Inorganic pyrophosphate

compartment_description

Extracellular matrix and vesicle surface

experimental_model

Genetic and ex vivo pyrophosphate/mineralization experiments

limitations

Pi and PPi labels pool protonation states; this is not evidence that calcium activates TNAP.

nutrient_topic

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

organism

Mus musculus

plain_language

TNAP removes a local brake on calcium phosphate crystal growth.

primary_references

[hessle2002] Tissue-nonspecific alkaline phosphatase and plasma cell membrane glycoprotein-1 are central antagonistic regulators of bone mineralization (2002). https://pmc.ncbi.nlm.nih.gov/articles/PMC123160/ DOI: 10.1073/pnas.142063399

tissue_or_cell_type

Osteoblast matrix and matrix vesicles

Calcium: mechanism-first literature curation (2026-09-17) · lines 931–941

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Genetic and ex vivo pyrophosphate/mineralization experiments · source_derived_draft · unverified_draft

### alpl-pyrophosphate-hydrolysis ALPL/TNAP hydrolyzes extracellular pyrophosphate to inorganic phosphate, reducing an inhibitor of matrix mineralization. Condition category: normal nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: TNAP removes a local brake on calcium phosphate crystal growth. organism: Mus musculus tissue_or_cell_type: Osteoblast matrix and matrix vesicles experimental_model: Genetic and ex vivo pyrophosphate/mineralization experiments limitations: Pi and PPi labels pool protonation states; this is not evidence that calcium activates TNAP. compartment_description: Extracellular matrix and vesicle surface [hessle2002] Tissue-nonspecific alkaline phosphatase and plasma cell membrane glycoprotein-1 are central antagonistic regulators of bone mineralization (2002). https://pmc.ncbi.nlm.nih.gov/articles/PMC123160/ DOI: 10.1073/pnas.142063399

availability_state

machinery_impairment Imported condition classification; unverified.

experimental_model

Single versus combined Alpl/Enpp1 knockout

limitations

The genetic rescue supports local PPi control; it is not a calcium-supplement experiment.

nutrient_topic

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

organism

Mus musculus

plain_language

Mineral formation depends on controlling an inhibitor as well as supplying calcium.

primary_references

[hessle2002] Tissue-nonspecific alkaline phosphatase and plasma cell membrane glycoprotein-1 are central antagonistic regulators of bone mineralization (2002). https://pmc.ncbi.nlm.nih.gov/articles/PMC123160/ DOI: 10.1073/pnas.142063399

tissue_or_cell_type

Bone and cultured osteoblast matrix

trigger_kind

machinery_impairment Imported condition classification; unverified.

Calcium: mechanism-first literature curation (2026-09-17) · lines 943–952

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Single versus combined Alpl/Enpp1 knockout · source_derived_draft · unverified_draft

### pyrophosphate-restrains-mineral-deposition In Alpl-deficient mice and osteoblast preparations, excess pyrophosphate accompanied poor mineralization; removing Enpp1 normalized pyrophosphate and improved mineral deposition. Condition category: machinery_impairment nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Mineral formation depends on controlling an inhibitor as well as supplying calcium. organism: Mus musculus tissue_or_cell_type: Bone and cultured osteoblast matrix experimental_model: Single versus combined Alpl/Enpp1 knockout limitations: The genetic rescue supports local PPi control; it is not a calcium-supplement experiment. [hessle2002] Tissue-nonspecific alkaline phosphatase and plasma cell membrane glycoprotein-1 are central antagonistic regulators of bone mineralization (2002). https://pmc.ncbi.nlm.nih.gov/articles/PMC123160/ DOI: 10.1073/pnas.142063399

compartment_description

Extracellular medium to oocyte

experimental_model

Heterologous expression and radiotracer uptake

limitations

Influx in this model does not establish physiological PPi efflux; retain alongside later ATP-release results.

nutrient_topic

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

organism

Mus musculus protein in Xenopus laevis oocytes

plain_language

An earlier assay measured movement into an egg cell, not export from human bone cells.

