All-trans-retinal

cross_nutrient

false

evidence_location

Abstract: irradiation and isomer analysis

experimental_model

Purified native RGR photochemistry

exposure

470-nm monochromatic or near-UV irradiation; duration absent from the abstract.

limitations

Abstract-limited; the finding does not establish relative flux in living human eyes.

nutrient

Vitamin A · Vitamin A

nutrient_topic

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

organism

Bos taurus

plain_language

Light lets RGR reverse the retinal isomer change used in visual pigments.

primary_references

[vav-hao1999] The endogenous chromophore of retinal G protein-coupled receptor opsin from the pigment epithelium. (1999). https://pubmed.ncbi.nlm.nih.gov/10037690/ DOI: 10.1074/jbc.274.10.6085

tissue_or_cell_type

RPE-derived protein

Vitamin A expansion: reproduction, light-driven vision and shared mechanisms (2026-09-17) · lines 423–436

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

### vae-rgr-photoisomerization Illuminating native bovine RGR converted its bound all-trans-retinal stereospecifically to the 11-cis configuration. Condition category: normal nutrient_topic: Vitamin A expansion research collection; topical membership is not evidence of a direct dietary effect. plain_language: Light lets RGR reverse the retinal isomer change used in visual pigments. organism: Bos taurus tissue_or_cell_type: RPE-derived protein experimental_model: Purified native RGR photochemistry limitations: Abstract-limited; the finding does not establish relative flux in living human eyes. exposure: 470-nm monochromatic or near-UV irradiation; duration absent from the abstract. cross_nutrient: false evidence_location: Abstract: irradiation and isomer analysis nutrient: Vitamin A [vav-hao1999] The endogenous chromophore of retinal G protein-coupled receptor opsin from the pigment epithelium. (1999). https://pubmed.ncbi.nlm.nih.gov/10037690/ DOI: 10.1074/jbc.274.10.6085

cross_nutrient

false

evidence_location

Abstract: endogenous retinaloxime isomers

experimental_model

Native RGR purification and hydroxylamine derivatization

exposure

Dark-handled purified protein; retinal-oxime isomers identified.

limitations

Abstract-limited; binding composition does not quantify whole-eye recycling.

nutrient

Vitamin A · Vitamin A

nutrient_topic

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

organism

Bos taurus

plain_language

RGR carries the spent all-trans retinal isomer before light reaches it.

primary_references

[vav-hao1999] The endogenous chromophore of retinal G protein-coupled receptor opsin from the pigment epithelium. (1999). https://pubmed.ncbi.nlm.nih.gov/10037690/ DOI: 10.1074/jbc.274.10.6085

tissue_or_cell_type

retinal pigment epithelium

Vitamin A expansion: reproduction, light-driven vision and shared mechanisms (2026-09-17) · lines 408–421

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Native RGR purification and hydroxylamine derivatization · source_derived_draft · unverified_draft

### vae-rgr-dark-chromophore RGR purified from bovine RPE contained predominantly all-trans-retinal as its endogenous dark-state chromophore. Condition category: normal nutrient_topic: Vitamin A expansion research collection; topical membership is not evidence of a direct dietary effect. plain_language: RGR carries the spent all-trans retinal isomer before light reaches it. organism: Bos taurus tissue_or_cell_type: retinal pigment epithelium experimental_model: Native RGR purification and hydroxylamine derivatization limitations: Abstract-limited; binding composition does not quantify whole-eye recycling. exposure: Dark-handled purified protein; retinal-oxime isomers identified. cross_nutrient: false evidence_location: Abstract: endogenous retinaloxime isomers nutrient: Vitamin A [vav-hao1999] The endogenous chromophore of retinal G protein-coupled receptor opsin from the pigment epithelium. (1999). https://pubmed.ncbi.nlm.nih.gov/10037690/ DOI: 10.1074/jbc.274.10.6085

evidence_span

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experimental_model

Recombinant human AOX and human liver S9 kinetics, inhibitors and protein quantification

exposure

Retinaldehyde with/without NAD+; selective inhibitors

limitations

Ex-vivo contribution depends on substrate and NAD+ availability; no dietary molybdenum intervention or universal in-vivo percentage.

nutrient_topic

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

organism

Homo sapiens

plain_language

A molybdenum enzyme can contribute to making vitamin A signaling molecules.

primary_references

[mo-p33355213] Aldehyde Oxidase Contributes to All-Trans-Retinoic Acid Biosynthesis in Human Liver. (2021). https://pubmed.ncbi.nlm.nih.gov/33355213/ DOI: 10.1124/dmd.120.000296

tissue_or_cell_type

Purified enzyme and liver S9 fractions

Molybdenum: cofactor assembly, sulfur metabolism and nutrient interactions (2026-09-17) · lines 898–909

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human AOX and human liver S9 kinetics, inhibitors and protein quantification · source_derived_draft · unverified_draft

### mo-aox-retinoic-acid Recombinant human AOX converted all-trans-retinaldehyde to all-trans-retinoic acid, with an apparent Km near 1.5 micromolar. Condition category: normal nutrient_topic: Molybdenum research collection; topical membership is not evidence of a direct dietary effect. plain_language: A molybdenum enzyme can contribute to making vitamin A signaling molecules. organism: Homo sapiens tissue_or_cell_type: Purified enzyme and liver S9 fractions experimental_model: Recombinant human AOX and human liver S9 kinetics, inhibitors and protein quantification limitations: Ex-vivo contribution depends on substrate and NAD+ availability; no dietary molybdenum intervention or universal in-vivo percentage. exposure: Retinaldehyde with/without NAD+; selective inhibitors evidence_span: {"source_cache": "artifacts/molybdenum-research/33355213.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0edb31bff85231dfbde4a99d6858db611c099d2cd00982cad88616aa960b5aa2", "start_char": 0, "end_char": 2211, "text_sha256": "0edb31bff85231dfbde4a99d6858db611c099d2cd00982cad88616aa960b5aa2"} [mo-p33355213] Aldehyde Oxidase Contributes to All-Trans-Retinoic Acid Biosynthesis in Human Liver. (2021). https://pubmed.ncbi.nlm.nih.gov/33355213/ DOI: 10.1124/dmd.120.000296

experimental_model

Solid-state NMR before/after illumination

limitations

Bound chromophore conversion precedes release of free retinal.

nutrient_topic

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

organism

Bos taurus

plain_language

A photon changes the bound retinoid shape and starts the signal.

primary_references

[grobner-2000] Observations of light-induced structural changes of retinal within rhodopsin (2000). https://www.nature.com/articles/35015604 DOI: 10.1038/35015604

tissue_or_cell_type

Purified rhodopsin

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 655–664

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Solid-state NMR before/after illumination · source_derived_draft · unverified_draft

