Nutrient chapter

L-Alanine

Amino acid product of SCLY-catalyzed selenocysteine decomposition.

72 recorded mechanisms · 11 availability situations · 4 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.

Arteriovenous measurements identified alanine as the principal amino acid released by forearm muscle and extracted by the liver in postabsorptive and prolonged-fasting subjects.
L-Alanine → Human forearm release and hepatic extraction of alanine source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human arteriovenous balance study; postabsorptive state and 4–6 weeks of fasting.
limitations
Exchange measurements do not identify every intracellular reaction or prove that all released alanine becomes glucose.
nutrient_topic
L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
plain_language
Muscle can send both carbon and amino nitrogen to the liver as alanine.
primary_references
Alanine: key role in gluconeogenesis. · 1970 · https://pubmed.ncbi.nlm.nih.gov/5411169/ · DOI 10.1126/science.167.3920.1003
L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 16–22
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human arteriovenous balance study; postabsorptive state and 4–6 weeks of fasting. · source_derived_draft · unverified_draft
## alanine-human-forearm-liver Muscle can send both carbon and amino nitrogen to the liver as alanine. Arteriovenous measurements identified alanine as the principal amino acid released by forearm muscle and extracted by the liver in postabsorptive and prolonged-fasting subjects. Model: Human arteriovenous balance study; postabsorptive state and 4–6 weeks of fasting. Limitations: Exchange measurements do not identify every intracellular reaction or prove that all released alanine becomes glucose. Evidence access: Primary abstract Alanine: key role in gluconeogenesis. · 1970 · https://pubmed.ncbi.nlm.nih.gov/5411169/ · DOI 10.1126/science.167.3920.1003
Complete structured claim and evidence
Total forearm amino acid release decreased during prolonged fasting even though alanine retained a prominent interorgan role.
Prolonged fasting in humans → Total forearm amino acid release source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human balance measurements during prolonged fasting.
limitations
Not a recommendation for prolonged fasting, nor evidence for a fixed whole-body alanine flux.
nutrient_topic
L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
plain_language
The same pathway can remain important while its overall flow declines.
primary_references
Alanine: key role in gluconeogenesis. · 1970 · https://pubmed.ncbi.nlm.nih.gov/5411169/ · DOI 10.1126/science.167.3920.1003
L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 24–30
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human balance measurements during prolonged fasting. · source_derived_draft · unverified_draft
## alanine-fasting-flux-limit The same pathway can remain important while its overall flow declines. Total forearm amino acid release decreased during prolonged fasting even though alanine retained a prominent interorgan role. Model: Human balance measurements during prolonged fasting. Limitations: Not a recommendation for prolonged fasting, nor evidence for a fixed whole-body alanine flux. Evidence access: Primary abstract Alanine: key role in gluconeogenesis. · 1970 · https://pubmed.ncbi.nlm.nih.gov/5411169/ · DOI 10.1126/science.167.3920.1003
Complete structured claim and evidence
Purified untagged human AGXT catalyzed the PLP-dependent reaction alanine + glyoxylate ⇌ pyruvate + glycine; forward and reverse kinetic parameters were measured.
Human peroxisomal alanine:glyoxylate aminotransferase / AGXT → Glyoxylate source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Recombinant human liver enzyme expressed in E. coli; kinetic and cofactor-binding assays.
limitations
Peroxisomal enzyme identity does not mean intracellular flux or supplement benefit was measured.
nutrient_topic
L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
plain_language
Alanine supplies an amino group that turns glyoxylate into glycine.
primary_references
Construction, purification and characterization of untagged human liver alanine-glyoxylate aminotransferase expressed in Escherichia coli. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18289107/ · DOI 10.2174/092986608783489580
L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 32–38
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Recombinant human liver enzyme expressed in E. coli; kinetic and cofactor-binding assays. · source_derived_draft · unverified_draft
## alanine-agt-reaction Alanine supplies an amino group that turns glyoxylate into glycine. Purified untagged human AGXT catalyzed the PLP-dependent reaction alanine + glyoxylate ⇌ pyruvate + glycine; forward and reverse kinetic parameters were measured. Model: Recombinant human liver enzyme expressed in E. coli; kinetic and cofactor-binding assays. Limitations: Peroxisomal enzyme identity does not mean intracellular flux or supplement benefit was measured. Evidence access: Primary abstract Construction, purification and characterization of untagged human liver alanine-glyoxylate aminotransferase expressed in Escherichia coli. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18289107/ · DOI 10.2174/092986608783489580
Complete structured claim and evidence
Pre-steady-state analysis of human AGXT showed that PMP remained bound during its catalytic cycle and the AGXT–PMP complex reacted efficiently with oxo-acid substrates.
Human peroxisomal alanine:glyoxylate aminotransferase / AGXT → Pyridoxamine 5-prime-phosphate source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Purified human AGXT; PLP-form reactions with alanine/glycine and PMP-form reactions with pyruvate/glyoxylate.
limitations
Cofactor cycling is not evidence that B6 is irreversibly consumed once per reaction.
nutrient_topic
L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
plain_language
The B6 cofactor changes form while helping transfer nitrogen.
primary_references
Human wild-type alanine:glyoxylate aminotransferase and its naturally occurring G82E variant: functional properties and physiological implications. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17696873/ · DOI 10.1042/BJ20070637
L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 40–46
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified human AGXT; PLP-form reactions with alanine/glycine and PMP-form reactions with pyruvate/glyoxylate. · source_derived_draft · unverified_draft
## alanine-agt-pmp-cycle The B6 cofactor changes form while helping transfer nitrogen. Pre-steady-state analysis of human AGXT showed that PMP remained bound during its catalytic cycle and the AGXT–PMP complex reacted efficiently with oxo-acid substrates. Model: Purified human AGXT; PLP-form reactions with alanine/glycine and PMP-form reactions with pyruvate/glyoxylate. Limitations: Cofactor cycling is not evidence that B6 is irreversibly consumed once per reaction. Evidence access: Primary abstract Human wild-type alanine:glyoxylate aminotransferase and its naturally occurring G82E variant: functional properties and physiological implications. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17696873/ · DOI 10.1042/BJ20070637
Complete structured claim and evidence
The human AGXT G82E variant retained two PLP molecules per dimer at saturation but had reduced PLP/PMP affinity and about 0.1% of normal overall catalytic activity.
Human AGXT G82E catalytic impairment → Human peroxisomal alanine:glyoxylate aminotransferase / AGXT source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Purified human disease-associated variant; kinetic and spectroscopic assays.
limitations
Not a dietary B6 or alanine deficiency experiment, and not evidence that either supplement rescues this variant.
nutrient_topic
L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
plain_language
Having the nutrient available does not guarantee that damaged enzyme machinery can use it.
primary_references
Human wild-type alanine:glyoxylate aminotransferase and its naturally occurring G82E variant: functional properties and physiological implications. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17696873/ · DOI 10.1042/BJ20070637
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 48–54
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified human disease-associated variant; kinetic and spectroscopic assays. · source_derived_draft · unverified_draft
## alanine-agt-mutant Having the nutrient available does not guarantee that damaged enzyme machinery can use it. The human AGXT G82E variant retained two PLP molecules per dimer at saturation but had reduced PLP/PMP affinity and about 0.1% of normal overall catalytic activity. Model: Purified human disease-associated variant; kinetic and spectroscopic assays. Limitations: Not a dietary B6 or alanine deficiency experiment, and not evidence that either supplement rescues this variant. Evidence access: Primary abstract Human wild-type alanine:glyoxylate aminotransferase and its naturally occurring G82E variant: functional properties and physiological implications. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17696873/ · DOI 10.1042/BJ20070637
Complete structured claim and evidence
A human alanyl-tRNA synthetase cDNA restored growth in yeast carrying a disrupted essential ALA1 gene, supporting conserved alanine-tRNA recognition and aminoacylation function.
Human cytosolic alanyl-tRNA synthetase / AARS1 → Growth failure after yeast ALA1 disruption source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Human enzyme expressed in Saccharomyces cerevisiae; cross-species complementation.
limitations
Rescue in yeast is not a human supplementation trial. Conserved G3.U70 recognition was the study interpretation.
nutrient_topic
L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
plain_language
Alanine must be loaded onto the correct transfer RNA before proteins can be built.
primary_references
Wide cross-species aminoacyl-tRNA synthetase replacement in vivo: yeast cytoplasmic alanine enzyme replaced by human polymyositis serum antigen. · 1995 · https://pubmed.ncbi.nlm.nih.gov/7761427/ · DOI 10.1073/pnas.92.11.4932
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 56–62
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human enzyme expressed in Saccharomyces cerevisiae; cross-species complementation. · source_derived_draft · unverified_draft
## alanine-aars-complementation Alanine must be loaded onto the correct transfer RNA before proteins can be built. A human alanyl-tRNA synthetase cDNA restored growth in yeast carrying a disrupted essential ALA1 gene, supporting conserved alanine-tRNA recognition and aminoacylation function. Model: Human enzyme expressed in Saccharomyces cerevisiae; cross-species complementation. Limitations: Rescue in yeast is not a human supplementation trial. Conserved G3.U70 recognition was the study interpretation. Evidence access: Primary abstract Wide cross-species aminoacyl-tRNA synthetase replacement in vivo: yeast cytoplasmic alanine enzyme replaced by human polymyositis serum antigen. · 1995 · https://pubmed.ncbi.nlm.nih.gov/7761427/ · DOI 10.1073/pnas.92.11.4932
Complete structured claim and evidence
Binding assays with recombinant human AARS1 measured alanine binding with a reported dissociation constant of 0.45 micromolar, compared with 2.06 micromolar for lactate.
L-Alanine → Human cytosolic alanyl-tRNA synthetase / AARS1 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Purified human AARS1 binding experiments in a gastric-cancer mechanism study.
limitations
These assay affinities do not establish intracellular competition or an effect of oral alanine on lactylation.
nutrient_topic
L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
plain_language
One enzyme can recognize alanine and a second metabolite.
primary_references
The alanyl-tRNA synthetase AARS1 moonlights as a lactyltransferase to promote YAP signaling in gastric cancer. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38512451/ · DOI 10.1172/JCI174587
L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 64–70
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified human AARS1 binding experiments in a gastric-cancer mechanism study. · source_derived_draft · unverified_draft
## alanine-aars-alanine-binding One enzyme can recognize alanine and a second metabolite. Binding assays with recombinant human AARS1 measured alanine binding with a reported dissociation constant of 0.45 micromolar, compared with 2.06 micromolar for lactate. Model: Purified human AARS1 binding experiments in a gastric-cancer mechanism study. Limitations: These assay affinities do not establish intracellular competition or an effect of oral alanine on lactylation. Evidence access: Primary full text The alanyl-tRNA synthetase AARS1 moonlights as a lactyltransferase to promote YAP signaling in gastric cancer. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38512451/ · DOI 10.1172/JCI174587
Complete structured claim and evidence
Human AARS1 used lactate and ATP for protein lactylation; the study identified YAP K90 and TEAD1 K108 modification and activation in gastric cancer models.
Human cytosolic alanyl-tRNA synthetase / AARS1 → AARS1-dependent YAP/TEAD lactylation in human gastric cancer models source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Recombinant enzyme and human gastric cancer cell experiments.
limitations
This is an enzyme connection, not proof that adding L-alanine promotes or inhibits lactylation. Beta-alanine inhibitor findings must not be transferred to L-alanine.
nutrient_topic
L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
plain_language
The alanine-handling enzyme also has a separate lactate-driven signaling activity.
primary_references
The alanyl-tRNA synthetase AARS1 moonlights as a lactyltransferase to promote YAP signaling in gastric cancer. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38512451/ · DOI 10.1172/JCI174587
L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 72–78
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Recombinant enzyme and human gastric cancer cell experiments. · source_derived_draft · unverified_draft
## alanine-aars-lactylation The alanine-handling enzyme also has a separate lactate-driven signaling activity. Human AARS1 used lactate and ATP for protein lactylation; the study identified YAP K90 and TEAD1 K108 modification and activation in gastric cancer models. Model: Recombinant enzyme and human gastric cancer cell experiments. Limitations: This is an enzyme connection, not proof that adding L-alanine promotes or inhibits lactylation. Beta-alanine inhibitor findings must not be transferred to L-alanine. Evidence access: Primary full text The alanyl-tRNA synthetase AARS1 moonlights as a lactyltransferase to promote YAP signaling in gastric cancer. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38512451/ · DOI 10.1172/JCI174587
Complete structured claim and evidence
Alanine add-back restored growth and proliferation impaired by dialyzed-serum culture during initial activation of mouse naive T cells.
L-Alanine → Growth and proliferation during mouse T-cell activation source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Primary mouse naive CD4/CD8 cells activated ex vivo; dialyzed-serum medium with alanine add-back.
limitations
Dialysis removes multiple small nutrients; alanine rescue supports its contribution. This does not establish a human dietary deficiency or immune-boosting dose.
nutrient_topic
L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
plain_language
A cell may be able to make alanine yet fail to make it fast enough when demand rises.
primary_references
T Cell Activation Depends on Extracellular Alanine. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31533027/ · DOI 10.1016/j.celrep.2019.08.034
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 80–86
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Primary mouse naive CD4/CD8 cells activated ex vivo; dialyzed-serum medium with alanine add-back. · source_derived_draft · unverified_draft
## alanine-t-cell-growth A cell may be able to make alanine yet fail to make it fast enough when demand rises. Alanine add-back restored growth and proliferation impaired by dialyzed-serum culture during initial activation of mouse naive T cells. Model: Primary mouse naive CD4/CD8 cells activated ex vivo; dialyzed-serum medium with alanine add-back. Limitations: Dialysis removes multiple small nutrients; alanine rescue supports its contribution. This does not establish a human dietary deficiency or immune-boosting dose. Evidence access: Primary full text T Cell Activation Depends on Extracellular Alanine. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31533027/ · DOI 10.1016/j.celrep.2019.08.034
Complete structured claim and evidence
Activation increased SNAT1 transcript and protein in mouse T cells alongside their increased requirement for extracellular alanine.
