28 weeks at 18 US centers
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 1458–1469
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Multicenter randomized neonatal trial stopped early · source_derived_draft · unverified_draft
### ino-preterm-2018-mortality Mortality before 55 weeks postmenstrual age was 18% versus 11% (adjusted RR 1.66, 95% CI 1.14–2.43), prompting early trial termination. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: The increased deaths are essential evidence and cannot be hidden behind the earlier positive findings. organism: Homo sapiens tissue_or_cell_type: 638 infants born before 28 weeks at 18 US centers experimental_model: Multicenter randomized neonatal trial stopped early limitations: Early termination limits estimates but does not remove the mortality signal. Different era, gestational ages, treatment duration and endpoints may contribute to divergence from early trials; the explanation remains unresolved. exposure: Myo-inositol 40 mg/kg every 12 hours, initially IV then enteral, for up to 10 weeks versus placebo evidence_span: {"source_cache": "artifacts/inositol-research/30357297.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b3301c8c680b4b3c6424dfb6677ae55839221db1d3cd51d9df4724b9cf35d57f", "start_char": 0, "end_char": 2589, "text_sha256": "b3301c8c680b4b3c6424dfb6677ae55839221db1d3cd51d9df4724b9cf35d57f"} [ino-p30357297] Effects of Myo-inositol on Type 1 Retinopathy of Prematurity Among Preterm Infants <28 Weeks' Gestational Age: A Randomized Clinical Trial. (2018). https://pubmed.ncbi.nlm.nih.gov/30357297/ DOI: 10.1001/jama.2018.14996
Complete structured claim and evidence
The main 250-mg scyllo-inositol versus placebo analysis found no significant benefit on cognition or daily-function coprimary outcomes.
Scyllo-inositol → Cognition and daily function in Alzheimer disease trials source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/21917766.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "12c45a11b8cd0ee3075caa1f7572feae2130af237934a0be5f388322b64a1040", "start_char": 0, "end_char": 1479, "text_sha256": "12c45a11b8cd0ee3075caa1f7572feae2130af237934a0be5f388322b64a1040"}
experimental_model
Randomized dose-ranging phase 2 trial
exposure
Scyllo-inositol (ELND005) 250, 1000 or 2000 mg twice daily versus placebo for up to 78 weeks
limitations
Distinct stereoisomer from myo-inositol. Higher-dose arms stopped for safety imbalance; biomarker changes do not establish clinical benefit.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Homo sapiens
plain_language
Changing the inositol form does not guarantee a neurological benefit.
primary_references
[ino-p21917766] A phase 2 randomized trial of ELND005, scyllo-inositol, in mild to moderate Alzheimer disease. (2011). https://pubmed.ncbi.nlm.nih.gov/21917766/ DOI: 10.1212/wnl.0b013e3182309fa5
tissue_or_cell_type
353 participants with mild-to-moderate Alzheimer disease
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 1471–1482
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized dose-ranging phase 2 trial · source_derived_draft · unverified_draft
### ino-scyllo-clinical The main 250-mg scyllo-inositol versus placebo analysis found no significant benefit on cognition or daily-function coprimary outcomes. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: Changing the inositol form does not guarantee a neurological benefit. organism: Homo sapiens tissue_or_cell_type: 353 participants with mild-to-moderate Alzheimer disease experimental_model: Randomized dose-ranging phase 2 trial limitations: Distinct stereoisomer from myo-inositol. Higher-dose arms stopped for safety imbalance; biomarker changes do not establish clinical benefit. exposure: Scyllo-inositol (ELND005) 250, 1000 or 2000 mg twice daily versus placebo for up to 78 weeks evidence_span: {"source_cache": "artifacts/inositol-research/21917766.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "12c45a11b8cd0ee3075caa1f7572feae2130af237934a0be5f388322b64a1040", "start_char": 0, "end_char": 1479, "text_sha256": "12c45a11b8cd0ee3075caa1f7572feae2130af237934a0be5f388322b64a1040"} [ino-p21917766] A phase 2 randomized trial of ELND005, scyllo-inositol, in mild to moderate Alzheimer disease. (2011). https://pubmed.ncbi.nlm.nih.gov/21917766/ DOI: 10.1212/wnl.0b013e3182309fa5
Complete structured claim and evidence
The 250-mg twice-daily scyllo-inositol group had reduced CSF amyloid-beta x-42 despite no significant clinical benefit.
Scyllo-inositol → CSF amyloid-beta x-42 concentration source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/21917766.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "12c45a11b8cd0ee3075caa1f7572feae2130af237934a0be5f388322b64a1040", "start_char": 0, "end_char": 1479, "text_sha256": "12c45a11b8cd0ee3075caa1f7572feae2130af237934a0be5f388322b64a1040"}
experimental_model
Randomized dose-ranging phase 2 trial
exposure
Scyllo-inositol (ELND005) 250, 1000 or 2000 mg twice daily versus placebo for up to 78 weeks
limitations
Distinct stereoisomer from myo-inositol. Higher-dose arms stopped for safety imbalance; biomarker changes do not establish clinical benefit.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Homo sapiens
plain_language
A biomarker moved without demonstrated improvement in how patients functioned.
primary_references
[ino-p21917766] A phase 2 randomized trial of ELND005, scyllo-inositol, in mild to moderate Alzheimer disease. (2011). https://pubmed.ncbi.nlm.nih.gov/21917766/ DOI: 10.1212/wnl.0b013e3182309fa5
tissue_or_cell_type
353 participants with mild-to-moderate Alzheimer disease
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 1484–1495
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized dose-ranging phase 2 trial · source_derived_draft · unverified_draft
### ino-scyllo-biomarker The 250-mg twice-daily scyllo-inositol group had reduced CSF amyloid-beta x-42 despite no significant clinical benefit. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: A biomarker moved without demonstrated improvement in how patients functioned. organism: Homo sapiens tissue_or_cell_type: 353 participants with mild-to-moderate Alzheimer disease experimental_model: Randomized dose-ranging phase 2 trial limitations: Distinct stereoisomer from myo-inositol. Higher-dose arms stopped for safety imbalance; biomarker changes do not establish clinical benefit. exposure: Scyllo-inositol (ELND005) 250, 1000 or 2000 mg twice daily versus placebo for up to 78 weeks evidence_span: {"source_cache": "artifacts/inositol-research/21917766.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "12c45a11b8cd0ee3075caa1f7572feae2130af237934a0be5f388322b64a1040", "start_char": 0, "end_char": 1479, "text_sha256": "12c45a11b8cd0ee3075caa1f7572feae2130af237934a0be5f388322b64a1040"} [ino-p21917766] A phase 2 randomized trial of ELND005, scyllo-inositol, in mild to moderate Alzheimer disease. (2011). https://pubmed.ncbi.nlm.nih.gov/21917766/ DOI: 10.1212/wnl.0b013e3182309fa5
Complete structured claim and evidence
The 1000- and 2000-mg twice-daily scyllo-inositol groups were stopped early after an imbalance of infections and deaths.
Scyllo-inositol → Trial infection and death imbalance source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/inositol-research/21917766.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "12c45a11b8cd0ee3075caa1f7572feae2130af237934a0be5f388322b64a1040", "start_char": 0, "end_char": 1479, "text_sha256": "12c45a11b8cd0ee3075caa1f7572feae2130af237934a0be5f388322b64a1040"}
experimental_model
Randomized dose-ranging phase 2 trial
exposure
Scyllo-inositol (ELND005) 250, 1000 or 2000 mg twice daily versus placebo for up to 78 weeks
limitations
Distinct stereoisomer from myo-inositol. Higher-dose arms stopped for safety imbalance; biomarker changes do not establish clinical benefit.
nutrient_topic
Inositol research collection; topical membership is not evidence of a direct dietary effect. · Inositol (stereoisomer family)
organism
Homo sapiens
plain_language
Higher-dose safety findings belong to this stereoisomer and regimen, and should remain visible.
primary_references
[ino-p21917766] A phase 2 randomized trial of ELND005, scyllo-inositol, in mild to moderate Alzheimer disease. (2011). https://pubmed.ncbi.nlm.nih.gov/21917766/ DOI: 10.1212/wnl.0b013e3182309fa5
tissue_or_cell_type
353 participants with mild-to-moderate Alzheimer disease
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17) · lines 1497–1508
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized dose-ranging phase 2 trial · source_derived_draft · unverified_draft