### a-vision-photoisomerization Light activation changes rhodopsin-bound 11-cis-retinal into its all-trans geometry, coupled to receptor activation. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: A photon changes the bound retinoid shape and starts the signal. organism: Bos taurus tissue_or_cell_type: Purified rhodopsin experimental_model: Solid-state NMR before/after illumination limitations: Bound chromophore conversion precedes release of free retinal. [grobner-2000] Observations of light-induced structural changes of retinal within rhodopsin (2000). https://www.nature.com/articles/35015604 DOI: 10.1038/35015604

evidence_location

Abstract

experimental_model

Purified human BCO1 expressed in E. coli; substrate incubations and HPLC.

exposure

Purified BCO1 and alpha-carotene concentration series.

limitations

Lower catalytic efficiency than beta-carotene under these assay conditions.

nutrient_topic

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

organism

Homo sapiens protein expressed in Escherichia coli

outcome

Human BCO1 generated retinal from alpha-carotene in substrate assays.

plain_language

Alpha-carotene can feed retinal production.

primary_references

[va-delasena-2013] Substrate specificity of purified recombinant human beta-carotene 15,15'-oxygenase (BCO1) (2013). https://pubmed.ncbi.nlm.nih.gov/24187135/ DOI: 10.1074/jbc.M113.507160

tissue_or_cell_type

Cell-free enzyme

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 145–157

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human BCO1 expressed in E. coli; substrate incubations and HPLC. · source_derived_draft · unverified_draft

### va-bco1-alpha-carotene Human BCO1 generated retinal from alpha-carotene in substrate assays. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: Alpha-carotene can feed retinal production. organism: Homo sapiens protein expressed in Escherichia coli tissue_or_cell_type: Cell-free enzyme experimental_model: Purified human BCO1 expressed in E. coli; substrate incubations and HPLC. limitations: Lower catalytic efficiency than beta-carotene under these assay conditions. exposure: Purified BCO1 and alpha-carotene concentration series. outcome: Human BCO1 generated retinal from alpha-carotene in substrate assays. evidence_location: Abstract [va-delasena-2013] Substrate specificity of purified recombinant human beta-carotene 15,15'-oxygenase (BCO1) (2013). https://pubmed.ncbi.nlm.nih.gov/24187135/ DOI: 10.1074/jbc.M113.507160

evidence_location

Abstract

experimental_model

Purified human BCO1 expressed in E. coli; substrate incubations and HPLC.

exposure

Purified BCO1 and beta-cryptoxanthin concentration series.

limitations

Does not quantify competition with the BCO2 pathway in vivo.

nutrient_topic

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

organism

Homo sapiens protein expressed in Escherichia coli

outcome

Human BCO1 generated retinal from beta-cryptoxanthin in substrate assays.

plain_language

This hydroxylated carotenoid also supplies retinal in vitro.

primary_references

[va-delasena-2013] Substrate specificity of purified recombinant human beta-carotene 15,15'-oxygenase (BCO1) (2013). https://pubmed.ncbi.nlm.nih.gov/24187135/ DOI: 10.1074/jbc.M113.507160

tissue_or_cell_type

Cell-free enzyme

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 159–171

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human BCO1 expressed in E. coli; substrate incubations and HPLC. · source_derived_draft · unverified_draft

### va-bco1-beta-cryptoxanthin Human BCO1 generated retinal from beta-cryptoxanthin in substrate assays. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: This hydroxylated carotenoid also supplies retinal in vitro. organism: Homo sapiens protein expressed in Escherichia coli tissue_or_cell_type: Cell-free enzyme experimental_model: Purified human BCO1 expressed in E. coli; substrate incubations and HPLC. limitations: Does not quantify competition with the BCO2 pathway in vivo. exposure: Purified BCO1 and beta-cryptoxanthin concentration series. outcome: Human BCO1 generated retinal from beta-cryptoxanthin in substrate assays. evidence_location: Abstract [va-delasena-2013] Substrate specificity of purified recombinant human beta-carotene 15,15'-oxygenase (BCO1) (2013). https://pubmed.ncbi.nlm.nih.gov/24187135/ DOI: 10.1074/jbc.M113.507160

evidence_location

Figure 3

experimental_model

Purified human BCO1 expressed in E. coli; substrate incubations and HPLC.

exposure

20 micromolar beta-carotene, 500 ng enzyme/200 microliters, 37 C, 15 minutes.

limitations

Purified-enzyme rates do not determine dietary conversion efficiency.

nutrient_topic

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

organism

Homo sapiens protein expressed in Escherichia coli

outcome

Purified human BCO1 cleaved all-trans-beta-carotene centrally to all-trans-retinal.

plain_language

BCO1 turns a carotenoid precursor into retinal.

primary_references

[va-delasena-2013] Substrate specificity of purified recombinant human beta-carotene 15,15'-oxygenase (BCO1) (2013). https://pubmed.ncbi.nlm.nih.gov/24187135/ DOI: 10.1074/jbc.M113.507160

tissue_or_cell_type

Cell-free enzyme

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 131–143

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human BCO1 expressed in E. coli; substrate incubations and HPLC. · source_derived_draft · unverified_draft

### va-bco1-central-cleavage Purified human BCO1 cleaved all-trans-beta-carotene centrally to all-trans-retinal. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: BCO1 turns a carotenoid precursor into retinal. organism: Homo sapiens protein expressed in Escherichia coli tissue_or_cell_type: Cell-free enzyme experimental_model: Purified human BCO1 expressed in E. coli; substrate incubations and HPLC. limitations: Purified-enzyme rates do not determine dietary conversion efficiency. exposure: 20 micromolar beta-carotene, 500 ng enzyme/200 microliters, 37 C, 15 minutes. outcome: Purified human BCO1 cleaved all-trans-beta-carotene centrally to all-trans-retinal. evidence_location: Figure 3 [va-delasena-2013] Substrate specificity of purified recombinant human beta-carotene 15,15'-oxygenase (BCO1) (2013). https://pubmed.ncbi.nlm.nih.gov/24187135/ DOI: 10.1074/jbc.M113.507160

evidence_location

Abstract

experimental_model

Recombinant human BCO1 with isotopically labeled oxygen and water.

exposure

18O2 versus H2-18O incubations with beta-carotene.

limitations

Reaction chemistry; no claim about clinical hypoxia or oxygen supplementation.

nutrient_topic

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

organism

Homo sapiens recombinant protein

outcome

Isotope tracing showed that oxygen incorporated into both BCO1-generated retinal products originated from molecular oxygen.

plain_language

BCO1 cleavage uses oxygen gas to make the two retinal aldehydes.