Growth and proliferation during mouse T-cell activation → Mouse sodium-coupled neutral amino acid transporter 1 / Slc38a1 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Primary mouse naive CD4/CD8 cells activated ex vivo; dialyzed-serum medium with alanine add-back.
limitations
Expression was measured; this experiment did not genetically prove that SNAT1 alone accounts for alanine uptake.
nutrient_topic
L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
plain_language
Activated cells increase machinery for bringing alanine inside.
primary_references
T Cell Activation Depends on Extracellular Alanine. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31533027/ · DOI 10.1016/j.celrep.2019.08.034
L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 88–94
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Primary mouse naive CD4/CD8 cells activated ex vivo; dialyzed-serum medium with alanine add-back. · source_derived_draft · unverified_draft
## alanine-t-cell-transport Activated cells increase machinery for bringing alanine inside. Activation increased SNAT1 transcript and protein in mouse T cells alongside their increased requirement for extracellular alanine. Model: Primary mouse naive CD4/CD8 cells activated ex vivo; dialyzed-serum medium with alanine add-back. Limitations: Expression was measured; this experiment did not genetically prove that SNAT1 alone accounts for alanine uptake. Evidence access: Primary full text T Cell Activation Depends on Extracellular Alanine. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31533027/ · DOI 10.1016/j.celrep.2019.08.034
Complete structured claim and evidence
Uniformly carbon-13/nitrogen-15-labeled alanine supplied over half of protein-derived alanine by 24 hours after mouse T-cell activation, exclusively as intact m+4 label.
L-Alanine → Protein synthesis during mouse T-cell activation source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Mouse T-cell activation; isotope tracing and protein hydrolysis.
limitations
No detected transamination in this setting does not exclude alanine catabolism in other cell states or species.
nutrient_topic
L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
plain_language
The imported amino acid went directly into proteins rather than first being broken apart.
primary_references
T Cell Activation Depends on Extracellular Alanine. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31533027/ · DOI 10.1016/j.celrep.2019.08.034
L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 96–102
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse T-cell activation; isotope tracing and protein hydrolysis. · source_derived_draft · unverified_draft
## alanine-t-cell-intact-label The imported amino acid went directly into proteins rather than first being broken apart. Uniformly carbon-13/nitrogen-15-labeled alanine supplied over half of protein-derived alanine by 24 hours after mouse T-cell activation, exclusively as intact m+4 label. Model: Mouse T-cell activation; isotope tracing and protein hydrolysis. Limitations: No detected transamination in this setting does not exclude alanine catabolism in other cell states or species. Evidence access: Primary full text T Cell Activation Depends on Extracellular Alanine. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31533027/ · DOI 10.1016/j.celrep.2019.08.034
Complete structured claim and evidence
Alanine supplementation restored puromycin-measured active translation reduced in activated mouse T cells cultured with dialyzed serum.
L-Alanine → Protein synthesis during mouse T-cell activation source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Primary mouse naive CD4/CD8 cells activated ex vivo; dialyzed-serum medium with alanine add-back.
limitations
Dialysis removes multiple small nutrients; alanine rescue supports its contribution. This does not establish a human dietary deficiency or immune-boosting dose.
nutrient_topic
L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
plain_language
Insufficient available alanine can slow protein production.
primary_references
T Cell Activation Depends on Extracellular Alanine. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31533027/ · DOI 10.1016/j.celrep.2019.08.034
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 104–110
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Primary mouse naive CD4/CD8 cells activated ex vivo; dialyzed-serum medium with alanine add-back. · source_derived_draft · unverified_draft
## alanine-t-cell-translation Insufficient available alanine can slow protein production. Alanine supplementation restored puromycin-measured active translation reduced in activated mouse T cells cultured with dialyzed serum. Model: Primary mouse naive CD4/CD8 cells activated ex vivo; dialyzed-serum medium with alanine add-back. Limitations: Dialysis removes multiple small nutrients; alanine rescue supports its contribution. This does not establish a human dietary deficiency or immune-boosting dose. Evidence access: Primary full text T Cell Activation Depends on Extracellular Alanine. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31533027/ · DOI 10.1016/j.celrep.2019.08.034
Complete structured claim and evidence
ATF4 protein increased after three hours of T-cell activation in dialyzed-serum medium and returned toward control with alanine supplementation.
L-Alanine → Mouse activating transcription factor 4 / Atf4 source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Primary mouse naive CD4/CD8 cells activated ex vivo; dialyzed-serum medium with alanine add-back.
limitations
ATF4 measurement supports a stress response; direct GCN2 necessity was not established in this experiment.
nutrient_topic
L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
plain_language
Amino-acid stress signaling responded when alanine was restored.
primary_references
T Cell Activation Depends on Extracellular Alanine. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31533027/ · DOI 10.1016/j.celrep.2019.08.034
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 112–118
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Primary mouse naive CD4/CD8 cells activated ex vivo; dialyzed-serum medium with alanine add-back. · source_derived_draft · unverified_draft
## alanine-t-cell-stress Amino-acid stress signaling responded when alanine was restored. ATF4 protein increased after three hours of T-cell activation in dialyzed-serum medium and returned toward control with alanine supplementation. Model: Primary mouse naive CD4/CD8 cells activated ex vivo; dialyzed-serum medium with alanine add-back. Limitations: ATF4 measurement supports a stress response; direct GCN2 necessity was not established in this experiment. Evidence access: Primary full text T Cell Activation Depends on Extracellular Alanine. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31533027/ · DOI 10.1016/j.celrep.2019.08.034
Complete structured claim and evidence
Alanine add-back restored IFN-gamma and TNF production suppressed during five-hour antigen restimulation of mouse memory CD8 T cells in dialyzed-serum medium.
L-Alanine → IFN-gamma and TNF output after mouse memory T-cell restimulation source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
P14/LCMV mouse model; day-30 memory splenocytes, GP33–41 peptide ex vivo.
limitations
Granzyme B was not similarly reduced; do not describe every immune function as alanine-dependent.
nutrient_topic
L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
plain_language
Memory cells needed available alanine to restart these cytokine responses.
primary_references
T Cell Activation Depends on Extracellular Alanine. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31533027/ · DOI 10.1016/j.celrep.2019.08.034
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 120–126
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · P14/LCMV mouse model; day-30 memory splenocytes, GP33–41 peptide ex vivo. · source_derived_draft · unverified_draft
## alanine-memory-cytokines Memory cells needed available alanine to restart these cytokine responses. Alanine add-back restored IFN-gamma and TNF production suppressed during five-hour antigen restimulation of mouse memory CD8 T cells in dialyzed-serum medium. Model: P14/LCMV mouse model; day-30 memory splenocytes, GP33–41 peptide ex vivo. Limitations: Granzyme B was not similarly reduced; do not describe every immune function as alanine-dependent. Evidence access: Primary full text T Cell Activation Depends on Extracellular Alanine. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31533027/ · DOI 10.1016/j.celrep.2019.08.034
Complete structured claim and evidence
Day-8 LCMV effector cells showed no significant reduction in granzyme B, IFN-gamma, TNF or Ki67 during the tested five-hour dialyzed-serum restimulation.
Low extracellular alanine during mouse effector-cell restimulation → Measured effector outputs in day-8 mouse CD8 T cells source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Mouse P14/LCMV effector phase; ex vivo peptide restimulation.
limitations
A five-hour null result does not establish independence at every duration or tissue.
nutrient_topic
L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
plain_language
Already-active cells did not show the same short-term dependence as resting memory cells.
primary_references
T Cell Activation Depends on Extracellular Alanine. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31533027/ · DOI 10.1016/j.celrep.2019.08.034
L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 128–134
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse P14/LCMV effector phase; ex vivo peptide restimulation. · source_derived_draft · unverified_draft
## alanine-effector-state-limit Already-active cells did not show the same short-term dependence as resting memory cells. Day-8 LCMV effector cells showed no significant reduction in granzyme B, IFN-gamma, TNF or Ki67 during the tested five-hour dialyzed-serum restimulation. Model: Mouse P14/LCMV effector phase; ex vivo peptide restimulation. Limitations: A five-hour null result does not establish independence at every duration or tissue. Evidence access: Primary full text T Cell Activation Depends on Extracellular Alanine. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31533027/ · DOI 10.1016/j.celrep.2019.08.034
Complete structured claim and evidence
Human pancreatic cancer-conditioned medium increased autophagic flux in human pancreatic stellate cells measured with tandem LC3 reporters.
Conditioned medium from human PDAC cells → Autophagic flux in human pancreatic stellate cells source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Human PSC and PDAC culture models; LC3 reporter measurements.
limitations
Conditioned medium contains multiple signals; the responsible secreted factor was not identified here. Correction record: Publisher erratum corrects the second image label in Fig. 3a to hPSC-LC3 + 8988T, matching Fig. 3b; production labeling correction, not a retraction or independent study. https://www.nature.com/articles/nature19851.pdf
nutrient_topic
L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
plain_language
Cancer cells can alter how neighboring cells recycle material.
primary_references
Pancreatic stellate cells support tumour metabolism through autophagic alanine secretion. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27509858/ · DOI 10.1038/nature19084
L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 136–142
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human PSC and PDAC culture models; LC3 reporter measurements. · source_derived_draft · unverified_draft
## alanine-pdac-autophagy Cancer cells can alter how neighboring cells recycle material. Human pancreatic cancer-conditioned medium increased autophagic flux in human pancreatic stellate cells measured with tandem LC3 reporters. Model: Human PSC and PDAC culture models; LC3 reporter measurements. Limitations: Conditioned medium contains multiple signals; the responsible secreted factor was not identified here. Correction record: Publisher erratum corrects the second image label in Fig. 3a to hPSC-LC3 + 8988T, matching Fig. 3b; production labeling correction, not a retraction or independent study. https://www.nature.com/articles/nature19851.pdf Evidence access: Primary full text Pancreatic stellate cells support tumour metabolism through autophagic alanine secretion. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27509858/ · DOI 10.1038/nature19084
Complete structured claim and evidence
ATG5 knockdown in human pancreatic stellate cells reduced alanine concentrations in their conditioned medium.
Human ATG5 → Alanine secretion from human pancreatic stellate 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 PSC shRNA experiments; serum-free conditioned medium.
limitations
Knockdown is machinery impairment, not low dietary alanine; residual secretion and other autophagy effects remain. Correction record: Publisher erratum corrects the second image label in Fig. 3a to hPSC-LC3 + 8988T, matching Fig. 3b; production labeling correction, not a retraction or independent study. https://www.nature.com/articles/nature19851.pdf
nutrient_topic
L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
plain_language
Disrupting one part of autophagy reduced alanine supplied by neighboring cells.
primary_references
Pancreatic stellate cells support tumour metabolism through autophagic alanine secretion. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27509858/ · DOI 10.1038/nature19084
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 144–150
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human PSC shRNA experiments; serum-free conditioned medium. · source_derived_draft · unverified_draft
## alanine-psc-atg5 Disrupting one part of autophagy reduced alanine supplied by neighboring cells. ATG5 knockdown in human pancreatic stellate cells reduced alanine concentrations in their conditioned medium. Model: Human PSC shRNA experiments; serum-free conditioned medium. Limitations: Knockdown is machinery impairment, not low dietary alanine; residual secretion and other autophagy effects remain. Correction record: Publisher erratum corrects the second image label in Fig. 3a to hPSC-LC3 + 8988T, matching Fig. 3b; production labeling correction, not a retraction or independent study. https://www.nature.com/articles/nature19851.pdf Evidence access: Primary full text Pancreatic stellate cells support tumour metabolism through autophagic alanine secretion. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27509858/ · DOI 10.1038/nature19084
Complete structured claim and evidence
ATG7 knockdown in human pancreatic stellate cells reduced alanine secretion and reduced the ability of their conditioned medium to support PDAC oxygen consumption; alanine add-back rescued the metabolic response.
Autophagy related 7 / ATG7 → Alanine secretion from human pancreatic stellate 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 PSC/PDAC cultures; shRNA and 1 mM alanine rescue.
limitations
Autophagy releases other products too; this is not proof that alanine is the only stromal contribution. Correction record: Publisher erratum corrects the second image label in Fig. 3a to hPSC-LC3 + 8988T, matching Fig. 3b; production labeling correction, not a retraction or independent study. https://www.nature.com/articles/nature19851.pdf
nutrient_topic
L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
plain_language
The add-back experiment connects stromal recycling to a usable fuel.
primary_references
Pancreatic stellate cells support tumour metabolism through autophagic alanine secretion. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27509858/ · DOI 10.1038/nature19084
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 152–158
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human PSC/PDAC cultures; shRNA and 1 mM alanine rescue. · source_derived_draft · unverified_draft
## alanine-psc-atg7 The add-back experiment connects stromal recycling to a usable fuel. ATG7 knockdown in human pancreatic stellate cells reduced alanine secretion and reduced the ability of their conditioned medium to support PDAC oxygen consumption; alanine add-back rescued the metabolic response. Model: Human PSC/PDAC cultures; shRNA and 1 mM alanine rescue. Limitations: Autophagy releases other products too; this is not proof that alanine is the only stromal contribution. Correction record: Publisher erratum corrects the second image label in Fig. 3a to hPSC-LC3 + 8988T, matching Fig. 3b; production labeling correction, not a retraction or independent study. https://www.nature.com/articles/nature19851.pdf Evidence access: Primary full text Pancreatic stellate cells support tumour metabolism through autophagic alanine secretion. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27509858/ · DOI 10.1038/nature19084
Complete structured claim and evidence
Isotope tracing showed alanine carbon entering TCA intermediates, nonessential amino acids and lipid synthesis in the tested human PDAC cells.
