Component

NADK2

Human mitochondrial NAD kinase, historically C5orf33.

12 recorded relationships. Experimental role, claim status and evidence remain attached to each record.

Read recorded mechanisms Open recursive mind map

How nutrients influence it

Every nutrient with a recorded effect on this component, credited to the nutrient that acted rather than the chapter that recorded it. Open a nutrient to see the findings and the conditions they were measured under.

How nutrients reach it in more than one step

Chains of two or more recorded steps that end here, grouped by the nutrient they start from. Each step is a separate finding, so a chain is a route a mechanism could take, not proof that it does.

Tracing routes…

What it does

Every recorded relationship this component is part of, grouped by its role. Plain wording comes first; the technical statement follows.

Recorded relationships

What it acts on

  1. A separate study found NADK2 loss depleted mitochondrial NADPH, limited P5C generation and made tested mammalian cells dependent on exogenous proline for growth.

    NADK2 → P5C production during NADK2-dependent proline synthesis source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary abstract
    experimental_model
    Mammalian NADK2-deletion cell models; primary abstract.
    limitations
    Detailed model and exposure differences remain distinct; the two publications are not duplicate evidence records from one experiment.
    nutrient_topic
    L-Proline collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Proline
    plain_language
    A second research group found the same synthesis vulnerability.
    primary_references
    Mitochondrial NADP+ is essential for proline biosynthesis during cell growth. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33833463/ · DOI 10.1038/s42255-021-00374-y
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    L-Proline: synthesis, collagen processing, redox metabolism and cross-nutrient mechanisms (2026-09-19) · lines 78–84

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mammalian NADK2-deletion cell models; primary abstract. · source_derived_draft · unverified_draft

    ## l-proline-nadk2-independent-study A second research group found the same synthesis vulnerability. A separate study found NADK2 loss depleted mitochondrial NADPH, limited P5C generation and made tested mammalian cells dependent on exogenous proline for growth. Model: Mammalian NADK2-deletion cell models; primary abstract. Limitations: Detailed model and exposure differences remain distinct; the two publications are not duplicate evidence records from one experiment. Evidence access: Primary abstract Mitochondrial NADP+ is essential for proline biosynthesis during cell growth. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33833463/ · DOI 10.1038/s42255-021-00374-y
    Complete structured claim and evidence

  2. CRISPR deletion of NADK2 in human DLD1 cells reduced mitochondrial NADP(H) by more than 80% while whole-cell NADP(H) was not similarly depleted.

    NADK2 → Mitochondrial NADP(H) content source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary full text
    experimental_model
    Human DLD1 cells; immunopurified mitochondrial fractions and enzyme-cycling assays.
    limitations
    A compartment-specific genetic manipulation is not equivalent to dietary niacin deficiency.
    nutrient_topic
    L-Proline collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Proline
    plain_language
    The cofactor pool inside mitochondria can fail even when a whole-cell measurement looks adequate.
    primary_references
    Mitochondrial NADP(H) generation is essential for proline biosynthesis. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33888598/ · DOI 10.1126/science.abd5491
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    L-Proline: synthesis, collagen processing, redox metabolism and cross-nutrient mechanisms (2026-09-19) · lines 54–60

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human DLD1 cells; immunopurified mitochondrial fractions and enzyme-cycling assays. · source_derived_draft · unverified_draft

    ## l-proline-nadk2-pool The cofactor pool inside mitochondria can fail even when a whole-cell measurement looks adequate. CRISPR deletion of NADK2 in human DLD1 cells reduced mitochondrial NADP(H) by more than 80% while whole-cell NADP(H) was not similarly depleted. Model: Human DLD1 cells; immunopurified mitochondrial fractions and enzyme-cycling assays. Limitations: A compartment-specific genetic manipulation is not equivalent to dietary niacin deficiency. Evidence access: Primary full text Mitochondrial NADP(H) generation is essential for proline biosynthesis. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33888598/ · DOI 10.1126/science.abd5491
    Complete structured claim and evidence

  3. NADK2 deletion reduced glutamine-derived proline synthesis; mitochondrial NADP(H) was needed for the P5CS step reducing glutamate toward P5C.

