Pyruvate

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

evidence_access

Primary full text

experimental_model

Cancer-cell culture, complex-I-dependent respiration and nutrient manipulation.

limitations

Experimental concentrations and culture composition matter; not a medication adjustment or claim that metformin has one mechanism in all tissues.

nutrient_topic

NAD+ collection; molecular form, preparation, species, exposure and manipulation remain explicit. · NAD+

plain_language

Available nutrients can change the effect of an inhibitor on the same pathway.

primary_references

Environment Dictates Dependence on Mitochondrial Complex I for NAD+ and Aspartate Production and Determines Cancer Cell Sensitivity to Metformin. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27746050/ · DOI 10.1016/j.cmet.2016.09.006

NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19) · lines 220–226

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cancer-cell culture, complex-I-dependent respiration and nutrient manipulation. · source_derived_draft · unverified_draft

## nad-plus-pyruvate-metformin Available nutrients can change the effect of an inhibitor on the same pathway. Pyruvate supplied an alternative electron-acceptor route for NAD+ regeneration and aspartate synthesis, reducing the antiproliferative effect of metformin in the tested cancer cells. Model: Cancer-cell culture, complex-I-dependent respiration and nutrient manipulation. Limitations: Experimental concentrations and culture composition matter; not a medication adjustment or claim that metformin has one mechanism in all tissues. Evidence access: Primary full text Environment Dictates Dependence on Mitochondrial Complex I for NAD+ and Aspartate Production and Determines Cancer Cell Sensitivity to Metformin. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27746050/ · DOI 10.1016/j.cmet.2016.09.006

evidence_span

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experimental_model

Time-resolved cryo-EM and biochemical analysis of human PC

exposure

Pyruvate, ATP and acetyl-CoA catalytic conditions

limitations

Purified-enzyme regulation is not evidence that consuming B5 or biotin stimulates this pathway in every tissue.

nutrient_topic

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

organism

Homo sapiens

plain_language

PC replenishes a key carbon molecule used by several metabolic pathways.

primary_references

[b7-p36283412] Mechanistic insight into allosteric activation of human pyruvate carboxylase by acetyl-CoA. (2022). https://pubmed.ncbi.nlm.nih.gov/36283412/ DOI: 10.1016/j.molcel.2022.09.033

tissue_or_cell_type

Purified human pyruvate carboxylase

Biotin: carboxylases, recycling, deficiency and nutrient interactions (2026-09-17) · lines 546–557

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Time-resolved cryo-EM and biochemical analysis of human PC · source_derived_draft · unverified_draft

### b7-pc-reaction Human PC catalyzes two-step pyruvate carboxylation to oxaloacetate. Condition category: normal nutrient_topic: Biotin research collection; topical membership is not evidence of a direct dietary effect. plain_language: PC replenishes a key carbon molecule used by several metabolic pathways. organism: Homo sapiens tissue_or_cell_type: Purified human pyruvate carboxylase experimental_model: Time-resolved cryo-EM and biochemical analysis of human PC limitations: Purified-enzyme regulation is not evidence that consuming B5 or biotin stimulates this pathway in every tissue. exposure: Pyruvate, ATP and acetyl-CoA catalytic conditions evidence_span: {"source_cache": "artifacts/biotin-research/36283412.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2a5fb8ec1c27e243b8c8ba158f2c58ab1592d9895eecf16438175b2a5778de15", "start_char": 0, "end_char": 1060, "text_sha256": "2a5fb8ec1c27e243b8c8ba158f2c58ab1592d9895eecf16438175b2a5778de15"} [b7-p36283412] Mechanistic insight into allosteric activation of human pyruvate carboxylase by acetyl-CoA. (2022). https://pubmed.ncbi.nlm.nih.gov/36283412/ DOI: 10.1016/j.molcel.2022.09.033

evidence

[{"paper_key": "seifert-2006-pdh-catalysis", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]

experimental_model

Recombinant human E1; transient kinetics.