primary_references

[gurley2006] Biochemical and genetic analysis of ANK in arthritis and bone disease (2006). https://pubmed.ncbi.nlm.nih.gov/17186460/ DOI: 10.1086/509881

tissue_or_cell_type

Oocyte plasma membrane

Calcium: mechanism-first literature curation (2026-09-17) · lines 988–998

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

### ank-dependent-ppi-uptake-oocytes Mouse ANK expression increased saturable radiolabeled PPi uptake into Xenopus oocytes. Condition category: normal nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: An earlier assay measured movement into an egg cell, not export from human bone cells. organism: Mus musculus protein in Xenopus laevis oocytes tissue_or_cell_type: Oocyte plasma membrane experimental_model: Heterologous expression and radiotracer uptake limitations: Influx in this model does not establish physiological PPi efflux; retain alongside later ATP-release results. compartment_description: Extracellular medium to oocyte [gurley2006] Biochemical and genetic analysis of ANK in arthritis and bone disease (2006). https://pubmed.ncbi.nlm.nih.gov/17186460/ DOI: 10.1086/509881

compartment_description

Plasma membrane

experimental_model

Ank genetics and cell PPi measurements

limitations

Historical hypothesis, not a current unconditional transport assignment; later ATP/ENPP1 experiments require qualification.

nutrient_topic

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

organism

Mus musculus protein; cultured mammalian cells

plain_language

An older transport explanation was inferred from changes in PPi distribution.

primary_references

[ho2000] Role of the mouse ank gene in control of tissue calcification and arthritis (2000). https://pubmed.ncbi.nlm.nih.gov/10894769/ DOI: 10.1126/science.289.5477.265

tissue_or_cell_type

Joint-calcification context

Calcium: mechanism-first literature curation (2026-09-17) · lines 976–986

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Ank genetics and cell PPi measurements · source_derived_draft · unverified_draft

### ankh-historical-direct-ppi-export-hypothesis Early ANK-dependent changes in cellular and extracellular PPi motivated a proposal that ANK directly exports PPi. Condition category: normal nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: An older transport explanation was inferred from changes in PPi distribution. organism: Mus musculus protein; cultured mammalian cells tissue_or_cell_type: Joint-calcification context experimental_model: Ank genetics and cell PPi measurements limitations: Historical hypothesis, not a current unconditional transport assignment; later ATP/ENPP1 experiments require qualification. compartment_description: Plasma membrane [ho2000] Role of the mouse ank gene in control of tissue calcification and arthritis (2000). https://pubmed.ncbi.nlm.nih.gov/10894769/ DOI: 10.1126/science.289.5477.265

compartment_description

Extracellular space

experimental_model

ENPP1-proficient versus deficient cells

limitations

Other ectonucleotidases compete for ATP; PPi is not synonymous with orthophosphate.

nutrient_topic

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

organism

Homo sapiens

plain_language

An extracellular enzyme converts exported ATP into a mineralization inhibitor.

primary_references

[szeri2022] The mineralization regulator ANKH mediates cellular efflux of ATP, not pyrophosphate (2022). https://pmc.ncbi.nlm.nih.gov/articles/PMC9098669/ DOI: 10.1002/jbmr.4528

tissue_or_cell_type

HEK293 extracellular medium

Calcium: mechanism-first literature curation (2026-09-17) · lines 1012–1022

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · ENPP1-proficient versus deficient cells · source_derived_draft · unverified_draft

### enpp1-atp-to-pyrophosphate ENPP1 converts extracellular ATP into AMP and PPi; ANKH-expressing cells lacking ENPP1 released ATP without the accompanying PPi accumulation. Condition category: normal nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: An extracellular enzyme converts exported ATP into a mineralization inhibitor. organism: Homo sapiens tissue_or_cell_type: HEK293 extracellular medium experimental_model: ENPP1-proficient versus deficient cells limitations: Other ectonucleotidases compete for ATP; PPi is not synonymous with orthophosphate. compartment_description: Extracellular space [szeri2022] The mineralization regulator ANKH mediates cellular efflux of ATP, not pyrophosphate (2022). https://pmc.ncbi.nlm.nih.gov/articles/PMC9098669/ DOI: 10.1002/jbmr.4528

cross_nutrient

Vitamin D–calcium–phosphate regulation.

evidence_locator

Figure 6; Results: Increased circulating 1,25(OH)2D levels impair mineralization by upregulating mineralization inhibitors

evidence_scope

D3 active metabolite or VDR machinery experiment; not a direct D2-versus-D3 comparison.

experimental_model

Differentiated primary Vdr-intact mouse osteoblasts; conditioned-medium pyrophosphate normalized to DNA

exposure

10^-8 M calcitriol for 4 days after osteogenic differentiation.

limitations

Direct culture result does not imply that usual dietary vitamin D damages bone; physiological outcome also depends on intestinal mineral delivery.

nutrient

Vitamin D2 and D3 · Vitamin D2 and D3

nutrient_topic

Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin D2 and D3

organism

Mus musculus

plain_language

In this model, active vitamin D increased a molecule that restrains mineral deposition.