primary_references

[va-delasena-2014] The human enzyme that converts dietary provitamin A carotenoids to vitamin A is a dioxygenase (2014). https://pubmed.ncbi.nlm.nih.gov/24668807/ DOI: 10.1074/jbc.M114.557710

tissue_or_cell_type

Cell-free enzyme

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 173–185

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human BCO1 with isotopically labeled oxygen and water. · source_derived_draft · unverified_draft

### va-bco1-dioxygen-incorporation Isotope tracing showed that oxygen incorporated into both BCO1-generated retinal products originated from molecular oxygen. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: BCO1 cleavage uses oxygen gas to make the two retinal aldehydes. organism: Homo sapiens recombinant protein tissue_or_cell_type: Cell-free enzyme experimental_model: Recombinant human BCO1 with isotopically labeled oxygen and water. limitations: Reaction chemistry; no claim about clinical hypoxia or oxygen supplementation. exposure: 18O2 versus H2-18O incubations with beta-carotene. outcome: Isotope tracing showed that oxygen incorporated into both BCO1-generated retinal products originated from molecular oxygen. evidence_location: Abstract [va-delasena-2014] The human enzyme that converts dietary provitamin A carotenoids to vitamin A is a dioxygenase (2014). https://pubmed.ncbi.nlm.nih.gov/24668807/ DOI: 10.1074/jbc.M114.557710

cross_nutrient

NAD-dependent retinol oxidation connects vitamin A metabolism to nicotinamide redox-cofactor availability.

evidence_location

Results: cofactor preference

experimental_model

Human RDH10 in Sf9 microsomes and siRNA perturbation in human cells.

exposure

1 micromolar retinol and 1 millimolar NAD+ versus NADP+.

limitations

Cofactor specificity does not establish an effect of dietary niacin deficiency.

nutrient_topic

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

organism

Homo sapiens protein in Spodoptera frugiperda Sf9 cells

outcome

Recombinant human RDH10 oxidized all-trans-retinol with NAD+ in microsomal assays.

plain_language

RDH10 uses the oxidized nicotinamide cofactor to make retinal.

primary_references

[va-belyaeva-2008] Kinetic Analysis of Human Enzyme RDH10 Defines the Characteristics of a Physiologically Relevant Retinol Dehydrogenase (2008). https://pmc.ncbi.nlm.nih.gov/articles/PMC2459273/ DOI: 10.1074/jbc.M800019200

tissue_or_cell_type

Microsomes

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 487–500

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human RDH10 in Sf9 microsomes and siRNA perturbation in human cells. · source_derived_draft · unverified_draft

### va-rdh10-retinol-oxidation Recombinant human RDH10 oxidized all-trans-retinol with NAD+ in microsomal assays. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: RDH10 uses the oxidized nicotinamide cofactor to make retinal. organism: Homo sapiens protein in Spodoptera frugiperda Sf9 cells tissue_or_cell_type: Microsomes experimental_model: Human RDH10 in Sf9 microsomes and siRNA perturbation in human cells. limitations: Cofactor specificity does not establish an effect of dietary niacin deficiency. exposure: 1 micromolar retinol and 1 millimolar NAD+ versus NADP+. outcome: Recombinant human RDH10 oxidized all-trans-retinol with NAD+ in microsomal assays. evidence_location: Results: cofactor preference cross_nutrient: NAD-dependent retinol oxidation connects vitamin A metabolism to nicotinamide redox-cofactor availability. [va-belyaeva-2008] Kinetic Analysis of Human Enzyme RDH10 Defines the Characteristics of a Physiologically Relevant Retinol Dehydrogenase (2008). https://pmc.ncbi.nlm.nih.gov/articles/PMC2459273/ DOI: 10.1074/jbc.M800019200

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

false

evidence_location

Results/Figure 7a-c

experimental_model

Recombinant bovine wild-type/K255A RGR comparison

exposure

All-trans-retinal and 530-nm light, with CRALBP; Figure 7.

limitations

Construct-specific assay; K255A numbering is retained from this paper.

nutrient

Vitamin A · Vitamin A

nutrient_topic

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

organism

Bos taurus protein in Homo sapiens cells

plain_language

Disrupting the retinal-binding lysine impaired the light-driven reaction.

primary_references

[vav-zhang2019] Photic generation of 11-cis-retinal in bovine retinal pigment epithelium. (2019). https://pubmed.ncbi.nlm.nih.gov/31694912/ DOI: 10.1074/jbc.ra119.011169

tissue_or_cell_type

HEK293S GnTI-negative homogenates

trigger_kind

machinery_impairment Imported condition classification; unverified.

Vitamin A expansion: reproduction, light-driven vision and shared mechanisms (2026-09-17) · lines 453–466

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant bovine wild-type/K255A RGR comparison · source_derived_draft · unverified_draft

### vae-rgr-k255a-photoactivity Bovine RGR K255A produced little 11-cis-retinal under illumination despite expression comparable to wild-type RGR in HEK293S GnTI-negative cells. Condition category: machinery_impairment nutrient_topic: Vitamin A expansion research collection; topical membership is not evidence of a direct dietary effect. plain_language: Disrupting the retinal-binding lysine impaired the light-driven reaction. organism: Bos taurus protein in Homo sapiens cells tissue_or_cell_type: HEK293S GnTI-negative homogenates experimental_model: Recombinant bovine wild-type/K255A RGR comparison limitations: Construct-specific assay; K255A numbering is retained from this paper. exposure: All-trans-retinal and 530-nm light, with CRALBP; Figure 7. cross_nutrient: false evidence_location: Results/Figure 7a-c nutrient: Vitamin A [vav-zhang2019] Photic generation of 11-cis-retinal in bovine retinal pigment epithelium. (2019). https://pubmed.ncbi.nlm.nih.gov/31694912/ DOI: 10.1074/jbc.ra119.011169

evidence_span

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experimental_model

Retinaldehyde-liposome photosensitization with cells

exposure

4 micromolar zeaxanthin, 80 micromolar alpha-tocopherol; 0.5–2 mM ascorbate

limitations

Bath concentrations and irradiation are not oral doses or established human safety limits. Combination conditions and localization matter.

nutrient_topic

Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. · Dietary (3R,3-prime-R)-zeaxanthin

organism

Human ARPE-19 cells and unsaturated liposomes

plain_language

A higher concentration changed the interaction.

primary_references

[zeaxanthin-p35740030] Is There an Optimal Combination of AREDS2 Antioxidants Zeaxanthin, Vitamin E and Vitamin C on Light-Induced Toxicity of Vitamin A Aldehyde to the Retina? (2022). https://pubmed.ncbi.nlm.nih.gov/35740030/ DOI: 10.3390/antiox11061132

tissue_or_cell_type

RPE injury model

Zeaxanthin: metabolism, signaling and nutrient connections (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 · Retinaldehyde-liposome photosensitization with cells · source_derived_draft · unverified_draft