limitations

Purified-system evidence; nutritional response was not tested.

nutrient

Thiamine (vitamin B1) · Thiamine (vitamin B1)

nutrient_topic

Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)

organism

Homo sapiens

plain_language

Activated vitamin B1 temporarily holds pyruvate while one carbon leaves as carbon dioxide. This is the first reaction, before acetyl-CoA is made.

primary_references

[seifert-2006-pdh-catalysis] Direct kinetic evidence for half-of-the-sites reactivity in the E1 component of the human pyruvate dehydrogenase multienzyme complex through alternating sites cofactor activation (2006). https://pubmed.ncbi.nlm.nih.gov/17042496/ DOI: 10.1021/bi061582l

tissue_or_cell_type

Purified mitochondrial enzyme

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 663–674

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human E1; transient kinetics. · source_derived_draft · unverified_draft

### b1-pdh-pyruvate-covalent-decarboxylation Human PDH E1 forms a covalent lactyl-ThDP intermediate from pyruvate and decarboxylates it, retaining the two-carbon fragment on ThDP. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Activated vitamin B1 temporarily holds pyruvate while one carbon leaves as carbon dioxide. This is the first reaction, before acetyl-CoA is made. organism: Homo sapiens tissue_or_cell_type: Purified mitochondrial enzyme experimental_model: Recombinant human E1; transient kinetics. limitations: Purified-system evidence; nutritional response was not tested. evidence: [{"paper_key": "seifert-2006-pdh-catalysis", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] nutrient: Thiamine (vitamin B1) [seifert-2006-pdh-catalysis] Direct kinetic evidence for half-of-the-sites reactivity in the E1 component of the human pyruvate dehydrogenase multienzyme complex through alternating sites cofactor activation (2006). https://pubmed.ncbi.nlm.nih.gov/17042496/ DOI: 10.1021/bi061582l

evidence_access

Primary abstract

experimental_model

Purified human hepatic enzyme, activity assay and 2.5-angstrom crystal structure.

limitations

Enzyme capacity does not quantify its share of whole-body serine disposal.

nutrient_topic

L-Serine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Serine

plain_language

Serine carbon can enter central metabolism through a B6-dependent breakdown step.

primary_references

Crystal structure of the pyridoxal-5'-phosphate-dependent serine dehydratase from human liver. · 2005 · https://pubmed.ncbi.nlm.nih.gov/15689518/ · DOI 10.1110/ps.041179105

L-Serine: synthesis, one-carbon metabolism, lipids and cross-nutrient mechanisms (2026-09-19) · lines 366–372

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified human hepatic enzyme, activity assay and 2.5-angstrom crystal structure. · source_derived_draft · unverified_draft

## l-serine-sds-catabolism Serine carbon can enter central metabolism through a B6-dependent breakdown step. Human liver serine dehydratase uses PLP to convert L-serine to pyruvate and ammonia; its active holoenzyme was structurally characterized. Model: Purified human hepatic enzyme, activity assay and 2.5-angstrom crystal structure. Limitations: Enzyme capacity does not quantify its share of whole-body serine disposal. Evidence access: Primary abstract Crystal structure of the pyridoxal-5'-phosphate-dependent serine dehydratase from human liver. · 2005 · https://pubmed.ncbi.nlm.nih.gov/15689518/ · DOI 10.1110/ps.041179105

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

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

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

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

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

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

L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 368–374

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

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

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

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

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

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

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

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

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

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

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

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

experimental_model

Human HEK293T cells expressing human reference SLC16A11-V5 and pyronic FRET sensor

exposure

Addition and withdrawal of 0.4 mM pyruvate; neutral pH; Figure 3E reports n=11 and P<0.05. Methods: 2 microgram pyronic and 2 microgram transporter/empty-vector plasmid, transfected 24 hours after plating on coverslips 72 hours before assay.