primary_references

[vdm-lieben2012] Normocalcemia is maintained in mice under conditions of calcium malabsorption by vitamin D-induced inhibition of bone mineralization. (2012). https://pubmed.ncbi.nlm.nih.gov/22523068/ DOI: 10.1172/jci45890

tissue_or_cell_type

Osteoblast culture

Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 809–823

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Differentiated primary Vdr-intact mouse osteoblasts; conditioned-medium pyrophosphate normalized to DNA · source_derived_draft · unverified_draft

### vdm-calcitriol-increases-extracellular-ppi Calcitriol treatment increased extracellular pyrophosphate in differentiated Vdr-intact mouse osteoblast cultures. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: In this model, active vitamin D increased a molecule that restrains mineral deposition. organism: Mus musculus tissue_or_cell_type: Osteoblast culture experimental_model: Differentiated primary Vdr-intact mouse osteoblasts; conditioned-medium pyrophosphate normalized to DNA limitations: Direct culture result does not imply that usual dietary vitamin D damages bone; physiological outcome also depends on intestinal mineral delivery. exposure: 10^-8 M calcitriol for 4 days after osteogenic differentiation. cross_nutrient: Vitamin D–calcium–phosphate regulation. evidence_locator: Figure 6; Results: Increased circulating 1,25(OH)2D levels impair mineralization by upregulating mineralization inhibitors nutrient: Vitamin D2 and D3 evidence_scope: D3 active metabolite or VDR machinery experiment; not a direct D2-versus-D3 comparison. [vdm-lieben2012] Normocalcemia is maintained in mice under conditions of calcium malabsorption by vitamin D-induced inhibition of bone mineralization. (2012). https://pubmed.ncbi.nlm.nih.gov/22523068/ DOI: 10.1172/jci45890

cross_nutrient

Vitamin D–calcium–phosphate regulation.

evidence_locator

Figure 6 and adjacent Results: mineralization restored by TNAP

evidence_scope

D3 active metabolite or VDR machinery experiment; not a direct D2-versus-D3 comparison.

experimental_model

Differentiated primary mouse osteoblasts; Alizarin red mineralization and conditioned-medium pyrophosphate assays

exposure

10^-8 M calcitriol and 1 U/mL added TNAP for 4 days; companion cultures tested 5 x 10^-6 M pyrophosphate.

limitations

Enzyme-addition culture rescue supports pyrophosphate involvement; it does not quantify human bone outcomes or establish the contribution of each calcitriol-regulated gene.

nutrient

Vitamin D2 and D3 · Vitamin D2 and D3

nutrient_topic

Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin D2 and D3

organism

Mus musculus

plain_language

Removing the pyrophosphate brake restored mineral deposition in the treated cultures.

primary_references

[vdm-lieben2012] Normocalcemia is maintained in mice under conditions of calcium malabsorption by vitamin D-induced inhibition of bone mineralization. (2012). https://pubmed.ncbi.nlm.nih.gov/22523068/ DOI: 10.1172/jci45890

tissue_or_cell_type

Osteoblast extracellular matrix

Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 825–839

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Differentiated primary mouse osteoblasts; Alizarin red mineralization and conditioned-medium pyrophosphate assays · source_derived_draft · unverified_draft

### vdm-tnap-rescues-calcitriol-culture-mineralization Added TNAP restored mineralization in calcitriol-treated differentiated mouse osteoblast cultures while lowering extracellular pyrophosphate. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Removing the pyrophosphate brake restored mineral deposition in the treated cultures. organism: Mus musculus tissue_or_cell_type: Osteoblast extracellular matrix experimental_model: Differentiated primary mouse osteoblasts; Alizarin red mineralization and conditioned-medium pyrophosphate assays limitations: Enzyme-addition culture rescue supports pyrophosphate involvement; it does not quantify human bone outcomes or establish the contribution of each calcitriol-regulated gene. exposure: 10^-8 M calcitriol and 1 U/mL added TNAP for 4 days; companion cultures tested 5 x 10^-6 M pyrophosphate. cross_nutrient: Vitamin D–calcium–phosphate regulation. evidence_locator: Figure 6 and adjacent Results: mineralization restored by TNAP nutrient: Vitamin D2 and D3 evidence_scope: D3 active metabolite or VDR machinery experiment; not a direct D2-versus-D3 comparison. [vdm-lieben2012] Normocalcemia is maintained in mice under conditions of calcium malabsorption by vitamin D-induced inhibition of bone mineralization. (2012). https://pubmed.ncbi.nlm.nih.gov/22523068/ DOI: 10.1172/jci45890

evidence_location

FAD synthesis and reverse pyrophosphorolysis assays

experimental_model

Purified recombinant human FADS2 catalytic assays

exposure

ATP and FMN in FAD-synthesis assays.

