Nutrient chapter

L-Aspartate

61 recorded mechanisms · 12 availability situations · 7 preserved sources. Draft and verified records are labeled separately.

Read recorded mechanisms Open recursive mind map

The mechanisms

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

Dual-isotope tracing in eight enterally fed preterm infants measured splanchnic first-pass aspartate uptake of 77 ± 15%.
L-Aspartate → Splanchnic first-pass aspartate uptake in preterm infants source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Eight infants, gestational age 26–34 weeks; enteral and intravenous stable-isotope tracer protocol.
limitations
Do not substitute the paper title’s almost all for 100%, or extrapolate this percentage to healthy adults.
nutrient_topic
L-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Aspartate
plain_language
Much of the ingested amino acid was handled before reaching the wider circulation.
primary_references
Almost all enteral aspartate is taken up in first-pass metabolism in enterally fed preterm infants. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20022677/ · DOI 10.1016/j.clnu.2009.11.008
L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 18–24
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Eight infants, gestational age 26–34 weeks; enteral and intravenous stable-isotope tracer protocol. · source_derived_draft · unverified_draft
## l-aspartate-infant-first-pass Much of the ingested amino acid was handled before reaching the wider circulation. Dual-isotope tracing in eight enterally fed preterm infants measured splanchnic first-pass aspartate uptake of 77 ± 15%. Model: Eight infants, gestational age 26–34 weeks; enteral and intravenous stable-isotope tracer protocol. Limitations: Do not substitute the paper title’s almost all for 100%, or extrapolate this percentage to healthy adults. Evidence access: Primary abstract Almost all enteral aspartate is taken up in first-pass metabolism in enterally fed preterm infants. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20022677/ · DOI 10.1016/j.clnu.2009.11.008
Complete structured claim and evidence
About 80 ± 9% of labeled aspartate carbon used in first-pass metabolism was recovered in expired carbon dioxide.
L-Aspartate → Breath carbon dioxide from first-pass aspartate in infants source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Same eight preterm infants; carbon-13 recovery in breath.
limitations
The denominator is label used in first pass, not necessarily the entire administered dose; no adult efficacy inference.
nutrient_topic
L-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Aspartate
plain_language
The tracing supports extensive use of the carbon skeleton for energy metabolism.
primary_references
Almost all enteral aspartate is taken up in first-pass metabolism in enterally fed preterm infants. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20022677/ · DOI 10.1016/j.clnu.2009.11.008
L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 26–32
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Same eight preterm infants; carbon-13 recovery in breath. · source_derived_draft · unverified_draft
## l-aspartate-infant-oxidation The tracing supports extensive use of the carbon skeleton for energy metabolism. About 80 ± 9% of labeled aspartate carbon used in first-pass metabolism was recovered in expired carbon dioxide. Model: Same eight preterm infants; carbon-13 recovery in breath. Limitations: The denominator is label used in first pass, not necessarily the entire administered dose; no adult efficacy inference. Evidence access: Primary abstract Almost all enteral aspartate is taken up in first-pass metabolism in enterally fed preterm infants. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20022677/ · DOI 10.1016/j.clnu.2009.11.008
Complete structured claim and evidence
Human recessive SLC1A1 R445W and I395del variants were identified in dicarboxylic aminoaciduria with urinary glutamate and aspartate loss.
Human SLC1A1 R445W and I395del variants → Renal conservation of glutamate and aspartate source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Human families and functional characterization of disease-associated human transporter variants.
limitations
Gene-related renal handling is not evidence of an ordinary dietary deficiency; neurological associations do not establish one mechanism.
nutrient_topic
L-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Aspartate
plain_language
A transporter defect can cause nutrient loss even when intake is adequate.
primary_references
Loss-of-function mutations in the glutamate transporter SLC1A1 cause human dicarboxylic aminoaciduria. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21123949/ · DOI 10.1172/JCI44474
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 34–40
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human families and functional characterization of disease-associated human transporter variants. · source_derived_draft · unverified_draft
## l-aspartate-renal-gene-loss A transporter defect can cause nutrient loss even when intake is adequate. Human recessive SLC1A1 R445W and I395del variants were identified in dicarboxylic aminoaciduria with urinary glutamate and aspartate loss. Model: Human families and functional characterization of disease-associated human transporter variants. Limitations: Gene-related renal handling is not evidence of an ordinary dietary deficiency; neurological associations do not establish one mechanism. Evidence access: Primary abstract Loss-of-function mutations in the glutamate transporter SLC1A1 cause human dicarboxylic aminoaciduria. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21123949/ · DOI 10.1172/JCI44474
Complete structured claim and evidence
The disease-associated human SLC1A1 variants showed near-absent cell-surface expression in a canine kidney cell model, with impaired glutamate and cysteine transport in functional assays.
Human SLC1A1 R445W and I395del variants → Human excitatory amino acid transporter 3 / SLC1A1 source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Human constructs in heterologous functional assays and canine MDCK cells.
limitations
The accessed abstract reports glutamate/cysteine assays; do not mislabel them as direct aspartate uptake measurements.
nutrient_topic
L-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Aspartate
plain_language
Having a transporter gene is insufficient if the protein fails to reach the membrane.
primary_references
Loss-of-function mutations in the glutamate transporter SLC1A1 cause human dicarboxylic aminoaciduria. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21123949/ · DOI 10.1172/JCI44474
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 42–48
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human constructs in heterologous functional assays and canine MDCK cells. · source_derived_draft · unverified_draft
## l-aspartate-renal-trafficking Having a transporter gene is insufficient if the protein fails to reach the membrane. The disease-associated human SLC1A1 variants showed near-absent cell-surface expression in a canine kidney cell model, with impaired glutamate and cysteine transport in functional assays. Model: Human constructs in heterologous functional assays and canine MDCK cells. Limitations: The accessed abstract reports glutamate/cysteine assays; do not mislabel them as direct aspartate uptake measurements. Evidence access: Primary abstract Loss-of-function mutations in the glutamate transporter SLC1A1 cause human dicarboxylic aminoaciduria. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21123949/ · DOI 10.1172/JCI44474
Complete structured claim and evidence
Under electron-transport-chain inhibition, human GOT1 supported cytosolic aspartate synthesis rather than its usual aspartate-consuming shuttle direction.
Human cytosolic aspartate aminotransferase / GOT1 → L-Aspartate source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Human proliferating cell models; genetic screen and metabolic tracing during ETC inhibition.
limitations
Direction is conditional, not an intrinsic one-way label for GOT1.
nutrient_topic
L-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Aspartate
plain_language
A reversible enzyme can run in a different direction when the cell’s redox state changes.
primary_references
An Essential Role of the Mitochondrial Electron Transport Chain in Cell Proliferation Is to Enable Aspartate Synthesis. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26232224/ · DOI 10.1016/j.cell.2015.07.016
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 50–56
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human proliferating cell models; genetic screen and metabolic tracing during ETC inhibition. · source_derived_draft · unverified_draft
## l-aspartate-got1-reversal A reversible enzyme can run in a different direction when the cell’s redox state changes. Under electron-transport-chain inhibition, human GOT1 supported cytosolic aspartate synthesis rather than its usual aspartate-consuming shuttle direction. Model: Human proliferating cell models; genetic screen and metabolic tracing during ETC inhibition. Limitations: Direction is conditional, not an intrinsic one-way label for GOT1. Evidence access: Primary full text An Essential Role of the Mitochondrial Electron Transport Chain in Cell Proliferation Is to Enable Aspartate Synthesis. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26232224/ · DOI 10.1016/j.cell.2015.07.016
Complete structured claim and evidence
GOT1 loss prevented pyruvate from rescuing aspartate synthesis and proliferation during ETC dysfunction.
Human cytosolic aspartate aminotransferase / GOT1 → Aspartate production after human-cell ETC impairment source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Human Jurkat-centered genetic and metabolic experiments.
limitations
Pyruvate is not a universally effective rescue for every respiratory or transaminase defect.
nutrient_topic
L-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Aspartate
plain_language
Providing an electron acceptor did not bypass the need for functioning synthesis machinery.
primary_references
An Essential Role of the Mitochondrial Electron Transport Chain in Cell Proliferation Is to Enable Aspartate Synthesis. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26232224/ · DOI 10.1016/j.cell.2015.07.016
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 58–64
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human Jurkat-centered genetic and metabolic experiments. · source_derived_draft · unverified_draft
## l-aspartate-pyruvate-got1-gate Providing an electron acceptor did not bypass the need for functioning synthesis machinery. GOT1 loss prevented pyruvate from rescuing aspartate synthesis and proliferation during ETC dysfunction. Model: Human Jurkat-centered genetic and metabolic experiments. Limitations: Pyruvate is not a universally effective rescue for every respiratory or transaminase defect. Evidence access: Primary full text An Essential Role of the Mitochondrial Electron Transport Chain in Cell Proliferation Is to Enable Aspartate Synthesis. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26232224/ · DOI 10.1016/j.cell.2015.07.016
Complete structured claim and evidence
Aspartate supplementation relieved IMP accumulation and restored AMP and SAICAR pools in respiration-impaired 143B cells, while GMP did not similarly recover.
L-Aspartate → Adenine nucleotide pools in respiration-impaired human 143B 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 143B cytochrome-b-mutant cells; metabolomics after high extracellular aspartate.
limitations
The GMP branch also depends on redox chemistry; high culture supplementation does not establish oral delivery.
nutrient_topic
L-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Aspartate
plain_language
Restoring one substrate repaired some nucleotide steps without repairing all of them.
primary_references
Supporting Aspartate Biosynthesis Is an Essential Function of Respiration in Proliferating Cells. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26232225/ · DOI 10.1016/j.cell.2015.07.017
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 66–72
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human 143B cytochrome-b-mutant cells; metabolomics after high extracellular aspartate. · source_derived_draft · unverified_draft
## l-aspartate-purine-rescue Restoring one substrate repaired some nucleotide steps without repairing all of them. Aspartate supplementation relieved IMP accumulation and restored AMP and SAICAR pools in respiration-impaired 143B cells, while GMP did not similarly recover. Model: Human 143B cytochrome-b-mutant cells; metabolomics after high extracellular aspartate. Limitations: The GMP branch also depends on redox chemistry; high culture supplementation does not establish oral delivery. Evidence access: Primary full text Supporting Aspartate Biosynthesis Is an Essential Function of Respiration in Proliferating Cells. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26232225/ · DOI 10.1016/j.cell.2015.07.017
Complete structured claim and evidence
SLC1A3 manipulation changed aspartate import and cancer-cell sensitivity to respiratory inhibitors.
Human excitatory amino acid transporter 1 / SLC1A3 → Resistance to ETC-inhibitor growth suppression in human cancer 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 cancer-cell panels; SLC1A3 knockout/overexpression and inhibitor challenges.
limitations
SLC1A3 also transports glutamate; effects are model-specific rather than an oral supplementation result. Correction record: The 2018 author correction added a missing competing-interests statement declaring no competing interests; no mechanism or data change was stated. PMID 30089842; DOI 10.1038/s41556-018-0184-2. https://pubmed.ncbi.nlm.nih.gov/30089842/
nutrient_topic
L-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Aspartate
plain_language
Transport capacity determines whether a cell can use the aspartate available outside it.
primary_references
Aspartate is a limiting metabolite for cancer cell proliferation under hypoxia and in tumours. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29941933/ · DOI 10.1038/s41556-018-0118-z
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 74–80
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human cancer-cell panels; SLC1A3 knockout/overexpression and inhibitor challenges. · source_derived_draft · unverified_draft
## l-aspartate-eaat1-respiration Transport capacity determines whether a cell can use the aspartate available outside it. SLC1A3 manipulation changed aspartate import and cancer-cell sensitivity to respiratory inhibitors. Model: Human cancer-cell panels; SLC1A3 knockout/overexpression and inhibitor challenges. Limitations: SLC1A3 also transports glutamate; effects are model-specific rather than an oral supplementation result. Correction record: The 2018 author correction added a missing competing-interests statement declaring no competing interests; no mechanism or data change was stated. PMID 30089842; DOI 10.1038/s41556-018-0184-2. https://pubmed.ncbi.nlm.nih.gov/30089842/ Evidence access: Primary full text Aspartate is a limiting metabolite for cancer cell proliferation under hypoxia and in tumours. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29941933/ · DOI 10.1038/s41556-018-0118-z
Complete structured claim and evidence
Increasing SLC1A3-mediated uptake supplied aspartate for nucleotide synthesis and improved proliferation under low oxygen and growth in tumor xenograft models.