limitations

Selected primary main-text results, figure legend and methods reviewed through indexed PMC passages; supplements not independently reviewed. Difference was observed at neutral pH, not at acidic pH. This is not a K562 experiment and does not establish the mechanism of the genetic interaction. SLC16A11 has intracellular and cell-surface pools; pyruvate transport direction depends on gradients.

organism

Human

primary_locator

Results: SLC16A11 is a H+-coupled monocarboxylate transporter; Figure 3D-E; pyruvate transport methods.

primary_references

https://doi.org/10.1016/j.cell.2017.06.011

SLC16A11 and mitochondrial glutathione: published screen connection and transport evidence · lines 51–57

Primary sources 2022 and 2017, plus labelled descriptive reanalysis on 2026-09-20. · supports · Human HEK293T cells expressing human reference SLC16A11-V5 and pyronic FRET sensor · source_derived_draft · unverified_draft

HEK293T cells expressing reference SLC16A11 showed approximately 45 percent higher pyruvate efflux rate than empty-vector controls in the reported assay. primary_references: https://doi.org/10.1016/j.cell.2017.06.011 primary_locator: Results: SLC16A11 is a H+-coupled monocarboxylate transporter; Figure 3D-E; pyruvate transport methods. organism: Human experimental_model: Human HEK293T cells expressing human reference SLC16A11-V5 and pyronic FRET sensor exposure: Addition and withdrawal of 0.4 mM pyruvate; neutral pH; Figure 3E reports n=11 and P<0.05. Methods: 2 microgram pyronic and 2 microgram transporter/empty-vector plasmid, transfected 24 hours after plating on coverslips 72 hours before assay. limitations: Selected primary main-text results, figure legend and methods reviewed through indexed PMC passages; supplements not independently reviewed. Difference was observed at neutral pH, not at acidic pH. This is not a K562 experiment and does not establish the mechanism of the genetic interaction. SLC16A11 has intracellular and cell-surface pools; pyruvate transport direction depends on gradients.

experimental_model

Human HEK293T cells expressing human reference SLC16A11-V5 and pyronic FRET sensor

exposure

Addition and withdrawal of 0.4 mM pyruvate; neutral pH; Figure 3E reports n=11 and P<0.05. Methods: 2 microgram pyronic and 2 microgram transporter/empty-vector plasmid, transfected 24 hours after plating on coverslips 72 hours before assay.

limitations

Selected primary main-text results, figure legend and methods reviewed through indexed PMC passages; supplements not independently reviewed. Difference was observed at neutral pH, not at acidic pH. This is not a K562 experiment and does not establish the mechanism of the genetic interaction. SLC16A11 has intracellular and cell-surface pools; pyruvate transport direction depends on gradients.

organism

Human

primary_locator

Results: SLC16A11 is a H+-coupled monocarboxylate transporter; Figure 3D-E; pyruvate transport methods.

primary_references

https://doi.org/10.1016/j.cell.2017.06.011

SLC16A11 and mitochondrial glutathione: published screen connection and transport evidence · lines 42–48

Primary sources 2022 and 2017, plus labelled descriptive reanalysis on 2026-09-20. · supports · Human HEK293T cells expressing human reference SLC16A11-V5 and pyronic FRET sensor · source_derived_draft · unverified_draft

HEK293T cells expressing reference SLC16A11 showed approximately 45 percent higher pyruvate influx rate than empty-vector controls in the reported assay. primary_references: https://doi.org/10.1016/j.cell.2017.06.011 primary_locator: Results: SLC16A11 is a H+-coupled monocarboxylate transporter; Figure 3D-E; pyruvate transport methods. organism: Human experimental_model: Human HEK293T cells expressing human reference SLC16A11-V5 and pyronic FRET sensor exposure: Addition and withdrawal of 0.4 mM pyruvate; neutral pH; Figure 3E reports n=11 and P<0.05. Methods: 2 microgram pyronic and 2 microgram transporter/empty-vector plasmid, transfected 24 hours after plating on coverslips 72 hours before assay. limitations: Selected primary main-text results, figure legend and methods reviewed through indexed PMC passages; supplements not independently reviewed. Difference was observed at neutral pH, not at acidic pH. This is not a K562 experiment and does not establish the mechanism of the genetic interaction. SLC16A11 has intracellular and cell-surface pools; pyruvate transport direction depends on gradients.