limitations

Adenylylation is distinct from RFK phosphorylation; reaction products should not be conflated.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Homo sapiens

plain_language

FLAD1 performs the second activation step, making FAD from FMN.

primary_references

[transport-fads2-2011] Human FAD synthase (isoform 2): a component of the machinery that delivers FAD to apo-flavoproteins. (2011). https://pubmed.ncbi.nlm.nih.gov/21951714/ DOI: 10.1111/j.1742-4658.2011.08368.x

tissue_or_cell_type

Purified protein

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 320–331

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified recombinant human FADS2 catalytic assays · source_derived_draft · unverified_draft

### transport-flad1-adenylylation Human FAD synthase isoform 2 adenylylates FMN with ATP to form FAD and pyrophosphate. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: FLAD1 performs the second activation step, making FAD from FMN. organism: Homo sapiens tissue_or_cell_type: Purified protein experimental_model: Purified recombinant human FADS2 catalytic assays limitations: Adenylylation is distinct from RFK phosphorylation; reaction products should not be conflated. exposure: ATP and FMN in FAD-synthesis assays. evidence_location: FAD synthesis and reverse pyrophosphorolysis assays [transport-fads2-2011] Human FAD synthase (isoform 2): a component of the machinery that delivers FAD to apo-flavoproteins. (2011). https://pubmed.ncbi.nlm.nih.gov/21951714/ DOI: 10.1111/j.1742-4658.2011.08368.x

evidence_span

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experimental_model

Purified human NAMPT reaction monitoring by 1H/31P NMR and substrate/product crystallography

exposure

Biochemical or structural assay; no dietary intervention

limitations

Purified-enzyme evidence does not establish dietary intake requirements or clinical outcomes.

nutrient_topic

Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)

organism

Homo sapiens

plain_language

Nicotinamide salvage first makes NMN.

primary_references

[b3-pre-nampt2009] Structure and reaction mechanism of human nicotinamide phosphoribosyltransferase. (2010). https://pubmed.ncbi.nlm.nih.gov/19819904/ DOI: 10.1093/jb/mvp152

tissue_or_cell_type

Purified recombinant protein; no intact tissue

Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 369–380

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human NAMPT reaction monitoring by 1H/31P NMR and substrate/product crystallography · source_derived_draft · unverified_draft

### b3-pre-nampt-reaction Human NAMPT converts nicotinamide and PRPP to nicotinamide mononucleotide and pyrophosphate. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Nicotinamide salvage first makes NMN. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Purified human NAMPT reaction monitoring by 1H/31P NMR and substrate/product crystallography limitations: Purified-enzyme evidence does not establish dietary intake requirements or clinical outcomes. exposure: Biochemical or structural assay; no dietary intervention evidence_span: {"source_cache": "artifacts/niacin-precursors-sources/nampt2009.abstract.txt", "locator": "Indexed primary abstract", "start_char": 0, "end_char": 1272, "file_sha256": "b67ca4decafccfc4132deba87ffddf2114e60542c77fa4354165d414aa0f13c5", "text_sha256": "b67ca4decafccfc4132deba87ffddf2114e60542c77fa4354165d414aa0f13c5"} [b3-pre-nampt2009] Structure and reaction mechanism of human nicotinamide phosphoribosyltransferase. (2010). https://pubmed.ncbi.nlm.nih.gov/19819904/ DOI: 10.1093/jb/mvp152

evidence_span

{"source_cache": "artifacts/niacin-precursors-sources/nampt2009.abstract.txt", "locator": "Indexed primary abstract", "start_char": 0, "end_char": 1272, "file_sha256": "b67ca4decafccfc4132deba87ffddf2114e60542c77fa4354165d414aa0f13c5", "text_sha256": "b67ca4decafccfc4132deba87ffddf2114e60542c77fa4354165d414aa0f13c5"}

experimental_model

Purified human NAMPT reaction monitoring by 1H/31P NMR and substrate/product crystallography

exposure

Biochemical or structural assay; no dietary intervention

limitations

An isolated reaction equilibrium does not establish net intracellular salvage flux.

nutrient_topic

Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)

organism

Homo sapiens

plain_language

This isolated chemical reaction can run in either direction.

primary_references

[b3-pre-nampt2009] Structure and reaction mechanism of human nicotinamide phosphoribosyltransferase. (2010). https://pubmed.ncbi.nlm.nih.gov/19819904/ DOI: 10.1093/jb/mvp152

tissue_or_cell_type

Purified recombinant protein; no intact tissue

Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 382–393

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human NAMPT reaction monitoring by 1H/31P NMR and substrate/product crystallography · source_derived_draft · unverified_draft