### ino-scyllo-safety The 1000- and 2000-mg twice-daily scyllo-inositol groups were stopped early after an imbalance of infections and deaths. Condition category: normal nutrient_topic: Inositol research collection; topical membership is not evidence of a direct dietary effect. plain_language: Higher-dose safety findings belong to this stereoisomer and regimen, and should remain visible. organism: Homo sapiens tissue_or_cell_type: 353 participants with mild-to-moderate Alzheimer disease experimental_model: Randomized dose-ranging phase 2 trial limitations: Distinct stereoisomer from myo-inositol. Higher-dose arms stopped for safety imbalance; biomarker changes do not establish clinical benefit. exposure: Scyllo-inositol (ELND005) 250, 1000 or 2000 mg twice daily versus placebo for up to 78 weeks evidence_span: {"source_cache": "artifacts/inositol-research/21917766.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "12c45a11b8cd0ee3075caa1f7572feae2130af237934a0be5f388322b64a1040", "start_char": 0, "end_char": 1479, "text_sha256": "12c45a11b8cd0ee3075caa1f7572feae2130af237934a0be5f388322b64a1040"} [ino-p21917766] A phase 2 randomized trial of ELND005, scyllo-inositol, in mild to moderate Alzheimer disease. (2011). https://pubmed.ncbi.nlm.nih.gov/21917766/ DOI: 10.1212/wnl.0b013e3182309fa5
Complete structured claim and evidence
Calcium binding participates in ITPR3 gating after IP3/ATP priming, with both active and inactive calcium-bound conformations resolved.
Calcium ion → Inositol 1,4,5-trisphosphate receptor type 3 / ITPR3 source_derived_draftungraded
Experimental context and source evidence
compartment_description
Cytosolic regulatory regions of ER channel
experimental_model
Recombinant human ITPR3; cryo-EM in ligand-bound gating states
limitations
Structural populations do not define a universal calcium threshold or prove all calcium-bound channels are active.
nutrient_topic
Calcium research collection; topical membership is not evidence of a direct dietary effect. · Calcium
organism
Homo sapiens
plain_language
Calcium helps control ITPR3 opening; binding does not guarantee that the channel stays open.
primary_references
[ca-schmitz2022] Structural basis for activation and gating of IP3 receptors (2022). https://pubmed.ncbi.nlm.nih.gov/35301323/ DOI: 10.1038/s41467-022-29073-2
research_relationship_category
regulation
tissue_or_cell_type
Recombinant ITPR3
Calcium: mechanism-first literature curation (2026-09-17) · lines 492–503
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human ITPR3; cryo-EM in ligand-bound gating states · source_derived_draft · unverified_draft
### ca-itpr3-calcium-coactivation Calcium binding participates in ITPR3 gating after IP3/ATP priming, with both active and inactive calcium-bound conformations resolved. Condition category: normal nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Calcium helps control ITPR3 opening; binding does not guarantee that the channel stays open. organism: Homo sapiens tissue_or_cell_type: Recombinant ITPR3 experimental_model: Recombinant human ITPR3; cryo-EM in ligand-bound gating states limitations: Structural populations do not define a universal calcium threshold or prove all calcium-bound channels are active. research_relationship_category: regulation compartment_description: Cytosolic regulatory regions of ER channel [ca-schmitz2022] Structural basis for activation and gating of IP3 receptors (2022). https://pubmed.ncbi.nlm.nih.gov/35301323/ DOI: 10.1038/s41467-022-29073-2
Complete structured claim and evidence
Human ITPR3 forms a calcium-release channel with an open pore in the IP3/ATP/Ca2+-bound structural state.
Inositol 1,4,5-trisphosphate receptor type 3 / ITPR3 → Calcium ion source_derived_draftungraded
Experimental context and source evidence
compartment_description
ER membrane
experimental_model
Recombinant human ITPR3; cryo-EM in ligand-bound gating states
limitations
Structure specifies ITPR3; it must not be relabeled as ITPR1 or a measurement of every receptor subtype.
nutrient_topic
Calcium research collection; topical membership is not evidence of a direct dietary effect. · Calcium
organism
Homo sapiens
plain_language
ITPR3 provides a route for calcium to leave the ER.
primary_references
[ca-schmitz2022] Structural basis for activation and gating of IP3 receptors (2022). https://pubmed.ncbi.nlm.nih.gov/35301323/ DOI: 10.1038/s41467-022-29073-2
research_relationship_category
transport
tissue_or_cell_type
Recombinant ITPR3
transport_effect
raises A calcium-release channel: the recorded direction is ER lumen to cytosol.
transport_or_reaction_direction
ER lumen to cytosol
transport_pool
cytosolic calcium A calcium-release channel: the recorded direction is ER lumen to cytosol.
Calcium: mechanism-first literature curation (2026-09-17) · lines 478–490
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human ITPR3; cryo-EM in ligand-bound gating states · source_derived_draft · unverified_draft
### ca-itpr3-er-calcium-channel Human ITPR3 forms a calcium-release channel with an open pore in the IP3/ATP/Ca2+-bound structural state. Condition category: normal nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: ITPR3 provides a route for calcium to leave the ER. organism: Homo sapiens tissue_or_cell_type: Recombinant ITPR3 experimental_model: Recombinant human ITPR3; cryo-EM in ligand-bound gating states limitations: Structure specifies ITPR3; it must not be relabeled as ITPR1 or a measurement of every receptor subtype. research_relationship_category: transport transport_or_reaction_direction: ER lumen to cytosol compartment_description: ER membrane [ca-schmitz2022] Structural basis for activation and gating of IP3 receptors (2022). https://pubmed.ncbi.nlm.nih.gov/35301323/ DOI: 10.1038/s41467-022-29073-2
Complete structured claim and evidence
Adding phytate to matched-Mg bread meals reduced fractional apparent Mg absorption in a dose-dependent pattern.
Phytic acid / phytate → Intestinal magnesium absorption source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Dietary phytate -> magnesium uptake; mineral content and fractional absorption are distinct.
experimental_model
Two human crossover stable-isotope studies, 8-9 adults each.
exposure
1.49 mmol phytate: 32.5% to 13.0%; 0.75 mmol: 32.2% to 24.0%; 3.6 mmol Mg per meal.
limitations
Absorption is measured; mineral complexation was not isolated. Does not show that whole grains are net Mg-poor.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Homo sapiens
plain_language
A food component can reduce how much magnesium reaches the body from a meal.
primary_references
[mg-bohn2004] Phytic acid added to white-wheat bread inhibits fractional apparent magnesium absorption in humans (2004). https://pubmed.ncbi.nlm.nih.gov/14985216/ DOI: 10.1093/ajcn/79.3.418
tissue_or_cell_type
Human intestinal absorption estimated by fecal isotope recovery
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1602–1613
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Two human crossover stable-isotope studies, 8-9 adults each. · source_derived_draft · unverified_draft
### mg-phytate-lowers-absorption Adding phytate to matched-Mg bread meals reduced fractional apparent Mg absorption in a dose-dependent pattern. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: A food component can reduce how much magnesium reaches the body from a meal. organism: Homo sapiens tissue_or_cell_type: Human intestinal absorption estimated by fecal isotope recovery experimental_model: Two human crossover stable-isotope studies, 8-9 adults each. limitations: Absorption is measured; mineral complexation was not isolated. Does not show that whole grains are net Mg-poor. cross_nutrient: Dietary phytate -> magnesium uptake; mineral content and fractional absorption are distinct. exposure: 1.49 mmol phytate: 32.5% to 13.0%; 0.75 mmol: 32.2% to 24.0%; 3.6 mmol Mg per meal. [mg-bohn2004] Phytic acid added to white-wheat bread inhibits fractional apparent magnesium absorption in humans (2004). https://pubmed.ncbi.nlm.nih.gov/14985216/ DOI: 10.1093/ajcn/79.3.418
Complete structured claim and evidence
Zinc absorption fractions were 32.8±2.3%, 26.9±2.4%, 39.4±2.4% and 26.2±2.3% (mean±SE) for moderate-Ca/low-phytate, moderate-Ca/high-phytate, high-Ca/low-phytate and high-Ca/high-phytate menus. Phytate reduced absorption; calcium did not significantly impair it.
Phytic acid / phytate → Intestinal zinc absorption source_derived_draftungraded
Experimental context and source evidence
absolute_absorption
Corresponding absolute absorption: 3.8±0.3, 3.0±0.3, 4.5±0.3 and 3.2±0.3 mg zinc/day (mean±SE).
cross_nutrient
Calcium (dietary_context); Zinc (measured_nutrient)
evidence_location
Indexed primary abstract.
evidence_span
{"source_cache": "artifacts/zinc-clinical-sources/hunt2009.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "d912d9f2c0890cde2ae13e9de7f1202bf130e661e3f14e13483563f179319f85", "utf8_bytes": 1659}
experimental_model
Two-by-two one-day feeding and 65Zn tracer study in ten healthy women
exposure
Approximately 700 versus 1800 mg calcium/day, and 440 versus 1800 mg phytate/day in conventional menus.
limitations