Human excitatory amino acid transporter 1 / SLC1A3 → Hypoxic proliferation of human cancer cells source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Human cancer cultures and xenografts in immunodeficient mice.
limitations
Not every tumor expresses this transporter, and this is not evidence that ordinary intake initiates cancer. Correction record: The 2018 author correction added a missing competing-interests statement declaring no competing interests; no mechanism or data change was stated. PMID 30089842; DOI 10.1038/s41556-018-0184-2. https://pubmed.ncbi.nlm.nih.gov/30089842/
nutrient_topic
L-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Aspartate
plain_language
Uptake partly bypassed a synthesis bottleneck in the tested tumors.
primary_references
Aspartate is a limiting metabolite for cancer cell proliferation under hypoxia and in tumours. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29941933/ · DOI 10.1038/s41556-018-0118-z
L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 82–88
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human cancer cultures and xenografts in immunodeficient mice. · source_derived_draft · unverified_draft
## l-aspartate-eaat1-hypoxia Uptake partly bypassed a synthesis bottleneck in the tested tumors. Increasing SLC1A3-mediated uptake supplied aspartate for nucleotide synthesis and improved proliferation under low oxygen and growth in tumor xenograft models. Model: Human cancer cultures and xenografts in immunodeficient mice. Limitations: Not every tumor expresses this transporter, and this is not evidence that ordinary intake initiates cancer. Correction record: The 2018 author correction added a missing competing-interests statement declaring no competing interests; no mechanism or data change was stated. PMID 30089842; DOI 10.1038/s41556-018-0184-2. https://pubmed.ncbi.nlm.nih.gov/30089842/ Evidence access: Primary full text Aspartate is a limiting metabolite for cancer cell proliferation under hypoxia and in tumours. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29941933/ · DOI 10.1038/s41556-018-0118-z
Complete structured claim and evidence
Aspartate abundance in primary human tumor samples negatively correlated with hypoxia-marker expression.
Hypoxia-marker expression in primary human tumors → Aspartate pool in sampled primary human tumors source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Human tumor metabolite and marker analysis.
limitations
Correlation alone cannot establish causal direction or a universal tissue threshold. Correction record: The 2018 author correction added a missing competing-interests statement declaring no competing interests; no mechanism or data change was stated. PMID 30089842; DOI 10.1038/s41556-018-0184-2. https://pubmed.ncbi.nlm.nih.gov/30089842/
nutrient_topic
L-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Aspartate
plain_language
Human tumor measurements were consistent with the oxygen-related mechanism.
primary_references
Aspartate is a limiting metabolite for cancer cell proliferation under hypoxia and in tumours. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29941933/ · DOI 10.1038/s41556-018-0118-z
trigger_kind
biomarker_context Imported condition classification; unverified.
L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 90–96
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human tumor metabolite and marker analysis. · source_derived_draft · unverified_draft
## l-aspartate-tumor-marker-limit Human tumor measurements were consistent with the oxygen-related mechanism. Aspartate abundance in primary human tumor samples negatively correlated with hypoxia-marker expression. Model: Human tumor metabolite and marker analysis. Limitations: Correlation alone cannot establish causal direction or a universal tissue threshold. Correction record: The 2018 author correction added a missing competing-interests statement declaring no competing interests; no mechanism or data change was stated. PMID 30089842; DOI 10.1038/s41556-018-0184-2. https://pubmed.ncbi.nlm.nih.gov/30089842/ Evidence access: Primary full text Aspartate is a limiting metabolite for cancer cell proliferation under hypoxia and in tumours. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29941933/ · DOI 10.1038/s41556-018-0118-z
Complete structured claim and evidence
Human citrin regulatory-domain structures resolved calcium at EF-hand 2; the other EF-hand motifs were not all calcium-binding sites.
Calcium ion → Human citrin / SLC25A13 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Human SLC25A13 regulatory-domain crystallography; calcium-bound and calcium-free structures.
limitations
Domain structures do not define a dietary calcium threshold or a treatment for citrin deficiency.
nutrient_topic
L-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Aspartate
plain_language
Several similarly named structural motifs do not mean several equivalent calcium switches.
primary_references
Calcium-induced conformational changes of the regulatory domain of human mitochondrial aspartate/glutamate carriers. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25410934/ · DOI 10.1038/ncomms6491
L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 98–104
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human SLC25A13 regulatory-domain crystallography; calcium-bound and calcium-free structures. · source_derived_draft · unverified_draft
## l-aspartate-citrin-calcium-site Several similarly named structural motifs do not mean several equivalent calcium switches. Human citrin regulatory-domain structures resolved calcium at EF-hand 2; the other EF-hand motifs were not all calcium-binding sites. Model: Human SLC25A13 regulatory-domain crystallography; calcium-bound and calcium-free structures. Limitations: Domain structures do not define a dietary calcium threshold or a treatment for citrin deficiency. Evidence access: Primary full text Calcium-induced conformational changes of the regulatory domain of human mitochondrial aspartate/glutamate carriers. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25410934/ · DOI 10.1038/ncomms6491
Complete structured claim and evidence
Calcium-bound human aralar regulatory-domain structures likewise identified EF-hand 2 as the calcium-binding site.
Calcium ion → Human aralar / SLC25A12 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Human SLC25A12 structural analysis.
limitations
The transport domain itself was not captured in a complete transport cycle.
nutrient_topic
L-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Aspartate
plain_language
The second mitochondrial aspartate carrier shares a calcium-sensitive regulatory feature.
primary_references
Calcium-induced conformational changes of the regulatory domain of human mitochondrial aspartate/glutamate carriers. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25410934/ · DOI 10.1038/ncomms6491
L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 106–112
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human SLC25A12 structural analysis. · source_derived_draft · unverified_draft
## l-aspartate-aralar-calcium-site The second mitochondrial aspartate carrier shares a calcium-sensitive regulatory feature. Calcium-bound human aralar regulatory-domain structures likewise identified EF-hand 2 as the calcium-binding site. Model: Human SLC25A12 structural analysis. Limitations: The transport domain itself was not captured in a complete transport cycle. Evidence access: Primary full text Calcium-induced conformational changes of the regulatory domain of human mitochondrial aspartate/glutamate carriers. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25410934/ · DOI 10.1038/ncomms6491
Complete structured claim and evidence
Calcium-associated movement of the mobile regulatory domain opened a vestibule in regulatory-domain structures; the authors proposed that this controls substrate access.
Calcium ion → Regulatory vestibule of human aspartate/glutamate carriers source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Human citrin/aralar domain structures and structural model.
limitations
The substrate-access gating mechanism is structure-supported interpretation, not direct observation of an entire transport cycle.
nutrient_topic
L-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Aspartate
plain_language
Calcium binding can change access to the transport machinery.
primary_references
Calcium-induced conformational changes of the regulatory domain of human mitochondrial aspartate/glutamate carriers. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25410934/ · DOI 10.1038/ncomms6491
L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 114–120
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human citrin/aralar domain structures and structural model. · source_derived_draft · unverified_draft
## l-aspartate-carrier-vestibule Calcium binding can change access to the transport machinery. Calcium-associated movement of the mobile regulatory domain opened a vestibule in regulatory-domain structures; the authors proposed that this controls substrate access. Model: Human citrin/aralar domain structures and structural model. Limitations: The substrate-access gating mechanism is structure-supported interpretation, not direct observation of an entire transport cycle. Evidence access: Primary full text Calcium-induced conformational changes of the regulatory domain of human mitochondrial aspartate/glutamate carriers. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25410934/ · DOI 10.1038/ncomms6491
Complete structured claim and evidence
Exogenous aralar expression reversed the increased NADH/NAD+ ratio in hepatocytes from citrin-null mice.
Mouse aralar / Slc25a12 → NADH/NAD+ balance in citrin-null mouse hepatocytes source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Mouse Slc25a13-null hepatocytes with exogenous aralar expression.
limitations
Gene-expression rescue is not proof that oral aspartate or calcium corrects human citrin deficiency.
nutrient_topic
L-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Aspartate
plain_language
A related carrier can substitute for part of the missing transport function in this model.
primary_references
Exogenous aralar/slc25a12 can replace citrin/slc25a13 as malate aspartate shuttle component in liver. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36967723/ · DOI 10.1016/j.ymgmr.2023.100967
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 122–128
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse Slc25a13-null hepatocytes with exogenous aralar expression. · source_derived_draft · unverified_draft
## l-aspartate-citrin-aralar-rescue A related carrier can substitute for part of the missing transport function in this model. Exogenous aralar expression reversed the increased NADH/NAD+ ratio in hepatocytes from citrin-null mice. Model: Mouse Slc25a13-null hepatocytes with exogenous aralar expression. Limitations: Gene-expression rescue is not proof that oral aspartate or calcium corrects human citrin deficiency. Evidence access: Primary full text Exogenous aralar/slc25a12 can replace citrin/slc25a13 as malate aspartate shuttle component in liver. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36967723/ · DOI 10.1016/j.ymgmr.2023.100967
Complete structured claim and evidence
Liver-specific transgenic aralar expression increased residual shuttle activity in citrin-null mouse mitochondria by approximately 4–6 nmol per mg protein per minute.
Mouse aralar / Slc25a12 → Malate–aspartate shuttle activity in citrin-null mouse liver source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Isolated liver mitochondria from genetically modified mice.
limitations
Small ex vivo flux increment; not human therapeutic efficacy.
nutrient_topic
L-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Aspartate
plain_language
A measurable transport rescue did not amount to proof of complete disease correction.
primary_references
Exogenous aralar/slc25a12 can replace citrin/slc25a13 as malate aspartate shuttle component in liver. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36967723/ · DOI 10.1016/j.ymgmr.2023.100967
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 130–136
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Isolated liver mitochondria from genetically modified mice. · source_derived_draft · unverified_draft
## l-aspartate-citrin-shuttle-rescue A measurable transport rescue did not amount to proof of complete disease correction. Liver-specific transgenic aralar expression increased residual shuttle activity in citrin-null mouse mitochondria by approximately 4–6 nmol per mg protein per minute. Model: Isolated liver mitochondria from genetically modified mice. Limitations: Small ex vivo flux increment; not human therapeutic efficacy. Evidence access: Primary full text Exogenous aralar/slc25a12 can replace citrin/slc25a13 as malate aspartate shuttle component in liver. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36967723/ · DOI 10.1016/j.ymgmr.2023.100967
Complete structured claim and evidence
Absolute proteomics found citrin/aralar molar ratios of about 7.8 in mouse liver and 397 in human liver, indicating much less endogenous aralar relative to citrin in humans.
Species-dependent liver aspartate-carrier expression → Human aralar / SLC25A12 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Mouse and human liver quantitative proteomics.
limitations
Sampled expression ratios are not universal constants or proof of a clinical rescue strategy.
nutrient_topic
L-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Aspartate
plain_language
A mouse may compensate for a missing carrier more readily than a human.
primary_references
Exogenous aralar/slc25a12 can replace citrin/slc25a13 as malate aspartate shuttle component in liver. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36967723/ · DOI 10.1016/j.ymgmr.2023.100967
L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 138–144
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse and human liver quantitative proteomics. · source_derived_draft · unverified_draft
## l-aspartate-carrier-species-expression A mouse may compensate for a missing carrier more readily than a human. Absolute proteomics found citrin/aralar molar ratios of about 7.8 in mouse liver and 397 in human liver, indicating much less endogenous aralar relative to citrin in humans. Model: Mouse and human liver quantitative proteomics. Limitations: Sampled expression ratios are not universal constants or proof of a clinical rescue strategy. Evidence access: Primary full text Exogenous aralar/slc25a12 can replace citrin/slc25a13 as malate aspartate shuttle component in liver. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36967723/ · DOI 10.1016/j.ymgmr.2023.100967
Complete structured claim and evidence
Purified human CAD aspartate-transcarbamylase domain converted carbamoyl phosphate and aspartate to carbamoyl-aspartate in an initial-rate assay.