### b3-pre-nampt-reversible NMR monitoring demonstrated reversibility of the purified human NAMPT reaction; the measured equilibrium constant was 0.14 under the study conditions. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: This isolated chemical reaction can run in either direction. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Purified human NAMPT reaction monitoring by 1H/31P NMR and substrate/product crystallography limitations: An isolated reaction equilibrium does not establish net intracellular salvage flux. exposure: Biochemical or structural assay; no dietary intervention evidence_span: {"source_cache": "artifacts/niacin-precursors-sources/nampt2009.abstract.txt", "locator": "Indexed primary abstract", "start_char": 0, "end_char": 1272, "file_sha256": "b67ca4decafccfc4132deba87ffddf2114e60542c77fa4354165d414aa0f13c5", "text_sha256": "b67ca4decafccfc4132deba87ffddf2114e60542c77fa4354165d414aa0f13c5"} [b3-pre-nampt2009] Structure and reaction mechanism of human nicotinamide phosphoribosyltransferase. (2010). https://pubmed.ncbi.nlm.nih.gov/19819904/ DOI: 10.1093/jb/mvp152

evidence_span

{"source_cache": "artifacts/niacin-precursors-sources/naprt2015.abstract.txt", "locator": "Indexed primary abstract", "start_char": 0, "end_char": 1606, "file_sha256": "df6e36cf3464d4cda171d06ee24065532dee0d8b5fd5c3ccafcb1cc8df951bbe", "text_sha256": "df6e36cf3464d4cda171d06ee24065532dee0d8b5fd5c3ccafcb1cc8df951bbe"}

experimental_model

Recombinant human NAPRT crystallography and docking; purified protein, no intact tissue

exposure

Biochemical or structural assay; no dietary intervention

limitations

Purified-enzyme evidence does not establish dietary intake requirements or clinical outcomes.

nutrient_topic

Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)

organism

Homo sapiens

plain_language

Nicotinic acid enters its NAD-building route through NAPRT.

primary_references

[b3-pre-naprt2015] Crystal structure of human nicotinic acid phosphoribosyltransferase. (2015). https://pubmed.ncbi.nlm.nih.gov/26042198/ DOI: 10.1016/j.fob.2015.05.002

tissue_or_cell_type

Purified recombinant protein; no intact tissue

Niacin: NAD metabolism, deficiency and nutrient interactions (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 · Recombinant human NAPRT crystallography and docking; purified protein, no intact tissue · source_derived_draft · unverified_draft

### b3-pre-naprt-reaction Human NAPRT catalyzes phosphoribosyl transfer from PRPP to nicotinic acid, producing nicotinic acid mononucleotide and pyrophosphate. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Nicotinic acid enters its NAD-building route through NAPRT. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Recombinant human NAPRT crystallography and docking; purified protein, no intact tissue limitations: Purified-enzyme evidence does not establish dietary intake requirements or clinical outcomes. exposure: Biochemical or structural assay; no dietary intervention evidence_span: {"source_cache": "artifacts/niacin-precursors-sources/naprt2015.abstract.txt", "locator": "Indexed primary abstract", "start_char": 0, "end_char": 1606, "file_sha256": "df6e36cf3464d4cda171d06ee24065532dee0d8b5fd5c3ccafcb1cc8df951bbe", "text_sha256": "df6e36cf3464d4cda171d06ee24065532dee0d8b5fd5c3ccafcb1cc8df951bbe"} [b3-pre-naprt2015] Crystal structure of human nicotinic acid phosphoribosyltransferase. (2015). https://pubmed.ncbi.nlm.nih.gov/26042198/ DOI: 10.1016/j.fob.2015.05.002

evidence_span

{"source_cache": "artifacts/niacin-precursors-sources/qprt2016.paragraphs.txt", "locator": "Normalized full-text paragraphs 13–15 (0-based)", "start_char": 10597, "end_char": 15612, "file_sha256": "85fcc4a79a17f4f3846301f67698a444c3c9930829e167d86a96adbb72d830e6", "text_sha256": "8da78d25a53af6507018eece4ce553705dc505d0b169f678affad49ee21b10f6"}

experimental_model

Purified recombinant human QPRT crystallography, calorimetry and oligomer studies

exposure

Biochemical or structural assay; no dietary intervention

limitations

Structural and biochemical enzyme study; does not establish how much dietary tryptophan becomes NAD in a person.

nutrient_topic

Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)

organism

Homo sapiens

plain_language

Quinolinate enters the same deamidated mononucleotide route used by nicotinic acid.