### zeaxanthin-ascorbate-high At 2 mM, ascorbate exacerbated phototoxicity; zeaxanthin or alpha-tocopherol partly ameliorated it. Condition category: normal nutrient_topic: Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A higher concentration changed the interaction. organism: Human ARPE-19 cells and unsaturated liposomes tissue_or_cell_type: RPE injury model experimental_model: Retinaldehyde-liposome photosensitization with cells limitations: Bath concentrations and irradiation are not oral doses or established human safety limits. Combination conditions and localization matter. exposure: 4 micromolar zeaxanthin, 80 micromolar alpha-tocopherol; 0.5–2 mM ascorbate evidence_span: {"source_cache": "artifacts/zeaxanthin-research/35740030.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6c66a3183f1b2cc985ad22d5350f53aaeaf65b2519e89ddc13e0460a035903e8", "start_char": 0, "end_char": 1784, "text_sha256": "6c66a3183f1b2cc985ad22d5350f53aaeaf65b2519e89ddc13e0460a035903e8"} [zeaxanthin-p35740030] Is There an Optimal Combination of AREDS2 Antioxidants Zeaxanthin, Vitamin E and Vitamin C on Light-Induced Toxicity of Vitamin A Aldehyde to the Retina? (2022). https://pubmed.ncbi.nlm.nih.gov/35740030/ DOI: 10.3390/antiox11061132

evidence_span

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experimental_model

Retinaldehyde-liposome photosensitization with cells

exposure

4 micromolar zeaxanthin, 80 micromolar alpha-tocopherol; 0.5–2 mM ascorbate

limitations

Bath concentrations and irradiation are not oral doses or established human safety limits. Combination conditions and localization matter.

nutrient_topic

Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. · Dietary (3R,3-prime-R)-zeaxanthin

organism

Human ARPE-19 cells and unsaturated liposomes

plain_language

Vitamin C added protection under this condition.

primary_references

[zeaxanthin-p35740030] Is There an Optimal Combination of AREDS2 Antioxidants Zeaxanthin, Vitamin E and Vitamin C on Light-Induced Toxicity of Vitamin A Aldehyde to the Retina? (2022). https://pubmed.ncbi.nlm.nih.gov/35740030/ DOI: 10.3390/antiox11061132

tissue_or_cell_type

RPE injury model

Zeaxanthin: metabolism, signaling and nutrient connections (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 · Retinaldehyde-liposome photosensitization with cells · source_derived_draft · unverified_draft

### zeaxanthin-ascorbate-low Adding 0.5 mM ascorbate to the combination raised viability to approximately 69%. Condition category: normal nutrient_topic: Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin C added protection under this condition. organism: Human ARPE-19 cells and unsaturated liposomes tissue_or_cell_type: RPE injury model experimental_model: Retinaldehyde-liposome photosensitization with cells limitations: Bath concentrations and irradiation are not oral doses or established human safety limits. Combination conditions and localization matter. exposure: 4 micromolar zeaxanthin, 80 micromolar alpha-tocopherol; 0.5–2 mM ascorbate evidence_span: {"source_cache": "artifacts/zeaxanthin-research/35740030.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6c66a3183f1b2cc985ad22d5350f53aaeaf65b2519e89ddc13e0460a035903e8", "start_char": 0, "end_char": 1784, "text_sha256": "6c66a3183f1b2cc985ad22d5350f53aaeaf65b2519e89ddc13e0460a035903e8"} [zeaxanthin-p35740030] Is There an Optimal Combination of AREDS2 Antioxidants Zeaxanthin, Vitamin E and Vitamin C on Light-Induced Toxicity of Vitamin A Aldehyde to the Retina? (2022). https://pubmed.ncbi.nlm.nih.gov/35740030/ DOI: 10.3390/antiox11061132

evidence_span

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experimental_model

Retinaldehyde-liposome photosensitization with cells

exposure

4 micromolar zeaxanthin, 80 micromolar alpha-tocopherol; 0.5–2 mM ascorbate

limitations

Bath concentrations and irradiation are not oral doses or established human safety limits. Combination conditions and localization matter.

nutrient_topic

Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. · Dietary (3R,3-prime-R)-zeaxanthin

organism

Human ARPE-19 cells and unsaturated liposomes

plain_language

The pair protected cells against this defined light challenge.

primary_references

[zeaxanthin-p35740030] Is There an Optimal Combination of AREDS2 Antioxidants Zeaxanthin, Vitamin E and Vitamin C on Light-Induced Toxicity of Vitamin A Aldehyde to the Retina? (2022). https://pubmed.ncbi.nlm.nih.gov/35740030/ DOI: 10.3390/antiox11061132

tissue_or_cell_type

RPE injury model

Zeaxanthin: metabolism, signaling and nutrient connections (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 · Retinaldehyde-liposome photosensitization with cells · source_derived_draft · unverified_draft

### zeaxanthin-c-e-z-protection Combined zeaxanthin and alpha-tocopherol raised viability from about 26% to 63% in the tested model. Condition category: normal nutrient_topic: Zeaxanthin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The pair protected cells against this defined light challenge. organism: Human ARPE-19 cells and unsaturated liposomes tissue_or_cell_type: RPE injury model experimental_model: Retinaldehyde-liposome photosensitization with cells limitations: Bath concentrations and irradiation are not oral doses or established human safety limits. Combination conditions and localization matter. exposure: 4 micromolar zeaxanthin, 80 micromolar alpha-tocopherol; 0.5–2 mM ascorbate evidence_span: {"source_cache": "artifacts/zeaxanthin-research/35740030.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6c66a3183f1b2cc985ad22d5350f53aaeaf65b2519e89ddc13e0460a035903e8", "start_char": 0, "end_char": 1784, "text_sha256": "6c66a3183f1b2cc985ad22d5350f53aaeaf65b2519e89ddc13e0460a035903e8"} [zeaxanthin-p35740030] Is There an Optimal Combination of AREDS2 Antioxidants Zeaxanthin, Vitamin E and Vitamin C on Light-Induced Toxicity of Vitamin A Aldehyde to the Retina? (2022). https://pubmed.ncbi.nlm.nih.gov/35740030/ DOI: 10.3390/antiox11061132

evidence_span

{"source_cache": "artifacts/molybdenum-research/33355213.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0edb31bff85231dfbde4a99d6858db611c099d2cd00982cad88616aa960b5aa2", "start_char": 0, "end_char": 2211, "text_sha256": "0edb31bff85231dfbde4a99d6858db611c099d2cd00982cad88616aa960b5aa2"}

experimental_model

Recombinant human AOX and human liver S9 kinetics, inhibitors and protein quantification

exposure

Retinaldehyde with/without NAD+; selective inhibitors

limitations

Ex-vivo contribution depends on substrate and NAD+ availability; no dietary molybdenum intervention or universal in-vivo percentage.