Short controlled menus in ten women; null calcium effect does not cover every formulation, population or dose.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Homo sapiens
plain_language
Phytate reduced zinc uptake in these menus, while extra calcium did not.
primary_references
[zn-clin-hunt2009] Dietary calcium does not exacerbate phytate inhibition of zinc absorption by women from conventional diets. (2009). https://pubmed.ncbi.nlm.nih.gov/19176739/ DOI: 10.3945/ajcn.2008.27175
tissue_or_cell_type
Intestinal absorption
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 1271–1285
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Two-by-two one-day feeding and 65Zn tracer study in ten healthy women · source_derived_draft · unverified_draft
### zn-clin-phytate-calcium Zinc absorption fractions were 32.8±2.3%, 26.9±2.4%, 39.4±2.4% and 26.2±2.3% (mean±SE) for moderate-Ca/low-phytate, moderate-Ca/high-phytate, high-Ca/low-phytate and high-Ca/high-phytate menus. Phytate reduced absorption; calcium did not significantly impair it. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: Phytate reduced zinc uptake in these menus, while extra calcium did not. organism: Homo sapiens tissue_or_cell_type: Intestinal absorption experimental_model: Two-by-two one-day feeding and 65Zn tracer study in ten healthy women limitations: Short controlled menus in ten women; null calcium effect does not cover every formulation, population or dose. exposure: Approximately 700 versus 1800 mg calcium/day, and 440 versus 1800 mg phytate/day in conventional menus. cross_nutrient: Calcium (dietary_context); Zinc (measured_nutrient) evidence_location: Indexed primary abstract. evidence_span: {"source_cache": "artifacts/zinc-clinical-sources/hunt2009.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "d912d9f2c0890cde2ae13e9de7f1202bf130e661e3f14e13483563f179319f85", "utf8_bytes": 1659} absolute_absorption: Corresponding absolute absorption: 3.8±0.3, 3.0±0.3, 4.5±0.3 and 3.2±0.3 mg zinc/day (mean±SE). [zn-clin-hunt2009] Dietary calcium does not exacerbate phytate inhibition of zinc absorption by women from conventional diets. (2009). https://pubmed.ncbi.nlm.nih.gov/19176739/ DOI: 10.3945/ajcn.2008.27175
Complete structured claim and evidence
At the same ascending phytate-P additions, seven-day calcium retention was 31%, 28%, 27%, 26%, 22%, 19%, 14% and 11%; reduction was significant from 100 mg phytate-P in this study.
Phytic acid / phytate → Whole-body calcium retention source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Calcium (retained_nutrient); Zinc (concurrently_measured_nutrient)
evidence_location
Indexed primary abstract.
evidence_span
{"source_cache": "artifacts/zinc-clinical-sources/hallberg2006.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "3a8556f5e4076009ed9adbf018205c8a3b2d0aaae43cccc866dc6be0271451d4", "utf8_bytes": 1603}
experimental_model
Human dual-radioisotope meal study: 40 subjects, 105 meals
exposure
Wheat-roll meals contained 3.1 mg zinc and 266 mg calcium; added sodium phytate supplied 0–250 mg phytate phosphorus.
limitations
Phytate-P mass is phosphorus mass, not total phytate mass. Seven-day calcium retention and zinc absorption are distinct endpoints; meal-specific significance levels are not universal thresholds.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Homo sapiens
plain_language
The same meal manipulation also reduced retained calcium.
primary_references
[zn-clin-hallberg2006] Absorption of zinc and retention of calcium: dose-dependent inhibition by phytate. (2006). https://pubmed.ncbi.nlm.nih.gov/16632176/ DOI: 10.1016/j.jtemb.2006.01.003
tissue_or_cell_type
Intestinal zinc absorption and whole-body calcium retention
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 1302–1315
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human dual-radioisotope meal study: 40 subjects, 105 meals · source_derived_draft · unverified_draft
### zn-clin-phytate-calcium-retention At the same ascending phytate-P additions, seven-day calcium retention was 31%, 28%, 27%, 26%, 22%, 19%, 14% and 11%; reduction was significant from 100 mg phytate-P in this study. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: The same meal manipulation also reduced retained calcium. organism: Homo sapiens tissue_or_cell_type: Intestinal zinc absorption and whole-body calcium retention experimental_model: Human dual-radioisotope meal study: 40 subjects, 105 meals limitations: Phytate-P mass is phosphorus mass, not total phytate mass. Seven-day calcium retention and zinc absorption are distinct endpoints; meal-specific significance levels are not universal thresholds. exposure: Wheat-roll meals contained 3.1 mg zinc and 266 mg calcium; added sodium phytate supplied 0–250 mg phytate phosphorus. cross_nutrient: Calcium (retained_nutrient); Zinc (concurrently_measured_nutrient) evidence_location: Indexed primary abstract. evidence_span: {"source_cache": "artifacts/zinc-clinical-sources/hallberg2006.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "3a8556f5e4076009ed9adbf018205c8a3b2d0aaae43cccc866dc6be0271451d4", "utf8_bytes": 1603} [zn-clin-hallberg2006] Absorption of zinc and retention of calcium: dose-dependent inhibition by phytate. (2006). https://pubmed.ncbi.nlm.nih.gov/16632176/ DOI: 10.1016/j.jtemb.2006.01.003
Complete structured claim and evidence
At added phytate-P levels of 0, 25, 50, 75, 100, 140, 175 and 250 mg, mean zinc absorption was 22%, 16%, 14%, 11%, 7%, 7%, 7% and 6%. Reductions were significant from 50 mg phytate-P in these meals.
Phytic acid / phytate → Intestinal zinc absorption source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Zinc (absorbed_nutrient); Calcium (meal_context)
evidence_location
Indexed primary abstract.
evidence_span
{"source_cache": "artifacts/zinc-clinical-sources/hallberg2006.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "3a8556f5e4076009ed9adbf018205c8a3b2d0aaae43cccc866dc6be0271451d4", "utf8_bytes": 1603}
experimental_model
Human dual-radioisotope meal study: 40 subjects, 105 meals
exposure
Wheat-roll meals contained 3.1 mg zinc and 266 mg calcium; added sodium phytate supplied 0–250 mg phytate phosphorus.
limitations
Phytate-P mass is phosphorus mass, not total phytate mass. Seven-day calcium retention and zinc absorption are distinct endpoints; meal-specific significance levels are not universal thresholds.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Homo sapiens
plain_language
Increasing phytate progressively reduced zinc uptake in the test meal.
primary_references
[zn-clin-hallberg2006] Absorption of zinc and retention of calcium: dose-dependent inhibition by phytate. (2006). https://pubmed.ncbi.nlm.nih.gov/16632176/ DOI: 10.1016/j.jtemb.2006.01.003
tissue_or_cell_type
Intestinal zinc absorption and whole-body calcium retention
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 1287–1300
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human dual-radioisotope meal study: 40 subjects, 105 meals · source_derived_draft · unverified_draft
### zn-clin-phytate-gradient At added phytate-P levels of 0, 25, 50, 75, 100, 140, 175 and 250 mg, mean zinc absorption was 22%, 16%, 14%, 11%, 7%, 7%, 7% and 6%. Reductions were significant from 50 mg phytate-P in these meals. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: Increasing phytate progressively reduced zinc uptake in the test meal. organism: Homo sapiens tissue_or_cell_type: Intestinal zinc absorption and whole-body calcium retention experimental_model: Human dual-radioisotope meal study: 40 subjects, 105 meals limitations: Phytate-P mass is phosphorus mass, not total phytate mass. Seven-day calcium retention and zinc absorption are distinct endpoints; meal-specific significance levels are not universal thresholds. exposure: Wheat-roll meals contained 3.1 mg zinc and 266 mg calcium; added sodium phytate supplied 0–250 mg phytate phosphorus. cross_nutrient: Zinc (absorbed_nutrient); Calcium (meal_context) evidence_location: Indexed primary abstract. evidence_span: {"source_cache": "artifacts/zinc-clinical-sources/hallberg2006.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "3a8556f5e4076009ed9adbf018205c8a3b2d0aaae43cccc866dc6be0271451d4", "utf8_bytes": 1603} [zn-clin-hallberg2006] Absorption of zinc and retention of calcium: dose-dependent inhibition by phytate. (2006). https://pubmed.ncbi.nlm.nih.gov/16632176/ DOI: 10.1016/j.jtemb.2006.01.003
Complete structured claim and evidence
Adding phytate, phosphate or ascorbic acid to the formula test meals did not significantly alter manganese absorption in adults.
Intestinal manganese absorption → Phytic acid / phytate source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Added ascorbic acid significantly counteracted the inhibition of radiolabeled nonheme iron absorption caused by sodium phytate in wheat-roll meals.