    NADK2 → L-Proline source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary full text
    experimental_model
    Human cell deletion, isotope tracing and rescue experiments.
    limitations
    The limiting step was cofactor-dependent synthesis, not a demonstrated lack of glutamine in the diet.
    nutrient_topic
    L-Proline collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Proline
    plain_language
    Proline production needs reducing power in the right compartment.
    primary_references
    Mitochondrial NADP(H) generation is essential for proline biosynthesis. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33888598/ · DOI 10.1126/science.abd5491
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    L-Proline: synthesis, collagen processing, redox metabolism and cross-nutrient mechanisms (2026-09-19) · lines 62–68

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human cell deletion, isotope tracing and rescue experiments. · source_derived_draft · unverified_draft

    ## l-proline-nadk2-proline Proline production needs reducing power in the right compartment. NADK2 deletion reduced glutamine-derived proline synthesis; mitochondrial NADP(H) was needed for the P5CS step reducing glutamate toward P5C. Model: Human cell deletion, isotope tracing and rescue experiments. Limitations: The limiting step was cofactor-dependent synthesis, not a demonstrated lack of glutamine in the diet. Evidence access: Primary full text Mitochondrial NADP(H) generation is essential for proline biosynthesis. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33888598/ · DOI 10.1126/science.abd5491
    Complete structured claim and evidence

  4. Under the tested culture conditions, NADK2 deletion did not increase measured mitochondrial oxidative stress or disrupt mitochondrial folate pathway activity despite reduced proline synthesis.

    NADK2 → Oxidative-stress readouts in NADK2-deleted human cells source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary full text
    experimental_model
    Human cell models; ROS probes, targeted redox sensors and serine isotope tracing.
    limitations
    The authors do not exclude effects during other physiological stresses; this is not a universal claim that mitochondrial NADPH is irrelevant to antioxidant defense.
    nutrient_topic
    L-Proline collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Proline
    plain_language
    Losing this cofactor pool did not shut down every pathway that might be connected to it.
    primary_references
    Mitochondrial NADP(H) generation is essential for proline biosynthesis. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33888598/ · DOI 10.1126/science.abd5491
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    L-Proline: synthesis, collagen processing, redox metabolism and cross-nutrient mechanisms (2026-09-19) · lines 86–92

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human cell models; ROS probes, targeted redox sensors and serine isotope tracing. · source_derived_draft · unverified_draft

    ## l-proline-nadk2-redox-boundary Losing this cofactor pool did not shut down every pathway that might be connected to it. Under the tested culture conditions, NADK2 deletion did not increase measured mitochondrial oxidative stress or disrupt mitochondrial folate pathway activity despite reduced proline synthesis. Model: Human cell models; ROS probes, targeted redox sensors and serine isotope tracing. Limitations: The authors do not exclude effects during other physiological stresses; this is not a universal claim that mitochondrial NADPH is irrelevant to antioxidant defense. Evidence access: Primary full text Mitochondrial NADP(H) generation is essential for proline biosynthesis. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33888598/ · DOI 10.1126/science.abd5491
    Complete structured claim and evidence

  5. NADK2 knockdown reduced measured mitochondrial-fraction NAD kinase activity to 47% of control in HEK293A cells.

    NADK2 → Mitochondrial NAD kinase activity source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_span
    {"source_cache": "artifacts/niacin-redox-sources/nadk2-2012.fulltext.txt", "locator": "Results", "start_char": 16830, "end_char": 18219, "file_sha256": "65209c0b4ea7220bc95afdd182e40910f2445345172956e85552d5c6db649648", "text_sha256": "5de49f80d76c73b6a308096c07b330e8d3d53ee28c6a06f4b2a331e4798b45d7"}
    experimental_model
    siRNA knockdown
    exposure
    Three days after siRNA transfection
    limitations
    Scoped experimental observation; no dietary niacin or magnesium deficiency threshold or treatment benefit was tested.
    nutrient_topic
    Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
    organism
    Homo sapiens
    plain_language
    Reducing the kinase reduced the mitochondrial capacity to make NADP+.
    primary_references
    [nadk2-2012] Identification and characterization of a human mitochondrial NAD kinase. (2012). https://pubmed.ncbi.nlm.nih.gov/23212377/ DOI: 10.1038/ncomms2262
    tissue_or_cell_type
    HEK293A mitochondrial fraction
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Niacin: NAD metabolism, deficiency and nutrient interactions (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 · siRNA knockdown · source_derived_draft · unverified_draft