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

Endogenous lipoate synthesis is a separate requirement of the thiamine-dependent PDH pathway.

evidence

[{"paper_key": "mayr-2011-lias", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]

experimental_model

Patient biochemical analysis.

limitations

Single patient; no proof of thiamine-treatment failure mechanism.

nutrient

Thiamine (vitamin B1) · Thiamine (vitamin B1)

nutrient_topic

Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)

organism

Homo sapiens

plain_language

A B1-dependent pathway can fail because its lipoyl machinery is defective. This case does not show that adding thiamine corrects the defect.

primary_references

[mayr-2011-lias] Lipoic acid synthetase deficiency causes neonatal-onset epilepsy, defective mitochondrial energy metabolism, and glycine elevation (2011). https://pubmed.ncbi.nlm.nih.gov/22152680/ DOI: 10.1016/j.ajhg.2011.11.011

tissue_or_cell_type

Muscle and cultured fibroblasts

trigger_kind

machinery_impairment Imported condition classification; unverified.

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 759–771

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

### b1-lias-defect-reduces-pdh The LIAS Arg249His patient had depleted protein-bound lipoyl signal and reduced PDH activity/pyruvate oxidation in investigated muscle and fibroblast preparations. Condition category: machinery_impairment nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A B1-dependent pathway can fail because its lipoyl machinery is defective. This case does not show that adding thiamine corrects the defect. organism: Homo sapiens tissue_or_cell_type: Muscle and cultured fibroblasts experimental_model: Patient biochemical analysis. limitations: Single patient; no proof of thiamine-treatment failure mechanism. evidence: [{"paper_key": "mayr-2011-lias", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] cross_nutrient: Endogenous lipoate synthesis is a separate requirement of the thiamine-dependent PDH pathway. nutrient: Thiamine (vitamin B1) [mayr-2011-lias] Lipoic acid synthetase deficiency causes neonatal-onset epilepsy, defective mitochondrial energy metabolism, and glycine elevation (2011). https://pubmed.ncbi.nlm.nih.gov/22152680/ DOI: 10.1016/j.ajhg.2011.11.011

cross_nutrient

Thiamine-dependent carbon chemistry requires the separate protein-bound lipoyl carrier; free lipoic-acid supplementation was not tested.

evidence

[{"paper_key": "kato-2008-pdh-phosphorylation", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-19", "p-25"], "locator": "incorporation", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]

experimental_model

Human recombinant proteins; radiolabeled pyruvate assay.

limitations

Purified-system evidence; nutritional response was not tested.

nutrient

Thiamine (vitamin B1) · Thiamine (vitamin B1)

nutrient_topic

Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)

organism

Homo sapiens

plain_language

The B1-dependent enzyme passes pyruvate-derived carbon to a lipoyl arm on a different protein. Protein-bound lipoate therefore links E1 chemistry to the next reaction.

primary_references

[kato-2008-pdh-phosphorylation] Structural basis for inactivation of the human pyruvate dehydrogenase complex by phosphorylation: role of disordered phosphorylation loops (2008). https://pubmed.ncbi.nlm.nih.gov/19081061/ DOI: 10.1016/j.str.2008.10.010

tissue_or_cell_type

Purified proteins

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 676–688

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human recombinant proteins; radiolabeled pyruvate assay. · source_derived_draft · unverified_draft