L-Ascorbic acid → Nonheme iron absorption source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Meal composition modifies the vitamin C/iron interaction.
experimental_model
Human alternate-day paired radiolabeled wheat-roll experiments.
exposure
Seven sodium phytate levels spanning 2–250 mg expressed as phytate phosphorus, with and without ascorbic acid; 55Fe/59Fe labels. Exact C dose and participant count are not extracted from the abstract.
limitations
Single-meal tracer result; does not prove full cancellation of inhibition or long-term correction of anemia.
nutrient_topic
Vitamin C research collection; topical membership is not evidence of a direct dietary effect. · Vitamin C
organism
Homo sapiens
plain_language
Vitamin C helped offset an iron-absorption inhibitor in the tested meals.
primary_references
[c-hallberg1989] Iron absorption in man: ascorbic acid and dose-dependent inhibition by phytate (1989). https://pubmed.ncbi.nlm.nih.gov/2911999/ DOI: 10.1093/ajcn/49.1.140
tissue_or_cell_type
Human blood or whole-person endpoints
Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1580–1591
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human alternate-day paired radiolabeled wheat-roll experiments. · source_derived_draft · unverified_draft
### c-phytate-iron-inhibition-counteraction Added ascorbic acid significantly counteracted the inhibition of radiolabeled nonheme iron absorption caused by sodium phytate in wheat-roll meals. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin C helped offset an iron-absorption inhibitor in the tested meals. organism: Homo sapiens tissue_or_cell_type: Human blood or whole-person endpoints experimental_model: Human alternate-day paired radiolabeled wheat-roll experiments. limitations: Single-meal tracer result; does not prove full cancellation of inhibition or long-term correction of anemia. exposure: Seven sodium phytate levels spanning 2–250 mg expressed as phytate phosphorus, with and without ascorbic acid; 55Fe/59Fe labels. Exact C dose and participant count are not extracted from the abstract. cross_nutrient: Meal composition modifies the vitamin C/iron interaction. [c-hallberg1989] Iron absorption in man: ascorbic acid and dose-dependent inhibition by phytate (1989). https://pubmed.ncbi.nlm.nih.gov/2911999/ DOI: 10.1093/ajcn/49.1.140
Complete structured claim and evidence
Intestinal Trpm7 deletion lowered magnesium availability in early postnatal mice.
Intestine-specific Trpm7-null mouse genotype → Serum magnesium concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence-system
Villin1-Cre conditional deletion and mineral phenotyping
experimental_model
Villin1-Cre conditional deletion and mineral phenotyping
limitations
Early developmental model; not a test of dietary Mg restriction.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Mouse
plain_language
Suckling mice required intestinal TRPM7 to maintain their magnesium supply.
primary_references
[mittermeier-2019-trpm7] TRPM7 is the central gatekeeper of intestinal mineral absorption essential for postnatal survival (2019). https://pubmed.ncbi.nlm.nih.gov/30770447/ DOI: 10.1073/pnas.1810633116
tissue
Intestinal enterocytes; serum
tissue_or_cell_type
Intestinal enterocytes; serum
trigger_kind
machinery_impairment Imported condition classification; unverified.
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 975–986
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Villin1-Cre conditional deletion and mineral phenotyping · source_derived_draft · unverified_draft
### intestinal-trpm7-loss-magnesium Intestinal Trpm7 deletion lowered magnesium availability in early postnatal mice. Condition category: machinery_impairment nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Suckling mice required intestinal TRPM7 to maintain their magnesium supply. organism: Mouse tissue_or_cell_type: Intestinal enterocytes; serum experimental_model: Villin1-Cre conditional deletion and mineral phenotyping limitations: Early developmental model; not a test of dietary Mg restriction. evidence-system: Villin1-Cre conditional deletion and mineral phenotyping tissue: Intestinal enterocytes; serum [mittermeier-2019-trpm7] TRPM7 is the central gatekeeper of intestinal mineral absorption essential for postnatal survival (2019). https://pubmed.ncbi.nlm.nih.gov/30770447/ DOI: 10.1073/pnas.1810633116
Complete structured claim and evidence
Intestinal Trpm7 deletion reduced serum and bone calcium in suckling mice.
Intestine-specific Trpm7-null mouse genotype → Serum calcium concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
TRPM7 is shared machinery for magnesium and calcium handling in this developmental model; causal Mg-to-Ca nutritional dependence was not isolated.
evidence-system
Conditional knockout; postnatal mineral phenotyping
experimental_model
Conditional knockout; postnatal mineral phenotyping
limitations
Shared channel loss; does not prove low Mg intake causes calcium malabsorption.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Mouse
plain_language
The same epithelial channel machinery supports calcium as well as magnesium supply.
primary_references
[mittermeier-2019-trpm7] TRPM7 is the central gatekeeper of intestinal mineral absorption essential for postnatal survival (2019). https://pubmed.ncbi.nlm.nih.gov/30770447/ DOI: 10.1073/pnas.1810633116
tissue
Intestine; serum and bone
tissue_or_cell_type
Intestine; serum and bone
trigger_kind
machinery_impairment Imported condition classification; unverified.
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 988–1000
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Conditional knockout; postnatal mineral phenotyping · source_derived_draft · unverified_draft
### intestinal-trpm7-loss-calcium Intestinal Trpm7 deletion reduced serum and bone calcium in suckling mice. Condition category: machinery_impairment nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The same epithelial channel machinery supports calcium as well as magnesium supply. organism: Mouse tissue_or_cell_type: Intestine; serum and bone experimental_model: Conditional knockout; postnatal mineral phenotyping limitations: Shared channel loss; does not prove low Mg intake causes calcium malabsorption. cross_nutrient: TRPM7 is shared machinery for magnesium and calcium handling in this developmental model; causal Mg-to-Ca nutritional dependence was not isolated. evidence-system: Conditional knockout; postnatal mineral phenotyping tissue: Intestine; serum and bone [mittermeier-2019-trpm7] TRPM7 is the central gatekeeper of intestinal mineral absorption essential for postnatal survival (2019). https://pubmed.ncbi.nlm.nih.gov/30770447/ DOI: 10.1073/pnas.1810633116
Complete structured claim and evidence
Intestinal Trpm7 deletion reduced circulating zinc in early postnatal mice.
Intestine-specific Trpm7-null mouse genotype → Serum zinc concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
Shared intestinal TRPM7 machinery links zinc and magnesium availability; Mg deficiency as the cause of Zn deficiency was not demonstrated.
evidence-system
Conditional intestinal knockout and mineral phenotyping
experimental_model
Conditional intestinal knockout and mineral phenotyping
limitations
Not evidence that magnesium supplementation universally increases zinc absorption.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Mouse
plain_language
A single epithelial machinery defect depleted zinc along with magnesium.
primary_references
[mittermeier-2019-trpm7] TRPM7 is the central gatekeeper of intestinal mineral absorption essential for postnatal survival (2019). https://pubmed.ncbi.nlm.nih.gov/30770447/ DOI: 10.1073/pnas.1810633116
tissue
Intestine; serum
tissue_or_cell_type
Intestine; serum
trigger_kind
machinery_impairment Imported condition classification; unverified.
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 1002–1014
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Conditional intestinal knockout and mineral phenotyping · source_derived_draft · unverified_draft
### intestinal-trpm7-loss-zinc Intestinal Trpm7 deletion reduced circulating zinc in early postnatal mice. Condition category: machinery_impairment nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: A single epithelial machinery defect depleted zinc along with magnesium. organism: Mouse tissue_or_cell_type: Intestine; serum experimental_model: Conditional intestinal knockout and mineral phenotyping limitations: Not evidence that magnesium supplementation universally increases zinc absorption. cross_nutrient: Shared intestinal TRPM7 machinery links zinc and magnesium availability; Mg deficiency as the cause of Zn deficiency was not demonstrated. evidence-system: Conditional intestinal knockout and mineral phenotyping tissue: Intestine; serum [mittermeier-2019-trpm7] TRPM7 is the central gatekeeper of intestinal mineral absorption essential for postnatal survival (2019). https://pubmed.ncbi.nlm.nih.gov/30770447/ DOI: 10.1073/pnas.1810633116
Complete structured claim and evidence