    ### b3-redox-nadk2-knockdown-activity NADK2 knockdown reduced measured mitochondrial-fraction NAD kinase activity to 47% of control in HEK293A cells. Condition category: machinery_impairment nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Reducing the kinase reduced the mitochondrial capacity to make NADP+. organism: Homo sapiens tissue_or_cell_type: HEK293A mitochondrial fraction experimental_model: siRNA knockdown limitations: Scoped experimental observation; no dietary niacin or magnesium deficiency threshold or treatment benefit was tested. exposure: Three days after siRNA transfection evidence_span: {"source_cache": "artifacts/niacin-redox-sources/nadk2-2012.fulltext.txt", "locator": "Results", "start_char": 16830, "end_char": 18219, "file_sha256": "65209c0b4ea7220bc95afdd182e40910f2445345172956e85552d5c6db649648", "text_sha256": "5de49f80d76c73b6a308096c07b330e8d3d53ee28c6a06f4b2a331e4798b45d7"} [nadk2-2012] Identification and characterization of a human mitochondrial NAD kinase. (2012). https://pubmed.ncbi.nlm.nih.gov/23212377/ DOI: 10.1038/ncomms2262
    Complete structured claim and evidence

  6. Three days after NADK2 knockdown, HEK293A intracellular ROS-probe signals increased with and without the tested menadione challenge.

    NADK2 → Cellular ROS assay signal source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_span
    {"source_cache": "artifacts/niacin-redox-sources/nadk2-2012.fulltext.txt", "locator": "Results", "start_char": 16830, "end_char": 18219, "file_sha256": "65209c0b4ea7220bc95afdd182e40910f2445345172956e85552d5c6db649648", "text_sha256": "5de49f80d76c73b6a308096c07b330e8d3d53ee28c6a06f4b2a331e4798b45d7"}
    experimental_model
    siRNA knockdown; CM-H2DCFDA readout
    exposure
    Three-day knockdown; vehicle or 100 μM menadione for 30 min in ROS assay
    limitations
    CM-H2DCFDA is an intracellular probe; do not relabel this result as a direct measurement of mitochondrial ROS or assume dietary niacin deficiency.
    nutrient_topic
    Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
    organism
    Homo sapiens
    plain_language
    Loss of the kinase increased a cellular oxidant readout in this experiment.
    primary_references
    [nadk2-2012] Identification and characterization of a human mitochondrial NAD kinase. (2012). https://pubmed.ncbi.nlm.nih.gov/23212377/ DOI: 10.1038/ncomms2262
    tissue_or_cell_type
    HEK293A cells
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Niacin: NAD metabolism, deficiency and nutrient interactions (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 · siRNA knockdown; CM-H2DCFDA readout · source_derived_draft · unverified_draft

    ### b3-redox-nadk2-knockdown-ros Three days after NADK2 knockdown, HEK293A intracellular ROS-probe signals increased with and without the tested menadione challenge. Condition category: machinery_impairment nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Loss of the kinase increased a cellular oxidant readout in this experiment. organism: Homo sapiens tissue_or_cell_type: HEK293A cells experimental_model: siRNA knockdown; CM-H2DCFDA readout limitations: CM-H2DCFDA is an intracellular probe; do not relabel this result as a direct measurement of mitochondrial ROS or assume dietary niacin deficiency. exposure: Three-day knockdown; vehicle or 100 μM menadione for 30 min in ROS assay evidence_span: {"source_cache": "artifacts/niacin-redox-sources/nadk2-2012.fulltext.txt", "locator": "Results", "start_char": 16830, "end_char": 18219, "file_sha256": "65209c0b4ea7220bc95afdd182e40910f2445345172956e85552d5c6db649648", "text_sha256": "5de49f80d76c73b6a308096c07b330e8d3d53ee28c6a06f4b2a331e4798b45d7"} [nadk2-2012] Identification and characterization of a human mitochondrial NAD kinase. (2012). https://pubmed.ncbi.nlm.nih.gov/23212377/ DOI: 10.1038/ncomms2262
    Complete structured claim and evidence

  7. The same short NADK2-knockdown experiment did not detect reduced HEK293A viability, including in the tested menadione condition.