nutrient_topic

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

organism

Homo sapiens

plain_language

Different enzymes share vitamin A processing, and their contributions depend on the conditions.

primary_references

[mo-p33355213] Aldehyde Oxidase Contributes to All-Trans-Retinoic Acid Biosynthesis in Human Liver. (2021). https://pubmed.ncbi.nlm.nih.gov/33355213/ DOI: 10.1124/dmd.120.000296

tissue_or_cell_type

Purified enzyme and liver S9 fractions

Molybdenum: cofactor assembly, sulfur metabolism and nutrient interactions (2026-09-17) · lines 911–922

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human AOX and human liver S9 kinetics, inhibitors and protein quantification · source_derived_draft · unverified_draft

### mo-aox-aldh-partition In human liver S9, AOX inhibition reduced retinoic-acid formation by 20-50%, versus 50-80% with ALDH1A1 inhibition; AOX had lower affinity and higher capacity. Condition category: normal nutrient_topic: Molybdenum research collection; topical membership is not evidence of a direct dietary effect. plain_language: Different enzymes share vitamin A processing, and their contributions depend on the conditions. organism: Homo sapiens tissue_or_cell_type: Purified enzyme and liver S9 fractions experimental_model: Recombinant human AOX and human liver S9 kinetics, inhibitors and protein quantification limitations: Ex-vivo contribution depends on substrate and NAD+ availability; no dietary molybdenum intervention or universal in-vivo percentage. exposure: Retinaldehyde with/without NAD+; selective inhibitors evidence_span: {"source_cache": "artifacts/molybdenum-research/33355213.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0edb31bff85231dfbde4a99d6858db611c099d2cd00982cad88616aa960b5aa2", "start_char": 0, "end_char": 2211, "text_sha256": "0edb31bff85231dfbde4a99d6858db611c099d2cd00982cad88616aa960b5aa2"} [mo-p33355213] Aldehyde Oxidase Contributes to All-Trans-Retinoic Acid Biosynthesis in Human Liver. (2021). https://pubmed.ncbi.nlm.nih.gov/33355213/ DOI: 10.1124/dmd.120.000296

experimental_model

Proteoliposomes and native disc transport assays

limitations

The assayed substrate is the adduct, not a requirement for free retinal diffusion.

nutrient_topic

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

organism

Bovine/mouse discs; recombinant transporter

plain_language

ABCA4 moves the trapped retinal-lipid adduct to the disposal side of the disc.

primary_references

[quazi-2012] ABCA4 is an N-retinylidene-phosphatidylethanolamine and phosphatidylethanolamine importer (2012). https://pmc.ncbi.nlm.nih.gov/articles/PMC3871175/ DOI: 10.1038/ncomms1927

tissue_or_cell_type

Photoreceptor disc membrane

transport_direction

disc lumen leaflet to cytoplasmic leaflet

transport_effect

raises Recorded as ATP-dependent transport from the disc lumen-facing leaflet toward the cytoplasmic leaflet.

transport_pool

the cytoplasmic leaflet of the disc membrane Recorded as ATP-dependent transport from the disc lumen-facing leaflet toward the cytoplasmic leaflet.

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 801–811

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Proteoliposomes and native disc transport assays · source_derived_draft · unverified_draft

### a-vision-abca4-retinoid-flip ABCA4 drove ATP-dependent transport of retinal-PE adduct from the disc lumen-facing leaflet toward the cytoplasmic leaflet. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: ABCA4 moves the trapped retinal-lipid adduct to the disposal side of the disc. organism: Bovine/mouse discs; recombinant transporter tissue_or_cell_type: Photoreceptor disc membrane experimental_model: Proteoliposomes and native disc transport assays limitations: The assayed substrate is the adduct, not a requirement for free retinal diffusion. transport_direction: disc lumen leaflet to cytoplasmic leaflet [quazi-2012] ABCA4 is an N-retinylidene-phosphatidylethanolamine and phosphatidylethanolamine importer (2012). https://pmc.ncbi.nlm.nih.gov/articles/PMC3871175/ DOI: 10.1038/ncomms1927

availability_state

machinery_impairment Imported condition classification; unverified.

experimental_model

Double-knockout retinoid and retinal phenotype

limitations

Light and genetic background influence phenotype; the experiment does not isolate A2E as sole cause.

nutrient_topic

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

organism

Mus musculus

plain_language

Removing both disposal routes made the retina vulnerable.

primary_references

[maeda-2008] Retinopathy in mice induced by disrupted all-trans-retinal clearance (2008). https://pubmed.ncbi.nlm.nih.gov/18658157/ DOI: 10.1074/jbc.M804505200

tissue_or_cell_type

RPE and photoreceptors

trigger_kind

machinery_impairment Imported condition classification; unverified.

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 825–834

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Double-knockout retinoid and retinal phenotype · source_derived_draft · unverified_draft

### a-vision-clearance-retinopathy Abca4/Rdh8 double-knockout mice developed early RPE/photoreceptor dystrophy in the retinal-clearance study. Condition category: machinery_impairment nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: Removing both disposal routes made the retina vulnerable. organism: Mus musculus tissue_or_cell_type: RPE and photoreceptors experimental_model: Double-knockout retinoid and retinal phenotype limitations: Light and genetic background influence phenotype; the experiment does not isolate A2E as sole cause. [maeda-2008] Retinopathy in mice induced by disrupted all-trans-retinal clearance (2008). https://pubmed.ncbi.nlm.nih.gov/18658157/ DOI: 10.1074/jbc.M804505200

experimental_model

Purified-enzyme cofactor/substrate kinetics

limitations

Biochemical cofactor preference does not demonstrate a dietary niacin-deficiency visual phenotype.

nutrient_topic

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

organism

Homo sapiens protein

plain_language

The reductase uses NADPH reducing power to convert retinal into retinol.

primary_references

[belyaeva-2005] Biochemical properties of purified human retinol dehydrogenase 12 (RDH12): catalytic efficiency toward retinoids and C9 aldehydes and effects of cellular retinol-binding protein type I (CRBPI) and cellular retinaldehyde-binding protein (CRALBP) on the oxidation and reduction of retinoids (2005). https://pubmed.ncbi.nlm.nih.gov/15865448/ DOI: 10.1021/bi050226k

tissue_or_cell_type

Recombinant enzyme preparation

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 778–787

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified-enzyme cofactor/substrate kinetics · source_derived_draft · unverified_draft