Human CAD multifunctional pyrimidine synthesis enzyme → N-Carbamoyl-L-aspartate source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Recombinant human CAD ATCase domain fused to MBP; biochemical assay.
limitations
Isolated-domain kinetics are not whole-cell nucleotide flux.
nutrient_topic
L-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Aspartate
plain_language
Aspartate becomes part of the precursor used to build pyrimidine bases.
primary_references
Succinate dehydrogenase loss suppresses pyrimidine biosynthesis via succinate-mediated inhibition of aspartate transcarbamylase. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42082831/ · DOI 10.1038/s42255-026-01524-w
L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 146–152
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Recombinant human CAD ATCase domain fused to MBP; biochemical assay. · source_derived_draft · unverified_draft
## l-aspartate-cad-aspartate-reaction Aspartate becomes part of the precursor used to build pyrimidine bases. Purified human CAD aspartate-transcarbamylase domain converted carbamoyl phosphate and aspartate to carbamoyl-aspartate in an initial-rate assay. Model: Recombinant human CAD ATCase domain fused to MBP; biochemical assay. Limitations: Isolated-domain kinetics are not whole-cell nucleotide flux. Evidence access: Primary full text Succinate dehydrogenase loss suppresses pyrimidine biosynthesis via succinate-mediated inhibition of aspartate transcarbamylase. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42082831/ · DOI 10.1038/s42255-026-01524-w
Complete structured claim and evidence
S6K1 directly phosphorylated CAD at Ser1859, connecting mTORC1 signaling to increased de novo pyrimidine synthesis.
Human p70 S6 kinase / RPS6KB1 → Human CAD multifunctional pyrimidine synthesis enzyme source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Human HEK293E CAD expression, phosphosite mutation and kinase assays; complementary mouse cell tracing.
limitations
This is a signaling dependency, not evidence that a specific nutrient supplement necessarily increases CAD activity.
nutrient_topic
L-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Aspartate
plain_language
Growth signals can accelerate use of aspartate for nucleotide production.
primary_references
Stimulation of de novo pyrimidine synthesis by growth signaling through mTOR and S6K1. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23429703/ · DOI 10.1126/science.1228792
L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 154–160
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human HEK293E CAD expression, phosphosite mutation and kinase assays; complementary mouse cell tracing. · source_derived_draft · unverified_draft
## l-aspartate-cad-s6k1 Growth signals can accelerate use of aspartate for nucleotide production. S6K1 directly phosphorylated CAD at Ser1859, connecting mTORC1 signaling to increased de novo pyrimidine synthesis. Model: Human HEK293E CAD expression, phosphosite mutation and kinase assays; complementary mouse cell tracing. Limitations: This is a signaling dependency, not evidence that a specific nutrient supplement necessarily increases CAD activity. Evidence access: Primary full text Stimulation of de novo pyrimidine synthesis by growth signaling through mTOR and S6K1. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23429703/ · DOI 10.1126/science.1228792
Complete structured claim and evidence
S6K1 depletion blocked insulin-stimulated aspartate-carbon incorporation into RNA and DNA while sparing incorporation of supplied pyrimidines in the compared assays.
Mouse S6 kinase 1 / Rps6kb1 → Aspartate incorporation into mouse-cell nucleic acids source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Mouse wild-type embryonic fibroblasts; S6K1 siRNA, 15-hour serum starvation, 100 nM insulin for six hours during RNA/DNA labeling, with pyrimidine salvage controls.
limitations
An isotope-incorporation endpoint is not a measurement of dietary aspartate efficacy.
nutrient_topic
L-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Aspartate
plain_language
Blocking new nucleotide production differs from blocking every route for supplying nucleotides.
primary_references
Stimulation of de novo pyrimidine synthesis by growth signaling through mTOR and S6K1. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23429703/ · DOI 10.1126/science.1228792
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 162–168
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse wild-type embryonic fibroblasts; S6K1 siRNA, 15-hour serum starvation, 100 nM insulin for six hours during RNA/DNA labeling, with pyrimidine salvage controls. · source_derived_draft · unverified_draft
## l-aspartate-cad-s6k1-flux Blocking new nucleotide production differs from blocking every route for supplying nucleotides. S6K1 depletion blocked insulin-stimulated aspartate-carbon incorporation into RNA and DNA while sparing incorporation of supplied pyrimidines in the compared assays. Model: Mouse wild-type embryonic fibroblasts; S6K1 siRNA, 15-hour serum starvation, 100 nM insulin for six hours during RNA/DNA labeling, with pyrimidine salvage controls. Limitations: An isotope-incorporation endpoint is not a measurement of dietary aspartate efficacy. Evidence access: Primary full text Stimulation of de novo pyrimidine synthesis by growth signaling through mTOR and S6K1. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23429703/ · DOI 10.1126/science.1228792
Complete structured claim and evidence
Reduced ASS1 activity increased cytosolic aspartate availability and CAD-dependent pyrimidine synthesis in the studied cancer models.
Reduced ASS1 activity in human tumor models → L-Aspartate source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Human cancer-cell perturbations, metabolic analysis and disease-related comparisons.
limitations
The finding does not mean reducing nitrogen disposal is beneficial; it is a tumor-model mechanism.
nutrient_topic
L-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Aspartate
plain_language
Using less aspartate for arginine synthesis can leave more for nucleotide synthesis.
primary_references
Diversion of aspartate in ASS1-deficient tumours fosters de novo pyrimidine synthesis. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26560030/ · DOI 10.1038/nature15529
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 170–176
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human cancer-cell perturbations, metabolic analysis and disease-related comparisons. · source_derived_draft · unverified_draft
## l-aspartate-ass1-diversion Using less aspartate for arginine synthesis can leave more for nucleotide synthesis. Reduced ASS1 activity increased cytosolic aspartate availability and CAD-dependent pyrimidine synthesis in the studied cancer models. Model: Human cancer-cell perturbations, metabolic analysis and disease-related comparisons. Limitations: The finding does not mean reducing nitrogen disposal is beneficial; it is a tumor-model mechanism. Evidence access: Primary abstract Diversion of aspartate in ASS1-deficient tumours fosters de novo pyrimidine synthesis. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26560030/ · DOI 10.1038/nature15529
Complete structured claim and evidence
ASS1-deficient citrullinemia type I models showed greater pyrimidine synthesis and proliferation than citrin-deficient type II models, where aspartate delivery was restricted.
Comparison of ASS1 deficiency and citrin deficiency → Pyrimidine synthesis in citrullinemia study models source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Human disorder-derived observations and experimental disease/cancer comparisons.
limitations
Neither condition is simple low dietary aspartate; do not turn cellular proliferation measures into patient cancer-risk estimates.
nutrient_topic
L-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Aspartate
plain_language
Two defects affecting the same cycle can leave very different amounts of substrate for another pathway.
primary_references
Diversion of aspartate in ASS1-deficient tumours fosters de novo pyrimidine synthesis. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26560030/ · DOI 10.1038/nature15529
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 178–184
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human disorder-derived observations and experimental disease/cancer comparisons. · source_derived_draft · unverified_draft
## l-aspartate-ass1-citrin-difference Two defects affecting the same cycle can leave very different amounts of substrate for another pathway. ASS1-deficient citrullinemia type I models showed greater pyrimidine synthesis and proliferation than citrin-deficient type II models, where aspartate delivery was restricted. Model: Human disorder-derived observations and experimental disease/cancer comparisons. Limitations: Neither condition is simple low dietary aspartate; do not turn cellular proliferation measures into patient cancer-risk estimates. Evidence access: Primary abstract Diversion of aspartate in ASS1-deficient tumours fosters de novo pyrimidine synthesis. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26560030/ · DOI 10.1038/nature15529
Complete structured claim and evidence
Human ASNS catalyzes ATP-dependent conversion of aspartate and glutamine to asparagine and glutamate through coupled glutaminase and synthetase chemistry.
Human asparagine synthetase / ASNS → L-Asparagine source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Human recombinant ASNS structural and biochemical study; reaction characterized in the study framework.
limitations
A functioning reaction does not guarantee that adding substrate raises the product in every tissue. Correction record: The 2019 author correction added omitted author affiliations and funding acknowledgements; no mechanism or data change was stated. PMID 31799439; DOI 10.1038/s42003-019-0690-1. https://www.nature.com/articles/s42003-019-0690-1
nutrient_topic
L-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Aspartate
plain_language
Making asparagine needs both aspartate and a nitrogen donor, plus energy.
primary_references
High-resolution crystal structure of human asparagine synthetase enables analysis of inhibitor binding and selectivity. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31552298/ · DOI 10.1038/s42003-019-0587-z
L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 186–192
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human recombinant ASNS structural and biochemical study; reaction characterized in the study framework. · source_derived_draft · unverified_draft
## l-aspartate-asns-reaction Making asparagine needs both aspartate and a nitrogen donor, plus energy. Human ASNS catalyzes ATP-dependent conversion of aspartate and glutamine to asparagine and glutamate through coupled glutaminase and synthetase chemistry. Model: Human recombinant ASNS structural and biochemical study; reaction characterized in the study framework. Limitations: A functioning reaction does not guarantee that adding substrate raises the product in every tissue. Correction record: The 2019 author correction added omitted author affiliations and funding acknowledgements; no mechanism or data change was stated. PMID 31799439; DOI 10.1038/s42003-019-0690-1. https://www.nature.com/articles/s42003-019-0690-1 Evidence access: Primary full text High-resolution crystal structure of human asparagine synthetase enables analysis of inhibitor binding and selectivity. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31552298/ · DOI 10.1038/s42003-019-0587-z
Complete structured claim and evidence
The human ASNS structure separates glutamine-processing and ATP-dependent synthetase domains, with an internal path supporting nitrogen transfer toward activated aspartate.
Human asparagine synthetase / ASNS → Coupled glutaminase and synthetase domains of human ASNS source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Human ASNS 1.85-angstrom structure and comparison with mechanistic data.
limitations
Structural interpretation is distinguished from measuring every transient chemical intermediate in intact cells. Correction record: The 2019 author correction added omitted author affiliations and funding acknowledgements; no mechanism or data change was stated. PMID 31799439; DOI 10.1038/s42003-019-0690-1. https://www.nature.com/articles/s42003-019-0690-1
nutrient_topic
L-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Aspartate
plain_language
The enzyme coordinates two reactions rather than attaching free glutamine directly to aspartate.
primary_references
High-resolution crystal structure of human asparagine synthetase enables analysis of inhibitor binding and selectivity. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31552298/ · DOI 10.1038/s42003-019-0587-z
L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 194–200
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human ASNS 1.85-angstrom structure and comparison with mechanistic data. · source_derived_draft · unverified_draft
## l-aspartate-asns-two-sites The enzyme coordinates two reactions rather than attaching free glutamine directly to aspartate. The human ASNS structure separates glutamine-processing and ATP-dependent synthetase domains, with an internal path supporting nitrogen transfer toward activated aspartate. Model: Human ASNS 1.85-angstrom structure and comparison with mechanistic data. Limitations: Structural interpretation is distinguished from measuring every transient chemical intermediate in intact cells. Correction record: The 2019 author correction added omitted author affiliations and funding acknowledgements; no mechanism or data change was stated. PMID 31799439; DOI 10.1038/s42003-019-0690-1. https://www.nature.com/articles/s42003-019-0690-1 Evidence access: Primary full text High-resolution crystal structure of human asparagine synthetase enables analysis of inhibitor binding and selectivity. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31552298/ · DOI 10.1038/s42003-019-0587-z
Complete structured claim and evidence
SDH inhibition produced early aspartate depletion followed by a rebound, while proliferation remained impaired over the compared interval.
SDH inhibition or loss in human cell models → Aspartate rebound after SDH inhibition source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Human 143B and other cell models; live aspartate biosensor and time-resolved metabolomics.
limitations
Responses are time- and model-dependent; later adaptation does not make the early block disappear.
nutrient_topic
L-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Aspartate
plain_language
A restored metabolite concentration did not show that the cell could use it normally.
primary_references
Succinate dehydrogenase loss suppresses pyrimidine biosynthesis via succinate-mediated inhibition of aspartate transcarbamylase. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42082831/ · DOI 10.1038/s42255-026-01524-w
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 202–208
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human 143B and other cell models; live aspartate biosensor and time-resolved metabolomics. · source_derived_draft · unverified_draft
## l-aspartate-sdh-aspartate-rebound A restored metabolite concentration did not show that the cell could use it normally. SDH inhibition produced early aspartate depletion followed by a rebound, while proliferation remained impaired over the compared interval. Model: Human 143B and other cell models; live aspartate biosensor and time-resolved metabolomics. Limitations: Responses are time- and model-dependent; later adaptation does not make the early block disappear. Evidence access: Primary full text Succinate dehydrogenase loss suppresses pyrimidine biosynthesis via succinate-mediated inhibition of aspartate transcarbamylase. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42082831/ · DOI 10.1038/s42255-026-01524-w
Complete structured claim and evidence
Succinate competitively inhibited aspartate utilization by the purified human CAD ATCase domain.