### b1-pdh-lipoyl-acetyl-transfer Recombinant human E1 transferred radiolabel from pyruvate to the lipoylated DLAT L2 domain, directly measuring reductive acetylation. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The B1-dependent enzyme passes pyruvate-derived carbon to a lipoyl arm on a different protein. Protein-bound lipoate therefore links E1 chemistry to the next reaction. organism: Homo sapiens tissue_or_cell_type: Purified proteins experimental_model: Human recombinant proteins; radiolabeled pyruvate assay. limitations: Purified-system evidence; nutritional response was not tested. evidence: [{"paper_key": "kato-2008-pdh-phosphorylation", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-19", "p-25"], "locator": "incorporation", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] cross_nutrient: Thiamine-dependent carbon chemistry requires the separate protein-bound lipoyl carrier; free lipoic-acid supplementation was not tested. nutrient: Thiamine (vitamin B1) [kato-2008-pdh-phosphorylation] Structural basis for inactivation of the human pyruvate dehydrogenase complex by phosphorylation: role of disordered phosphorylation loops (2008). https://pubmed.ncbi.nlm.nih.gov/19081061/ DOI: 10.1016/j.str.2008.10.010

availability_state

nutrient_deficiency Imported condition classification; unverified.

experimental_model

Six postoperative cases with severely limited oral intake.

exposure

Study-specific exposure described in the model; no regimen inferred beyond the accessed evidence.

limitations

Clinical observations; no isolated test of PDH activity or tissue-specific thiamine threshold.

nutrient_topic

Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)

organism

Homo sapiens

plain_language

Calories alone did not supply the cofactors needed to use them normally.

primary_references

[b1-nakasaki1997] Clinical and biochemical aspects of thiamine treatment for metabolic acidosis during total parenteral nutrition (1997). https://pubmed.ncbi.nlm.nih.gov/9106788/ DOI: 10.1016/s0899-9007(96)00384-x

tissue_or_cell_type

Blood/systemic metabolism

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1783–1793

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Six postoperative cases with severely limited oral intake. · source_derived_draft · unverified_draft

### b1-tpn-lactate-pyruvate Six patients developed severe lactic acidosis within four weeks of vitamin-unsupplemented parenteral nutrition; lactate and pyruvate were elevated. Condition category: nutrient_deficiency nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Calories alone did not supply the cofactors needed to use them normally. organism: Homo sapiens tissue_or_cell_type: Blood/systemic metabolism experimental_model: Six postoperative cases with severely limited oral intake. limitations: Clinical observations; no isolated test of PDH activity or tissue-specific thiamine threshold. exposure: Study-specific exposure described in the model; no regimen inferred beyond the accessed evidence. [b1-nakasaki1997] Clinical and biochemical aspects of thiamine treatment for metabolic acidosis during total parenteral nutrition (1997). https://pubmed.ncbi.nlm.nih.gov/9106788/ DOI: 10.1016/s0899-9007(96)00384-x

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_location

Abstract

evidence_span

State 4 respiration did not change

experimental_model

Rats fed a low-thiamine diet with pyrithiamine; intact coupled brain mitochondria isolated and assayed with defined respiratory substrates.

exposure

Low-thiamine diet plus pyrithiamine in rats

limitations

Does not demonstrate that thiamine directly forms part of the respiratory chain or that all electron-transport activity fails.

nutrient_topic

Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)

organism

Rattus norvegicus

plain_language

The mitochondrial deficit depended on both substrate and respiratory state.

primary_references

[parker-1984-brain-mitochondria] Brain mitochondrial metabolism in experimental thiamine deficiency (1984). https://pubmed.ncbi.nlm.nih.gov/6493495/ DOI: 10.1212/wnl.34.11.1477

tissue_or_cell_type

Isolated brain mitochondria

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1127–1139

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rats fed a low-thiamine diet with pyrithiamine; intact coupled brain mitochondria isolated and assayed with defined respiratory substrates. · source_derived_draft · unverified_draft