### a-vision-rdh12-nadph Purified human RDH12 used NADPH for retinal reduction and had much lower apparent cofactor Km for NADP(H) than NAD(H). Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: The reductase uses NADPH reducing power to convert retinal into retinol. organism: Homo sapiens protein tissue_or_cell_type: Recombinant enzyme preparation experimental_model: Purified-enzyme cofactor/substrate kinetics limitations: Biochemical cofactor preference does not demonstrate a dietary niacin-deficiency visual phenotype. [belyaeva-2005] Biochemical properties of purified human retinol dehydrogenase 12 (RDH12): catalytic efficiency toward retinoids and C9 aldehydes and effects of cellular retinol-binding protein type I (CRBPI) and cellular retinaldehyde-binding protein (CRALBP) on the oxidation and reduction of retinoids (2005). https://pubmed.ncbi.nlm.nih.gov/15865448/ DOI: 10.1021/bi050226k

experimental_model

Knockout rod imaging and exogenous retinal challenge

limitations

The inferred protection of organelles is not itself a clinical outcome.

nutrient_topic

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

organism

Mus musculus

plain_language

RDH12 helps clear retinal that reaches the cell interior.

primary_references

[chen-2012] Reduction of all-trans-retinal in vertebrate rod photoreceptors requires the combined action of RDH8 and RDH12 (2012). https://pubmed.ncbi.nlm.nih.gov/22621924/ DOI: 10.1074/jbc.M112.354514

tissue_or_cell_type

Rod inner segment

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 767–776

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Knockout rod imaging and exogenous retinal challenge · source_derived_draft · unverified_draft

### a-vision-rdh12-reduction Mouse rod imaging identified RDH12-dependent reduction of retinaldehyde entering inner segments from the outer segment or extracellular medium. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: RDH12 helps clear retinal that reaches the cell interior. organism: Mus musculus tissue_or_cell_type: Rod inner segment experimental_model: Knockout rod imaging and exogenous retinal challenge limitations: The inferred protection of organelles is not itself a clinical outcome. [chen-2012] Reduction of all-trans-retinal in vertebrate rod photoreceptors requires the combined action of RDH8 and RDH12 (2012). https://pubmed.ncbi.nlm.nih.gov/22621924/ DOI: 10.1074/jbc.M112.354514

experimental_model

Wild-type/Rdh8-null/Rdh12-null rod fluorescence

limitations

Residual reductases exist; this does not establish an exclusive enzyme.

nutrient_topic

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

organism

Mus musculus

plain_language

RDH8 converts the aldehyde photoproduct back to retinol in the outer segment.

primary_references

[chen-2012] Reduction of all-trans-retinal in vertebrate rod photoreceptors requires the combined action of RDH8 and RDH12 (2012). https://pubmed.ncbi.nlm.nih.gov/22621924/ DOI: 10.1074/jbc.M112.354514

tissue_or_cell_type

Rod outer segment

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 756–765

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Wild-type/Rdh8-null/Rdh12-null rod fluorescence · source_derived_draft · unverified_draft

### a-vision-rdh8-reduction Single-cell knockout comparisons showed RDH8 supplies most reduction of bleach-generated all-trans-retinal in mouse rod outer segments. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: RDH8 converts the aldehyde photoproduct back to retinol in the outer segment. organism: Mus musculus tissue_or_cell_type: Rod outer segment experimental_model: Wild-type/Rdh8-null/Rdh12-null rod fluorescence limitations: Residual reductases exist; this does not establish an exclusive enzyme. [chen-2012] Reduction of all-trans-retinal in vertebrate rod photoreceptors requires the combined action of RDH8 and RDH12 (2012). https://pubmed.ncbi.nlm.nih.gov/22621924/ DOI: 10.1074/jbc.M112.354514

evidence_location

Abstract

experimental_model

Side-by-side recombinant human ALDH1A1, ALDH1A2 and ALDH1A3 kinetic assays.

exposure

Side-by-side retinaldehyde kinetic measurements by HPLC.

limitations

In vitro catalytic efficiency does not specify its contribution in a particular tissue.

nutrient_topic

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

organism

Homo sapiens recombinant protein

outcome

Human ALDH1A1 oxidized all-trans-retinaldehyde to retinoic acid in comparative enzyme assays.

plain_language

This independently identified enzyme supplies the acid form used for signaling.

primary_references

[va-pequerul-2020] Structural and kinetic features of aldehyde dehydrogenase 1A (ALDH1A) subfamily members, cancer stem cell markers active in retinoic acid biosynthesis (2020). https://pubmed.ncbi.nlm.nih.gov/31923393/ DOI: 10.1016/j.abb.2020.108256

tissue_or_cell_type

Cell-free enzyme

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 559–571

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Side-by-side recombinant human ALDH1A1, ALDH1A2 and ALDH1A3 kinetic assays. · source_derived_draft · unverified_draft

### va-aldh1a1-retinal-oxidation Human ALDH1A1 oxidized all-trans-retinaldehyde to retinoic acid in comparative enzyme assays. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: This independently identified enzyme supplies the acid form used for signaling. organism: Homo sapiens recombinant protein tissue_or_cell_type: Cell-free enzyme experimental_model: Side-by-side recombinant human ALDH1A1, ALDH1A2 and ALDH1A3 kinetic assays. limitations: In vitro catalytic efficiency does not specify its contribution in a particular tissue. exposure: Side-by-side retinaldehyde kinetic measurements by HPLC. outcome: Human ALDH1A1 oxidized all-trans-retinaldehyde to retinoic acid in comparative enzyme assays. evidence_location: Abstract [va-pequerul-2020] Structural and kinetic features of aldehyde dehydrogenase 1A (ALDH1A) subfamily members, cancer stem cell markers active in retinoic acid biosynthesis (2020). https://pubmed.ncbi.nlm.nih.gov/31923393/ DOI: 10.1016/j.abb.2020.108256

evidence_location

Abstract

experimental_model

Side-by-side recombinant human ALDH1A1, ALDH1A2 and ALDH1A3 kinetic assays.

exposure

Side-by-side retinaldehyde kinetic measurements by HPLC.

limitations

In vitro catalytic efficiency does not specify its contribution in a particular tissue.

nutrient_topic

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

organism

Homo sapiens recombinant protein

outcome

Human ALDH1A2 oxidized all-trans-retinaldehyde to retinoic acid in comparative enzyme assays.

plain_language

This independently identified enzyme supplies the acid form used for signaling.

primary_references

[va-pequerul-2020] Structural and kinetic features of aldehyde dehydrogenase 1A (ALDH1A) subfamily members, cancer stem cell markers active in retinoic acid biosynthesis (2020). https://pubmed.ncbi.nlm.nih.gov/31923393/ DOI: 10.1016/j.abb.2020.108256

tissue_or_cell_type

Cell-free enzyme

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 573–585

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Side-by-side recombinant human ALDH1A1, ALDH1A2 and ALDH1A3 kinetic assays. · source_derived_draft · unverified_draft