Succinate → Human CAD multifunctional pyrimidine synthesis enzyme source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Recombinant human ATCase kinetic experiments with succinate and substrate titration.
limitations
This is not proof that ordinary dietary succinate or aspartate concentrations cause the same inhibition in a person.
nutrient_topic
L-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Aspartate
plain_language
An accumulated carbon-cycle metabolite competes with aspartate at a nucleotide-making enzyme.
primary_references
Succinate dehydrogenase loss suppresses pyrimidine biosynthesis via succinate-mediated inhibition of aspartate transcarbamylase. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42082831/ · DOI 10.1038/s42255-026-01524-w
L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 210–216
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Recombinant human ATCase kinetic experiments with succinate and substrate titration. · source_derived_draft · unverified_draft
## l-aspartate-succinate-atcase An accumulated carbon-cycle metabolite competes with aspartate at a nucleotide-making enzyme. Succinate competitively inhibited aspartate utilization by the purified human CAD ATCase domain. Model: Recombinant human ATCase kinetic experiments with succinate and substrate titration. Limitations: This is not proof that ordinary dietary succinate or aspartate concentrations cause the same inhibition in a person. Evidence access: Primary full text Succinate dehydrogenase loss suppresses pyrimidine biosynthesis via succinate-mediated inhibition of aspartate transcarbamylase. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42082831/ · DOI 10.1038/s42255-026-01524-w
Complete structured claim and evidence
SDH loss increased succinate, impaired aspartate entry into pyrimidine synthesis and produced nucleotide insufficiency with replication stress and increased ATR-inhibitor sensitivity.
SDH inhibition or loss in human cell models → Pyrimidine production after human-cell SDH impairment 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 genetic/pharmacological SDH perturbations; nucleotide and replication readouts.
limitations
Not a clinical treatment recommendation or proof that extra aspartate universally overcomes the competitive block.
nutrient_topic
L-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Aspartate
plain_language
The effect propagated from metabolism into DNA replication control.
primary_references
Succinate dehydrogenase loss suppresses pyrimidine biosynthesis via succinate-mediated inhibition of aspartate transcarbamylase. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42082831/ · DOI 10.1038/s42255-026-01524-w
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 218–224
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human cell genetic/pharmacological SDH perturbations; nucleotide and replication readouts. · source_derived_draft · unverified_draft
## l-aspartate-sdh-pyrimidine-stress The effect propagated from metabolism into DNA replication control. SDH loss increased succinate, impaired aspartate entry into pyrimidine synthesis and produced nucleotide insufficiency with replication stress and increased ATR-inhibitor sensitivity. Model: Human cell genetic/pharmacological SDH perturbations; nucleotide and replication readouts. Limitations: Not a clinical treatment recommendation or proof that extra aspartate universally overcomes the competitive block. Evidence access: Primary full text Succinate dehydrogenase loss suppresses pyrimidine biosynthesis via succinate-mediated inhibition of aspartate transcarbamylase. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42082831/ · DOI 10.1038/s42255-026-01524-w
Complete structured claim and evidence
Increasing aspartate availability enhanced malate–aspartate shuttle use and mitochondrial metabolism of glucose-derived pyruvate in proliferating cell experiments.
L-Aspartate → Malate–aspartate shuttle use in human proliferating cells source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract and primary figure descriptions
experimental_model
Proliferating-cell perturbation and tracer study, including human NSCLC models.
limitations
Substrate availability in cell models is not evidence for benefits of oral L-aspartate.
nutrient_topic
L-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Aspartate
plain_language
Aspartate demand for building material can compete with its participation in redox transfer.
primary_references
Aspartate availability drives differential engagement of the malate-aspartate shuttle. · 2026 · https://pubmed.ncbi.nlm.nih.gov/41759528/ · DOI 10.1016/j.molcel.2026.02.004
L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 226–232
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Proliferating-cell perturbation and tracer study, including human NSCLC models. · source_derived_draft · unverified_draft
## l-aspartate-shuttle-aspartate-availability Aspartate demand for building material can compete with its participation in redox transfer. Increasing aspartate availability enhanced malate–aspartate shuttle use and mitochondrial metabolism of glucose-derived pyruvate in proliferating cell experiments. Model: Proliferating-cell perturbation and tracer study, including human NSCLC models. Limitations: Substrate availability in cell models is not evidence for benefits of oral L-aspartate. Evidence access: Primary abstract and primary figure descriptions Aspartate availability drives differential engagement of the malate-aspartate shuttle. · 2026 · https://pubmed.ncbi.nlm.nih.gov/41759528/ · DOI 10.1016/j.molcel.2026.02.004
Complete structured claim and evidence
Loss of shuttle components reduced pyruvate/lactate ratios and glucose-derived serine synthesis in the studied human A549 models.
Genetic loss of shuttle components in human A549 cells → Glucose-derived serine synthesis in human A549 cells source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract and primary figure descriptions
experimental_model
Human lung-cancer cell gene editing, metabolite ratios and carbon tracing.
limitations
A ratio is a redox proxy, and no dietary serine/aspartate deficiency threshold was measured.
nutrient_topic
L-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Aspartate
plain_language
Redox handling connects aspartate machinery to synthesis of another amino acid.
primary_references
Aspartate availability drives differential engagement of the malate-aspartate shuttle. · 2026 · https://pubmed.ncbi.nlm.nih.gov/41759528/ · DOI 10.1016/j.molcel.2026.02.004
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 234–240
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human lung-cancer cell gene editing, metabolite ratios and carbon tracing. · source_derived_draft · unverified_draft
## l-aspartate-shuttle-serine-link Redox handling connects aspartate machinery to synthesis of another amino acid. Loss of shuttle components reduced pyruvate/lactate ratios and glucose-derived serine synthesis in the studied human A549 models. Model: Human lung-cancer cell gene editing, metabolite ratios and carbon tracing. Limitations: A ratio is a redox proxy, and no dietary serine/aspartate deficiency threshold was measured. Evidence access: Primary abstract and primary figure descriptions Aspartate availability drives differential engagement of the malate-aspartate shuttle. · 2026 · https://pubmed.ncbi.nlm.nih.gov/41759528/ · DOI 10.1016/j.molcel.2026.02.004
Complete structured claim and evidence
Got2 knockout impaired mouse PDAC-cell growth at 0.5% oxygen more strongly than under normoxia; ETC inhibitor exposure instead exposed a distinct Got1 dependency.
Mouse mitochondrial aspartate aminotransferase / Got2 → Hypoxic growth of mouse PDAC cells source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Mouse HY15549-centered CRISPR screens and knockout comparisons.
limitations
Do not assign all ETC-inhibitor findings to tumor hypoxia or all culture dependencies to animal tumors.
nutrient_topic
L-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Aspartate
plain_language
Low oxygen and a respiratory-chain drug were not identical metabolic conditions.
primary_references
Adaptive stimulation of macropinocytosis overcomes aspartate limitation in cancer cells under hypoxia. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35726024/ · DOI 10.1038/s42255-022-00583-z
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 242–248
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse HY15549-centered CRISPR screens and knockout comparisons. · source_derived_draft · unverified_draft
## l-aspartate-pdac-got2-hypoxia Low oxygen and a respiratory-chain drug were not identical metabolic conditions. Got2 knockout impaired mouse PDAC-cell growth at 0.5% oxygen more strongly than under normoxia; ETC inhibitor exposure instead exposed a distinct Got1 dependency. Model: Mouse HY15549-centered CRISPR screens and knockout comparisons. Limitations: Do not assign all ETC-inhibitor findings to tumor hypoxia or all culture dependencies to animal tumors. Evidence access: Primary full text Adaptive stimulation of macropinocytosis overcomes aspartate limitation in cancer cells under hypoxia. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35726024/ · DOI 10.1038/s42255-022-00583-z
Complete structured claim and evidence
GOT2 deletion did not reduce MIA PaCa-2 tumor size in the tested mouse xenografts, despite the synthesis dependency observed in hypoxic culture systems.
GOT2 loss in human pancreatic cancer cells → Growth of human GOT2-null PDAC xenografts source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Human MIA PaCa-2 cells implanted in mice; companion murine and PDX experiments.
limitations
This does not prove GOT2 is dispensable in every tumor or that it never contributes to growth.
nutrient_topic
L-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Aspartate
plain_language
An animal tumor had alternative nutrient routes unavailable in the simplified culture.
primary_references
Adaptive stimulation of macropinocytosis overcomes aspartate limitation in cancer cells under hypoxia. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35726024/ · DOI 10.1038/s42255-022-00583-z
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 250–256
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human MIA PaCa-2 cells implanted in mice; companion murine and PDX experiments. · source_derived_draft · unverified_draft
## l-aspartate-pdac-got2-invivo-limit An animal tumor had alternative nutrient routes unavailable in the simplified culture. GOT2 deletion did not reduce MIA PaCa-2 tumor size in the tested mouse xenografts, despite the synthesis dependency observed in hypoxic culture systems. Model: Human MIA PaCa-2 cells implanted in mice; companion murine and PDX experiments. Limitations: This does not prove GOT2 is dispensable in every tumor or that it never contributes to growth. Evidence access: Primary full text Adaptive stimulation of macropinocytosis overcomes aspartate limitation in cancer cells under hypoxia. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35726024/ · DOI 10.1038/s42255-022-00583-z
Complete structured claim and evidence
Bovine albumin supplementation restored aspartate and pyrimidine-related metabolites and partly rescued hypoxic growth in the tested KRAS-mutant human PDAC cultures.
Bovine serum albumin → Aspartate supplied by protein scavenging in human PDAC cells source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Human MIA PaCa-2-centered hypoxic culture, albumin addition and macropinocytosis experiments.
limitations
This is an extracellular protein-scavenging mechanism, not evidence of direct intact dietary protein delivery to a tumor.
nutrient_topic
L-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Aspartate
plain_language
Cells can obtain amino acids by digesting extracellular protein.
primary_references
Adaptive stimulation of macropinocytosis overcomes aspartate limitation in cancer cells under hypoxia. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35726024/ · DOI 10.1038/s42255-022-00583-z
L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 258–264
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human MIA PaCa-2-centered hypoxic culture, albumin addition and macropinocytosis experiments. · source_derived_draft · unverified_draft
## l-aspartate-protein-scavenging-rescue Cells can obtain amino acids by digesting extracellular protein. Bovine albumin supplementation restored aspartate and pyrimidine-related metabolites and partly rescued hypoxic growth in the tested KRAS-mutant human PDAC cultures. Model: Human MIA PaCa-2-centered hypoxic culture, albumin addition and macropinocytosis experiments. Limitations: This is an extracellular protein-scavenging mechanism, not evidence of direct intact dietary protein delivery to a tumor. Evidence access: Primary full text Adaptive stimulation of macropinocytosis overcomes aspartate limitation in cancer cells under hypoxia. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35726024/ · DOI 10.1038/s42255-022-00583-z
Complete structured claim and evidence
Genetic and pharmacological experiments linked hypoxia-enhanced macropinocytosis to HIF1A and its target CA9 in KRAS-mutant PDAC models.
HIF-1 alpha → Macropinocytic protein scavenging by human PDAC cells source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Human and mouse PDAC model program; human-cell HIF1A/CA9 manipulations.
limitations
CA9 is a mediator in the tested models, not a universal aspartate transporter.
nutrient_topic
L-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Aspartate
plain_language
An oxygen-response program increased an alternative nutrient-acquisition route.
primary_references
Adaptive stimulation of macropinocytosis overcomes aspartate limitation in cancer cells under hypoxia. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35726024/ · DOI 10.1038/s42255-022-00583-z
L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 266–272
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human and mouse PDAC model program; human-cell HIF1A/CA9 manipulations. · source_derived_draft · unverified_draft
## l-aspartate-hypoxia-hif-ca9 An oxygen-response program increased an alternative nutrient-acquisition route. Genetic and pharmacological experiments linked hypoxia-enhanced macropinocytosis to HIF1A and its target CA9 in KRAS-mutant PDAC models. Model: Human and mouse PDAC model program; human-cell HIF1A/CA9 manipulations. Limitations: CA9 is a mediator in the tested models, not a universal aspartate transporter. Evidence access: Primary full text Adaptive stimulation of macropinocytosis overcomes aspartate limitation in cancer cells under hypoxia. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35726024/ · DOI 10.1038/s42255-022-00583-z
Complete structured claim and evidence
Carbon-13 glutamine tracing during mouse Listeria infection showed substantial glutamine contribution to aspartate and pyrimidine synthesis in early effector CD8 T cells.