L-Alanine → Alanine carbon use in human pancreatic cancer cells source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Human pancreatic cancer cultures with labeled alanine.
limitations
Tumor-cell utilization is not evidence that dietary alanine initiates cancer. Correction record: Publisher erratum corrects the second image label in Fig. 3a to hPSC-LC3 + 8988T, matching Fig. 3b; production labeling correction, not a retraction or independent study. https://www.nature.com/articles/nature19851.pdf
nutrient_topic
L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
plain_language
The same amino acid can supply building material and mitochondrial fuel.
primary_references
Pancreatic stellate cells support tumour metabolism through autophagic alanine secretion. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27509858/ · DOI 10.1038/nature19084
L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 160–166
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human pancreatic cancer cultures with labeled alanine. · source_derived_draft · unverified_draft
## alanine-pdac-carbon The same amino acid can supply building material and mitochondrial fuel. Isotope tracing showed alanine carbon entering TCA intermediates, nonessential amino acids and lipid synthesis in the tested human PDAC cells. Model: Human pancreatic cancer cultures with labeled alanine. Limitations: Tumor-cell utilization is not evidence that dietary alanine initiates cancer. Correction record: Publisher erratum corrects the second image label in Fig. 3a to hPSC-LC3 + 8988T, matching Fig. 3b; production labeling correction, not a retraction or independent study. https://www.nature.com/articles/nature19851.pdf Evidence access: Primary full text Pancreatic stellate cells support tumour metabolism through autophagic alanine secretion. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27509858/ · DOI 10.1038/nature19084
Complete structured claim and evidence
Adding 1 mM alanine or pyruvate rescued proliferation under 0.5 mM glucose in the tested human PDAC cultures, while 1 mM lactate did not reproduce that rescue.
L-Alanine → Growth of human PDAC cells under low glucose source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
8988T, Tu8902 and MiaPaCa2 cell experiments.
limitations
Culture rescue does not establish safe dietary restriction or supplementation strategies. Correction record: Publisher erratum corrects the second image label in Fig. 3a to hPSC-LC3 + 8988T, matching Fig. 3b; production labeling correction, not a retraction or independent study. https://www.nature.com/articles/nature19851.pdf
nutrient_topic
L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
plain_language
Different carbon sources were not interchangeable in the nutrient-limited culture.
primary_references
Pancreatic stellate cells support tumour metabolism through autophagic alanine secretion. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27509858/ · DOI 10.1038/nature19084
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 168–174
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · 8988T, Tu8902 and MiaPaCa2 cell experiments. · source_derived_draft · unverified_draft
## alanine-pdac-glucose-rescue Different carbon sources were not interchangeable in the nutrient-limited culture. Adding 1 mM alanine or pyruvate rescued proliferation under 0.5 mM glucose in the tested human PDAC cultures, while 1 mM lactate did not reproduce that rescue. Model: 8988T, Tu8902 and MiaPaCa2 cell experiments. Limitations: Culture rescue does not establish safe dietary restriction or supplementation strategies. Correction record: Publisher erratum corrects the second image label in Fig. 3a to hPSC-LC3 + 8988T, matching Fig. 3b; production labeling correction, not a retraction or independent study. https://www.nature.com/articles/nature19851.pdf Evidence access: Primary full text Pancreatic stellate cells support tumour metabolism through autophagic alanine secretion. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27509858/ · DOI 10.1038/nature19084
Complete structured claim and evidence
SLC1A4 perturbation and isotope-flux studies supported a role for SLC1A4, alongside other transporters, in rapid alanine exchange by human pancreatic stellate cells.
Human neutral amino acid exchanger ASCT1 / SLC1A4 → Alanine secretion from human pancreatic stellate cells source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Human PSC transporter and flux experiments.
limitations
SLC1A4 was not the sole alanine exporter and exchange is not equivalent to an irreversible one-way pump.
nutrient_topic
L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
plain_language
An exchanger helps neighboring cells share alanine.
primary_references
Selective Alanine Transporter Utilization Creates a Targetable Metabolic Niche in Pancreatic Cancer. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32341021/ · DOI 10.1158/2159-8290.CD-19-0959
L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 176–182
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human PSC transporter and flux experiments. · source_derived_draft · unverified_draft
## alanine-psc-exchanger An exchanger helps neighboring cells share alanine. SLC1A4 perturbation and isotope-flux studies supported a role for SLC1A4, alongside other transporters, in rapid alanine exchange by human pancreatic stellate cells. Model: Human PSC transporter and flux experiments. Limitations: SLC1A4 was not the sole alanine exporter and exchange is not equivalent to an irreversible one-way pump. Evidence access: Primary full text Selective Alanine Transporter Utilization Creates a Targetable Metabolic Niche in Pancreatic Cancer. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32341021/ · DOI 10.1158/2159-8290.CD-19-0959
Complete structured claim and evidence
Loss of SLC38A2 prevented human PDAC cells from effectively taking up and concentrating environmental alanine.
Human sodium-coupled neutral amino acid transporter 2 / SLC38A2 → Intracellular alanine concentration in human 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
Human PDAC genetic transporter perturbation and stable-isotope flux assays.
limitations
Tissue-specific transporter dependence; not every cell uses SLC38A2 as its dominant route.
nutrient_topic
L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
plain_language
An intact uptake system can be as important as having alanine outside the cell.
primary_references
Selective Alanine Transporter Utilization Creates a Targetable Metabolic Niche in Pancreatic Cancer. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32341021/ · DOI 10.1158/2159-8290.CD-19-0959
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 184–190
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human PDAC genetic transporter perturbation and stable-isotope flux assays. · source_derived_draft · unverified_draft
## alanine-pdac-snat2 An intact uptake system can be as important as having alanine outside the cell. Loss of SLC38A2 prevented human PDAC cells from effectively taking up and concentrating environmental alanine. Model: Human PDAC genetic transporter perturbation and stable-isotope flux assays. Limitations: Tissue-specific transporter dependence; not every cell uses SLC38A2 as its dominant route. Evidence access: Primary full text Selective Alanine Transporter Utilization Creates a Targetable Metabolic Niche in Pancreatic Cancer. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32341021/ · DOI 10.1158/2159-8290.CD-19-0959
Complete structured claim and evidence
SLC38A2-deficient PDAC cells increased de novo alanine synthesis and passive efflux, diverting mitochondrial pyruvate and amino-nitrogen sources toward alanine production.
SLC38A2 loss in human PDAC cells → De novo alanine synthesis in human 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
Human PDAC flux and compartmental metabolism experiments.
limitations
Reported metabolic crisis is not a universal consequence of reduced dietary alanine.
nutrient_topic
L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
plain_language
Losing uptake can force a cell to spend other nutrients making the missing amino acid.
primary_references
Selective Alanine Transporter Utilization Creates a Targetable Metabolic Niche in Pancreatic Cancer. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32341021/ · DOI 10.1158/2159-8290.CD-19-0959
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 192–198
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human PDAC flux and compartmental metabolism experiments. · source_derived_draft · unverified_draft
## alanine-pdac-snat2-carbon-cost Losing uptake can force a cell to spend other nutrients making the missing amino acid. SLC38A2-deficient PDAC cells increased de novo alanine synthesis and passive efflux, diverting mitochondrial pyruvate and amino-nitrogen sources toward alanine production. Model: Human PDAC flux and compartmental metabolism experiments. Limitations: Reported metabolic crisis is not a universal consequence of reduced dietary alanine. Evidence access: Primary full text Selective Alanine Transporter Utilization Creates a Targetable Metabolic Niche in Pancreatic Cancer. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32341021/ · DOI 10.1158/2159-8290.CD-19-0959
Complete structured claim and evidence
UK-5099 inhibition of mitochondrial pyruvate transport reduced alanine synthesis/secretion and increased uptake of extracellular alanine; alanine supplementation restored intracellular levels.
Mitochondrial pyruvate carrier inhibition in human PDAC → L-Alanine source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Human PDAC cultures; MPC inhibitor and isotope tracing.
limitations
A pharmacological perturbation is not evidence that usual alanine intake bypasses every mitochondrial defect.
nutrient_topic
L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
plain_language
When pyruvate cannot reach the synthesis compartment, imported alanine becomes more important.
primary_references
Selective Alanine Transporter Utilization Creates a Targetable Metabolic Niche in Pancreatic Cancer. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32341021/ · DOI 10.1158/2159-8290.CD-19-0959
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 200–206
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human PDAC cultures; MPC inhibitor and isotope tracing. · source_derived_draft · unverified_draft
## alanine-pdac-mpc When pyruvate cannot reach the synthesis compartment, imported alanine becomes more important. UK-5099 inhibition of mitochondrial pyruvate transport reduced alanine synthesis/secretion and increased uptake of extracellular alanine; alanine supplementation restored intracellular levels. Model: Human PDAC cultures; MPC inhibitor and isotope tracing. Limitations: A pharmacological perturbation is not evidence that usual alanine intake bypasses every mitochondrial defect. Evidence access: Primary full text Selective Alanine Transporter Utilization Creates a Targetable Metabolic Niche in Pancreatic Cancer. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32341021/ · DOI 10.1158/2159-8290.CD-19-0959
Complete structured claim and evidence
Genetic SLC38A2 suppression impaired human PDAC tumor growth and the support provided by co-injected stellate cells in mouse xenograft experiments.
SLC38A2 loss in human PDAC cells → Human PDAC xenograft growth in mice source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Human PDAC cells in immunodeficient mice; transporter perturbation.
limitations
Preclinical tumor dependency, not clinical efficacy or proof that alanine restriction is beneficial.
nutrient_topic
L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
plain_language
A local nutrient-import dependency persisted in the animal tumor model.
primary_references
Selective Alanine Transporter Utilization Creates a Targetable Metabolic Niche in Pancreatic Cancer. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32341021/ · DOI 10.1158/2159-8290.CD-19-0959
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 208–214
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human PDAC cells in immunodeficient mice; transporter perturbation. · source_derived_draft · unverified_draft
## alanine-pdac-tumor-transporter A local nutrient-import dependency persisted in the animal tumor model. Genetic SLC38A2 suppression impaired human PDAC tumor growth and the support provided by co-injected stellate cells in mouse xenograft experiments. Model: Human PDAC cells in immunodeficient mice; transporter perturbation. Limitations: Preclinical tumor dependency, not clinical efficacy or proof that alanine restriction is beneficial. Evidence access: Primary full text Selective Alanine Transporter Utilization Creates a Targetable Metabolic Niche in Pancreatic Cancer. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32341021/ · DOI 10.1158/2159-8290.CD-19-0959
Complete structured claim and evidence
Hepatocyte-specific Gpt2 deletion reduced labeled alanine contribution to glucose production in mouse hepatocyte experiments.
Mouse mitochondrial alanine aminotransferase / Gpt2 → Mouse hepatic glucose production from alanine source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Mouse liver Gpt2 genetic deletion; isotope tracing.
limitations
Does not mean GPT2 is the only route; lean knockout animals did not develop a general failure of glucose control. Correction record: Published correction adds the originally omitted disclosure that B.N.F. was a scientific advisory board member and stockholder of Cirius Therapeutics, which develops MPC inhibitors. Disclosure correction, not a data retraction. https://pmc.ncbi.nlm.nih.gov/articles/PMC9713851/
nutrient_topic
L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
plain_language
Mitochondrial transamination can feed alanine carbon into glucose.
primary_references
Silencing alanine transaminase 2 in diabetic liver attenuates hyperglycemia by reducing gluconeogenesis from amino acids. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35476997/ · DOI 10.1016/j.celrep.2022.110733
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 216–222
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse liver Gpt2 genetic deletion; isotope tracing. · source_derived_draft · unverified_draft
## alanine-liver-gpt2-flux Mitochondrial transamination can feed alanine carbon into glucose. Hepatocyte-specific Gpt2 deletion reduced labeled alanine contribution to glucose production in mouse hepatocyte experiments. Model: Mouse liver Gpt2 genetic deletion; isotope tracing. Limitations: Does not mean GPT2 is the only route; lean knockout animals did not develop a general failure of glucose control. Correction record: Published correction adds the originally omitted disclosure that B.N.F. was a scientific advisory board member and stockholder of Cirius Therapeutics, which develops MPC inhibitors. Disclosure correction, not a data retraction. https://pmc.ncbi.nlm.nih.gov/articles/PMC9713851/ Evidence access: Primary full text Silencing alanine transaminase 2 in diabetic liver attenuates hyperglycemia by reducing gluconeogenesis from amino acids. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35476997/ · DOI 10.1016/j.celrep.2022.110733
Complete structured claim and evidence
The study linked ATF4-dependent stress signaling to increased hepatic Gpt2 expression in the examined mouse ER-stress and obesity settings.
Mouse activating transcription factor 4 / Atf4 → Mouse mitochondrial alanine aminotransferase / Gpt2 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Mouse hepatocyte/liver interventions and expression assays.
limitations
Expression regulation is context-specific and does not establish a human supplementation response. Correction record: Published correction adds the originally omitted disclosure that B.N.F. was a scientific advisory board member and stockholder of Cirius Therapeutics, which develops MPC inhibitors. Disclosure correction, not a data retraction. https://pmc.ncbi.nlm.nih.gov/articles/PMC9713851/
nutrient_topic
L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
plain_language
Stress can change how much alanine-processing enzyme a liver expresses.
primary_references
Silencing alanine transaminase 2 in diabetic liver attenuates hyperglycemia by reducing gluconeogenesis from amino acids. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35476997/ · DOI 10.1016/j.celrep.2022.110733
L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 224–230
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse hepatocyte/liver interventions and expression assays. · source_derived_draft · unverified_draft
## alanine-liver-atf4 Stress can change how much alanine-processing enzyme a liver expresses. The study linked ATF4-dependent stress signaling to increased hepatic Gpt2 expression in the examined mouse ER-stress and obesity settings. Model: Mouse hepatocyte/liver interventions and expression assays. Limitations: Expression regulation is context-specific and does not establish a human supplementation response. Correction record: Published correction adds the originally omitted disclosure that B.N.F. was a scientific advisory board member and stockholder of Cirius Therapeutics, which develops MPC inhibitors. Disclosure correction, not a data retraction. https://pmc.ncbi.nlm.nih.gov/articles/PMC9713851/ Evidence access: Primary full text Silencing alanine transaminase 2 in diabetic liver attenuates hyperglycemia by reducing gluconeogenesis from amino acids. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35476997/ · DOI 10.1016/j.celrep.2022.110733
Complete structured claim and evidence
Hepatic Gpt2 suppression improved hyperglycemia in db/db mice, whereas liver-specific loss in lean mice did not similarly alter ordinary blood glucose.