The deposited mouse alpha-TTP complex contains alpha-tocopherol and PI(4,5)P2, with phosphoinositide binding at the protein surface linked to opening of its ligand pocket.
Mouse alpha-tocopherol transfer protein → Phosphatidylinositol 4,5-bisphosphate source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
false
experimental_model
X-ray complex PDB 3W68
exposure
Crystallized protein with alpha-tocopherol and PI(4,5)P2.
limitations
Structure is mouse protein; no dietary phosphorus requirement or human affinity value is inferred.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Mus musculus protein
plain_language
A membrane phosphoinositide interacts with the vitamin E transfer protein.
primary_references
[kono2013] Impaired α-TTP-PIPs interaction underlies familial vitamin E deficiency. (2013). https://pubmed.ncbi.nlm.nih.gov/23599266/ DOI: 10.1126/science.1233508
tissue_or_cell_type
Purified protein-lipid complex
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 324–335
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · X-ray complex PDB 3W68 · source_derived_draft · unverified_draft
### ve-transport-mouse-ttp-pip2-binding The deposited mouse alpha-TTP complex contains alpha-tocopherol and PI(4,5)P2, with phosphoinositide binding at the protein surface linked to opening of its ligand pocket. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: A membrane phosphoinositide interacts with the vitamin E transfer protein. organism: Mus musculus protein tissue_or_cell_type: Purified protein-lipid complex experimental_model: X-ray complex PDB 3W68 limitations: Structure is mouse protein; no dietary phosphorus requirement or human affinity value is inferred. exposure: Crystallized protein with alpha-tocopherol and PI(4,5)P2. cross_nutrient: false [kono2013] Impaired α-TTP-PIPs interaction underlies familial vitamin E deficiency. (2013). https://pubmed.ncbi.nlm.nih.gov/23599266/ DOI: 10.1126/science.1233508
Complete structured claim and evidence
Engineered depletion of plasma-membrane PI(4,5)P2 impaired TTP-dependent NBD-alpha-tocopherol secretion in McARH7777 cells.
Plasma membrane PI(4,5)P2 depletion → TTP-dependent NBD-alpha-tocopherol secretion source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
false
experimental_model
Human TTP-expressing cells with membrane-targeted inositol phosphatase; Figure 5
exposure
IPP-CAAX expression; pulse loading with 10 µM serum-complexed NBD-alpha-tocopherol.
limitations
Phosphoinositide machinery perturbation and fluorescent analog; not dietary phosphorus or vitamin E deprivation as the causal contrast.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Rattus norvegicus cells; Homo sapiens TTP
plain_language
A membrane lipid signal was needed for efficient reporter export.
primary_references
[chung2016] Vitamin E and Phosphoinositides Regulate the Intracellular Localization of the Hepatic α-Tocopherol Transfer Protein. (2016). https://pubmed.ncbi.nlm.nih.gov/27307040/ DOI: 10.1074/jbc.m116.734210
tissue_or_cell_type
Hepatoma cells
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 363–374
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human TTP-expressing cells with membrane-targeted inositol phosphatase; Figure 5 · source_derived_draft · unverified_draft
### ve-transport-pip2-depletion-ttp-export Engineered depletion of plasma-membrane PI(4,5)P2 impaired TTP-dependent NBD-alpha-tocopherol secretion in McARH7777 cells. Condition category: machinery_impairment nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: A membrane lipid signal was needed for efficient reporter export. organism: Rattus norvegicus cells; Homo sapiens TTP tissue_or_cell_type: Hepatoma cells experimental_model: Human TTP-expressing cells with membrane-targeted inositol phosphatase; Figure 5 limitations: Phosphoinositide machinery perturbation and fluorescent analog; not dietary phosphorus or vitamin E deprivation as the causal contrast. exposure: IPP-CAAX expression; pulse loading with 10 µM serum-complexed NBD-alpha-tocopherol. cross_nutrient: false [chung2016] Vitamin E and Phosphoinositides Regulate the Intracellular Localization of the Hepatic α-Tocopherol Transfer Protein. (2016). https://pubmed.ncbi.nlm.nih.gov/27307040/ DOI: 10.1074/jbc.m116.734210
Complete structured claim and evidence
Human fibroblast ALPL hydrolyzed extracellular micromolar PLP at physiological pH; intact-cell and PI-PLC experiments supported lipid-anchored ecto-orientation.
Tissue-nonspecific alkaline phosphatase ALPL / TNAP → PLP source_derived_draftungraded
Experimental context and source evidence
evidence_location
Indexed abstract: intact/disrupted cells, PI-PLC and patient enzyme activity
experimental_model
Normal and hypophosphatasia human skin fibroblasts.
exposure
Extracellular PLP; intact versus disrupted cells; PI-PLC release.
limitations
Directly demonstrated in fibroblasts; does not itself measure brain entry.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
Cell-surface ALPL processes PLP outside the cell.
primary_references
[fedde1990] Alkaline phosphatase (tissue-nonspecific isoenzyme) is a phosphoethanolamine and pyridoxal-5'-phosphate ectophosphatase: normal and hypophosphatasia fibroblast study. (1990). https://pubmed.ncbi.nlm.nih.gov/2220817/
tissue_or_cell_type
Skin fibroblasts
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 309–320
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Normal and hypophosphatasia human skin fibroblasts. · source_derived_draft · unverified_draft
### b6-transport-alpl-ecto Human fibroblast ALPL hydrolyzed extracellular micromolar PLP at physiological pH; intact-cell and PI-PLC experiments supported lipid-anchored ecto-orientation. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Cell-surface ALPL processes PLP outside the cell. organism: Homo sapiens tissue_or_cell_type: Skin fibroblasts experimental_model: Normal and hypophosphatasia human skin fibroblasts. limitations: Directly demonstrated in fibroblasts; does not itself measure brain entry. exposure: Extracellular PLP; intact versus disrupted cells; PI-PLC release. evidence_location: Indexed abstract: intact/disrupted cells, PI-PLC and patient enzyme activity [fedde1990] Alkaline phosphatase (tissue-nonspecific isoenzyme) is a phosphoethanolamine and pyridoxal-5'-phosphate ectophosphatase: normal and hypophosphatasia fibroblast study. (1990). https://pubmed.ncbi.nlm.nih.gov/2220817/
Complete structured claim and evidence
ZDHHC6 palmitoylates IP3R, producing the palmitoylated receptor state.
ZDHHC6 → Palmitoylated IP3R source_derived_draftsupplied_source_only
Experimental context and source evidence
cell_type
· T cell
evidence_scope
Source-derived draft; primary-source verification required
organism
· Human
Selenium in immune cells · lines 22–28
Selenium immune-cell mechanism draft · supports · Source draft; model details require primary-source verification · source_derived_draft · unverified_draft
3. ZDHHC6 palmitoylates: • IP3R (all three isoforms) • calnexin • itself (autopalmitoylation) 4. Palmitoylated IP3R = stable, correctly localized, functional channel Non-palmitoylated IP3R = degraded / non-functional
Selenium: the molecular cascade · lines 135–143
Selenium molecular cascade draft · supports · Source draft; model details require primary-source verification · source_derived_draft · unverified_draft
**SELENOO** — the strangest protein in the set. Its bacterial ortholog **SelO** looks exactly like a protein kinase but binds ATP **flipped backwards** in the pocket, so it transfers **AMP instead of phosphate**. It's an **AMPylase**, activated by oxidative stress, AMPylating GAPDH and other redox enzymes. A pseudokinase that runs in reverse. Human SELENOO is mitochondrial and largely uncharacterized. **MSRB1 (SELENOR)** — redox control of the cytoskeleton. **MICAL1/2** oxidizes actin **Met44 and Met47** to the R-sulfoxide → actin depolymerizes. MSRB1 reduces it back → repolymerization. In macrophages this gates phagocytic cup formation. **Selenium is a direct rheostat on actin dynamics.** Almost nobody knows this. **SELENOK** — not a peroxidase. It's the essential cofactor for **ZDHHC6**, the palmitoyl transferase. No SELENOK → failed palmitoylation of IP3R, calnexin, and others → broken Ca²⁺ flux in T cells. **Selenium regulating lipid post-translational modification.** **SELENOI (EPT1)** — the only selenoprotein with **zero redox function**. It's an ethanolamine phosphotransferase making phosphatidylethanolamine. Mutations → hereditary spastic paraplegia **SPG81**. (And PE is exactly the lipid GPX4 protects. There's a loop there worth pulling on.) **SELENON** — ER membrane, regulates **RyR1** redox state and SERCA2b. Mutations → SEPN1-related myopathy / rigid spine syndrome.
Complete structured claim and evidence