### thiamine-def-brain-state3-respiration Brain mitochondrial state 3 respiration fell with pyruvate/malate, 2-oxoglutarate or glutamate as substrates; state 4 respiration did not change. Condition category: nutrient_deficiency nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The mitochondrial deficit depended on both substrate and respiratory state. organism: Rattus norvegicus tissue_or_cell_type: Isolated brain mitochondria experimental_model: Rats fed a low-thiamine diet with pyrithiamine; intact coupled brain mitochondria isolated and assayed with defined respiratory substrates. limitations: Does not demonstrate that thiamine directly forms part of the respiratory chain or that all electron-transport activity fails. evidence_location: Abstract evidence_span: State 4 respiration did not change exposure: Low-thiamine diet plus pyrithiamine in rats [parker-1984-brain-mitochondria] Brain mitochondrial metabolism in experimental thiamine deficiency (1984). https://pubmed.ncbi.nlm.nih.gov/6493495/ DOI: 10.1212/wnl.34.11.1477

evidence_span

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experimental_model

High-fat-fed mice and differentiated C2C12 myotube experiments

exposure

Dietary mangiferin in mice; pharmacological cell exposures

limitations

Preclinical experiments; no proof of direct binding or correction of human vitamin deficiency.

nutrient_topic

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

organism

Mus musculus

plain_language

An enzyme complex linking glycolysis to mitochondrial metabolism became more active.

primary_references

[mangiferin-p24848064] Mangiferin stimulates carbohydrate oxidation and protects against metabolic disorders induced by high-fat diets. (2014). https://pubmed.ncbi.nlm.nih.gov/24848064/ DOI: 10.2337/db14-0006

tissue_or_cell_type

Skeletal muscle and cultured myotubes

Mangiferin: metabolism, signaling and nutrient connections (2026-09-17) · lines 340–351

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · High-fat-fed mice and differentiated C2C12 myotube experiments · source_derived_draft · unverified_draft

### mangiferin-pdh-activity PDH activity increased in assays using mitochondrial protein from mangiferin-treated C2C12 cells. Condition category: normal nutrient_topic: Mangiferin research collection; topical membership is not evidence of a direct dietary effect. plain_language: An enzyme complex linking glycolysis to mitochondrial metabolism became more active. organism: Mus musculus tissue_or_cell_type: Skeletal muscle and cultured myotubes experimental_model: High-fat-fed mice and differentiated C2C12 myotube experiments limitations: Preclinical experiments; no proof of direct binding or correction of human vitamin deficiency. exposure: Dietary mangiferin in mice; pharmacological cell exposures evidence_span: {"source_cache": "artifacts/mangiferin-research/24848064.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5f12809489e236c3dd9888aae3746eb22ff9cbea4271c9f60764bed3b5f9d251", "start_char": 0, "end_char": 1761, "text_sha256": "5f12809489e236c3dd9888aae3746eb22ff9cbea4271c9f60764bed3b5f9d251"} [mangiferin-p24848064] Mangiferin stimulates carbohydrate oxidation and protects against metabolic disorders induced by high-fat diets. (2014). https://pubmed.ncbi.nlm.nih.gov/24848064/ DOI: 10.2337/db14-0006

evidence_access

Primary abstract

experimental_model

Intact-mitochondrial IC50 approximately 163 micromolar.

limitations

Transport limitation is an interpretation; no direct MPC binding or biotin antagonism was shown.

nutrient_topic

Fisetin collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Fisetin

plain_language

Membrane access may matter more than direct carboxylase inhibition.

primary_references

The actions of fisetin on glucose metabolism in the rat liver. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20084677/ · DOI 10.1002/cbf.1635

Fisetin: metabolism, cell-state responses and cross-nutrient mechanisms (2026-09-19) · lines 328–334

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Intact-mitochondrial IC50 approximately 163 micromolar. · source_derived_draft · unverified_draft