    NADK2 → HEK293A cell viability source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_span
    {"source_cache": "artifacts/niacin-redox-sources/nadk2-2012.fulltext.txt", "locator": "Results", "start_char": 16830, "end_char": 18219, "file_sha256": "65209c0b4ea7220bc95afdd182e40910f2445345172956e85552d5c6db649648", "text_sha256": "5de49f80d76c73b6a308096c07b330e8d3d53ee28c6a06f4b2a331e4798b45d7"}
    experimental_model
    siRNA; calcein-AM and supporting MTT assays
    exposure
    Three-day knockdown; viability experiment used 12.5 μM menadione for 20 h
    limitations
    Null short-term viability result does not exclude longer-term injury or other cell-type responses; ROS and viability challenges used different concentrations.
    nutrient_topic
    Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
    organism
    Homo sapiens
    plain_language
    The oxidant readout rose without a detected loss of viability over this interval.
    primary_references
    [nadk2-2012] Identification and characterization of a human mitochondrial NAD kinase. (2012). https://pubmed.ncbi.nlm.nih.gov/23212377/ DOI: 10.1038/ncomms2262
    tissue_or_cell_type
    HEK293A cells
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Niacin: NAD metabolism, deficiency and nutrient interactions (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 · siRNA; calcein-AM and supporting MTT assays · source_derived_draft · unverified_draft

    ### b3-redox-nadk2-knockdown-viability-null The same short NADK2-knockdown experiment did not detect reduced HEK293A viability, including in the tested menadione condition. Condition category: machinery_impairment nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The oxidant readout rose without a detected loss of viability over this interval. organism: Homo sapiens tissue_or_cell_type: HEK293A cells experimental_model: siRNA; calcein-AM and supporting MTT assays limitations: Null short-term viability result does not exclude longer-term injury or other cell-type responses; ROS and viability challenges used different concentrations. exposure: Three-day knockdown; viability experiment used 12.5 μM menadione for 20 h evidence_span: {"source_cache": "artifacts/niacin-redox-sources/nadk2-2012.fulltext.txt", "locator": "Results", "start_char": 16830, "end_char": 18219, "file_sha256": "65209c0b4ea7220bc95afdd182e40910f2445345172956e85552d5c6db649648", "text_sha256": "5de49f80d76c73b6a308096c07b330e8d3d53ee28c6a06f4b2a331e4798b45d7"} [nadk2-2012] Identification and characterization of a human mitochondrial NAD kinase. (2012). https://pubmed.ncbi.nlm.nih.gov/23212377/ DOI: 10.1038/ncomms2262
    Complete structured claim and evidence

  8. Full-length human NADK2 localized to mitochondria in HEK293A cells; deletion of its first 62 residues disrupted that localization.

    NADK2 → Mitochondria source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/niacin-redox-sources/nadk2-2012.fulltext.txt", "locator": "Results", "start_char": 12522, "end_char": 13722, "file_sha256": "65209c0b4ea7220bc95afdd182e40910f2445345172956e85552d5c6db649648", "text_sha256": "bdd61af93db3bf8e573fc599daf7a38da7f5b844d9b5da00d86e955657611875"}
    experimental_model
    FLAG-tagged proteins and endogenous-protein fractionation
    exposure
    Full-length versus Δ62 construct
    limitations
    Evidence resolves mitochondrial localization, not precise submitochondrial position.
    nutrient_topic
    Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
    organism
    Homo sapiens
    plain_language
    The N-terminal targeting region directs this kinase into mitochondria.
    primary_references
    [nadk2-2012] Identification and characterization of a human mitochondrial NAD kinase. (2012). https://pubmed.ncbi.nlm.nih.gov/23212377/ DOI: 10.1038/ncomms2262
    tissue_or_cell_type
    HEK293A cells

    Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 912–923

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · FLAG-tagged proteins and endogenous-protein fractionation · source_derived_draft · unverified_draft