Hepatic Gpt2 suppression in mice → Hyperglycemia in db/db mice source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Diabetic and lean mouse genetic experiments.
limitations
Not a demonstrated human diabetes treatment; compensatory pathways remain. Correction record: Published correction adds the originally omitted disclosure that B.N.F. was a scientific advisory board member and stockholder of Cirius Therapeutics, which develops MPC inhibitors. Disclosure correction, not a data retraction. https://pmc.ncbi.nlm.nih.gov/articles/PMC9713851/
nutrient_topic
L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
plain_language
The consequence of blocking one pathway depended on metabolic state.
primary_references
Silencing alanine transaminase 2 in diabetic liver attenuates hyperglycemia by reducing gluconeogenesis from amino acids. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35476997/ · DOI 10.1016/j.celrep.2022.110733
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 232–238
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Diabetic and lean mouse genetic experiments. · source_derived_draft · unverified_draft
## alanine-liver-diabetes-context The consequence of blocking one pathway depended on metabolic state. Hepatic Gpt2 suppression improved hyperglycemia in db/db mice, whereas liver-specific loss in lean mice did not similarly alter ordinary blood glucose. Model: Diabetic and lean mouse genetic experiments. Limitations: Not a demonstrated human diabetes treatment; compensatory pathways remain. Correction record: Published correction adds the originally omitted disclosure that B.N.F. was a scientific advisory board member and stockholder of Cirius Therapeutics, which develops MPC inhibitors. Disclosure correction, not a data retraction. https://pmc.ncbi.nlm.nih.gov/articles/PMC9713851/ Evidence access: Primary full text Silencing alanine transaminase 2 in diabetic liver attenuates hyperglycemia by reducing gluconeogenesis from amino acids. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35476997/ · DOI 10.1016/j.celrep.2022.110733
Complete structured claim and evidence
Human hepatic GPT2 mRNA decreased after bariatric surgery in the study samples.
Bariatric surgery-associated weight loss → Human mitochondrial alanine aminotransferase / GPT2 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Human liver expression measurements before/after surgical weight loss.
limitations
Multiple metabolic changes accompany surgery; this is not an alanine intervention. Correction record: Published correction adds the originally omitted disclosure that B.N.F. was a scientific advisory board member and stockholder of Cirius Therapeutics, which develops MPC inhibitors. Disclosure correction, not a data retraction. https://pmc.ncbi.nlm.nih.gov/articles/PMC9713851/
nutrient_topic
L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
plain_language
A human association complements the mouse mechanism but does not establish the same cause.
primary_references
Silencing alanine transaminase 2 in diabetic liver attenuates hyperglycemia by reducing gluconeogenesis from amino acids. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35476997/ · DOI 10.1016/j.celrep.2022.110733
L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 240–246
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human liver expression measurements before/after surgical weight loss. · source_derived_draft · unverified_draft
## alanine-human-bariatric-expression A human association complements the mouse mechanism but does not establish the same cause. Human hepatic GPT2 mRNA decreased after bariatric surgery in the study samples. Model: Human liver expression measurements before/after surgical weight loss. Limitations: Multiple metabolic changes accompany surgery; this is not an alanine intervention. Correction record: Published correction adds the originally omitted disclosure that B.N.F. was a scientific advisory board member and stockholder of Cirius Therapeutics, which develops MPC inhibitors. Disclosure correction, not a data retraction. https://pmc.ncbi.nlm.nih.gov/articles/PMC9713851/ Evidence access: Primary full text Silencing alanine transaminase 2 in diabetic liver attenuates hyperglycemia by reducing gluconeogenesis from amino acids. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35476997/ · DOI 10.1016/j.celrep.2022.110733
Complete structured claim and evidence
Acute alanine treatment increased AMPK and downstream ACC phosphorylation in rat H4IIE liver cells over the tested 0.25–10 mM range.
L-Alanine → Rat AMP-activated protein kinase complex source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Rat H4IIE cells; acute millimolar alanine exposure.
limitations
Phosphorylation in culture is not proof of clinical benefit or a universal response to dietary alanine.
nutrient_topic
L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
plain_language
Alanine metabolism can generate an energy-stress signal in this experimental setting.
primary_references
l-Alanine activates hepatic AMP-activated protein kinase and modulates systemic glucose metabolism. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30190193/ · DOI 10.1016/j.molmet.2018.08.002
L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 248–254
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat H4IIE cells; acute millimolar alanine exposure. · source_derived_draft · unverified_draft
## alanine-ampk-acute Alanine metabolism can generate an energy-stress signal in this experimental setting. Acute alanine treatment increased AMPK and downstream ACC phosphorylation in rat H4IIE liver cells over the tested 0.25–10 mM range. Model: Rat H4IIE cells; acute millimolar alanine exposure. Limitations: Phosphorylation in culture is not proof of clinical benefit or a universal response to dietary alanine. Evidence access: Primary full text l-Alanine activates hepatic AMP-activated protein kinase and modulates systemic glucose metabolism. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30190193/ · DOI 10.1016/j.molmet.2018.08.002
Complete structured claim and evidence
ALT1 siRNA reduced rat H4IIE ALT protein by about 77% and reduced alanine-stimulated AMPK activation by about 49%.
Rat cytosolic alanine aminotransferase / Gpt → Rat AMP-activated protein kinase complex source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Rat H4IIE cells; siRNA knockdown with alanine challenge.
limitations
Partial knockdown and partial attenuation do not prove ALT1 is the only contributing pathway.
nutrient_topic
L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
plain_language
The response partly depended on processing alanine, rather than simply sensing it outside the cell.
primary_references
l-Alanine activates hepatic AMP-activated protein kinase and modulates systemic glucose metabolism. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30190193/ · DOI 10.1016/j.molmet.2018.08.002
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 256–262
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat H4IIE cells; siRNA knockdown with alanine challenge. · source_derived_draft · unverified_draft
## alanine-ampk-alt1-dependence The response partly depended on processing alanine, rather than simply sensing it outside the cell. ALT1 siRNA reduced rat H4IIE ALT protein by about 77% and reduced alanine-stimulated AMPK activation by about 49%. Model: Rat H4IIE cells; siRNA knockdown with alanine challenge. Limitations: Partial knockdown and partial attenuation do not prove ALT1 is the only contributing pathway. Evidence access: Primary full text l-Alanine activates hepatic AMP-activated protein kinase and modulates systemic glucose metabolism. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30190193/ · DOI 10.1016/j.molmet.2018.08.002
Complete structured claim and evidence
Alanine increased the AMP/ATP ratio and glutamate while decreasing 2-oxoglutarate and other TCA intermediate pools in rat H4IIE cells.
L-Alanine → AMP/ATP ratio in rat H4IIE cells source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Acute rat H4IIE metabolomics; AMP/ATP approximately 1.5-fold higher at 15 minutes.
limitations
Pool sizes are not flux measurements; increased ATP-consuming urea synthesis was proposed rather than directly proven.
nutrient_topic
L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
plain_language
Moving amino nitrogen changed the cell’s carbon pools and energy balance.
primary_references
l-Alanine activates hepatic AMP-activated protein kinase and modulates systemic glucose metabolism. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30190193/ · DOI 10.1016/j.molmet.2018.08.002
L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 264–270
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Acute rat H4IIE metabolomics; AMP/ATP approximately 1.5-fold higher at 15 minutes. · source_derived_draft · unverified_draft
## alanine-ampk-pools Moving amino nitrogen changed the cell’s carbon pools and energy balance. Alanine increased the AMP/ATP ratio and glutamate while decreasing 2-oxoglutarate and other TCA intermediate pools in rat H4IIE cells. Model: Acute rat H4IIE metabolomics; AMP/ATP approximately 1.5-fold higher at 15 minutes. Limitations: Pool sizes are not flux measurements; increased ATP-consuming urea synthesis was proposed rather than directly proven. Evidence access: Primary full text l-Alanine activates hepatic AMP-activated protein kinase and modulates systemic glucose metabolism. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30190193/ · DOI 10.1016/j.molmet.2018.08.002
Complete structured claim and evidence
Pyruvate or TCA-intermediate supplementation restored ATP and attenuated alanine-induced AMPK phosphorylation in the tested liver-cell experiments.
Pyruvate → Rat AMP-activated protein kinase complex source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Rat H4IIE nutrient-addition experiments.
limitations
A biochemical rescue does not establish a supplement combination for humans.
nutrient_topic
L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
plain_language
Providing usable carbon changed the signaling response to alanine.
primary_references
l-Alanine activates hepatic AMP-activated protein kinase and modulates systemic glucose metabolism. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30190193/ · DOI 10.1016/j.molmet.2018.08.002
L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 272–278
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat H4IIE nutrient-addition experiments. · source_derived_draft · unverified_draft
## alanine-ampk-carbon-rescue Providing usable carbon changed the signaling response to alanine. Pyruvate or TCA-intermediate supplementation restored ATP and attenuated alanine-induced AMPK phosphorylation in the tested liver-cell experiments. Model: Rat H4IIE nutrient-addition experiments. Limitations: A biochemical rescue does not establish a supplement combination for humans. Evidence access: Primary full text l-Alanine activates hepatic AMP-activated protein kinase and modulates systemic glucose metabolism. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30190193/ · DOI 10.1016/j.molmet.2018.08.002
Complete structured claim and evidence
Ammonium chloride exposure reproduced increases in AMP/ATP and AMPK/ACC phosphorylation, and pyruvate attenuated these responses.
Ammonium chloride → Rat AMP-activated protein kinase complex source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Rat H4IIE experiments; 2–5 mM ammonium chloride comparison.
limitations
Mimicry is not proof that ammonia is the sole mediator of alanine effects or that urea-cycle ATP use accounts for them.
nutrient_topic
L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
plain_language
A nitrogen-handling byproduct may contribute to the energy signal.
primary_references
l-Alanine activates hepatic AMP-activated protein kinase and modulates systemic glucose metabolism. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30190193/ · DOI 10.1016/j.molmet.2018.08.002
L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 280–286
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat H4IIE experiments; 2–5 mM ammonium chloride comparison. · source_derived_draft · unverified_draft
## alanine-ampk-ammonia A nitrogen-handling byproduct may contribute to the energy signal. Ammonium chloride exposure reproduced increases in AMP/ATP and AMPK/ACC phosphorylation, and pyruvate attenuated these responses. Model: Rat H4IIE experiments; 2–5 mM ammonium chloride comparison. Limitations: Mimicry is not proof that ammonia is the sole mediator of alanine effects or that urea-cycle ATP use accounts for them. Evidence access: Primary full text l-Alanine activates hepatic AMP-activated protein kinase and modulates systemic glucose metabolism. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30190193/ · DOI 10.1016/j.molmet.2018.08.002
Complete structured claim and evidence
Acute oral alanine at roughly 1–1.5 g/kg improved glucose tolerance in the studied chow- and high-fat-fed mice; reduced AMPK activity attenuated efficacy in the tested model.
L-Alanine → Glucose tolerance after alanine gavage in mice source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Mouse acute gavage and glucose-tolerance experiments.
limitations
High animal exposure; hepatic AMPK was not established as the sole cause, and human oral efficacy was not tested.
nutrient_topic
L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
plain_language
Whole-body glucose responses can differ from the simple prediction that a glucose precursor must raise glucose.
primary_references
l-Alanine activates hepatic AMP-activated protein kinase and modulates systemic glucose metabolism. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30190193/ · DOI 10.1016/j.molmet.2018.08.002
L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 288–294
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse acute gavage and glucose-tolerance experiments. · source_derived_draft · unverified_draft
## alanine-ampk-mouse-glucose Whole-body glucose responses can differ from the simple prediction that a glucose precursor must raise glucose. Acute oral alanine at roughly 1–1.5 g/kg improved glucose tolerance in the studied chow- and high-fat-fed mice; reduced AMPK activity attenuated efficacy in the tested model. Model: Mouse acute gavage and glucose-tolerance experiments. Limitations: High animal exposure; hepatic AMPK was not established as the sole cause, and human oral efficacy was not tested. Evidence access: Primary full text l-Alanine activates hepatic AMP-activated protein kinase and modulates systemic glucose metabolism. · 2018 · https://pubmed.ncbi.nlm.nih.gov/30190193/ · DOI 10.1016/j.molmet.2018.08.002
Complete structured claim and evidence
The human GPT2 p.Arg404* and p.Pro272Leu variants were biochemically loss-of-function in kindreds with developmental disability, postnatal microcephaly and frequent progressive motor symptoms.