L-Glutamine → L-Aspartate source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Mouse in vivo tracer infusions and sorted effector T cells.
limitations
Fuel use changed across infection stages; no generalized human glutamine/aspartate supplementation benefit was tested.
nutrient_topic
L-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Aspartate
plain_language
The immune cell used one amino acid to help supply another and build nucleotides.
primary_references
13C metabolite tracing reveals glutamine and acetate as critical in vivo fuels for CD8 T cells. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38809979/ · DOI 10.1126/sciadv.adj1431
L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 274–280
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse in vivo tracer infusions and sorted effector T cells. · source_derived_draft · unverified_draft
## l-aspartate-tcell-glutamine-carbon The immune cell used one amino acid to help supply another and build nucleotides. Carbon-13 glutamine tracing during mouse Listeria infection showed substantial glutamine contribution to aspartate and pyrimidine synthesis in early effector CD8 T cells. Model: Mouse in vivo tracer infusions and sorted effector T cells. Limitations: Fuel use changed across infection stages; no generalized human glutamine/aspartate supplementation benefit was tested. Evidence access: Primary full text 13C metabolite tracing reveals glutamine and acetate as critical in vivo fuels for CD8 T cells. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38809979/ · DOI 10.1126/sciadv.adj1431
Complete structured claim and evidence
Got1 knockdown reduced glutamine-derived aspartate and impaired effector CD8 T-cell expansion in the mouse infection model.
Mouse cytosolic aspartate aminotransferase / Got1 → Mouse effector CD8 T-cell expansion source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Mouse OT-I CD8 cells, shRNA and Listeria infection.
limitations
Knockdown affects related metabolic functions as well; do not attribute all outcomes only to the aspartate pool.
nutrient_topic
L-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Aspartate
plain_language
Internal synthesis machinery supported the expanding immune population.
primary_references
13C metabolite tracing reveals glutamine and acetate as critical in vivo fuels for CD8 T cells. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38809979/ · DOI 10.1126/sciadv.adj1431
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 282–288
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse OT-I CD8 cells, shRNA and Listeria infection. · source_derived_draft · unverified_draft
## l-aspartate-tcell-got1-expansion Internal synthesis machinery supported the expanding immune population. Got1 knockdown reduced glutamine-derived aspartate and impaired effector CD8 T-cell expansion in the mouse infection model. Model: Mouse OT-I CD8 cells, shRNA and Listeria infection. Limitations: Knockdown affects related metabolic functions as well; do not attribute all outcomes only to the aspartate pool. Evidence access: Primary full text 13C metabolite tracing reveals glutamine and acetate as critical in vivo fuels for CD8 T cells. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38809979/ · DOI 10.1126/sciadv.adj1431
Complete structured claim and evidence
Removing extracellular aspartate selectively reduced proliferation of Got1-silenced mouse CD8 cells, whereas control cells better tolerated its removal and viability was unchanged.
L-Aspartate → Mouse effector CD8 T-cell expansion source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Mouse CD8 culture; Got1 knockdown with/without medium aspartate.
limitations
Conditional auxotrophy is not a demonstrated human dietary deficiency.
nutrient_topic
L-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Aspartate
plain_language
Cells depended more on external supply when synthesis was impaired.
primary_references
13C metabolite tracing reveals glutamine and acetate as critical in vivo fuels for CD8 T cells. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38809979/ · DOI 10.1126/sciadv.adj1431
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 290–296
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse CD8 culture; Got1 knockdown with/without medium aspartate. · source_derived_draft · unverified_draft
## l-aspartate-tcell-external-gate Cells depended more on external supply when synthesis was impaired. Removing extracellular aspartate selectively reduced proliferation of Got1-silenced mouse CD8 cells, whereas control cells better tolerated its removal and viability was unchanged. Model: Mouse CD8 culture; Got1 knockdown with/without medium aspartate. Limitations: Conditional auxotrophy is not a demonstrated human dietary deficiency. Evidence access: Primary full text 13C metabolite tracing reveals glutamine and acetate as critical in vivo fuels for CD8 T cells. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38809979/ · DOI 10.1126/sciadv.adj1431
Complete structured claim and evidence
Got1 deficiency lowered 2-oxoglutarate production from glutamine metabolism and caused toxic ammonia accumulation in mouse CD8 T cells during chronic infection.
T-cell-specific Got1 loss in mice → Ammonia accumulation in Got1-deficient mouse T cells source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Mouse T-cell-specific gene deletion and chronic LCMV infection.
limitations
This is a cell-state-specific mechanism, not a universal definition of malate–aspartate shuttle function.
nutrient_topic
L-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Aspartate
plain_language
The transaminase also helped manage the nitrogen released while using glutamine.
primary_references
The malate shuttle detoxifies ammonia in exhausted T cells by producing 2-ketoglutarate. · 2023 · https://pubmed.ncbi.nlm.nih.gov/37813964/ · DOI 10.1038/s41590-023-01636-5
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 298–304
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse T-cell-specific gene deletion and chronic LCMV infection. · source_derived_draft · unverified_draft
## l-aspartate-tcell-ammonia The transaminase also helped manage the nitrogen released while using glutamine. Got1 deficiency lowered 2-oxoglutarate production from glutamine metabolism and caused toxic ammonia accumulation in mouse CD8 T cells during chronic infection. Model: Mouse T-cell-specific gene deletion and chronic LCMV infection. Limitations: This is a cell-state-specific mechanism, not a universal definition of malate–aspartate shuttle function. Evidence access: Primary abstract The malate shuttle detoxifies ammonia in exhausted T cells by producing 2-ketoglutarate. · 2023 · https://pubmed.ncbi.nlm.nih.gov/37813964/ · DOI 10.1038/s41590-023-01636-5
Complete structured claim and evidence
2-Oxoglutarate supplementation promoted ammonia assimilation and restored antiviral responses in Got1-deficient T-cell experiments.
2-Oxoglutarate → Mouse effector CD8 T-cell expansion source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Mouse Got1-deficient T-cell and chronic-infection experiments.
limitations
Experimental rescue does not establish a human dosing strategy or replacement for intact immunity.
nutrient_topic
L-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Aspartate
plain_language
Restoring a missing nitrogen-accepting metabolite helped recover function.
primary_references
The malate shuttle detoxifies ammonia in exhausted T cells by producing 2-ketoglutarate. · 2023 · https://pubmed.ncbi.nlm.nih.gov/37813964/ · DOI 10.1038/s41590-023-01636-5
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 306–312
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse Got1-deficient T-cell and chronic-infection experiments. · source_derived_draft · unverified_draft
## l-aspartate-tcell-akg-rescue Restoring a missing nitrogen-accepting metabolite helped recover function. 2-Oxoglutarate supplementation promoted ammonia assimilation and restored antiviral responses in Got1-deficient T-cell experiments. Model: Mouse Got1-deficient T-cell and chronic-infection experiments. Limitations: Experimental rescue does not establish a human dosing strategy or replacement for intact immunity. Evidence access: Primary abstract The malate shuttle detoxifies ammonia in exhausted T cells by producing 2-ketoglutarate. · 2023 · https://pubmed.ncbi.nlm.nih.gov/37813964/ · DOI 10.1038/s41590-023-01636-5
Complete structured claim and evidence
Increasing the NAD+/NADH ratio did not restore the impaired antiviral T-cell response after Got1 loss in the tested chronic-infection setting.
Experimental NAD+/NADH-ratio restoration in Got1-deficient T cells → Mouse effector CD8 T-cell expansion source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Mouse T-cell genetic and redox-restoration experiments.
limitations
Not evidence that NAD metabolism is irrelevant in other cell states.
nutrient_topic
L-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Aspartate
plain_language
Correcting one metabolic measurement did not fix the nitrogen-handling problem.
primary_references
The malate shuttle detoxifies ammonia in exhausted T cells by producing 2-ketoglutarate. · 2023 · https://pubmed.ncbi.nlm.nih.gov/37813964/ · DOI 10.1038/s41590-023-01636-5
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 314–320
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse T-cell genetic and redox-restoration experiments. · source_derived_draft · unverified_draft
## l-aspartate-tcell-redox-insufficient Correcting one metabolic measurement did not fix the nitrogen-handling problem. Increasing the NAD+/NADH ratio did not restore the impaired antiviral T-cell response after Got1 loss in the tested chronic-infection setting. Model: Mouse T-cell genetic and redox-restoration experiments. Limitations: Not evidence that NAD metabolism is irrelevant in other cell states. Evidence access: Primary abstract The malate shuttle detoxifies ammonia in exhausted T cells by producing 2-ketoglutarate. · 2023 · https://pubmed.ncbi.nlm.nih.gov/37813964/ · DOI 10.1038/s41590-023-01636-5
Complete structured claim and evidence
Isolated mouse brown-fat mitochondria reconstituted with cytosolic shuttle enzymes oxidized extramitochondrial NADH in a glutamate-dependent manner.
L-Glutamate → Extramitochondrial NADH oxidation in a mouse brown-fat shuttle assay source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Mouse C57BL/6J brown-fat mitochondria and reconstituted enzyme system.
limitations
An isolated-organelle assay does not prove that oral aspartate increases thermogenesis.
nutrient_topic
L-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Aspartate
plain_language
The transport cycle linked a cytosolic redox pool to mitochondrial machinery.
primary_references
The malate-aspartate shuttle supports thermogenic lipid mobilization in brown adipocytes. · 2026 · https://pubmed.ncbi.nlm.nih.gov/41704162/ · DOI 10.1111/febs.70461
L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 322–328
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse C57BL/6J brown-fat mitochondria and reconstituted enzyme system. · source_derived_draft · unverified_draft
## l-aspartate-brown-shuttle-redox The transport cycle linked a cytosolic redox pool to mitochondrial machinery. Isolated mouse brown-fat mitochondria reconstituted with cytosolic shuttle enzymes oxidized extramitochondrial NADH in a glutamate-dependent manner. Model: Mouse C57BL/6J brown-fat mitochondria and reconstituted enzyme system. Limitations: An isolated-organelle assay does not prove that oral aspartate increases thermogenesis. Evidence access: Primary full text The malate-aspartate shuttle supports thermogenic lipid mobilization in brown adipocytes. · 2026 · https://pubmed.ncbi.nlm.nih.gov/41704162/ · DOI 10.1111/febs.70461
Complete structured claim and evidence
Aralar1 silencing in primary mouse brown adipocytes impaired norepinephrine-induced lipid mobilization and increased small lipid-droplet accumulation.
Mouse aralar / Slc25a12 → Norepinephrine-stimulated lipolysis in mouse brown adipocytes source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Mouse primary brown adipocytes; approximately 80% knockdown in the reported experiment.
limitations
This does not establish human weight-loss effects or a nutrient-intake threshold.
nutrient_topic
L-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Aspartate
plain_language
Disrupting the carrier changed fat handling in the cell.
primary_references
The malate-aspartate shuttle supports thermogenic lipid mobilization in brown adipocytes. · 2026 · https://pubmed.ncbi.nlm.nih.gov/41704162/ · DOI 10.1111/febs.70461
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 330–336
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse primary brown adipocytes; approximately 80% knockdown in the reported experiment. · source_derived_draft · unverified_draft
## l-aspartate-brown-aralar-lipids Disrupting the carrier changed fat handling in the cell. Aralar1 silencing in primary mouse brown adipocytes impaired norepinephrine-induced lipid mobilization and increased small lipid-droplet accumulation. Model: Mouse primary brown adipocytes; approximately 80% knockdown in the reported experiment. Limitations: This does not establish human weight-loss effects or a nutrient-intake threshold. Evidence access: Primary full text The malate-aspartate shuttle supports thermogenic lipid mobilization in brown adipocytes. · 2026 · https://pubmed.ncbi.nlm.nih.gov/41704162/ · DOI 10.1111/febs.70461
Complete structured claim and evidence
Oxoglutarate-carrier silencing similarly increased small lipid droplets and impaired norepinephrine-induced lipolysis in mouse brown adipocytes.