    ### b3-redox-nadk2-localization Full-length human NADK2 localized to mitochondria in HEK293A cells; deletion of its first 62 residues disrupted that localization. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The N-terminal targeting region directs this kinase into mitochondria. organism: Homo sapiens tissue_or_cell_type: HEK293A cells experimental_model: FLAG-tagged proteins and endogenous-protein fractionation limitations: Evidence resolves mitochondrial localization, not precise submitochondrial position. exposure: Full-length versus Δ62 construct evidence_span: {"source_cache": "artifacts/niacin-redox-sources/nadk2-2012.fulltext.txt", "locator": "Results", "start_char": 12522, "end_char": 13722, "file_sha256": "65209c0b4ea7220bc95afdd182e40910f2445345172956e85552d5c6db649648", "text_sha256": "bdd61af93db3bf8e573fc599daf7a38da7f5b844d9b5da00d86e955657611875"} [nadk2-2012] Identification and characterization of a human mitochondrial NAD kinase. (2012). https://pubmed.ncbi.nlm.nih.gov/23212377/ DOI: 10.1038/ncomms2262
    Complete structured claim and evidence

  9. Transfection with functional NADK2 rescued deficient DECR activity in the patient-cell experiments.

    NADK2 → Dienoyl-CoA reductase activity source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_span
    {"source_cache": "artifacts/niacin-redox-sources/nadk2-patient-2014.abstract.txt", "locator": "Indexed abstract, rescue experiment", "start_char": 706, "end_char": 1462, "file_sha256": "0e8ce719f0454f41ce98a5c35f75c88a21f5219f0d9b574cf8a793697f39db5a", "text_sha256": "3e8d0b720e24732ab8f9603138f761f1dc2974876c1f81919cf5ecdae2f71eeb"}
    experimental_model
    Functional NADK2 transfection of patient fibroblasts
    exposure
    Genetic complementation
    limitations
    Cellular gene rescue; neither dietary niacin nor NADPH dosing was shown to reproduce it.
    nutrient_topic
    Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
    organism
    Homo sapiens
    plain_language
    Replacing the defective kinase restored the enzyme readout in cells.
    primary_references
    [nadk2-patient-2014] Mitochondrial NADP(H) deficiency due to a mutation in NADK2 causes dienoyl-CoA reductase deficiency with hyperlysinemia. (2014). https://pubmed.ncbi.nlm.nih.gov/24847004/ DOI: 10.1093/hmg/ddu218
    tissue_or_cell_type
    Fibroblasts
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 990–1001

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Functional NADK2 transfection of patient fibroblasts · source_derived_draft · unverified_draft

    ### b3-redox-nadk2-patient-decr-rescue Transfection with functional NADK2 rescued deficient DECR activity in the patient-cell experiments. Condition category: machinery_impairment nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Replacing the defective kinase restored the enzyme readout in cells. organism: Homo sapiens tissue_or_cell_type: Fibroblasts experimental_model: Functional NADK2 transfection of patient fibroblasts limitations: Cellular gene rescue; neither dietary niacin nor NADPH dosing was shown to reproduce it. exposure: Genetic complementation evidence_span: {"source_cache": "artifacts/niacin-redox-sources/nadk2-patient-2014.abstract.txt", "locator": "Indexed abstract, rescue experiment", "start_char": 706, "end_char": 1462, "file_sha256": "0e8ce719f0454f41ce98a5c35f75c88a21f5219f0d9b574cf8a793697f39db5a", "text_sha256": "3e8d0b720e24732ab8f9603138f761f1dc2974876c1f81919cf5ecdae2f71eeb"} [nadk2-patient-2014] Mitochondrial NADP(H) deficiency due to a mutation in NADK2 causes dienoyl-CoA reductase deficiency with hyperlysinemia. (2014). https://pubmed.ncbi.nlm.nih.gov/24847004/ DOI: 10.1093/hmg/ddu218
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. Adding proline restored growth of NADK2-deleted human cells in minimal medium, whereas the defect was largely absent in nutrient-rich medium.