Human recessive GPT2 loss-of-function variants → Human mitochondrial alanine aminotransferase / GPT2 source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Human families plus biochemical variant assays; accompanying mouse metabolic experiments.
limitations
Clinical association and enzyme loss do not establish that low dietary alanine caused the phenotype or that supplementation treats it.
nutrient_topic
L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
plain_language
A genetic defect in alanine-related metabolism can affect brain growth and movement.
primary_references
Mutations in mitochondrial enzyme GPT2 cause metabolic dysfunction and neurological disease with developmental and progressive features. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27601654/ · DOI 10.1073/pnas.1609221113
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 296–302
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human families plus biochemical variant assays; accompanying mouse metabolic experiments. · source_derived_draft · unverified_draft
## alanine-human-gpt2-variants A genetic defect in alanine-related metabolism can affect brain growth and movement. The human GPT2 p.Arg404* and p.Pro272Leu variants were biochemically loss-of-function in kindreds with developmental disability, postnatal microcephaly and frequent progressive motor symptoms. Model: Human families plus biochemical variant assays; accompanying mouse metabolic experiments. Limitations: Clinical association and enzyme loss do not establish that low dietary alanine caused the phenotype or that supplementation treats it. Evidence access: Primary abstract Mutations in mitochondrial enzyme GPT2 cause metabolic dysfunction and neurological disease with developmental and progressive features. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27601654/ · DOI 10.1073/pnas.1609221113
Complete structured claim and evidence
Neuron-specific Gpt2 deletion impaired alanine synthesis and metabolic replenishment and reproduced severe motor abnormalities and pre-weaning mortality.
Mouse mitochondrial alanine aminotransferase / Gpt2 → Alanine synthesis and TCA replenishment in mouse neurons source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Mouse neuron-specific deletion and metabolomic experiments.
limitations
The phenotype is not an ordinary dietary alanine deficiency.
nutrient_topic
L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
plain_language
Neurons require functioning synthesis machinery as well as available carbon and nitrogen.
primary_references
Mitochondrial enzyme GPT2 regulates metabolic mechanisms required for neuron growth and motor function in vivo. · 2022 · https://pubmed.ncbi.nlm.nih.gov/34519342/ · DOI 10.1093/hmg/ddab269
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 304–310
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse neuron-specific deletion and metabolomic experiments. · source_derived_draft · unverified_draft
## alanine-neuron-gpt2 Neurons require functioning synthesis machinery as well as available carbon and nitrogen. Neuron-specific Gpt2 deletion impaired alanine synthesis and metabolic replenishment and reproduced severe motor abnormalities and pre-weaning mortality. Model: Mouse neuron-specific deletion and metabolomic experiments. Limitations: The phenotype is not an ordinary dietary alanine deficiency. Evidence access: Primary abstract Mitochondrial enzyme GPT2 regulates metabolic mechanisms required for neuron growth and motor function in vivo. · 2022 · https://pubmed.ncbi.nlm.nih.gov/34519342/ · DOI 10.1093/hmg/ddab269
Complete structured claim and evidence
Exogenous alanine was necessary for survival of Gpt2-null neurons in culture, while Gpt2-null astrocytes did not show the same requirement.
L-Alanine → Survival of Gpt2-null mouse neurons source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Mouse neuron and astrocyte cultures with Gpt2 loss.
limitations
Culture survival rescue is not proof of full neurological recovery.
nutrient_topic
L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
plain_language
Different brain cell types had different needs after the same enzyme loss.
primary_references
Mitochondrial enzyme GPT2 regulates metabolic mechanisms required for neuron growth and motor function in vivo. · 2022 · https://pubmed.ncbi.nlm.nih.gov/34519342/ · DOI 10.1093/hmg/ddab269
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 312–318
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse neuron and astrocyte cultures with Gpt2 loss. · source_derived_draft · unverified_draft
## alanine-neuron-alanine-rescue Different brain cell types had different needs after the same enzyme loss. Exogenous alanine was necessary for survival of Gpt2-null neurons in culture, while Gpt2-null astrocytes did not show the same requirement. Model: Mouse neuron and astrocyte cultures with Gpt2 loss. Limitations: Culture survival rescue is not proof of full neurological recovery. Evidence access: Primary abstract Mitochondrial enzyme GPT2 regulates metabolic mechanisms required for neuron growth and motor function in vivo. · 2022 · https://pubmed.ncbi.nlm.nih.gov/34519342/ · DOI 10.1093/hmg/ddab269
Complete structured claim and evidence
Dietary alanine supplementation improved survival and brain metabolic profiles in Gpt2-null mice but did not alone appear to correct motor function.
L-Alanine → Survival and motor outcomes in Gpt2-null mice source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Gpt2-null mouse dietary intervention.
limitations
No validated human treatment or dose follows; survival and motor outcomes are separate.
nutrient_topic
L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
plain_language
Restoring a metabolite helped some outcomes while leaving major problems unresolved.
primary_references
Mitochondrial enzyme GPT2 regulates metabolic mechanisms required for neuron growth and motor function in vivo. · 2022 · https://pubmed.ncbi.nlm.nih.gov/34519342/ · DOI 10.1093/hmg/ddab269
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 320–326
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Gpt2-null mouse dietary intervention. · source_derived_draft · unverified_draft
## alanine-neuron-diet-limits Restoring a metabolite helped some outcomes while leaving major problems unresolved. Dietary alanine supplementation improved survival and brain metabolic profiles in Gpt2-null mice but did not alone appear to correct motor function. Model: Gpt2-null mouse dietary intervention. Limitations: No validated human treatment or dose follows; survival and motor outcomes are separate. Evidence access: Primary abstract Mitochondrial enzyme GPT2 regulates metabolic mechanisms required for neuron growth and motor function in vivo. · 2022 · https://pubmed.ncbi.nlm.nih.gov/34519342/ · DOI 10.1093/hmg/ddab269
Complete structured claim and evidence
Intravenous alanine significantly increased insulin secretion compared with saline in the study of 12 healthy men.
L-Alanine → Insulin response to intravenous alanine source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Double-blind randomized crossover in 12 healthy men; equimolar IV amino-acid boluses on separate days after an overnight fast.
limitations
IV exposure bypasses intestinal handling; no equivalent oral supplement effect is demonstrated.
nutrient_topic
L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
plain_language
An alanine bolus can trigger insulin in humans.
primary_references
Intravenous Arginine Stimulates Glucagon Secretion More Than Equimolar Alanine, Leucine, Glutamine, and Proline in Humans. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40980546/ · DOI 10.1210/jendso/bvaf139
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Double-blind randomized crossover in 12 healthy men; equimolar IV amino-acid boluses on separate days after an overnight fast. · source_derived_draft · unverified_draft
## alanine-human-insulin An alanine bolus can trigger insulin in humans. Intravenous alanine significantly increased insulin secretion compared with saline in the study of 12 healthy men. Model: Double-blind randomized crossover in 12 healthy men; equimolar IV amino-acid boluses on separate days after an overnight fast. Limitations: IV exposure bypasses intestinal handling; no equivalent oral supplement effect is demonstrated. Evidence access: Primary full text Intravenous Arginine Stimulates Glucagon Secretion More Than Equimolar Alanine, Leucine, Glutamine, and Proline in Humans. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40980546/ · DOI 10.1210/jendso/bvaf139
Complete structured claim and evidence
Intravenous alanine produced a minor increase in peak glucagon, whereas arginine was the strongest tested stimulus and significantly increased both peak and 30-minute incremental area.
L-Alanine → Glucagon response to intravenous alanine source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Double-blind randomized crossover in 12 healthy men; equimolar IV amino-acid boluses on separate days after an overnight fast.
limitations
A peak response is not equivalent to a significant integrated response; small male-only study.
nutrient_topic
L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
plain_language
Alanine and arginine were not interchangeable glucagon signals.
primary_references
Intravenous Arginine Stimulates Glucagon Secretion More Than Equimolar Alanine, Leucine, Glutamine, and Proline in Humans. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40980546/ · DOI 10.1210/jendso/bvaf139
L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 336–342
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Double-blind randomized crossover in 12 healthy men; equimolar IV amino-acid boluses on separate days after an overnight fast. · source_derived_draft · unverified_draft
## alanine-human-glucagon Alanine and arginine were not interchangeable glucagon signals. Intravenous alanine produced a minor increase in peak glucagon, whereas arginine was the strongest tested stimulus and significantly increased both peak and 30-minute incremental area. Model: Double-blind randomized crossover in 12 healthy men; equimolar IV amino-acid boluses on separate days after an overnight fast. Limitations: A peak response is not equivalent to a significant integrated response; small male-only study. Evidence access: Primary full text Intravenous Arginine Stimulates Glucagon Secretion More Than Equimolar Alanine, Leucine, Glutamine, and Proline in Humans. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40980546/ · DOI 10.1210/jendso/bvaf139
Complete structured claim and evidence
Leucine suppressed alanine- and arginine-stimulated glucagon secretion in isolated human and mouse islets under the tested low-glucose conditions.
L-Leucine → Alanine-evoked glucagon in isolated human and mouse islets source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human and mouse islet perifusion; low-glucose amino-acid challenges.
limitations
Mixed-species functional observation, not a human supplementation trial; nutrient concentrations and glucose state determine interpretation.
nutrient_topic
L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
plain_language
One amino acid can reduce the hormone response to another.
primary_references
Leucine Suppresses α-Cell cAMP and Glucagon Secretion via a Combination of Cell-Intrinsic and Islet Paracrine Signaling. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38870025/ · DOI 10.2337/db23-1013
L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 344–350
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human and mouse islet perifusion; low-glucose amino-acid challenges. · source_derived_draft · unverified_draft
## alanine-leucine-glucagon One amino acid can reduce the hormone response to another. Leucine suppressed alanine- and arginine-stimulated glucagon secretion in isolated human and mouse islets under the tested low-glucose conditions. Model: Human and mouse islet perifusion; low-glucose amino-acid challenges. Limitations: Mixed-species functional observation, not a human supplementation trial; nutrient concentrations and glucose state determine interpretation. Evidence access: Primary abstract Leucine Suppresses α-Cell cAMP and Glucagon Secretion via a Combination of Cell-Intrinsic and Islet Paracrine Signaling. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38870025/ · DOI 10.2337/db23-1013
Complete structured claim and evidence
Leucine reduced mouse alpha-cell cAMP even when beta/delta-cell paracrine signaling was limited; cyanide blocked the inhibitory response, supporting mitochondrial-metabolism dependence.
L-Leucine → cAMP in mouse pancreatic alpha cells source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Mouse islet and dispersed-cell experiments; paracrine blockers and metabolic inhibitors.
limitations
Cyanide is broad; the experiment does not identify one unique mitochondrial enzyme as the leucine target.
nutrient_topic
L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
plain_language
Part of the suppression arose inside the glucagon-producing cell.
primary_references
Leucine Suppresses α-Cell cAMP and Glucagon Secretion via a Combination of Cell-Intrinsic and Islet Paracrine Signaling. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38870025/ · DOI 10.2337/db23-1013
L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 352–358
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse islet and dispersed-cell experiments; paracrine blockers and metabolic inhibitors. · source_derived_draft · unverified_draft
## alanine-leucine-alpha-camp Part of the suppression arose inside the glucagon-producing cell. Leucine reduced mouse alpha-cell cAMP even when beta/delta-cell paracrine signaling was limited; cyanide blocked the inhibitory response, supporting mitochondrial-metabolism dependence. Model: Mouse islet and dispersed-cell experiments; paracrine blockers and metabolic inhibitors. Limitations: Cyanide is broad; the experiment does not identify one unique mitochondrial enzyme as the leucine target. Evidence access: Primary abstract Leucine Suppresses α-Cell cAMP and Glucagon Secretion via a Combination of Cell-Intrinsic and Islet Paracrine Signaling. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38870025/ · DOI 10.2337/db23-1013
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
Adding 10 mM alanine to 16.7 mM glucose increased glucose utilization about 2.4-fold in BRIN-BD11 cells and increased measured oxidative and nonoxidative metabolism.
L-Alanine → Glucose utilization in rat BRIN-BD11 cells source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Rat clonal beta-cell NMR experiments.
limitations
Millimolar culture exposures; normal rat islets show different responses under other conditions.
nutrient_topic
L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
plain_language
Alanine changed how the cultured cell processed glucose.
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
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AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat clonal beta-cell NMR experiments. · source_derived_draft · unverified_draft
## alanine-beta-glucose-flux Alanine changed how the cultured cell processed glucose. Adding 10 mM alanine to 16.7 mM glucose increased glucose utilization about 2.4-fold in BRIN-BD11 cells and increased measured oxidative and nonoxidative metabolism. Model: Rat clonal beta-cell NMR experiments. Limitations: Millimolar culture exposures; normal rat islets show different responses under other conditions. 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
Alanine augmented insulin release evoked by leucine or 2-ketoisocaproate in normal adult rat islets, while not significantly changing glucose-induced secretion.
L-Alanine → Insulin secretion from normal adult rat islets source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Isolated normal adult rat islets.
limitations
This setting differs from clonal cells; model and substrate conditions are retained rather than treated as an unexplained contradiction.
nutrient_topic
L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
plain_language
The accompanying nutrient changed whether alanine increased insulin.
primary_references
The stimulus-secretion coupling of amino acid-induced insulin release. Insulinotropic action of L-alanine. · 2002 · https://pubmed.ncbi.nlm.nih.gov/12383948/ · DOI 10.1016/s0304-4165(02)00337-9
L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 376–382
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Isolated normal adult rat islets. · source_derived_draft · unverified_draft
## alanine-islet-leucine-combination The accompanying nutrient changed whether alanine increased insulin. Alanine augmented insulin release evoked by leucine or 2-ketoisocaproate in normal adult rat islets, while not significantly changing glucose-induced secretion. Model: Isolated normal adult rat islets. Limitations: This setting differs from clonal cells; model and substrate conditions are retained rather than treated as an unexplained contradiction. Evidence access: Primary abstract The stimulus-secretion coupling of amino acid-induced insulin release. Insulinotropic action of L-alanine. · 2002 · https://pubmed.ncbi.nlm.nih.gov/12383948/ · DOI 10.1016/s0304-4165(02)00337-9
Complete structured claim and evidence
Alanine stimulated calcium-45 uptake in rat islets without another exogenous nutrient.