Mouse mitochondrial oxoglutarate carrier / Slc25a11 → Norepinephrine-stimulated lipolysis in mouse brown adipocytes source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Mouse primary brown adipocytes; adenoviral shRNA with metabolic assays.
limitations
Shared pathway dependence does not make the two carriers interchangeable.
nutrient_topic
L-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Aspartate
plain_language
A second carrier in the same shuttle also affected lipid mobilization.
primary_references
The malate-aspartate shuttle supports thermogenic lipid mobilization in brown adipocytes. · 2026 · https://pubmed.ncbi.nlm.nih.gov/41704162/ · DOI 10.1111/febs.70461
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 338–344
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse primary brown adipocytes; adenoviral shRNA with metabolic assays. · source_derived_draft · unverified_draft
## l-aspartate-brown-ogc-lipids A second carrier in the same shuttle also affected lipid mobilization. Oxoglutarate-carrier silencing similarly increased small lipid droplets and impaired norepinephrine-induced lipolysis in mouse brown adipocytes. Model: Mouse primary brown adipocytes; adenoviral shRNA with metabolic assays. Limitations: Shared pathway dependence does not make the two carriers interchangeable. Evidence access: Primary full text The malate-aspartate shuttle supports thermogenic lipid mobilization in brown adipocytes. · 2026 · https://pubmed.ncbi.nlm.nih.gov/41704162/ · DOI 10.1111/febs.70461
Complete structured claim and evidence
Silencing either carrier had no apparent effect on the measured respiratory rates despite changes in lipid handling.
Aralar1 or OGC silencing in mouse brown adipocytes → Respiratory rate in mouse brown adipocyte carrier-knockdown experiments source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Same mouse primary-cell experiments; respiration measurements.
limitations
The null result is limited to the tested conditions and does not establish that the shuttle never contributes to respiration.
nutrient_topic
L-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Aspartate
plain_language
A lipid-storage phenotype did not imply that mitochondrial oxygen consumption had collapsed.
primary_references
The malate-aspartate shuttle supports thermogenic lipid mobilization in brown adipocytes. · 2026 · https://pubmed.ncbi.nlm.nih.gov/41704162/ · DOI 10.1111/febs.70461
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 346–352
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Same mouse primary-cell experiments; respiration measurements. · source_derived_draft · unverified_draft
## l-aspartate-brown-respiration-limit A lipid-storage phenotype did not imply that mitochondrial oxygen consumption had collapsed. Silencing either carrier had no apparent effect on the measured respiratory rates despite changes in lipid handling. Model: Same mouse primary-cell experiments; respiration measurements. Limitations: The null result is limited to the tested conditions and does not establish that the shuttle never contributes to respiration. Evidence access: Primary full text The malate-aspartate shuttle supports thermogenic lipid mobilization in brown adipocytes. · 2026 · https://pubmed.ncbi.nlm.nih.gov/41704162/ · DOI 10.1111/febs.70461
Complete structured claim and evidence
Human cytosolic DARS1 catalyzes attachment of aspartate to its cognate tRNA; its 2.25-angstrom homodimer structure defines the cytosolic enzyme separately from mitochondrial DARS2.
Human cytosolic aspartyl-tRNA synthetase / DARS1 → Human cytosolic aspartate tRNA source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Human recombinant cytosolic enzyme structural study.
limitations
Structural suggestions about release from the multisynthetase complex are not treated as demonstrated nutrient signaling.
nutrient_topic
L-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Aspartate
plain_language
Aspartate must be placed on the correct transfer RNA to enter proteins.
primary_references
Crystal structure of human cytosolic aspartyl-tRNA synthetase, a component of multi-tRNA synthetase complex. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23609930/ · DOI 10.1002/prot.24306
L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 354–360
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human recombinant cytosolic enzyme structural study. · source_derived_draft · unverified_draft
## l-aspartate-dars1-translation Aspartate must be placed on the correct transfer RNA to enter proteins. Human cytosolic DARS1 catalyzes attachment of aspartate to its cognate tRNA; its 2.25-angstrom homodimer structure defines the cytosolic enzyme separately from mitochondrial DARS2. Model: Human recombinant cytosolic enzyme structural study. Limitations: Structural suggestions about release from the multisynthetase complex are not treated as demonstrated nutrient signaling. Evidence access: Primary full text Crystal structure of human cytosolic aspartyl-tRNA synthetase, a component of multi-tRNA synthetase complex. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23609930/ · DOI 10.1002/prot.24306
Complete structured claim and evidence
Human mitochondrial aspartyl-tRNA synthetase showed a broader catalytic groove and distinct tRNA-binding thermodynamics compared with its bacterial structural homologue.
Human mitochondrial aspartyl-tRNA synthetase / DARS2 → Human mitochondrial aspartate tRNA source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Purified human mitochondrial DARS2, crystallography and isothermal titration calorimetry.
limitations
Bacterial structural comparison is not a human aspartate-deficiency model or proof of supplement rescue.
nutrient_topic
L-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Aspartate
plain_language
Mitochondrial translation has its own aspartate-handling machinery.
primary_references
Thermodynamic properties distinguish human mitochondrial aspartyl-tRNA synthetase from bacterial homolog with same 3D architecture. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23275545/ · DOI 10.1093/nar/gks1322
L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 362–368
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified human mitochondrial DARS2, crystallography and isothermal titration calorimetry. · source_derived_draft · unverified_draft
## l-aspartate-dars2-compartment Mitochondrial translation has its own aspartate-handling machinery. Human mitochondrial aspartyl-tRNA synthetase showed a broader catalytic groove and distinct tRNA-binding thermodynamics compared with its bacterial structural homologue. Model: Purified human mitochondrial DARS2, crystallography and isothermal titration calorimetry. Limitations: Bacterial structural comparison is not a human aspartate-deficiency model or proof of supplement rescue. Evidence access: Primary full text Thermodynamic properties distinguish human mitochondrial aspartyl-tRNA synthetase from bacterial homolog with same 3D architecture. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23275545/ · DOI 10.1093/nar/gks1322
Complete structured claim and evidence
Coexpressing mouse Nat8l and Rimklb in CHO-K1 or HEK293T cells enabled NAAG production from the NAA-synthesis pathway.
Mouse aspartate N-acetyltransferase / Nat8l → Mouse NAAG synthetase I / Rimklb source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract and primary methods/figure text
experimental_model
Mouse-brain cDNA constructs in hamster/human cell hosts; product identified by HPLC and tandem mass spectrometry.
limitations
Host-cell species is not the enzyme species; no dietary brain-delivery effect was tested.
nutrient_topic
L-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Aspartate
plain_language
Aspartate-derived NAA can feed a second, glutamate-containing product.
primary_references
Molecular characterization of N-acetylaspartylglutamate synthetase. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20643647/ · DOI 10.1074/jbc.M110.111765
L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 370–376
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse-brain cDNA constructs in hamster/human cell hosts; product identified by HPLC and tandem mass spectrometry. · source_derived_draft · unverified_draft
## l-aspartate-naa-naag-supply Aspartate-derived NAA can feed a second, glutamate-containing product. Coexpressing mouse Nat8l and Rimklb in CHO-K1 or HEK293T cells enabled NAAG production from the NAA-synthesis pathway. Model: Mouse-brain cDNA constructs in hamster/human cell hosts; product identified by HPLC and tandem mass spectrometry. Limitations: Host-cell species is not the enzyme species; no dietary brain-delivery effect was tested. Evidence access: Primary abstract and primary methods/figure text Molecular characterization of N-acetylaspartylglutamate synthetase. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20643647/ · DOI 10.1074/jbc.M110.111765
Complete structured claim and evidence
Coexpression of the mouse NaDC3 transporter with Rimklb enabled supplied NAA to support NAAG synthesis in heterologous cells.
Mouse sodium-dependent dicarboxylate transporter 3 / Slc13a3 → Mouse NAAG synthetase I / Rimklb source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract and primary methods/figure text
experimental_model
Mouse transporter/enzyme cDNAs; CHO-K1 and HEK293T cell experiments.
limitations
This is NAA transport, not proof that NaDC3 transports free L-aspartate in the tested assay.
nutrient_topic
L-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Aspartate
plain_language
Transport of the intermediate can gate the next synthesis step.
primary_references
Molecular characterization of N-acetylaspartylglutamate synthetase. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20643647/ · DOI 10.1074/jbc.M110.111765
L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 378–384
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse transporter/enzyme cDNAs; CHO-K1 and HEK293T cell experiments. · source_derived_draft · unverified_draft
## l-aspartate-naag-import-route Transport of the intermediate can gate the next synthesis step. Coexpression of the mouse NaDC3 transporter with Rimklb enabled supplied NAA to support NAAG synthesis in heterologous cells. Model: Mouse transporter/enzyme cDNAs; CHO-K1 and HEK293T cell experiments. Limitations: This is NAA transport, not proof that NaDC3 transports free L-aspartate in the tested assay. Evidence access: Primary abstract and primary methods/figure text Molecular characterization of N-acetylaspartylglutamate synthetase. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20643647/ · DOI 10.1074/jbc.M110.111765
Complete structured claim and evidence
A homozygous 19-base-pair NAT8L deletion in a patient with absent brain NAA produced a frameshift and failure to produce a functional enzyme.
Human NAT8L 19-base-pair deletion → Human aspartate N-acetyltransferase / NAT8L source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Human patient genetic study with functional expression characterization.
limitations
A single rare disorder is not evidence of dietary aspartate deficiency or that supplying aspartate fixes the defect.
nutrient_topic
L-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Aspartate
plain_language
Lack of the derived metabolite can reflect faulty synthesis machinery.
primary_references
Molecular identification of aspartate N-acetyltransferase and its mutation in hypoacetylaspartia. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19807691/ · DOI 10.1042/BJ20091024
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 386–392
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human patient genetic study with functional expression characterization. · source_derived_draft · unverified_draft
## l-aspartate-human-nat8l-loss Lack of the derived metabolite can reflect faulty synthesis machinery. A homozygous 19-base-pair NAT8L deletion in a patient with absent brain NAA produced a frameshift and failure to produce a functional enzyme. Model: Human patient genetic study with functional expression characterization. Limitations: A single rare disorder is not evidence of dietary aspartate deficiency or that supplying aspartate fixes the defect. Evidence access: Primary abstract Molecular identification of aspartate N-acetyltransferase and its mutation in hypoacetylaspartia. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19807691/ · DOI 10.1042/BJ20091024
Complete structured claim and evidence
L-aspartate evoked currents from recombinant rat GluN1/GluN2D receptors expressed in HEK293 cells when glycine was present.
L-Aspartate → Rat GluN1/GluN2D NMDA receptor complex source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Rat receptor constructs; 1-second 1 mM agonist pulse with 0.05 mM glycine.
limitations
This does not demonstrate brain entry, cognitive benefit or excitotoxicity after oral intake.
nutrient_topic
L-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Aspartate
plain_language
L-aspartate can act at a receptor in a controlled electrophysiology experiment.
primary_references
Ligand-specific deactivation time course of GluN1/GluN2D NMDA receptors. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21522138/ · DOI 10.1038/ncomms1295
L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 394–400
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat receptor constructs; 1-second 1 mM agonist pulse with 0.05 mM glycine. · source_derived_draft · unverified_draft
## l-aspartate-nmda-agonism L-aspartate can act at a receptor in a controlled electrophysiology experiment. L-aspartate evoked currents from recombinant rat GluN1/GluN2D receptors expressed in HEK293 cells when glycine was present. Model: Rat receptor constructs; 1-second 1 mM agonist pulse with 0.05 mM glycine. Limitations: This does not demonstrate brain entry, cognitive benefit or excitotoxicity after oral intake. Evidence access: Primary full text Ligand-specific deactivation time course of GluN1/GluN2D NMDA receptors. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21522138/ · DOI 10.1038/ncomms1295
Complete structured claim and evidence
L-aspartate-evoked GluN1/GluN2D currents deactivated faster than L-glutamate-evoked currents under matched recording conditions.
L-Aspartate → Rat GluN1/GluN2D NMDA receptor complex source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Rat recombinant receptors in HEK293 cells; voltage-clamp and structural comparisons.
limitations
Not a universal rank of potency or toxicity across all NMDA receptor subtypes.
nutrient_topic
L-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Aspartate
plain_language
Two agonists at the same receptor can produce different signal durations.
primary_references
Ligand-specific deactivation time course of GluN1/GluN2D NMDA receptors. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21522138/ · DOI 10.1038/ncomms1295
L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 402–408
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat recombinant receptors in HEK293 cells; voltage-clamp and structural comparisons. · source_derived_draft · unverified_draft
## l-aspartate-nmda-deactivation Two agonists at the same receptor can produce different signal durations. L-aspartate-evoked GluN1/GluN2D currents deactivated faster than L-glutamate-evoked currents under matched recording conditions. Model: Rat recombinant receptors in HEK293 cells; voltage-clamp and structural comparisons. Limitations: Not a universal rank of potency or toxicity across all NMDA receptor subtypes. Evidence access: Primary full text Ligand-specific deactivation time course of GluN1/GluN2D NMDA receptors. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21522138/ · DOI 10.1038/ncomms1295
Complete structured claim and evidence
Human GOT1 catalyzes reversible amino transfer between aspartate and 2-oxoglutarate, producing oxaloacetate and glutamate.