primary_references

[b3-pre-qprt2016] Structural Insights into the Quaternary Catalytic Mechanism of Hexameric Human Quinolinate Phosphoribosyltransferase, a Key Enzyme in de novo NAD Biosynthesis. (2016). https://pubmed.ncbi.nlm.nih.gov/26805589/ DOI: 10.1038/srep19681

supporting_evidence_spans

[{"source_cache": "artifacts/niacin-precursors-sources/qprt2016.paragraphs.txt", "locator": "Normalized full-text paragraphs 4–4 (0-based)", "start_char": 1453, "end_char": 3871, "file_sha256": "85fcc4a79a17f4f3846301f67698a444c3c9930829e167d86a96adbb72d830e6", "text_sha256": "be14ed97ccf53b635f2cb35969188ce42c84dd739db897a24cbf3e65d8a3e3d1"}]

tissue_or_cell_type

Purified recombinant protein; no intact tissue

Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 537–549

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified recombinant human QPRT crystallography, calorimetry and oligomer studies · source_derived_draft · unverified_draft

### b3-pre-qprt-namn Human QPRT converts quinolinate and PRPP toward nicotinic acid mononucleotide; the human enzyme structures resolve reactant quinolinate and product NaMN complexes. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Quinolinate enters the same deamidated mononucleotide route used by nicotinic acid. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Purified recombinant human QPRT crystallography, calorimetry and oligomer studies limitations: Structural and biochemical enzyme study; does not establish how much dietary tryptophan becomes NAD in a person. exposure: Biochemical or structural assay; no dietary intervention evidence_span: {"source_cache": "artifacts/niacin-precursors-sources/qprt2016.paragraphs.txt", "locator": "Normalized full-text paragraphs 13–15 (0-based)", "start_char": 10597, "end_char": 15612, "file_sha256": "85fcc4a79a17f4f3846301f67698a444c3c9930829e167d86a96adbb72d830e6", "text_sha256": "8da78d25a53af6507018eece4ce553705dc505d0b169f678affad49ee21b10f6"} supporting_evidence_spans: [{"source_cache": "artifacts/niacin-precursors-sources/qprt2016.paragraphs.txt", "locator": "Normalized full-text paragraphs 4–4 (0-based)", "start_char": 1453, "end_char": 3871, "file_sha256": "85fcc4a79a17f4f3846301f67698a444c3c9930829e167d86a96adbb72d830e6", "text_sha256": "be14ed97ccf53b635f2cb35969188ce42c84dd739db897a24cbf3e65d8a3e3d1"}] [b3-pre-qprt2016] Structural Insights into the Quaternary Catalytic Mechanism of Hexameric Human Quinolinate Phosphoribosyltransferase, a Key Enzyme in de novo NAD Biosynthesis. (2016). https://pubmed.ncbi.nlm.nih.gov/26805589/ DOI: 10.1038/srep19681

experimental_model

Human LysRS cryo-EM and aminoacylation assays

limitations

The structural experiment used tRNA-Lys3; KARS1 is not the leucyl-tRNA synthetase LARS1.

organism

Homo sapiens

plain_language

ATP activates lysine before it is attached to its carrier RNA.

primary_references

[devarkar2025] Structural basis for aminoacylation of cellular modified tRNALys3 by human lysyl-tRNA synthetase (2025). https://pubmed.ncbi.nlm.nih.gov/40036503/ DOI: 10.1093/nar/gkaf114

tissue_or_cell_type

Cytosolic tRNA charging

L-Lysine: mechanism-first literature curation (2026-09-17) · lines 54–62

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human LysRS cryo-EM and aminoacylation assays · source_derived_draft · unverified_draft

### lysine-adenylation KARS1 activates lysine with ATP, forming enzyme-bound lysyl-adenylate and releasing pyrophosphate. Plain language: ATP activates lysine before it is attached to its carrier RNA. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Cytosolic tRNA charging experimental_model: Human LysRS cryo-EM and aminoacylation assays limitations: The structural experiment used tRNA-Lys3; KARS1 is not the leucyl-tRNA synthetase LARS1. [devarkar2025] Structural basis for aminoacylation of cellular modified tRNALys3 by human lysyl-tRNA synthetase (2025). https://pubmed.ncbi.nlm.nih.gov/40036503/ DOI: 10.1093/nar/gkaf114

cross_nutrient

false

experimental_model

Recombinant human PPCS, PPCDC and COASY expressed in Escherichia coli; coupled enzyme assays and HPLC reconstitution

exposure

Forward PPAT assays: 5–500 micromolar phosphopantetheine and 5 mM ATP; 0.15–0.3 micrograms/mL recombinant COASY.