### va-aldh1a2-retinal-oxidation Human ALDH1A2 oxidized all-trans-retinaldehyde to retinoic acid in comparative enzyme assays. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: This independently identified enzyme supplies the acid form used for signaling. organism: Homo sapiens recombinant protein tissue_or_cell_type: Cell-free enzyme experimental_model: Side-by-side recombinant human ALDH1A1, ALDH1A2 and ALDH1A3 kinetic assays. limitations: In vitro catalytic efficiency does not specify its contribution in a particular tissue. exposure: Side-by-side retinaldehyde kinetic measurements by HPLC. outcome: Human ALDH1A2 oxidized all-trans-retinaldehyde to retinoic acid in comparative enzyme assays. evidence_location: Abstract [va-pequerul-2020] Structural and kinetic features of aldehyde dehydrogenase 1A (ALDH1A) subfamily members, cancer stem cell markers active in retinoic acid biosynthesis (2020). https://pubmed.ncbi.nlm.nih.gov/31923393/ DOI: 10.1016/j.abb.2020.108256

evidence_location

Abstract

experimental_model

Side-by-side recombinant human ALDH1A1, ALDH1A2 and ALDH1A3 kinetic assays.

exposure

Side-by-side retinaldehyde kinetic measurements by HPLC.

limitations

In vitro catalytic efficiency does not specify its contribution in a particular tissue.

nutrient_topic

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

organism

Homo sapiens recombinant protein

outcome

Human ALDH1A3 oxidized all-trans-retinaldehyde to retinoic acid in comparative enzyme assays.

plain_language

This independently identified enzyme supplies the acid form used for signaling.

primary_references

[va-pequerul-2020] Structural and kinetic features of aldehyde dehydrogenase 1A (ALDH1A) subfamily members, cancer stem cell markers active in retinoic acid biosynthesis (2020). https://pubmed.ncbi.nlm.nih.gov/31923393/ DOI: 10.1016/j.abb.2020.108256

tissue_or_cell_type

Cell-free enzyme

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 587–599

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Side-by-side recombinant human ALDH1A1, ALDH1A2 and ALDH1A3 kinetic assays. · source_derived_draft · unverified_draft

### va-aldh1a3-retinal-oxidation Human ALDH1A3 oxidized all-trans-retinaldehyde to retinoic acid in comparative enzyme assays. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: This independently identified enzyme supplies the acid form used for signaling. organism: Homo sapiens recombinant protein tissue_or_cell_type: Cell-free enzyme experimental_model: Side-by-side recombinant human ALDH1A1, ALDH1A2 and ALDH1A3 kinetic assays. limitations: In vitro catalytic efficiency does not specify its contribution in a particular tissue. exposure: Side-by-side retinaldehyde kinetic measurements by HPLC. outcome: Human ALDH1A3 oxidized all-trans-retinaldehyde to retinoic acid in comparative enzyme assays. evidence_location: Abstract [va-pequerul-2020] Structural and kinetic features of aldehyde dehydrogenase 1A (ALDH1A) subfamily members, cancer stem cell markers active in retinoic acid biosynthesis (2020). https://pubmed.ncbi.nlm.nih.gov/31923393/ DOI: 10.1016/j.abb.2020.108256

experimental_model

Cell-free assay and cell lines.

limitations

ATRA direct activity was not reproduced in the 2024 assays; no clinical or nutrient-replacement inference.

nutrient_topic

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

organism

Homo sapiens

plain_language

Different vitamin A forms were protective in the tested systems.

primary_references

[va-jakaria2023] Vitamin A metabolites inhibit ferroptosis (2023). https://pubmed.ncbi.nlm.nih.gov/37236031/ DOI: 10.1016/j.biopha.2023.114930

tissue_or_cell_type

Cell-free chemistry and cell cultures

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1789–1798

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell-free assay and cell lines. · source_derived_draft · unverified_draft

### va-atra-direct-radical-trapping2023 The 2023 study reported direct radical-trapping activity for retinol, retinal and ATRA alongside ferroptosis protection. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: Different vitamin A forms were protective in the tested systems. organism: Homo sapiens tissue_or_cell_type: Cell-free chemistry and cell cultures experimental_model: Cell-free assay and cell lines. limitations: ATRA direct activity was not reproduced in the 2024 assays; no clinical or nutrient-replacement inference. [va-jakaria2023] Vitamin A metabolites inhibit ferroptosis (2023). https://pubmed.ncbi.nlm.nih.gov/37236031/ DOI: 10.1016/j.biopha.2023.114930

experimental_model

Cell-free assays.

limitations

Does not establish universal absence of antioxidant chemistry.

nutrient_topic

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

organism

Homo sapiens

plain_language

Chemical form and assay conditions matter.

primary_references

[va-berndt2024] Suppression of ferroptosis by vitamin A or radical-trapping antioxidants is essential for neuronal development (2024). https://pubmed.ncbi.nlm.nih.gov/39218970/ DOI: 10.1038/s41467-024-51996-1

tissue_or_cell_type

Cell-free chemistry

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1800–1809

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

### va-atra-no-direct-radical-trapping2024 ATRA showed no direct activity in AAPH/C11-BODIPY and DPPH assays; retinol and retinal were active in the AAPH assay. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: Chemical form and assay conditions matter. organism: Homo sapiens tissue_or_cell_type: Cell-free chemistry experimental_model: Cell-free assays. limitations: Does not establish universal absence of antioxidant chemistry. [va-berndt2024] Suppression of ferroptosis by vitamin A or radical-trapping antioxidants is essential for neuronal development (2024). https://pubmed.ncbi.nlm.nih.gov/39218970/ DOI: 10.1038/s41467-024-51996-1

cross_nutrient

NADPH supports a retinoid buffering reaction.

evidence_location

Figure 5 and Table 1

experimental_model

Human RDH10/DHRS3 coexpression in HEK293 and Sf9 cells, plus Dhrs3-null embryos.

exposure

DHRS3 coexpressed with RDH10; retinal plus NADPH.

limitations

Cofactor dependency is not a dietary niacin intervention.

nutrient_topic

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

organism

Homo sapiens proteins in Sf9 and HEK293 systems

outcome

RDH10-activated DHRS3 reduced all-trans-retinal to retinol preferentially using NADPH.

plain_language

This reverse step restrains retinal available for acid production.

primary_references

[va-adams-2014] The retinaldehyde reductase activity of DHRS3 is reciprocally activated by retinol dehydrogenase 10 to control retinoid homeostasis (2014). https://pmc.ncbi.nlm.nih.gov/articles/PMC4031538/ DOI: 10.1074/jbc.M114.552257

tissue_or_cell_type

Microsomal/cellular retinoid system

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 516–529

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human RDH10/DHRS3 coexpression in HEK293 and Sf9 cells, plus Dhrs3-null embryos. · source_derived_draft · unverified_draft