Human cytosolic aspartate aminotransferase / GOT1 → L-Aspartate source_derived_draftungraded
Experimental context and source evidence
experimental_model
Purified human cytosolic GOT1 and GPT; coupled kinetic assays
exposure
Kinetic assays at pH 7.4 and 37 C
limitations
Purified-enzyme evidence does not define dietary requirements or cellular PLP thresholds.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
This B6-dependent enzyme links amino-acid and carbon metabolism.
primary_references
[b6-transaminases-2022] Using Steady-State Kinetics to Quantitate Substrate Selectivity and Specificity: A Case Study with Two Human Transaminases. (2022). https://pmc.ncbi.nlm.nih.gov/articles/PMC8875635/ DOI: 10.3390/molecules27041398
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 741–751
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human cytosolic GOT1 and GPT; coupled kinetic assays · source_derived_draft · unverified_draft
### b6-met-got1-reaction Human GOT1 catalyzes reversible amino transfer between aspartate and 2-oxoglutarate, producing oxaloacetate and glutamate. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: This B6-dependent enzyme links amino-acid and carbon metabolism. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Purified human cytosolic GOT1 and GPT; coupled kinetic assays limitations: Purified-enzyme evidence does not define dietary requirements or cellular PLP thresholds. exposure: Kinetic assays at pH 7.4 and 37 C [b6-transaminases-2022] Using Steady-State Kinetics to Quantitate Substrate Selectivity and Specificity: A Case Study with Two Human Transaminases. (2022). https://pmc.ncbi.nlm.nih.gov/articles/PMC8875635/ DOI: 10.3390/molecules27041398
Complete structured claim and evidence
Liver-specific Pcx deletion depleted aspartate and impaired urea-cycle function, with hyperammonemia.
Liver-specific Pcx-null mouse genotype → Mouse liver aspartate pool source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/biotin-research/31006591.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0dcedbfac623863bd4ae86ed1bb97cef0ef56bd417bd0d49507ef47d16af7b4e", "start_char": 0, "end_char": 1141, "text_sha256": "0dcedbfac623863bd4ae86ed1bb97cef0ef56bd417bd0d49507ef47d16af7b4e"}
experimental_model
Liver-specific Pcx-knockout mice
exposure
Genetic deletion of hepatic pyruvate carboxylase
limitations
Genetic enzyme deletion is not a dietary biotin experiment. Cross-nutrient implications identify pathway dependence rather than a proven supplement response.
nutrient_topic
Biotin research collection; topical membership is not evidence of a direct dietary effect. · Biotin
organism
Mus musculus
plain_language
Loss of carbon replenishment also constrained nitrogen disposal.
primary_references
[b7-p31006591] Pyruvate-Carboxylase-Mediated Anaplerosis Promotes Antioxidant Capacity by Sustaining TCA Cycle and Redox Metabolism in Liver. (2019). https://pubmed.ncbi.nlm.nih.gov/31006591/ DOI: 10.1016/j.cmet.2019.03.014
tissue_or_cell_type
Liver and systemic metabolism
trigger_kind
machinery_impairment Imported condition classification; unverified.
Biotin: carboxylases, recycling, deficiency and nutrient interactions (2026-09-17) · lines 858–869
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Liver-specific Pcx-knockout mice · source_derived_draft · unverified_draft
### b7-pc-null-aspartate Liver-specific Pcx deletion depleted aspartate and impaired urea-cycle function, with hyperammonemia. Condition category: machinery_impairment nutrient_topic: Biotin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Loss of carbon replenishment also constrained nitrogen disposal. organism: Mus musculus tissue_or_cell_type: Liver and systemic metabolism experimental_model: Liver-specific Pcx-knockout mice limitations: Genetic enzyme deletion is not a dietary biotin experiment. Cross-nutrient implications identify pathway dependence rather than a proven supplement response. exposure: Genetic deletion of hepatic pyruvate carboxylase evidence_span: {"source_cache": "artifacts/biotin-research/31006591.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0dcedbfac623863bd4ae86ed1bb97cef0ef56bd417bd0d49507ef47d16af7b4e", "start_char": 0, "end_char": 1141, "text_sha256": "0dcedbfac623863bd4ae86ed1bb97cef0ef56bd417bd0d49507ef47d16af7b4e"} [b7-p31006591] Pyruvate-Carboxylase-Mediated Anaplerosis Promotes Antioxidant Capacity by Sustaining TCA Cycle and Redox Metabolism in Liver. (2019). https://pubmed.ncbi.nlm.nih.gov/31006591/ DOI: 10.1016/j.cmet.2019.03.014
Complete structured claim and evidence
Human ASS1 combines citrulline and aspartate to form argininosuccinate in an ATP-dependent reaction.
Human argininosuccinate synthetase 1 / ASS1 → L-Argininosuccinate source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/citrulline-research/18323623.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "079be80a0ea1a47308efb069d3c9522c96c0aa5923ad1d7ce79ac620b2d9502f", "start_char": 0, "end_char": 840, "text_sha256": "079be80a0ea1a47308efb069d3c9522c96c0aa5923ad1d7ce79ac620b2d9502f"}
experimental_model
Crystal structure and biochemical reaction characterization
exposure
Citrulline and aspartate bound to recombinant enzyme
limitations
Structure and established reaction; no clinical magnesium, aspartate or ATP deficiency threshold is established.
nutrient_topic
Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline
organism
Human ASS1
plain_language
Citrulline needs a second amino acid and an enzyme-controlled step before it becomes arginine.
primary_references
[citrulline-p18323623] Structure of human argininosuccinate synthetase. (2008). https://pubmed.ncbi.nlm.nih.gov/18323623/ DOI: 10.1107/s0907444907067455
tissue_or_cell_type
Cytosolic arginine-regeneration reaction
Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 125–136
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Crystal structure and biochemical reaction characterization · source_derived_draft · unverified_draft
### citrulline-ass1-reaction Human ASS1 combines citrulline and aspartate to form argininosuccinate in an ATP-dependent reaction. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Citrulline needs a second amino acid and an enzyme-controlled step before it becomes arginine. organism: Human ASS1 tissue_or_cell_type: Cytosolic arginine-regeneration reaction experimental_model: Crystal structure and biochemical reaction characterization limitations: Structure and established reaction; no clinical magnesium, aspartate or ATP deficiency threshold is established. exposure: Citrulline and aspartate bound to recombinant enzyme evidence_span: {"source_cache": "artifacts/citrulline-research/18323623.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "079be80a0ea1a47308efb069d3c9522c96c0aa5923ad1d7ce79ac620b2d9502f", "start_char": 0, "end_char": 840, "text_sha256": "079be80a0ea1a47308efb069d3c9522c96c0aa5923ad1d7ce79ac620b2d9502f"} [citrulline-p18323623] Structure of human argininosuccinate synthetase. (2008). https://pubmed.ncbi.nlm.nih.gov/18323623/ DOI: 10.1107/s0907444907067455
Complete structured claim and evidence
Human ASL catalyzes reversible cleavage of argininosuccinate to arginine and fumarate.
Human argininosuccinate lyase / ASL → L-Arginine source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/citrulline-research/11747433.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1d57b633c558211169c38f4dc40cceeeb373c63d291c80d2523c8e48b54427b1", "start_char": 0, "end_char": 1617, "text_sha256": "1d57b633c558211169c38f4dc40cceeeb373c63d291c80d2523c8e48b54427b1"}
experimental_model
Recombinant human enzyme complementation and stability experiments
exposure
Wild type and Q286R, D87G, M360T or A398D variants
limitations
Reaction identity and complementation are established in enzyme systems; these variants do not describe all ASL deficiencies.
nutrient_topic
Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline
organism
Human ASL expressed experimentally
plain_language
The second enzyme releases arginine from the intermediate.
primary_references
[citrulline-p11747433] Mechanisms for intragenic complementation at the human argininosuccinate lyase locus. (2001). https://pubmed.ncbi.nlm.nih.gov/11747433/ DOI: 10.1021/bi011526e
tissue_or_cell_type
Argininosuccinate cleavage
Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 177–188
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human enzyme complementation and stability experiments · source_derived_draft · unverified_draft
### citrulline-asl-arginine Human ASL catalyzes reversible cleavage of argininosuccinate to arginine and fumarate. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: The second enzyme releases arginine from the intermediate. organism: Human ASL expressed experimentally tissue_or_cell_type: Argininosuccinate cleavage experimental_model: Recombinant human enzyme complementation and stability experiments limitations: Reaction identity and complementation are established in enzyme systems; these variants do not describe all ASL deficiencies. exposure: Wild type and Q286R, D87G, M360T or A398D variants evidence_span: {"source_cache": "artifacts/citrulline-research/11747433.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1d57b633c558211169c38f4dc40cceeeb373c63d291c80d2523c8e48b54427b1", "start_char": 0, "end_char": 1617, "text_sha256": "1d57b633c558211169c38f4dc40cceeeb373c63d291c80d2523c8e48b54427b1"} [citrulline-p11747433] Mechanisms for intragenic complementation at the human argininosuccinate lyase locus. (2001). https://pubmed.ncbi.nlm.nih.gov/11747433/ DOI: 10.1021/bi011526e
Complete structured claim and evidence
Reconstituted citrin exchanged aspartate for glutamate plus a proton.
Human citrin / SLC25A13 → Mitochondrial aspartate/glutamate exchange source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/citrulline-research/11566871.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "25151a91c1f832fb2e3f86421ef070fb3a7c92390b5b1e7c0038e1db1d6a0734", "start_char": 0, "end_char": 1249, "text_sha256": "25151a91c1f832fb2e3f86421ef070fb3a7c92390b5b1e7c0038e1db1d6a0734"}
experimental_model
Reconstituted transporter and transfected-cell assays
exposure
Aspartate exchange for glutamate plus proton; external calcium stimulation
limitations
Cell and liposome experiments; no evidence that calcium supplementation corrects citrin deficiency.
nutrient_topic
Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline
organism
Human citrin and aralar proteins
plain_language
Moving aspartate between compartments helps connect nitrogen handling and redox metabolism.
primary_references
[citrulline-p11566871] Citrin and aralar1 are Ca(2+)-stimulated aspartate/glutamate transporters in mitochondria. (2001). https://pubmed.ncbi.nlm.nih.gov/11566871/ DOI: 10.1093/emboj/20.18.5060
tissue_or_cell_type
Inner mitochondrial membrane transport; malate-aspartate shuttle
Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 359–370
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Reconstituted transporter and transfected-cell assays · source_derived_draft · unverified_draft
### citrulline-citrin-aspartate Reconstituted citrin exchanged aspartate for glutamate plus a proton. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: Moving aspartate between compartments helps connect nitrogen handling and redox metabolism. organism: Human citrin and aralar proteins tissue_or_cell_type: Inner mitochondrial membrane transport; malate-aspartate shuttle experimental_model: Reconstituted transporter and transfected-cell assays limitations: Cell and liposome experiments; no evidence that calcium supplementation corrects citrin deficiency. exposure: Aspartate exchange for glutamate plus proton; external calcium stimulation evidence_span: {"source_cache": "artifacts/citrulline-research/11566871.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "25151a91c1f832fb2e3f86421ef070fb3a7c92390b5b1e7c0038e1db1d6a0734", "start_char": 0, "end_char": 1249, "text_sha256": "25151a91c1f832fb2e3f86421ef070fb3a7c92390b5b1e7c0038e1db1d6a0734"} [citrulline-p11566871] Citrin and aralar1 are Ca(2+)-stimulated aspartate/glutamate transporters in mitochondria. (2001). https://pubmed.ncbi.nlm.nih.gov/11566871/ DOI: 10.1093/emboj/20.18.5060
Complete structured claim and evidence
Citrin overexpression increased malate-aspartate shuttle activity in transfected human cells.