limitations

Direct biochemical reaction, distinct from the final phosphorylation; does not establish efficient entry of an oral intermediate into human cells.

nutrient_topic

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

organism

Homo sapiens

plain_language

COASY adds the adenosine-containing portion of CoA.

primary_references

[b5-bio-daugherty2002] Complete reconstitution of the human coenzyme A biosynthetic pathway via comparative genomics. (2002). https://pubmed.ncbi.nlm.nih.gov/11923312/ DOI: 10.1074/jbc.m201708200

tissue_or_cell_type

Purified recombinant protein; no intact tissue

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (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 · Recombinant human PPCS, PPCDC and COASY expressed in Escherichia coli; coupled enzyme assays and HPLC reconstitution · source_derived_draft · unverified_draft

### b5-bio-coasy-adenylylation Human COASY phosphopantetheine adenylyltransferase activity used ATP and 4′-phosphopantetheine to form dephospho-CoA. Condition category: normal nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: COASY adds the adenosine-containing portion of CoA. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Recombinant human PPCS, PPCDC and COASY expressed in Escherichia coli; coupled enzyme assays and HPLC reconstitution limitations: Direct biochemical reaction, distinct from the final phosphorylation; does not establish efficient entry of an oral intermediate into human cells. exposure: Forward PPAT assays: 5–500 micromolar phosphopantetheine and 5 mM ATP; 0.15–0.3 micrograms/mL recombinant COASY. cross_nutrient: false [b5-bio-daugherty2002] Complete reconstitution of the human coenzyme A biosynthetic pathway via comparative genomics. (2002). https://pubmed.ncbi.nlm.nih.gov/11923312/ DOI: 10.1074/jbc.m201708200

cross_nutrient

true

experimental_model

Recombinant human PPCS, PPCDC and COASY expressed in Escherichia coli; coupled enzyme assays and HPLC reconstitution

exposure

Coupled PPCS assay: 1.5 mM phosphopantothenate, 5 mM cysteine and 1 mM ATP or CTP; 2 mM MgCl2, pH 8.0, 37°C.

limitations

Human enzyme expressed in E. coli; assay substrate supply is not evidence that oral cysteine raises human CoA or that low blood cysteine gates B5 repletion.

nutrient_topic

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

organism

Homo sapiens

plain_language

Cysteine supplies the sulfur-containing portion of the developing CoA molecule.

primary_references

[b5-bio-daugherty2002] Complete reconstitution of the human coenzyme A biosynthetic pathway via comparative genomics. (2002). https://pubmed.ncbi.nlm.nih.gov/11923312/ DOI: 10.1074/jbc.m201708200

tissue_or_cell_type

Purified recombinant protein; no intact tissue

Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (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 · Recombinant human PPCS, PPCDC and COASY expressed in Escherichia coli; coupled enzyme assays and HPLC reconstitution · source_derived_draft · unverified_draft

### b5-bio-ppcs-ligation Recombinant human PPCS ligated L-cysteine to 4′-phosphopantothenate in a nucleotide-dependent reaction forming 4′-phosphopantothenoylcysteine. Condition category: normal nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Cysteine supplies the sulfur-containing portion of the developing CoA molecule. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Recombinant human PPCS, PPCDC and COASY expressed in Escherichia coli; coupled enzyme assays and HPLC reconstitution limitations: Human enzyme expressed in E. coli; assay substrate supply is not evidence that oral cysteine raises human CoA or that low blood cysteine gates B5 repletion. exposure: Coupled PPCS assay: 1.5 mM phosphopantothenate, 5 mM cysteine and 1 mM ATP or CTP; 2 mM MgCl2, pH 8.0, 37°C. cross_nutrient: true [b5-bio-daugherty2002] Complete reconstitution of the human coenzyme A biosynthetic pathway via comparative genomics. (2002). https://pubmed.ncbi.nlm.nih.gov/11923312/ DOI: 10.1074/jbc.m201708200

evidence_span

{"source_cache": "artifacts/phosphorus-research/24580380.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7ffa6a3c6ccf9f3a9d52240080160bfcf00d832210168f91b7ac0b9a39be30a2", "start_char": 0, "end_char": 1081, "text_sha256": "7ffa6a3c6ccf9f3a9d52240080160bfcf00d832210168f91b7ac0b9a39be30a2"}

experimental_model

dNTP leaving-group analogue kinetics

exposure

Beta/gamma pyrophosphate-mimicking dNTP analogues across matched and mismatched base pairs

limitations

Chemistry with designed nucleotide analogues, not a measurement of dietary phosphorus and DNA repair; no free-phosphate-to-DNA shortcut is asserted.