    L-Proline → Human NADK2-null cell proliferation in minimal medium source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary full text
    experimental_model
    Human NADK2-knockout cell cultures; DMEM compared with DMEM/F12 and individual amino-acid add-back.
    limitations
    Cell-culture rescue does not establish a treatment for inherited NADK2 disease.
    nutrient_topic
    L-Proline collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Proline
    plain_language
    An external supply can bypass a synthesis bottleneck in these cells.
    primary_references
    Mitochondrial NADP(H) generation is essential for proline biosynthesis. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33888598/ · DOI 10.1126/science.abd5491
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    L-Proline: synthesis, collagen processing, redox metabolism and cross-nutrient mechanisms (2026-09-19) · lines 70–76

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human NADK2-knockout cell cultures; DMEM compared with DMEM/F12 and individual amino-acid add-back. · source_derived_draft · unverified_draft

    ## l-proline-nadk2-rescue An external supply can bypass a synthesis bottleneck in these cells. Adding proline restored growth of NADK2-deleted human cells in minimal medium, whereas the defect was largely absent in nutrient-rich medium. Model: Human NADK2-knockout cell cultures; DMEM compared with DMEM/F12 and individual amino-acid add-back. Limitations: Cell-culture rescue does not establish a treatment for inherited NADK2 disease. Evidence access: Primary full text Mitochondrial NADP(H) generation is essential for proline biosynthesis. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33888598/ · DOI 10.1126/science.abd5491
    Complete structured claim and evidence

  2. Patient fibroblasts bearing a pathogenic NADK2 alteration had reduced mitochondrial NADP(H).

    NADK2 loss-of-function genotype → Mitochondrial NADP(H) content source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_span
    {"source_cache": "artifacts/niacin-redox-sources/nadk2-patient-2014.abstract.txt", "locator": "Indexed abstract, genetic and fibroblast results", "start_char": 357, "end_char": 1462, "file_sha256": "0e8ce719f0454f41ce98a5c35f75c88a21f5219f0d9b574cf8a793697f39db5a", "text_sha256": "e468b1beee1be208d337cdf94488aca05296b2dd3fcbba587ca323b8db6d2c96"}
    experimental_model
    Patient-derived fibroblasts
    exposure
    Inherited NADK2 alteration
    limitations
    Single described patient context; mitochondrial NADP(H) shortage arose from kinase machinery impairment, not demonstrated dietary niacin shortage.
    nutrient_topic
    Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
    organism
    Homo sapiens
    plain_language
    The genetic defect impaired the mitochondrial phosphorylated cofactor pool.
    primary_references
    [nadk2-patient-2014] Mitochondrial NADP(H) deficiency due to a mutation in NADK2 causes dienoyl-CoA reductase deficiency with hyperlysinemia. (2014). https://pubmed.ncbi.nlm.nih.gov/24847004/ DOI: 10.1093/hmg/ddu218
    tissue_or_cell_type
    Fibroblasts
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 964–975

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

    ### b3-redox-nadk2-patient-pool Patient fibroblasts bearing a pathogenic NADK2 alteration had reduced mitochondrial NADP(H). Condition category: machinery_impairment nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The genetic defect impaired the mitochondrial phosphorylated cofactor pool. organism: Homo sapiens tissue_or_cell_type: Fibroblasts experimental_model: Patient-derived fibroblasts limitations: Single described patient context; mitochondrial NADP(H) shortage arose from kinase machinery impairment, not demonstrated dietary niacin shortage. exposure: Inherited NADK2 alteration evidence_span: {"source_cache": "artifacts/niacin-redox-sources/nadk2-patient-2014.abstract.txt", "locator": "Indexed abstract, genetic and fibroblast results", "start_char": 357, "end_char": 1462, "file_sha256": "0e8ce719f0454f41ce98a5c35f75c88a21f5219f0d9b574cf8a793697f39db5a", "text_sha256": "e468b1beee1be208d337cdf94488aca05296b2dd3fcbba587ca323b8db6d2c96"} [nadk2-patient-2014] Mitochondrial NADP(H) deficiency due to a mutation in NADK2 causes dienoyl-CoA reductase deficiency with hyperlysinemia. (2014). https://pubmed.ncbi.nlm.nih.gov/24847004/ DOI: 10.1093/hmg/ddu218
    Complete structured claim and evidence

  3. Purified human NADK2 Δ62 converted NAD+ to NADP+ with ATP in MgCl2-containing reactions; TLC also detected ADP formation.