### va-dhrs3-retinal-reduction RDH10-activated DHRS3 reduced all-trans-retinal to retinol preferentially using NADPH. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: This reverse step restrains retinal available for acid production. organism: Homo sapiens proteins in Sf9 and HEK293 systems tissue_or_cell_type: Microsomal/cellular retinoid system experimental_model: Human RDH10/DHRS3 coexpression in HEK293 and Sf9 cells, plus Dhrs3-null embryos. limitations: Cofactor dependency is not a dietary niacin intervention. exposure: DHRS3 coexpressed with RDH10; retinal plus NADPH. outcome: RDH10-activated DHRS3 reduced all-trans-retinal to retinol preferentially using NADPH. evidence_location: Figure 5 and Table 1 cross_nutrient: NADPH supports a retinoid buffering reaction. [va-adams-2014] The retinaldehyde reductase activity of DHRS3 is reciprocally activated by retinol dehydrogenase 10 to control retinoid homeostasis (2014). https://pmc.ncbi.nlm.nih.gov/articles/PMC4031538/ DOI: 10.1074/jbc.M114.552257

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

Iron availability supports provitamin A cleavage in this in vitro model.

evidence_location

Abstract

experimental_model

Human small-intestinal mucosa and Caco-2 TC7 cells; desferrioxamine and iron addition.

exposure

Increasing desferrioxamine concentrations.

limitations

Drug-induced chelation; BCO1 protein abundance and human dietary deficiency were not directly established.

nutrient_topic

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

organism

Homo sapiens

outcome

Desferrioxamine reduced beta-carotene-cleaving activity in human intestinal mucosa and TC7 cells.

plain_language

Sequestering iron limited conversion of provitamin A to retinal.

primary_references

[va-during-2001] beta-Carotene 15,15'-Dioxygenase activity in human tissues and cells: evidence of an iron dependency (2001). https://pubmed.ncbi.nlm.nih.gov/12031257/ DOI: 10.1016/S0955-2863(01)00184-X

tissue_or_cell_type

Small-intestinal mucosa and Caco-2 TC7 cells

trigger_kind

machinery_impairment Imported condition classification; unverified.

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 187–200

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human small-intestinal mucosa and Caco-2 TC7 cells; desferrioxamine and iron addition. · source_derived_draft · unverified_draft

### va-iron-chelation-cleavage Desferrioxamine reduced beta-carotene-cleaving activity in human intestinal mucosa and TC7 cells. Condition category: machinery_impairment nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: Sequestering iron limited conversion of provitamin A to retinal. organism: Homo sapiens tissue_or_cell_type: Small-intestinal mucosa and Caco-2 TC7 cells experimental_model: Human small-intestinal mucosa and Caco-2 TC7 cells; desferrioxamine and iron addition. limitations: Drug-induced chelation; BCO1 protein abundance and human dietary deficiency were not directly established. exposure: Increasing desferrioxamine concentrations. outcome: Desferrioxamine reduced beta-carotene-cleaving activity in human intestinal mucosa and TC7 cells. evidence_location: Abstract cross_nutrient: Iron availability supports provitamin A cleavage in this in vitro model. [va-during-2001] beta-Carotene 15,15'-Dioxygenase activity in human tissues and cells: evidence of an iron dependency (2001). https://pubmed.ncbi.nlm.nih.gov/12031257/ DOI: 10.1016/S0955-2863(01)00184-X

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_location

Experimental Procedures: siRNA-mediated Knockdowns; Results: endogenous SDR silencing

experimental_model

Human RDH10 in Sf9 microsomes and siRNA perturbation in human cells.

exposure

RDH10 siRNA at 100 nanomolar, two transfections 24 hours apart; 10 micromolar retinol for 24 hours after silencing.

limitations

Residual activity and other enzymes prevent an exclusive RDH10 interpretation.

nutrient_topic

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

organism

Homo sapiens

outcome

Silencing endogenous RDH10 reduced retinoic-acid production from retinol in human cells.

plain_language

Reducing precursor oxidation lowered downstream active retinoid production.

primary_references

[va-belyaeva-2008] Kinetic Analysis of Human Enzyme RDH10 Defines the Characteristics of a Physiologically Relevant Retinol Dehydrogenase (2008). https://pmc.ncbi.nlm.nih.gov/articles/PMC2459273/ DOI: 10.1074/jbc.M800019200

tissue_or_cell_type

HEK293 cells

trigger_kind

machinery_impairment Imported condition classification; unverified.

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 502–514

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human RDH10 in Sf9 microsomes and siRNA perturbation in human cells. · source_derived_draft · unverified_draft

### va-rdh10-silencing-ra Silencing endogenous RDH10 reduced retinoic-acid production from retinol in human cells. Condition category: machinery_impairment nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: Reducing precursor oxidation lowered downstream active retinoid production. organism: Homo sapiens tissue_or_cell_type: HEK293 cells experimental_model: Human RDH10 in Sf9 microsomes and siRNA perturbation in human cells. limitations: Residual activity and other enzymes prevent an exclusive RDH10 interpretation. exposure: RDH10 siRNA at 100 nanomolar, two transfections 24 hours apart; 10 micromolar retinol for 24 hours after silencing. outcome: Silencing endogenous RDH10 reduced retinoic-acid production from retinol in human cells. evidence_location: Experimental Procedures: siRNA-mediated Knockdowns; Results: endogenous SDR silencing [va-belyaeva-2008] Kinetic Analysis of Human Enzyme RDH10 Defines the Characteristics of a Physiologically Relevant Retinol Dehydrogenase (2008). https://pmc.ncbi.nlm.nih.gov/articles/PMC2459273/ DOI: 10.1074/jbc.M800019200

availability_state

nutrient_deficiency Imported condition classification; unverified.

experimental_model

Same hepatic activity assays.

limitations

Activity is not whole-body flux or proof of a direct zinc-binding requirement.

nutrient_topic

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

organism

Rattus norvegicus

plain_language

Vitamin A processing did not simply stop at every step.

primary_references

[va-kim1988] Effect of zinc deficiency on hepatic enzymes regulating vitamin A status (1988). https://pubmed.ncbi.nlm.nih.gov/3404291/ DOI: 10.1093/jn/118.8.995

tissue_or_cell_type

Liver

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1531–1540

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

### va-zinc-deficiency-retinal-oxidation-increase The same zinc-deficient rats showed increased retinal oxidase activity, with no detected REH/ARAT activity changes. Condition category: nutrient_deficiency nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin A processing did not simply stop at every step. organism: Rattus norvegicus tissue_or_cell_type: Liver experimental_model: Same hepatic activity assays. limitations: Activity is not whole-body flux or proof of a direct zinc-binding requirement. [va-kim1988] Effect of zinc deficiency on hepatic enzymes regulating vitamin A status (1988). https://pubmed.ncbi.nlm.nih.gov/3404291/ DOI: 10.1093/jn/118.8.995