Human citrin / SLC25A13 → Malate-aspartate shuttle activity source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/citrulline-research/11566871.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "25151a91c1f832fb2e3f86421ef070fb3a7c92390b5b1e7c0038e1db1d6a0734", "start_char": 0, "end_char": 1249, "text_sha256": "25151a91c1f832fb2e3f86421ef070fb3a7c92390b5b1e7c0038e1db1d6a0734"}
experimental_model
Reconstituted transporter and transfected-cell assays
exposure
Aspartate exchange for glutamate plus proton; external calcium stimulation
limitations
Cell and liposome experiments; no evidence that calcium supplementation corrects citrin deficiency.
nutrient_topic
Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline
organism
Human citrin and aralar proteins
plain_language
The same transporter participates in moving reducing equivalents between compartments.
primary_references
[citrulline-p11566871] Citrin and aralar1 are Ca(2+)-stimulated aspartate/glutamate transporters in mitochondria. (2001). https://pubmed.ncbi.nlm.nih.gov/11566871/ DOI: 10.1093/emboj/20.18.5060
tissue_or_cell_type
Inner mitochondrial membrane transport; malate-aspartate shuttle
Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 385–396
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Reconstituted transporter and transfected-cell assays · source_derived_draft · unverified_draft
### citrulline-citrin-shuttle Citrin overexpression increased malate-aspartate shuttle activity in transfected human cells. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: The same transporter participates in moving reducing equivalents between compartments. organism: Human citrin and aralar proteins tissue_or_cell_type: Inner mitochondrial membrane transport; malate-aspartate shuttle experimental_model: Reconstituted transporter and transfected-cell assays limitations: Cell and liposome experiments; no evidence that calcium supplementation corrects citrin deficiency. exposure: Aspartate exchange for glutamate plus proton; external calcium stimulation evidence_span: {"source_cache": "artifacts/citrulline-research/11566871.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "25151a91c1f832fb2e3f86421ef070fb3a7c92390b5b1e7c0038e1db1d6a0734", "start_char": 0, "end_char": 1249, "text_sha256": "25151a91c1f832fb2e3f86421ef070fb3a7c92390b5b1e7c0038e1db1d6a0734"} [citrulline-p11566871] Citrin and aralar1 are Ca(2+)-stimulated aspartate/glutamate transporters in mitochondria. (2001). https://pubmed.ncbi.nlm.nih.gov/11566871/ DOI: 10.1093/emboj/20.18.5060
Complete structured claim and evidence
Respiration-deficient proliferating cells became limited in aspartate synthesis; alpha-ketobutyrate restored proliferation as an electron acceptor without supplying carbon or ATP.
Respiration-deficient proliferating cell models → L-Aspartate source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Cultured proliferating mammalian cells with impaired respiration.
limitations
ATP is not generally dispensable; this experiment isolates an electron-acceptor bottleneck in supplied culture conditions.
nutrient_topic
NAD+ collection; molecular form, preparation, species, exposure and manipulation remain explicit. · NAD+
plain_language
Respiration supports building material by restoring electron acceptors, as well as producing ATP.
primary_references
Supporting Aspartate Biosynthesis Is an Essential Function of Respiration in Proliferating Cells. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26232225/ · DOI 10.1016/j.cell.2015.07.017
trigger_kind
machinery_impairment Imported condition classification; unverified.
NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19) · lines 204–210
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cultured proliferating mammalian cells with impaired respiration. · source_derived_draft · unverified_draft
## nad-plus-electron-acceptor-aspartate Respiration supports building material by restoring electron acceptors, as well as producing ATP. Respiration-deficient proliferating cells became limited in aspartate synthesis; alpha-ketobutyrate restored proliferation as an electron acceptor without supplying carbon or ATP. Model: Cultured proliferating mammalian cells with impaired respiration. Limitations: ATP is not generally dispensable; this experiment isolates an electron-acceptor bottleneck in supplied culture conditions. Evidence access: Primary full text Supporting Aspartate Biosynthesis Is an Essential Function of Respiration in Proliferating Cells. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26232225/ · DOI 10.1016/j.cell.2015.07.017
Complete structured claim and evidence
Aspartate supplementation rescued proliferation of the tested respiration-deficient cells.
L-Aspartate → Proliferation of respiration-deficient cells source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Mammalian cell-culture respiration perturbation and rescue.
limitations
Cell-culture rescue does not establish oral aspartate delivery or therapeutic efficacy in people.
nutrient_topic
NAD+ collection; molecular form, preparation, species, exposure and manipulation remain explicit. · NAD+
plain_language
Supplying the missing product can bypass a biosynthetic bottleneck.
primary_references
Supporting Aspartate Biosynthesis Is an Essential Function of Respiration in Proliferating Cells. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26232225/ · DOI 10.1016/j.cell.2015.07.017
trigger_kind
machinery_impairment Imported condition classification; unverified.
NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19) · lines 212–218
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mammalian cell-culture respiration perturbation and rescue. · source_derived_draft · unverified_draft
## nad-plus-aspartate-rescue Supplying the missing product can bypass a biosynthetic bottleneck. Aspartate supplementation rescued proliferation of the tested respiration-deficient cells. Model: Mammalian cell-culture respiration perturbation and rescue. Limitations: Cell-culture rescue does not establish oral aspartate delivery or therapeutic efficacy in people. Evidence access: Primary full text Supporting Aspartate Biosynthesis Is an Essential Function of Respiration in Proliferating Cells. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26232225/ · DOI 10.1016/j.cell.2015.07.017
Complete structured claim and evidence
Pyruvate supplied an alternative electron-acceptor route for NAD+ regeneration and aspartate synthesis, reducing the antiproliferative effect of metformin in the tested cancer cells.
Pyruvate → NAD regeneration in metformin-treated cancer cells source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Cancer-cell culture, complex-I-dependent respiration and nutrient manipulation.
limitations
Experimental concentrations and culture composition matter; not a medication adjustment or claim that metformin has one mechanism in all tissues.
nutrient_topic
NAD+ collection; molecular form, preparation, species, exposure and manipulation remain explicit. · NAD+
plain_language
Available nutrients can change the effect of an inhibitor on the same pathway.
primary_references
Environment Dictates Dependence on Mitochondrial Complex I for NAD+ and Aspartate Production and Determines Cancer Cell Sensitivity to Metformin. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27746050/ · DOI 10.1016/j.cmet.2016.09.006
NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19) · lines 220–226
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cancer-cell culture, complex-I-dependent respiration and nutrient manipulation. · source_derived_draft · unverified_draft
## nad-plus-pyruvate-metformin Available nutrients can change the effect of an inhibitor on the same pathway. Pyruvate supplied an alternative electron-acceptor route for NAD+ regeneration and aspartate synthesis, reducing the antiproliferative effect of metformin in the tested cancer cells. Model: Cancer-cell culture, complex-I-dependent respiration and nutrient manipulation. Limitations: Experimental concentrations and culture composition matter; not a medication adjustment or claim that metformin has one mechanism in all tissues. Evidence access: Primary full text Environment Dictates Dependence on Mitochondrial Complex I for NAD+ and Aspartate Production and Determines Cancer Cell Sensitivity to Metformin. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27746050/ · DOI 10.1016/j.cmet.2016.09.006
Complete structured claim and evidence
The human GART transformylase domain binds a folate formyl donor and GAR-site acceptor in a ternary complex supporting GAR formylation to FGAR.
Human trifunctional GART → Glycinamide ribonucleotide source_derived_draftungraded
Experimental context and source evidence
experimental_model
X-ray crystallography
exposure
Assay conditions described in the linked primary study.
limitations
Structures used 10-formyl-dideazafolate and hydroxyacetamide ribonucleotide analogues.
nutrient_topic
Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. · Folate (vitamin B9)
organism
Homo sapiens
plain_language
Folate donates one carbon early in purine-base construction.
primary_references
[dahms-2005] The apo and ternary complex structures of a chemotherapeutic target: human glycinamide ribonucleotide transformylase (2005). https://pubmed.ncbi.nlm.nih.gov/16026156/ DOI: 10.1021/bi050307g
tissue_or_cell_type
Purified domain
Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 998–1008
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · X-ray crystallography · source_derived_draft · unverified_draft
### gart-formyl-transfer The human GART transformylase domain binds a folate formyl donor and GAR-site acceptor in a ternary complex supporting GAR formylation to FGAR. Condition category: normal nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Folate donates one carbon early in purine-base construction. organism: Homo sapiens tissue_or_cell_type: Purified domain experimental_model: X-ray crystallography limitations: Structures used 10-formyl-dideazafolate and hydroxyacetamide ribonucleotide analogues. exposure: Assay conditions described in the linked primary study. [dahms-2005] The apo and ternary complex structures of a chemotherapeutic target: human glycinamide ribonucleotide transformylase (2005). https://pubmed.ncbi.nlm.nih.gov/16026156/ DOI: 10.1021/bi050307g
Complete structured claim and evidence
Purified human ATIC uses 10-formyl-THF for its AICAR formyltransferase reaction, yielding FAICAR.
Human bifunctional ATIC → 5-Aminoimidazole-4-carboxamide ribonucleotide source_derived_draftungraded
Experimental context and source evidence
experimental_model
Recombinant enzyme kinetics
exposure
Assay conditions described in the linked primary study.
limitations
Reported folate kinetics used a 6R/6S mixture.
nutrient_topic
Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. · Folate (vitamin B9)
organism
Homo sapiens
plain_language
A second folate donation helps finish the purine ring.
primary_references
[rayl-1996] The human purH gene product, 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase. Cloning, sequencing, expression, purification, kinetic analysis, and domain mapping (1996). https://pubmed.ncbi.nlm.nih.gov/8567683/ DOI: 10.1074/jbc.271.4.2225
tissue_or_cell_type
Cell-free
Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1010–1020
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant enzyme kinetics · source_derived_draft · unverified_draft
### atic-aicar-formylation Purified human ATIC uses 10-formyl-THF for its AICAR formyltransferase reaction, yielding FAICAR. Condition category: normal nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: A second folate donation helps finish the purine ring. organism: Homo sapiens tissue_or_cell_type: Cell-free experimental_model: Recombinant enzyme kinetics limitations: Reported folate kinetics used a 6R/6S mixture. exposure: Assay conditions described in the linked primary study. [rayl-1996] The human purH gene product, 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase. Cloning, sequencing, expression, purification, kinetic analysis, and domain mapping (1996). https://pubmed.ncbi.nlm.nih.gov/8567683/ DOI: 10.1074/jbc.271.4.2225
Complete structured claim and evidence
Carbon-13 NMR detected alanine-derived glutamate and aspartate in BRIN-BD11 cells; oligomycin attenuated alanine-stimulated insulin secretion.
L-Alanine → Alanine oxidative metabolism in rat BRIN-BD11 cells source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Rat clonal BRIN-BD11 beta-cell experiments.
limitations
Oligomycin broadly blocks oxidative phosphorylation; this is not a selective proof of one alanine enzyme.
nutrient_topic
L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
plain_language
Oxidative metabolism contributed to the secretory response in this cell line.
primary_references
A nuclear magnetic resonance-based demonstration of substantial oxidative L-alanine metabolism and L-alanine-enhanced glucose metabolism in a clonal pancreatic beta-cell line: metabolism of L-alanine is important to the regulation of insulin secretion. · 2002 · https://pubmed.ncbi.nlm.nih.gov/12031957/ · DOI 10.2337/diabetes.51.6.1714
L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 360–366
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat clonal BRIN-BD11 beta-cell experiments. · source_derived_draft · unverified_draft
## alanine-beta-oxidation Oxidative metabolism contributed to the secretory response in this cell line. Carbon-13 NMR detected alanine-derived glutamate and aspartate in BRIN-BD11 cells; oligomycin attenuated alanine-stimulated insulin secretion. Model: Rat clonal BRIN-BD11 beta-cell experiments. Limitations: Oligomycin broadly blocks oxidative phosphorylation; this is not a selective proof of one alanine enzyme. Evidence access: Primary abstract A nuclear magnetic resonance-based demonstration of substantial oxidative L-alanine metabolism and L-alanine-enhanced glucose metabolism in a clonal pancreatic beta-cell line: metabolism of L-alanine is important to the regulation of insulin secretion. · 2002 · https://pubmed.ncbi.nlm.nih.gov/12031957/ · DOI 10.2337/diabetes.51.6.1714
Complete structured claim and evidence

Availability and dependencies

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

Renal transport failure changes amino-acid conservation

Condition: machinery_impairment · Human SLC1A1 disease variants impair transporter function and localization.