L-Alanine → Calcium uptake in normal rat islets source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Normal rat islets; radiocalcium uptake.
limitations
This does not identify a unique sodium transporter or calcium-channel isoform.
nutrient_topic
L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
plain_language
Amino-acid exposure can affect the ion signal used for secretion.
primary_references
The stimulus-secretion coupling of amino acid-induced insulin release. Insulinotropic action of L-alanine. · 2002 · https://pubmed.ncbi.nlm.nih.gov/12383948/ · DOI 10.1016/s0304-4165(02)00337-9
L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 384–390
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Normal rat islets; radiocalcium uptake. · source_derived_draft · unverified_draft
## alanine-islet-calcium Amino-acid exposure can affect the ion signal used for secretion. Alanine stimulated calcium-45 uptake in rat islets without another exogenous nutrient. Model: Normal rat islets; radiocalcium uptake. Limitations: This does not identify a unique sodium transporter or calcium-channel isoform. Evidence access: Primary abstract The stimulus-secretion coupling of amino acid-induced insulin release. Insulinotropic action of L-alanine. · 2002 · https://pubmed.ncbi.nlm.nih.gov/12383948/ · DOI 10.1016/s0304-4165(02)00337-9
Complete structured claim and evidence
Alanine inhibited pyruvate kinase activity in normal rat islet homogenates.
L-Alanine → Pyruvate kinase activity in normal rat islet homogenates source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Rat islet homogenate enzyme assay.
limitations
Isoform not resolved from the accessed abstract; do not automatically assign PKM2 or a human protein.
nutrient_topic
L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
plain_language
A substrate entering one pathway can also regulate another metabolic step.
primary_references
The stimulus-secretion coupling of amino acid-induced insulin release. Insulinotropic action of L-alanine. · 2002 · https://pubmed.ncbi.nlm.nih.gov/12383948/ · DOI 10.1016/s0304-4165(02)00337-9
L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 392–398
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat islet homogenate enzyme assay. · source_derived_draft · unverified_draft
## alanine-islet-pyruvate-kinase A substrate entering one pathway can also regulate another metabolic step. Alanine inhibited pyruvate kinase activity in normal rat islet homogenates. Model: Rat islet homogenate enzyme assay. Limitations: Isoform not resolved from the accessed abstract; do not automatically assign PKM2 or a human protein. Evidence access: Primary abstract The stimulus-secretion coupling of amino acid-induced insulin release. Insulinotropic action of L-alanine. · 2002 · https://pubmed.ncbi.nlm.nih.gov/12383948/ · DOI 10.1016/s0304-4165(02)00337-9
Complete structured claim and evidence
Prolonged alanine culture reduced subsequent acute alanine-stimulated insulin secretion by 74%, without reducing responses to glucose, KCl or ketoisocaproate; 18 hours without alanine partly restored responsiveness.
L-Alanine → Alanine-stimulated insulin secretion in BRIN-BD11 cells source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Rat BRIN-BD11 culture, washout and rechallenge experiments.
limitations
Exposure concentration/duration before washout are not resolved in the accessed abstract; no human chronic-use threshold is inferred.
nutrient_topic
L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
plain_language
A strong acute response need not persist after prolonged exposure.
primary_references
Prolonged L-alanine exposure induces changes in metabolism, Ca(2+) handling and desensitization of insulin secretion in clonal pancreatic beta-cells. · 2009 · https://pubmed.ncbi.nlm.nih.gov/18702613/ · DOI 10.1042/CS20080138
L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 400–406
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat BRIN-BD11 culture, washout and rechallenge experiments. · source_derived_draft · unverified_draft
## alanine-beta-chronic-desensitization A strong acute response need not persist after prolonged exposure. Prolonged alanine culture reduced subsequent acute alanine-stimulated insulin secretion by 74%, without reducing responses to glucose, KCl or ketoisocaproate; 18 hours without alanine partly restored responsiveness. Model: Rat BRIN-BD11 culture, washout and rechallenge experiments. Limitations: Exposure concentration/duration before washout are not resolved in the accessed abstract; no human chronic-use threshold is inferred. Evidence access: Primary abstract Prolonged L-alanine exposure induces changes in metabolism, Ca(2+) handling and desensitization of insulin secretion in clonal pancreatic beta-cells. · 2009 · https://pubmed.ncbi.nlm.nih.gov/18702613/ · DOI 10.1042/CS20080138
Complete structured claim and evidence
Prior prolonged alanine culture attenuated subsequent alanine-evoked depolarization and intracellular calcium rise in BRIN-BD11 cells.
L-Alanine → Depolarization and calcium rise after alanine rechallenge source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Rat clonal beta-cell chronic exposure and acute rechallenge.
limitations
Linked measurements do not prove which upstream molecular change caused desensitization.
nutrient_topic
L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
plain_language
The weakened insulin response was accompanied by weaker electrical and calcium signals.
primary_references
Prolonged L-alanine exposure induces changes in metabolism, Ca(2+) handling and desensitization of insulin secretion in clonal pancreatic beta-cells. · 2009 · https://pubmed.ncbi.nlm.nih.gov/18702613/ · DOI 10.1042/CS20080138
L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 408–414
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat clonal beta-cell chronic exposure and acute rechallenge. · source_derived_draft · unverified_draft
## alanine-beta-chronic-calcium The weakened insulin response was accompanied by weaker electrical and calcium signals. Prior prolonged alanine culture attenuated subsequent alanine-evoked depolarization and intracellular calcium rise in BRIN-BD11 cells. Model: Rat clonal beta-cell chronic exposure and acute rechallenge. Limitations: Linked measurements do not prove which upstream molecular change caused desensitization. Evidence access: Primary abstract Prolonged L-alanine exposure induces changes in metabolism, Ca(2+) handling and desensitization of insulin secretion in clonal pancreatic beta-cells. · 2009 · https://pubmed.ncbi.nlm.nih.gov/18702613/ · DOI 10.1042/CS20080138
Complete structured claim and evidence
Prolonged alanine culture increased NMR-inferred pyruvate-dehydrogenase flux while reducing PDK2/PDK4 protein and cellular ATP.
L-Alanine → PDH flux and ATP after prolonged alanine culture source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Rat BRIN-BD11 tracing and protein measurements.
limitations
Concurrent changes are not a direct demonstration that PDK loss caused the ATP or secretion phenotype.
nutrient_topic
L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
plain_language
More flux through one metabolic step did not mean more stored ATP or stronger insulin release.
primary_references
Prolonged L-alanine exposure induces changes in metabolism, Ca(2+) handling and desensitization of insulin secretion in clonal pancreatic beta-cells. · 2009 · https://pubmed.ncbi.nlm.nih.gov/18702613/ · DOI 10.1042/CS20080138
L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 416–422
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat BRIN-BD11 tracing and protein measurements. · source_derived_draft · unverified_draft
## alanine-beta-chronic-pdh More flux through one metabolic step did not mean more stored ATP or stronger insulin release. Prolonged alanine culture increased NMR-inferred pyruvate-dehydrogenase flux while reducing PDK2/PDK4 protein and cellular ATP. Model: Rat BRIN-BD11 tracing and protein measurements. Limitations: Concurrent changes are not a direct demonstration that PDK loss caused the ATP or secretion phenotype. Evidence access: Primary abstract Prolonged L-alanine exposure induces changes in metabolism, Ca(2+) handling and desensitization of insulin secretion in clonal pancreatic beta-cells. · 2009 · https://pubmed.ncbi.nlm.nih.gov/18702613/ · DOI 10.1042/CS20080138
Complete structured claim and evidence
Human SPTLC1 mutant expression in HEK cells shifted substrate use toward alanine and increased production of deoxysphingolipids; amino-acid availability modulated this production.
Human HSAN1-associated SPTLC1 variants → 1-Deoxysphingolipids source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Human SPTLC1 variants expressed in HEK cells.
limitations
Variant-dependent abnormal chemistry is not a universal response to alanine intake.
nutrient_topic
L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
plain_language
An enzyme can make different lipids when its substrate preference changes.
primary_references
Oral L-serine supplementation reduces production of neurotoxic deoxysphingolipids in mice and humans with hereditary sensory autonomic neuropathy type 1. · 2011 · https://pubmed.ncbi.nlm.nih.gov/22045570/ · DOI 10.1172/JCI57549
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 424–430
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human SPTLC1 variants expressed in HEK cells. · source_derived_draft · unverified_draft
## alanine-spt-mutant-substrate An enzyme can make different lipids when its substrate preference changes. Human SPTLC1 mutant expression in HEK cells shifted substrate use toward alanine and increased production of deoxysphingolipids; amino-acid availability modulated this production. Model: Human SPTLC1 variants expressed in HEK cells. Limitations: Variant-dependent abnormal chemistry is not a universal response to alanine intake. Evidence access: Primary abstract Oral L-serine supplementation reduces production of neurotoxic deoxysphingolipids in mice and humans with hereditary sensory autonomic neuropathy type 1. · 2011 · https://pubmed.ncbi.nlm.nih.gov/22045570/ · DOI 10.1172/JCI57549
Complete structured claim and evidence
A 10% alanine-enriched diet increased deoxysphingolipids and led to severe peripheral neuropathy in mice expressing the HSAN1-associated C133W SPTLC1 transgene.
L-Alanine → 1-Deoxysphingolipids source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Transgenic HSAN1 mouse model; 10% enriched diet.
limitations
High-dose disease model, not a toxicity threshold for ordinary human alanine intake.
nutrient_topic
L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
plain_language
High alanine exposure worsened a specific genetically altered pathway.
primary_references
Oral L-serine supplementation reduces production of neurotoxic deoxysphingolipids in mice and humans with hereditary sensory autonomic neuropathy type 1. · 2011 · https://pubmed.ncbi.nlm.nih.gov/22045570/ · DOI 10.1172/JCI57549
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 432–438
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Transgenic HSAN1 mouse model; 10% enriched diet. · source_derived_draft · unverified_draft
## alanine-spt-mouse-alanine High alanine exposure worsened a specific genetically altered pathway. A 10% alanine-enriched diet increased deoxysphingolipids and led to severe peripheral neuropathy in mice expressing the HSAN1-associated C133W SPTLC1 transgene. Model: Transgenic HSAN1 mouse model; 10% enriched diet. Limitations: High-dose disease model, not a toxicity threshold for ordinary human alanine intake. Evidence access: Primary abstract Oral L-serine supplementation reduces production of neurotoxic deoxysphingolipids in mice and humans with hereditary sensory autonomic neuropathy type 1. · 2011 · https://pubmed.ncbi.nlm.nih.gov/22045570/ · DOI 10.1172/JCI57549
Complete structured claim and evidence
A 10% serine-enriched diet reduced deoxysphingolipids and improved selected motor and sensory outcomes in C133W SPTLC1 transgenic mice.
L-Serine → 1-Deoxysphingolipids source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
HSAN1 transgenic mouse dietary intervention.
limitations
Mouse neurological outcomes do not establish human clinical benefit.
nutrient_topic
L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
plain_language
Restoring the competing normal substrate changed the abnormal lipid output.
primary_references
Oral L-serine supplementation reduces production of neurotoxic deoxysphingolipids in mice and humans with hereditary sensory autonomic neuropathy type 1. · 2011 · https://pubmed.ncbi.nlm.nih.gov/22045570/ · DOI 10.1172/JCI57549
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 440–446
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · HSAN1 transgenic mouse dietary intervention. · source_derived_draft · unverified_draft
## alanine-spt-serine-rescue Restoring the competing normal substrate changed the abnormal lipid output. A 10% serine-enriched diet reduced deoxysphingolipids and improved selected motor and sensory outcomes in C133W SPTLC1 transgenic mice. Model: HSAN1 transgenic mouse dietary intervention. Limitations: Mouse neurological outcomes do not establish human clinical benefit. Evidence access: Primary abstract Oral L-serine supplementation reduces production of neurotoxic deoxysphingolipids in mice and humans with hereditary sensory autonomic neuropathy type 1. · 2011 · https://pubmed.ncbi.nlm.nih.gov/22045570/ · DOI 10.1172/JCI57549
Complete structured claim and evidence
A pilot study in 14 HSAN1 patients found reduced deoxysphingolipid levels during oral serine supplementation.
L-Serine → 1-Deoxysphingolipids source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Small human HSAN1 serine-supplementation pilot.
limitations
Biomarker lowering alone does not establish neurological recovery, and the intervention was serine rather than alanine.
nutrient_topic
L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
plain_language
The human pilot measured a biochemical response.
primary_references
Oral L-serine supplementation reduces production of neurotoxic deoxysphingolipids in mice and humans with hereditary sensory autonomic neuropathy type 1. · 2011 · https://pubmed.ncbi.nlm.nih.gov/22045570/ · DOI 10.1172/JCI57549
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 448–454
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Small human HSAN1 serine-supplementation pilot. · source_derived_draft · unverified_draft
## alanine-spt-human-serine The human pilot measured a biochemical response. A pilot study in 14 HSAN1 patients found reduced deoxysphingolipid levels during oral serine supplementation. Model: Small human HSAN1 serine-supplementation pilot. Limitations: Biomarker lowering alone does not establish neurological recovery, and the intervention was serine rather than alanine. Evidence access: Primary abstract Oral L-serine supplementation reduces production of neurotoxic deoxysphingolipids in mice and humans with hereditary sensory autonomic neuropathy type 1. · 2011 · https://pubmed.ncbi.nlm.nih.gov/22045570/ · DOI 10.1172/JCI57549
Complete structured claim and evidence
Serine/glycine restriction increased alanine-derived deoxysphingolipid synthesis in the tested colorectal cancer models and constrained growth.