    NADK2 Δ62 recombinant construct → NADP+ source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    Magnesium is present with ATP during phosphorylation of the niacin-derived dinucleotide; this assay does not quantify effects of dietary magnesium shortage.
    evidence_span
    [{"source_cache": "artifacts/niacin-redox-sources/nadk2-2012.fulltext.txt", "locator": "Results", "start_char": 8475, "end_char": 9580, "file_sha256": "65209c0b4ea7220bc95afdd182e40910f2445345172956e85552d5c6db649648", "text_sha256": "c86810a1a5342cd4e7ea126e070f28ed3182d81f17ea76c0fbb3833612c0f529"}, {"source_cache": "artifacts/niacin-redox-sources/nadk2-2012.fulltext.txt", "locator": "Methods, NADK activity assay", "start_char": 26694, "end_char": 28732, "file_sha256": "65209c0b4ea7220bc95afdd182e40910f2445345172956e85552d5c6db649648", "text_sha256": "907b651f0c0aae7a31306bdc42264cdfd22fb0e236e7ab8f37900467b0b0ab72"}]
    experimental_model
    Purified His-tagged Δ62C5orf33/NADK2
    exposure
    TLC: 5 mM NAD+, 5 mM ATP, 5 mM MgCl2; 37°C
    limitations
    Scoped experimental observation; no dietary niacin or magnesium deficiency threshold or treatment benefit was tested.
    nutrient_topic
    Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
    organism
    Homo sapiens
    plain_language
    The mitochondrial kinase uses a phosphate-transfer reaction to create NADP+.
    primary_references
    [nadk2-2012] Identification and characterization of a human mitochondrial NAD kinase. (2012). https://pubmed.ncbi.nlm.nih.gov/23212377/ DOI: 10.1038/ncomms2262
    tissue_or_cell_type
    Purified protein

    Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 871–883

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified His-tagged Δ62C5orf33/NADK2 · source_derived_draft · unverified_draft

    ### b3-redox-nadk2-phosphorylation Purified human NADK2 Δ62 converted NAD+ to NADP+ with ATP in MgCl2-containing reactions; TLC also detected ADP formation. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The mitochondrial kinase uses a phosphate-transfer reaction to create NADP+. organism: Homo sapiens tissue_or_cell_type: Purified protein experimental_model: Purified His-tagged Δ62C5orf33/NADK2 limitations: Scoped experimental observation; no dietary niacin or magnesium deficiency threshold or treatment benefit was tested. exposure: TLC: 5 mM NAD+, 5 mM ATP, 5 mM MgCl2; 37°C cross_nutrient: Magnesium is present with ATP during phosphorylation of the niacin-derived dinucleotide; this assay does not quantify effects of dietary magnesium shortage. evidence_span: [{"source_cache": "artifacts/niacin-redox-sources/nadk2-2012.fulltext.txt", "locator": "Results", "start_char": 8475, "end_char": 9580, "file_sha256": "65209c0b4ea7220bc95afdd182e40910f2445345172956e85552d5c6db649648", "text_sha256": "c86810a1a5342cd4e7ea126e070f28ed3182d81f17ea76c0fbb3833612c0f529"}, {"source_cache": "artifacts/niacin-redox-sources/nadk2-2012.fulltext.txt", "locator": "Methods, NADK activity assay", "start_char": 26694, "end_char": 28732, "file_sha256": "65209c0b4ea7220bc95afdd182e40910f2445345172956e85552d5c6db649648", "text_sha256": "907b651f0c0aae7a31306bdc42264cdfd22fb0e236e7ab8f37900467b0b0ab72"}] [nadk2-2012] Identification and characterization of a human mitochondrial NAD kinase. (2012). https://pubmed.ncbi.nlm.nih.gov/23212377/ DOI: 10.1038/ncomms2262
    Complete structured claim and evidence

In the sources

Preserved passages that mention this component, quoted exactly. Open one to read it in context.

    This is a research prototype built from draft material. It is not medical advice, and its statements still await verification against the original studies.

    Evidence, AI assistance and curation standards