Availability and dependencies

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

Valproate can alter synthesis indirectly in a yeast model

Condition: machinery_impairment · Valproate exposure in yeast expressing human ISYNA1.

Normal role: ISYNA1 helps sustain intracellular inositol.

Recorded consequence: Synthase activity and cellular inositol decreased; purified enzyme was not directly inhibited.

Scope: Human enzyme in yeast; not a measured human brain deficit.

Lithium inhibits a magnesium-dependent recycling enzyme

Condition: machinery_impairment · Li+ exposure in enzyme assays.

Normal role: IMPA1 regenerates free inositol.

Recorded consequence: Reduced monophosphatase activity.

Scope: Human enzyme kinetics; no claim that all clinical lithium effects use this route.

Loss of HMIT did not automatically deplete neuronal inositol

Condition: machinery_impairment · Targeted HMIT deletion in mice.

Normal role: Cells use multiple routes and pools for inositol handling.

Recorded consequence: Measured transport and homeostasis were unaffected in the reported assays.

Scope: Mouse knockout and the assays used; not exclusion of every intracellular role.

Synthesis failure makes some leukemia cells depend on import

Condition: machinery_impairment · ISYNA1 silencing in susceptible AML cells.

Normal role: Synthesis and SLC5A3-mediated uptake can sustain intracellular myo-inositol.

Recorded consequence: SLC5A3 becomes necessary for the nutrient dependency.