Serine/glycine restriction in human colorectal cancer models → 1-Deoxysphingolipids source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Human colorectal cancer cultures/spheroids with nutrient restriction and isotope tracing; accompanying mouse xenografts.
limitations
Cancer nutrient-restriction experiments are not a recommendation to restrict serine or glycine.
nutrient_topic
L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
plain_language
The ratio of available substrates can redirect a shared enzyme even without the inherited neuropathy setting.
primary_references
Serine restriction alters sphingolipid diversity to constrain tumour growth. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32788725/ · DOI 10.1038/s41586-020-2609-x
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 456–462
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human colorectal cancer cultures/spheroids with nutrient restriction and isotope tracing; accompanying mouse xenografts. · source_derived_draft · unverified_draft
## alanine-serine-restriction-lipids The ratio of available substrates can redirect a shared enzyme even without the inherited neuropathy setting. Serine/glycine restriction increased alanine-derived deoxysphingolipid synthesis in the tested colorectal cancer models and constrained growth. Model: Human colorectal cancer cultures/spheroids with nutrient restriction and isotope tracing; accompanying mouse xenografts. Limitations: Cancer nutrient-restriction experiments are not a recommendation to restrict serine or glycine. Evidence access: Primary full text Serine restriction alters sphingolipid diversity to constrain tumour growth. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32788725/ · DOI 10.1038/s41586-020-2609-x
Complete structured claim and evidence
Targeting mitochondrial pyruvate transport promoted alanine oxidation, reduced deoxysphingolipid production and restored growth under serine/glycine-restricted conditions.
Mitochondrial pyruvate carrier targeting in colorectal cancer models → 1-Deoxysphingolipids source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Colorectal cancer model metabolic interventions and tracing.
limitations
Context-specific rerouting; it does not establish a universal protective effect of MPC inhibition.
nutrient_topic
L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
plain_language
Changing use of alanine in mitochondria changed its availability to another pathway.
primary_references
Serine restriction alters sphingolipid diversity to constrain tumour growth. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32788725/ · DOI 10.1038/s41586-020-2609-x
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 464–470
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Colorectal cancer model metabolic interventions and tracing. · source_derived_draft · unverified_draft
## alanine-serine-mpc-interaction Changing use of alanine in mitochondria changed its availability to another pathway. Targeting mitochondrial pyruvate transport promoted alanine oxidation, reduced deoxysphingolipid production and restored growth under serine/glycine-restricted conditions. Model: Colorectal cancer model metabolic interventions and tracing. Limitations: Context-specific rerouting; it does not establish a universal protective effect of MPC inhibition. Evidence access: Primary full text Serine restriction alters sphingolipid diversity to constrain tumour growth. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32788725/ · DOI 10.1038/s41586-020-2609-x
Complete structured claim and evidence
Alanine add-back increased apical System B and System L uptake within five minutes in depleted Caco-2 cells, increasing both apparent Km and Vmax.
L-Alanine → Alanine transport in human Caco-2 cells source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human Caco-2 monolayers; sodium-dependent and sodium-independent transport assays.
limitations
Historical functional systems are not assigned to one modern transporter gene without direct evidence.
nutrient_topic
L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
plain_language
What is already inside an intestinal cell can change how quickly amino acids cross its membrane.
primary_references
Posttranslational alanine trans-stimulation of zwitterionic amino acid transport systems in human intestinal Caco-2 cells. · 2002 · https://pubmed.ncbi.nlm.nih.gov/11971679/ · DOI 10.1006/jsre.2002.6406
L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 472–478
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human Caco-2 monolayers; sodium-dependent and sodium-independent transport assays. · source_derived_draft · unverified_draft
## alanine-intestinal-transstimulation What is already inside an intestinal cell can change how quickly amino acids cross its membrane. Alanine add-back increased apical System B and System L uptake within five minutes in depleted Caco-2 cells, increasing both apparent Km and Vmax. Model: Human Caco-2 monolayers; sodium-dependent and sodium-independent transport assays. Limitations: Historical functional systems are not assigned to one modern transporter gene without direct evidence. Evidence access: Primary abstract Posttranslational alanine trans-stimulation of zwitterionic amino acid transport systems in human intestinal Caco-2 cells. · 2002 · https://pubmed.ncbi.nlm.nih.gov/11971679/ · DOI 10.1006/jsre.2002.6406
Complete structured claim and evidence
Other substrates of System B or L increased alanine uptake, whereas nonsubstrates did not; cycloheximide/actinomycin did not block acute activation and ATB0 mRNA did not change.
Other System B/L substrates in Caco-2 assays → Alanine transport in human Caco-2 cells source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human Caco-2 substrate challenges and expression/inhibitor measurements.
limitations
No blanket claim that all amino acids compete or that one oral mixture improves absorption.
nutrient_topic
L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
plain_language
Shared transport can produce rapid nutrient interactions without making new transporter protein.
primary_references
Posttranslational alanine trans-stimulation of zwitterionic amino acid transport systems in human intestinal Caco-2 cells. · 2002 · https://pubmed.ncbi.nlm.nih.gov/11971679/ · DOI 10.1006/jsre.2002.6406
L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 480–486
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human Caco-2 substrate challenges and expression/inhibitor measurements. · source_derived_draft · unverified_draft
## alanine-intestinal-other-substrates Shared transport can produce rapid nutrient interactions without making new transporter protein. Other substrates of System B or L increased alanine uptake, whereas nonsubstrates did not; cycloheximide/actinomycin did not block acute activation and ATB0 mRNA did not change. Model: Human Caco-2 substrate challenges and expression/inhibitor measurements. Limitations: No blanket claim that all amino acids compete or that one oral mixture improves absorption. Evidence access: Primary abstract Posttranslational alanine trans-stimulation of zwitterionic amino acid transport systems in human intestinal Caco-2 cells. · 2002 · https://pubmed.ncbi.nlm.nih.gov/11971679/ · DOI 10.1006/jsre.2002.6406
Complete structured claim and evidence
Resveratrol at 300 micromolar for 30 minutes reduced alanine-evoked short-circuit current in isolated porcine intestinal preparations.
Resveratrol → Alanine-evoked intestinal short-circuit current in pigs source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Pig jejunum/ileum Ussing chambers; alanine challenge.
limitations
Current is a functional proxy; associated AMPK/PKA changes were not established as the cause. No human malabsorption conclusion follows.
nutrient_topic
L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
plain_language
A second compound altered the electrical transport response to alanine.
primary_references
Resveratrol Inhibits Porcine Intestinal Glucose and Alanine Transport: Potential Roles of Na⁺/K⁺-ATPase Activity, Protein Kinase A, AMP-Activated Protein Kinase and the Association of Selected Nutrient Transport Proteins with Detergent Resistant Membranes. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29510506/ · DOI 10.3390/nu10030302
L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 488–494
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Pig jejunum/ileum Ussing chambers; alanine challenge. · source_derived_draft · unverified_draft
## alanine-intestinal-resveratrol A second compound altered the electrical transport response to alanine. Resveratrol at 300 micromolar for 30 minutes reduced alanine-evoked short-circuit current in isolated porcine intestinal preparations. Model: Pig jejunum/ileum Ussing chambers; alanine challenge. Limitations: Current is a functional proxy; associated AMPK/PKA changes were not established as the cause. No human malabsorption conclusion follows. Evidence access: Primary full text Resveratrol Inhibits Porcine Intestinal Glucose and Alanine Transport: Potential Roles of Na⁺/K⁺-ATPase Activity, Protein Kinase A, AMP-Activated Protein Kinase and the Association of Selected Nutrient Transport Proteins with Detergent Resistant Membranes. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29510506/ · DOI 10.3390/nu10030302
Complete structured claim and evidence
TGF-beta increased alanine synthesis in normal and IPF human lung fibroblasts, with GPT2 as the principal examined synthesis enzyme regulated by the glutamine/glutamate/2-oxoglutarate axis.
Transforming growth factor beta 1 → Alanine availability in human lung fibroblasts source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Human lung fibroblast cultures; TGF-beta 2 ng/mL and metabolic perturbations.
limitations
Medium composition matters; this is not proof that alanine intake causes lung fibrosis.
nutrient_topic
L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
plain_language
A differentiation signal coordinates alanine production with other amino-acid metabolism.
primary_references
TGF-β coordinates alanine synthesis and import for myofibroblast differentiation in pulmonary fibrosis. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42024472/ · DOI 10.1172/jci.insight.199449
L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 496–502
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human lung fibroblast cultures; TGF-beta 2 ng/mL and metabolic perturbations. · source_derived_draft · unverified_draft
## alanine-fibroblast-synthesis A differentiation signal coordinates alanine production with other amino-acid metabolism. TGF-beta increased alanine synthesis in normal and IPF human lung fibroblasts, with GPT2 as the principal examined synthesis enzyme regulated by the glutamine/glutamate/2-oxoglutarate axis. Model: Human lung fibroblast cultures; TGF-beta 2 ng/mL and metabolic perturbations. Limitations: Medium composition matters; this is not proof that alanine intake causes lung fibrosis. Evidence access: Primary full text TGF-β coordinates alanine synthesis and import for myofibroblast differentiation in pulmonary fibrosis. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42024472/ · DOI 10.1172/jci.insight.199449
Complete structured claim and evidence
SLC38A2 mediated alanine and glutamine uptake in human lung fibroblasts and increased with TGF-beta exposure or alanine deprivation.
Human sodium-coupled neutral amino acid transporter 2 / SLC38A2 → Alanine availability in human lung fibroblasts source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Normal and IPF human lung fibroblast transporter experiments.
limitations
Dual transport does not by itself prove clinically relevant competition at ordinary plasma concentrations.
nutrient_topic
L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
plain_language
A shared importer links access to two amino acids.
primary_references
TGF-β coordinates alanine synthesis and import for myofibroblast differentiation in pulmonary fibrosis. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42024472/ · DOI 10.1172/jci.insight.199449
L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 504–510
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Normal and IPF human lung fibroblast transporter experiments. · source_derived_draft · unverified_draft
## alanine-fibroblast-transporter A shared importer links access to two amino acids. SLC38A2 mediated alanine and glutamine uptake in human lung fibroblasts and increased with TGF-beta exposure or alanine deprivation. Model: Normal and IPF human lung fibroblast transporter experiments. Limitations: Dual transport does not by itself prove clinically relevant competition at ordinary plasma concentrations. Evidence access: Primary full text TGF-β coordinates alanine synthesis and import for myofibroblast differentiation in pulmonary fibrosis. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42024472/ · DOI 10.1172/jci.insight.199449
Complete structured claim and evidence
GPT2 inhibition lowered alanine and reduced TGF-beta-induced alpha-SMA and COL1A1 expression; 2 mM exogenous alanine rescued these readouts.
L-Alanine → Human lung myofibroblast differentiation source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Human lung fibroblast perturbation and add-back experiments.
limitations
Marker rescue in cells is not a clinical fibrosis outcome.
nutrient_topic
L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
plain_language
Alanine add-back bypassed part of the inhibited synthesis pathway.
primary_references
TGF-β coordinates alanine synthesis and import for myofibroblast differentiation in pulmonary fibrosis. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42024472/ · DOI 10.1172/jci.insight.199449
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 512–518
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human lung fibroblast perturbation and add-back experiments. · source_derived_draft · unverified_draft
## alanine-fibroblast-gpt2-rescue Alanine add-back bypassed part of the inhibited synthesis pathway. GPT2 inhibition lowered alanine and reduced TGF-beta-induced alpha-SMA and COL1A1 expression; 2 mM exogenous alanine rescued these readouts. Model: Human lung fibroblast perturbation and add-back experiments. Limitations: Marker rescue in cells is not a clinical fibrosis outcome. Evidence access: Primary full text TGF-β coordinates alanine synthesis and import for myofibroblast differentiation in pulmonary fibrosis. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42024472/ · DOI 10.1172/jci.insight.199449
Complete structured claim and evidence
Isotope experiments showed alanine supplying carbon and nitrogen to glutamate and proline synthesis in human lung fibroblasts, particularly during glutamine deprivation.
L-Alanine → L-Proline source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Human fibroblast stable-isotope tracing under specified media conditions.
limitations
Atom contribution is not a one-step alanine-to-proline reaction; other enzymes, carbon sources and cofactors remain necessary.
nutrient_topic
L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
plain_language
One amino acid can supply material used to make another.
primary_references
TGF-β coordinates alanine synthesis and import for myofibroblast differentiation in pulmonary fibrosis. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42024472/ · DOI 10.1172/jci.insight.199449
L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 520–526
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human fibroblast stable-isotope tracing under specified media conditions. · source_derived_draft · unverified_draft
## alanine-fibroblast-proline One amino acid can supply material used to make another. Isotope experiments showed alanine supplying carbon and nitrogen to glutamate and proline synthesis in human lung fibroblasts, particularly during glutamine deprivation. Model: Human fibroblast stable-isotope tracing under specified media conditions. Limitations: Atom contribution is not a one-step alanine-to-proline reaction; other enzymes, carbon sources and cofactors remain necessary. Evidence access: Primary full text TGF-β coordinates alanine synthesis and import for myofibroblast differentiation in pulmonary fibrosis. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42024472/ · DOI 10.1172/jci.insight.199449
Complete structured claim and evidence
Combined inhibition of alanine synthesis and uptake suppressed fibrogenic responses in human fibroblasts and precision-cut lung slices.
Combined alanine synthesis and uptake blockade → Human lung myofibroblast differentiation source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Human cells and ex vivo lung tissue; metabolic perturbations.
limitations
Preclinical work, not an established human antifibrotic therapy. The final paper and its preprint are one study lineage.
nutrient_topic
L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
plain_language
Blocking both supply routes had a stronger mechanistic rationale than assuming only one route mattered.
primary_references
TGF-β coordinates alanine synthesis and import for myofibroblast differentiation in pulmonary fibrosis. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42024472/ · DOI 10.1172/jci.insight.199449
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 528–534
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human cells and ex vivo lung tissue; metabolic perturbations. · source_derived_draft · unverified_draft
## alanine-fibroblast-dual-block Blocking both supply routes had a stronger mechanistic rationale than assuming only one route mattered. Combined inhibition of alanine synthesis and uptake suppressed fibrogenic responses in human fibroblasts and precision-cut lung slices. Model: Human cells and ex vivo lung tissue; metabolic perturbations. Limitations: Preclinical work, not an established human antifibrotic therapy. The final paper and its preprint are one study lineage. Evidence access: Primary full text TGF-β coordinates alanine synthesis and import for myofibroblast differentiation in pulmonary fibrosis. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42024472/ · DOI 10.1172/jci.insight.199449
Complete structured claim and evidence
Recombinant human GPT2 catalyzed alanine transamination, confirming a second human alanine aminotransferase distinct from GPT.