nutrient_topic

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

organism

Purified DNA polymerase beta; construct species unresolved in the inspected text

plain_language

The nucleotide’s phosphate-chain chemistry is part of DNA synthesis fidelity, not merely structural packaging.

primary_references

[phosphorus-p24580380] Transition state in DNA polymerase β catalysis: rate-limiting chemistry altered by base-pair configuration. (2014). https://pubmed.ncbi.nlm.nih.gov/24580380/ DOI: 10.1021/bi500101z

tissue_or_cell_type

Purified enzyme–primer–template system

Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 685–696

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · dNTP leaving-group analogue kinetics · source_derived_draft · unverified_draft

### phosphorus-dna-phosphate-chemistry Changing pyrophosphate-mimicking nucleotide leaving groups altered POLB chemical-step kinetics in a base-pair-dependent manner. Condition category: normal nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: The nucleotide’s phosphate-chain chemistry is part of DNA synthesis fidelity, not merely structural packaging. organism: Purified DNA polymerase beta; construct species unresolved in the inspected text tissue_or_cell_type: Purified enzyme–primer–template system experimental_model: dNTP leaving-group analogue kinetics limitations: Chemistry with designed nucleotide analogues, not a measurement of dietary phosphorus and DNA repair; no free-phosphate-to-DNA shortcut is asserted. exposure: Beta/gamma pyrophosphate-mimicking dNTP analogues across matched and mismatched base pairs evidence_span: {"source_cache": "artifacts/phosphorus-research/24580380.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7ffa6a3c6ccf9f3a9d52240080160bfcf00d832210168f91b7ac0b9a39be30a2", "start_char": 0, "end_char": 1081, "text_sha256": "7ffa6a3c6ccf9f3a9d52240080160bfcf00d832210168f91b7ac0b9a39be30a2"} [phosphorus-p24580380] Transition state in DNA polymerase β catalysis: rate-limiting chemistry altered by base-pair configuration. (2014). https://pubmed.ncbi.nlm.nih.gov/24580380/ DOI: 10.1021/bi500101z

evidence_span

{"source_cache": "artifacts/phosphorus-research/33656855.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1d45073f7187a06cfb9b2d630f94fa651239f0a9a5ae353b37d9af90750f2f38", "start_char": 0, "end_char": 1520, "text_sha256": "1d45073f7187a06cfb9b2d630f94fa651239f0a9a5ae353b37d9af90750f2f38"}

experimental_model

Human MAT2A kinetics, isotope exchange and inhibitor-bound crystallography

exposure

ATP/methionine reactions and PNPNP ligand complexes

limitations

Phosphoryl chemistry is not evidence that phosphate supplements boost methylation. Metal contacts were resolved with an experimental ATP-site ligand.

nutrient_topic

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

organism

Human recombinant enzyme

plain_language

ATP’s phosphate chain is processed into two separately tracked products.

primary_references

[phosphorus-p33656855] Mechanism and Inhibition of Human Methionine Adenosyltransferase 2A. (2021). https://pubmed.ncbi.nlm.nih.gov/33656855/ DOI: 10.1021/acs.biochem.0c00998

tissue_or_cell_type

Purified MAT2A active site

Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 646–657

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human MAT2A kinetics, isotope exchange and inhibitor-bound crystallography · source_derived_draft · unverified_draft

### phosphorus-mat-pi After SAM formation, MAT2A rapidly hydrolyzed the beta–gamma bond of triphosphate and released phosphate and pyrophosphate. Condition category: normal nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: ATP’s phosphate chain is processed into two separately tracked products. organism: Human recombinant enzyme tissue_or_cell_type: Purified MAT2A active site experimental_model: Human MAT2A kinetics, isotope exchange and inhibitor-bound crystallography limitations: Phosphoryl chemistry is not evidence that phosphate supplements boost methylation. Metal contacts were resolved with an experimental ATP-site ligand. exposure: ATP/methionine reactions and PNPNP ligand complexes evidence_span: {"source_cache": "artifacts/phosphorus-research/33656855.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1d45073f7187a06cfb9b2d630f94fa651239f0a9a5ae353b37d9af90750f2f38", "start_char": 0, "end_char": 1520, "text_sha256": "1d45073f7187a06cfb9b2d630f94fa651239f0a9a5ae353b37d9af90750f2f38"} [phosphorus-p33656855] Mechanism and Inhibition of Human Methionine Adenosyltransferase 2A. (2021). https://pubmed.ncbi.nlm.nih.gov/33656855/ DOI: 10.1021/acs.biochem.0c00998