Scope: Cell and leukemia-model findings, not a universal property of cancer.

Low free inositol need not mean all membrane PI is depleted

Condition: machinery_impairment · SMIT1 knockout in mice.

Normal role: Free and lipid-bound inositol are regulated pools.

Recorded consequence: Brain free inositol fell profoundly while measured phosphatidylinositol did not.

Scope: Lethal mouse model; cannot infer a human threshold from the magnitude.

Removing an inositol-pyrophosphate enzyme changes insulin signaling

Condition: machinery_impairment · Targeted Ip6k1 deletion in mice.

Normal role: Ip6k1 contributes to 5-InsP7 signaling.

Recorded consequence: Increased Akt signaling and insulin sensitivity.

Scope: Mouse genetic model, not a dietary inositol deficiency or supplementation response.

InsP8-generating machinery supports phosphate export

Condition: machinery_impairment · PPIP5K knockout or loss of its kinase activity.

Normal role: XPR1 exports phosphate under inositol-pyrophosphate regulation.

Recorded consequence: Reduced phosphate efflux, with rescue by active PPIP5K1 or delivered InsP8 analog.

Scope: Cell models; mineralization in tumor-derived cells does not establish healthy bone benefit.

ATP depletion can destabilize a PIP2-sensitive cardiac current

Condition: machinery_impairment · ATP depletion during cardiac-cell recording.

Normal role: ATP-dependent processes maintain the membrane lipid environment.

Recorded consequence: Current rundown could be countered by exogenous PIP2.

Scope: Cardiac MIC current; do not equate it unconditionally with human TRPM7.

A membrane-lipid deficit can impair potassium-dependent blood-flow signaling

Condition: machinery_impairment · PIP2 depletion in a genetic small-vessel-disease mouse model.

Normal role: Endothelial Kir2.1 participates in neurovascular coupling.

Recorded consequence: Kir2.1 activity and functional hyperemia were impaired; PIP2 delivery rescued responses.

Scope: Mouse endothelial mechanism, not low dietary potassium or inositol.

Loss of SELENOK impairs the receiver rather than IP3 production

Condition: machinery_impairment · Genetic loss of SELENOK or knockdown of DHHC6.

Normal role: SELENOK supports the ER palmitoylation machinery.

Recorded consequence: Reduced IP3R abundance and calcium flux.

Scope: Cell and mouse immune models.

Recycling-enzyme failure can restrict neuronal development

Condition: machinery_impairment · Inherited IMPA1 loss of function in patient-derived cells.

Normal role: IMPA1 supplies free inositol through synthesis completion and recycling.

Recorded consequence: Neuronal progenitor proliferation and survival were impaired; culture supplementation rescued the phenotype.

Scope: Human cell model, not ordinary inadequate dietary intake.

Inositol rescue depended on particular PKC isoforms in mouse embryos

Condition: machinery_impairment · Isoform-selective inhibition in curly-tail embryos.

Normal role: Specific PKCs mediate an inositol-responsive developmental pathway.

Recorded consequence: Inositol no longer prevented neural tube defects when required PKCs were blocked.

Scope: Folate-resistant mouse model; not a universal cause of human neural tube defects.

The sources

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

Calcium: mechanism-first literature curation (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Inositol: synthesis, signaling, mineral interactions and conditional deficiency (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Manganese: enzyme cofactors, glycosylation, transport and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Selenium in immune cellsSelenium immune-cell mechanism draft · unverified_draftRead preserved source
Selenium: the molecular cascadeSelenium molecular cascade draft · unverified_draftRead preserved source
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source

Recorded disagreements

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

Early neonatal benefit was not reproduced in the larger trial, which found increased mortalityThe early randomized trial reported reduced retinopathy, motivating an expectation of neonatal benefit; the later larger randomized trial instead found more death or type 1 ROP and increased mortality. This is a genuine unresolved clinical evidence disagreement, not a correction of the ledger. Populations, care era, regimen duration and endpoints differ, so it is not an identical-experiment contradiction.Read the recorded disagreement
Reported myo-to-D-chiro conversion versus no conversion detected by mouse isotope tracingRat radiotracer/cytosolic studies reported myo-to-chiro epimerase activity, while the later dietary-control and stable-isotope study detected no endogenous DCI production or conversion from labeled myo-inositol in mice. The latter paper explicitly questions identification of chiro-inositol in earlier tracer work. Different species and assays may contribute but do not yet resolve the disagreement.Read the recorded disagreement

Open questions in this collection

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

Which inositol formulations and patient subgroups have reproducible clinical benefit?Trials differ in stereoisomer, co-interventions, populations, outcomes and risk. Null and harmful results prevent a blanket benefit claim.
Why did the large preterm-infant trial show increased mortality when early trials suggested benefit?Care era, gestational age, duration and competing outcomes are candidate explanations, not established causal mechanisms.
Does changing oral inositol reliably repair PIP2-sensitive mineral channels or GPI-dependent B6 processing in humans?The graph connects experimentally supported components, but these combined clinical interventions have not been demonstrated by the cited studies.
What are the molecular identity and tissue regulation of the reported myo-to-D-chiro epimerase activity?Rat cytosolic cofactor dependence and human theca-cell activity do not by themselves identify a specific human protein or a universal 40:1 intake ratio.
How do XPR1 partner proteins and experimental conditions determine specificity for InsP6 versus InsP8?The InsP8 transport-rescue experiments and the InsP6-bound XPR1-KIDINS220 structures test different ligands and conditions. They do not yet define one universal intracellular ligand hierarchy.
Which tissue-specific human deficits are limited by intake, synthesis, transport or recycling?The collected studies do not define a universal human dietary inositol deficiency syndrome or a blood threshold that predicts all intracellular pools.
Does the 2004 SMIT1 brain-study erratum change any retained result?The primary index lists 10.1016/j.ymgme.2004.06.012, but the correction text was not retrievable. Original-abstract findings are flagged as provisional pending inspection; the ledger does not adopt the paper title as proof against every lithium mechanism.

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

Evidence, AI assistance and curation standards

Inositol (stereoisomer family)

The mechanisms

Recombinant human ISYNA1 converted D-glucose 6-phosphate to 1D-myo-inositol 3-phosphate, an entry step in de novo inositol synthesis.

Human inositol monophosphatase hydrolyzes inositol monophosphates to regenerate free inositol.

Human placental phosphatidylinositol synthase used myo-inositol and CDP-diacylglycerol to form phosphatidylinositol.

PLCB3 hydrolyzed PI(4,5)P2 to produce soluble IP3 and membrane-associated diacylglycerol.

Applied IP3 releases calcium from a nonmitochondrial intracellular store in permeabilized pancreatic acinar cells.

TRPM7 currents depended on PI(4,5)P2 in the reported experiments, and PLC-mediated PIP2 hydrolysis inhibited the current.

Human MIOX catalyzes oxidative cleavage of myo-inositol to D-glucuronate.

IP6K enzymes form 5-InsP7 from InsP6.

PPIP5K kinase activity converts 5-InsP7 to 1,5-InsP8.

InsP8 bound the XPR1 N-terminal region with a reported dissociation constant of 180 nM.

Human SMIT2 expression increased myo-inositol uptake 37-fold relative to vector control in rat L6 cells.

Ovulation occurred in 19/22 D-chiro-inositol recipients versus 6/22 placebo recipients in the 1999 PCOS trial.