Human mitochondrial alanine aminotransferase / GPT2 → L-Alanine source_derived_draftungraded
Experimental context and source evidence
experimental_model
Human GPT2 expressed in E. coli
limitations
Functional-expression evidence; this study did not quantify B6-deficiency sensitivity.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
Human alanine metabolism has a separately encoded second enzyme.
primary_references
[b6-gpt2-2002] cDNA cloning, genomic structure, chromosomal mapping, and functional expression of a novel human alanine aminotransferase (2002). https://pubmed.ncbi.nlm.nih.gov/11863375/ DOI: 10.1006/geno.2002.6722
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 776–785
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human GPT2 expressed in E. coli · source_derived_draft · unverified_draft
### b6-met-gpt2-reaction Recombinant human GPT2 catalyzed alanine transamination, confirming a second human alanine aminotransferase distinct from GPT. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Human alanine metabolism has a separately encoded second enzyme. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Human GPT2 expressed in E. coli limitations: Functional-expression evidence; this study did not quantify B6-deficiency sensitivity. [b6-gpt2-2002] cDNA cloning, genomic structure, chromosomal mapping, and functional expression of a novel human alanine aminotransferase (2002). https://pubmed.ncbi.nlm.nih.gov/11863375/ DOI: 10.1006/geno.2002.6722
Complete structured claim and evidence
Human GPT catalyzes reversible amino transfer between alanine and 2-oxoglutarate, producing pyruvate and glutamate.
Human cytosolic alanine aminotransferase / GPT → L-Alanine 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
B6-dependent alanine transamination links nitrogen transfer to pyruvate 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 753–763
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-gpt-reaction Human GPT catalyzes reversible amino transfer between alanine and 2-oxoglutarate, producing pyruvate and glutamate. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: B6-dependent alanine transamination links nitrogen transfer to pyruvate 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
The human PNPO structure localized tightly bound FMN at the conserved catalytic site of the homodimer.
Flavin mononucleotide → Pyridoxine 5-prime-phosphate oxidase / PNPO source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
B2-FMN is a cofactor for B6 activation.
evidence_location
Results: kinetic properties; Table 1; FMN-binding structure
experimental_model
Recombinant human PNPO expressed in E. coli; crystallography and purified-enzyme kinetics at 37 C.
exposure
Purified-enzyme assay
limitations
Biochemical evidence does not establish a dietary threshold or supplementation benefit.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
PNPO uses the FMN form of vitamin B2.
primary_references
[musayev2003] Structure and properties of recombinant human pyridoxine 5'-phosphate oxidase. (2003). https://pubmed.ncbi.nlm.nih.gov/12824491/ DOI: 10.1110/ps.0356203
tissue_or_cell_type
Purified recombinant enzyme; no intact tissue
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1136–1148
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human PNPO expressed in E. coli; crystallography and purified-enzyme kinetics at 37 C. · source_derived_draft · unverified_draft
### b2-pnpo-fmn-binding The human PNPO structure localized tightly bound FMN at the conserved catalytic site of the homodimer. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: PNPO uses the FMN form of vitamin B2. organism: Homo sapiens tissue_or_cell_type: Purified recombinant enzyme; no intact tissue experimental_model: Recombinant human PNPO expressed in E. coli; crystallography and purified-enzyme kinetics at 37 C. limitations: Biochemical evidence does not establish a dietary threshold or supplementation benefit. exposure: Purified-enzyme assay cross_nutrient: B2-FMN is a cofactor for B6 activation. evidence_location: Results: kinetic properties; Table 1; FMN-binding structure [musayev2003] Structure and properties of recombinant human pyridoxine 5'-phosphate oxidase. (2003). https://pubmed.ncbi.nlm.nih.gov/12824491/ DOI: 10.1110/ps.0356203
Complete structured claim and evidence
Purified human PNPO converted PNP to PLP with a turnover number of 0.19 per second at 37 C.
Pyridoxine 5-prime-phosphate oxidase / PNPO → Pyridoxine 5-prime-phosphate source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
B2-dependent oxidation activates one B6 precursor.
evidence_location
Results: kinetic properties; Table 1; FMN-binding structure
experimental_model
Recombinant human PNPO expressed in E. coli; crystallography and purified-enzyme kinetics at 37 C.
exposure
Purified-enzyme assay
limitations
Biochemical evidence does not establish a dietary threshold or supplementation benefit.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
PNPO changes phosphorylated pyridoxine into active B6.
primary_references
[musayev2003] Structure and properties of recombinant human pyridoxine 5'-phosphate oxidase. (2003). https://pubmed.ncbi.nlm.nih.gov/12824491/ DOI: 10.1110/ps.0356203
tissue_or_cell_type
Purified recombinant enzyme; no intact tissue
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1150–1162
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human PNPO expressed in E. coli; crystallography and purified-enzyme kinetics at 37 C. · source_derived_draft · unverified_draft
### b2-pnpo-pnp-oxidation Purified human PNPO converted PNP to PLP with a turnover number of 0.19 per second at 37 C. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: PNPO changes phosphorylated pyridoxine into active B6. organism: Homo sapiens tissue_or_cell_type: Purified recombinant enzyme; no intact tissue experimental_model: Recombinant human PNPO expressed in E. coli; crystallography and purified-enzyme kinetics at 37 C. limitations: Biochemical evidence does not establish a dietary threshold or supplementation benefit. exposure: Purified-enzyme assay cross_nutrient: B2-dependent oxidation activates one B6 precursor. evidence_location: Results: kinetic properties; Table 1; FMN-binding structure [musayev2003] Structure and properties of recombinant human pyridoxine 5'-phosphate oxidase. (2003). https://pubmed.ncbi.nlm.nih.gov/12824491/ DOI: 10.1110/ps.0356203
Complete structured claim and evidence
Human PNPO also converted PMP to PLP, with a turnover number of 0.20 per second at 37 C.
Pyridoxine 5-prime-phosphate oxidase / PNPO → Pyridoxamine 5-prime-phosphate source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
A second B6 precursor depends on the FMN enzyme.
evidence_location
Results: kinetic properties; Table 1; FMN-binding structure
experimental_model
Recombinant human PNPO expressed in E. coli; crystallography and purified-enzyme kinetics at 37 C.
exposure
Purified-enzyme assay
limitations
Biochemical evidence does not establish a dietary threshold or supplementation benefit.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
Phosphorylated pyridoxamine enters the same activation enzyme.
primary_references
[musayev2003] Structure and properties of recombinant human pyridoxine 5'-phosphate oxidase. (2003). https://pubmed.ncbi.nlm.nih.gov/12824491/ DOI: 10.1110/ps.0356203
tissue_or_cell_type
Purified recombinant enzyme; no intact tissue
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1164–1176
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human PNPO expressed in E. coli; crystallography and purified-enzyme kinetics at 37 C. · source_derived_draft · unverified_draft
### b2-pnpo-pmp-oxidation Human PNPO also converted PMP to PLP, with a turnover number of 0.20 per second at 37 C. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Phosphorylated pyridoxamine enters the same activation enzyme. organism: Homo sapiens tissue_or_cell_type: Purified recombinant enzyme; no intact tissue experimental_model: Recombinant human PNPO expressed in E. coli; crystallography and purified-enzyme kinetics at 37 C. limitations: Biochemical evidence does not establish a dietary threshold or supplementation benefit. exposure: Purified-enzyme assay cross_nutrient: A second B6 precursor depends on the FMN enzyme. evidence_location: Results: kinetic properties; Table 1; FMN-binding structure [musayev2003] Structure and properties of recombinant human pyridoxine 5'-phosphate oxidase. (2003). https://pubmed.ncbi.nlm.nih.gov/12824491/ DOI: 10.1110/ps.0356203
Complete structured claim and evidence
N-acetylglutamate binding reshaped human CPS1 and established the channel linking its two phosphorylation sites.
N-Acetyl-L-glutamate → Human carbamoyl-phosphate synthetase 1 / CPS1 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/citrulline-research/26592762.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "55b398f0f6c85b023e3eee96e6841df398d328bc8201dfb5207147aa871be581", "start_char": 0, "end_char": 1079, "text_sha256": "55b398f0f6c85b023e3eee96e6841df398d328bc8201dfb5207147aa871be581"}
experimental_model
Human recombinant enzyme crystallography and mutation analysis
exposure
Structures without NAG and with NAG plus nucleotides
limitations
Mechanism of enzyme activation; clinical effects of adding nutritional cofactors were not tested.
nutrient_topic
Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline
organism
Human CPS1
plain_language
An activator switches the upstream nitrogen-handling enzyme into a functional shape.
primary_references
[citrulline-p26592762] Structure of human carbamoyl phosphate synthetase: deciphering the on/off switch of human ureagenesis. (2015). https://pubmed.ncbi.nlm.nih.gov/26592762/ DOI: 10.1038/srep16950
tissue_or_cell_type
Mitochondrial carbamoyl-phosphate synthesis
Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 229–240
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human recombinant enzyme crystallography and mutation analysis · source_derived_draft · unverified_draft
### citrulline-cps1-nag N-acetylglutamate binding reshaped human CPS1 and established the channel linking its two phosphorylation sites. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: An activator switches the upstream nitrogen-handling enzyme into a functional shape. organism: Human CPS1 tissue_or_cell_type: Mitochondrial carbamoyl-phosphate synthesis experimental_model: Human recombinant enzyme crystallography and mutation analysis limitations: Mechanism of enzyme activation; clinical effects of adding nutritional cofactors were not tested. exposure: Structures without NAG and with NAG plus nucleotides evidence_span: {"source_cache": "artifacts/citrulline-research/26592762.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "55b398f0f6c85b023e3eee96e6841df398d328bc8201dfb5207147aa871be581", "start_char": 0, "end_char": 1079, "text_sha256": "55b398f0f6c85b023e3eee96e6841df398d328bc8201dfb5207147aa871be581"} [citrulline-p26592762] Structure of human carbamoyl phosphate synthetase: deciphering the on/off switch of human ureagenesis. (2015). https://pubmed.ncbi.nlm.nih.gov/26592762/ DOI: 10.1038/srep16950
Complete structured claim and evidence
CPS1 uses two ATP-dependent phosphorylation steps to convert bicarbonate and ammonia into carbamoyl phosphate.
Human carbamoyl-phosphate synthetase 1 / CPS1 → Carbamoyl phosphate source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/citrulline-research/26592762.fulltext.txt", "locator": "Primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9807338d87ba1b5602512aa3765c7cc48d391595cc1f35e6a43bcbe1250d3c7d", "start_char": 1169, "end_char": 1477, "text_sha256": "c5e2a8e1d3e3a09064b7b233635f7d573f8761b3f6ae18a68bc9b102a2d5874c"}
experimental_model
Human recombinant enzyme crystallography and mutation analysis
exposure
Structures without NAG and with NAG plus nucleotides
limitations
Mechanism of enzyme activation; clinical effects of adding nutritional cofactors were not tested.
nutrient_topic
Citrulline research collection; topical membership is not evidence of a direct dietary effect. · L-Citrulline
organism
Human CPS1
plain_language
The upstream part of citrulline synthesis consumes energy to handle ammonia.
primary_references
[citrulline-p26592762] Structure of human carbamoyl phosphate synthetase: deciphering the on/off switch of human ureagenesis. (2015). https://pubmed.ncbi.nlm.nih.gov/26592762/ DOI: 10.1038/srep16950
tissue_or_cell_type
Mitochondrial carbamoyl-phosphate synthesis
Citrulline: arginine recycling, nitrogen disposal and nutrient connections (2026-09-17) · lines 242–253
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human recombinant enzyme crystallography and mutation analysis · source_derived_draft · unverified_draft
### citrulline-cps1-product CPS1 uses two ATP-dependent phosphorylation steps to convert bicarbonate and ammonia into carbamoyl phosphate. Condition category: normal nutrient_topic: Citrulline research collection; topical membership is not evidence of a direct dietary effect. plain_language: The upstream part of citrulline synthesis consumes energy to handle ammonia. organism: Human CPS1 tissue_or_cell_type: Mitochondrial carbamoyl-phosphate synthesis experimental_model: Human recombinant enzyme crystallography and mutation analysis limitations: Mechanism of enzyme activation; clinical effects of adding nutritional cofactors were not tested. exposure: Structures without NAG and with NAG plus nucleotides evidence_span: {"source_cache": "artifacts/citrulline-research/26592762.fulltext.txt", "locator": "Primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9807338d87ba1b5602512aa3765c7cc48d391595cc1f35e6a43bcbe1250d3c7d", "start_char": 1169, "end_char": 1477, "text_sha256": "c5e2a8e1d3e3a09064b7b233635f7d573f8761b3f6ae18a68bc9b102a2d5874c"} [citrulline-p26592762] Structure of human carbamoyl phosphate synthetase: deciphering the on/off switch of human ureagenesis. (2015). https://pubmed.ncbi.nlm.nih.gov/26592762/ DOI: 10.1038/srep16950
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.

Activated and memory T cells can outstrip alanine supply

Condition: nutrient_deficiency · Mouse T cells are activated or restimulated in dialyzed-serum medium.

Normal role: Alanine is synthesized, transported and incorporated or metabolized according to cell demand and intact enzyme/cofactor machinery.

Recorded consequence: Alanine add-back restores selected translation, growth and cytokine readouts.