Human ISYNA1 used NAD+ in its catalytic assay, with a reported apparent Km of 8 micromolar.

K+ was among the stronger cation activators of purified human ISYNA1 under the tested assay conditions.

Zn2+ strongly inhibited purified human ISYNA1 in the cation comparison.

At 0.6 mM valproate, yeast expressing human ISYNA1 had approximately 25% less intracellular inositol; purified ISYNA1 was not inhibited at that concentration.

Mg2+ was essential for human inositol monophosphatase activity.

High Mg2+ concentrations inhibited human inositol monophosphatase uncompetitively with respect to substrate.

Li+ inhibited human inositol monophosphatase; parallel changes in Li+ and Mg2+ affinity across mutants supported a shared metal-binding site.

Human SMIT2 expression increased D-chiro-inositol uptake 159-fold in rat L6 cells.

Glucose competed for D-chiro-inositol uptake with a reported Ki of 6.1 mM in the SMIT2 expression system, without evidence that SMIT2 transported glucose in those assays.

Insulin exposure at 2 micromolar for 24 hours increased specific D-chiro-inositol uptake 18-fold in untransfected rat L6 cells.

A fitted five-state model of human SMIT2 currents included cooperative Na+ binding and a likely rate-limiting return of empty transporter.

Hypertonic MDCK culture increased sodium/myo-inositol transporter transcription, mRNA and transport activity with different time courses.

HMIT expressed in Xenopus oocytes mediated electrogenic proton-coupled myo-inositol uptake that increased as pH fell, with maximal tested activity near pH 5.

HMIT localized to the Golgi apparatus in primary cultured neurons; HMIT-mediated currents were not detected in rat neurons or brain slices.

HMIT-null mice did not show altered inositol transport or homeostasis in the reported analyses.

ISYNA1 transcriptional silencing characterized SLC5A3-dependent AML lines and produced an inositol auxotrophy.

Gain- and loss-of-function experiments supported redundant contributions of ISYNA1 synthesis and SLC5A3 transport to intracellular inositol and AML-cell fitness.

The original report described profound brain myo-inositol deficiency in its lethal mouse transport-loss model.

Despite severely reduced brain myo-inositol, measured brain phosphatidylinositol was not decreased in SMIT1-null mice.

Human MIOX contains a diiron catalytic center involved in oxygen-dependent inositol cleavage.

The human MIOX structure contained bound myo-inosose-1, an inhibitor rather than the normal myo-inositol substrate.

Purified human placental PI synthase required Mn2+ or Mg2+ for activity.

Mn2+ supported purified human placental PI synthase as an alternative activating divalent cation to Mg2+.

Ca2+ inhibited purified human placental PI synthase in the tested conditions.

Zn2+ inhibited purified human placental PI synthase in the tested conditions.

Recombinant human PI4K230, now designated PI4KA, showed phosphatidylinositol 4-kinase activity.

Human PIP5K1C_i4 displayed PI4P 5-kinase activity in vitro.

Human PIP5K1C_i5 also displayed PI4P 5-kinase activity in vitro.

The newly characterized 700-amino-acid PIP5K1C_i4 isoform localized to the nucleus.

The 707-amino-acid PIP5K1C_i5 isoform localized to vesicular structures.

Diacylglycerol was the lipid product of PLCB3-catalyzed PI(4,5)P2 hydrolysis.

G-alpha-q increased PLCB3 catalytic turnover in the membrane assay; relief of X-Y-linker autoinhibition was proposed as the mechanism.

G-beta-gamma and G-alpha-q could bind PLCB3 simultaneously, with dual stimulation following the product of their independent effects.

Human IPMK has IP3 3-kinase activity, producing inositol 1,3,4,5-tetrakisphosphate.

Human IPMK also has PI(4,5)P2 3-kinase activity, producing PI(3,4,5)P3.

Recombinant human IPMK phosphorylated IP3 at positions 3 and 6, reaching inositol 1,3,4,5,6-pentakisphosphate.

Human PTEN removed the 3-phosphate from PI(3,4,5)P3, forming PI(4,5)P2.

PTEN also showed 3-phosphatase activity toward soluble inositol 1,3,4,5-tetrakisphosphate.

Human IPPK used ATP to phosphorylate inositol 1,3,4,5,6-pentakisphosphate at position 2, producing InsP6.

The mouse Ippk structure identified a zinc-binding site involved in maintaining the enzyme’s structural organization.

5-InsP7 inhibited PDK1-dependent Akt phosphorylation and activation in the reported biochemical pathway.

Ip6k1-null mice showed increased insulin sensitivity and resistance to diet- or age-associated obesity.

PPIP5K proteins also possess InsP8 phosphatase activity, opposing their kinase reaction.

Inorganic phosphate inhibited PPIP5K InsP8 phosphatase activities by approximately 40–90% across 0–1 mM in the reported assays.

Phosphate increased PPIP5K2 5-InsP7 kinase activity approximately twofold across 0–5 mM.

Phosphate starvation lowered ATP and 5-InsP7, while InsP8 showed a larger and more sensitive response; levels recovered with phosphate replenishment.

PPIP5K knockout reduced XPR1-dependent phosphate efflux; wild-type PPIP5K1 rescued efflux whereas kinase-dead PPIP5K1 did not.

Liposomal delivery of a metabolically resistant InsP8 analog rescued phosphate efflux in PPIP5K-null cells; tested analogs of other inositol pyrophosphates did not.

XPR1 or PPIP5K knockout reduced phosphate export and accelerated the mineralization endpoint in Saos-2 cells.

In the presence of InsP6 and phosphate, human XPR1-KIDINS220 adopted an outward-open structure; InsP6 occupied SPX and juxtamembrane regions.

XPR1 alone remained closed even with InsP6 and phosphate in the tested structures, whereas the KIDINS220-containing complex could open.

PLC-dependent TRPM7 inhibition under whole-cell recording was observed only when intracellular Mg2+ was reduced below physiological levels.

PLC-coupled agonists activated TRPM7 currents under perforated-patch conditions that preserved physiological intracellular ions.

Hydrolyzable ATP supported maintenance of cardiac magnesium-inhibited cation current, whereas a nonhydrolyzable ATP analog did not substitute.

Exogenous PIP2 restored cardiac MIC current after rundown in ATP-depleted conditions.

PIP2 depletion in the studied mouse small-vessel disease model impaired endothelial Kir2.1 activity.

Soluble PIP2 administration restored Kir2.1-dependent neurovascular responses in the studied mouse model.

Rat arterial SMIT1 associated with Kv7.4/Kv7.5 channels in the reported interaction experiments.

Myo-inositol plus raffinose reduced methoxamine-induced contraction in rat arteries; Kv7 inhibition or knockdown prevented the effect.

Low-selenium culture conditions were associated with defective IP3R palmitoylation and reduced receptor expression in the SELENOK study.

SELENOK deficiency did not impair receptor-induced IP3 production in the reported experiments.

SELENOK and DHHC6 interacted at the ER membrane through SH3-related binding interactions.

DHHC6 knockdown reduced IP3R expression and IP3R-dependent calcium flux.

GPI N-acetylglucosaminyltransferase initiates anchor biosynthesis by transferring GlcNAc from UDP-GlcNAc to PI.

Human ARV1 associated with PIGQ; disrupting that association removed ARV1-mediated enhancement of GPI-GnT activity.

ARV1-containing GPI-GnT used PI more efficiently than the ARV1-less complex in vitro.