## fisetin-rat-pyruvate-access Membrane access may matter more than direct carboxylase inhibition. Fisetin inhibited pyruvate carboxylation in intact rat mitochondria, but not after freeze-thaw disruption. Model: Intact-mitochondrial IC50 approximately 163 micromolar. Limitations: Transport limitation is an interpretation; no direct MPC binding or biotin antagonism was shown. Evidence access: Primary abstract The actions of fisetin on glucose metabolism in the rat liver. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20084677/ · DOI 10.1002/cbf.1635

evidence_span

{"source_cache": "artifacts/metformin-research/15047621.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c4c648ab82a982482ec339309f3cc1c84ffe457073f010b546f7a47ffa2fbdf6", "start_char": 0, "end_char": 1613, "text_sha256": "c4c648ab82a982482ec339309f3cc1c84ffe457073f010b546f7a47ffa2fbdf6"}

experimental_model

Tissue homogenates, isolated mitochondria and intact rat soleus muscle

exposure

Metformin 30 mmol/l in homogenates and 270 micromol/l for 24 h in intact muscle, compared with thiazolidinediones

limitations

Millimolar concentrations in homogenates are far above therapeutic exposure. The comparison drugs are included because the paper measured them together, not as a metformin claim.

nutrient_topic

Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. · Metformin

organism

Rat tissue and isolated mitochondria

plain_language

When the chain is slowed, the cell disposes of pyruvate as lactate instead.

primary_references

[metformin-p15047621] Thiazolidinediones, like metformin, inhibit respiratory complex I: a common mechanism contributing to their antidiabetic actions? (2004). https://pubmed.ncbi.nlm.nih.gov/15047621/ DOI: 10.2337/diabetes.53.4.1052

tissue_or_cell_type

Skeletal muscle

Metformin: transport, molecular targets, gut mechanisms and nutrient interactions (2026-09-19) · lines 450–461

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Tissue homogenates, isolated mitochondria and intact rat soleus muscle · source_derived_draft · unverified_draft

### metformin-muscle-lactate-release Twenty-four-hour exposure of isolated rat soleus muscle to metformin reduced glucose oxidation by about 30% and increased lactate release by about 84%. Condition category: normal nutrient_topic: Metformin research collection; topical membership is not evidence of a direct clinical effect, and pharmacological exposure is not dietary intake. plain_language: When the chain is slowed, the cell disposes of pyruvate as lactate instead. organism: Rat tissue and isolated mitochondria tissue_or_cell_type: Skeletal muscle experimental_model: Tissue homogenates, isolated mitochondria and intact rat soleus muscle limitations: Millimolar concentrations in homogenates are far above therapeutic exposure. The comparison drugs are included because the paper measured them together, not as a metformin claim. exposure: Metformin 30 mmol/l in homogenates and 270 micromol/l for 24 h in intact muscle, compared with thiazolidinediones evidence_span: {"source_cache": "artifacts/metformin-research/15047621.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c4c648ab82a982482ec339309f3cc1c84ffe457073f010b546f7a47ffa2fbdf6", "start_char": 0, "end_char": 1613, "text_sha256": "c4c648ab82a982482ec339309f3cc1c84ffe457073f010b546f7a47ffa2fbdf6"} [metformin-p15047621] Thiazolidinediones, like metformin, inhibit respiratory complex I: a common mechanism contributing to their antidiabetic actions? (2004). https://pubmed.ncbi.nlm.nih.gov/15047621/ DOI: 10.2337/diabetes.53.4.1052

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Human cancer-cell pharmacological inhibition and proliferation assay.

limitations

Inhibitor results do not resolve individual LDH isoforms or establish a clinical combination.

nutrient_topic

NAD+ collection; molecular form, preparation, species, exposure and manipulation remain explicit. · NAD+

plain_language

Blocking the backup redox route removes its rescue effect.

primary_references

Environment Dictates Dependence on Mitochondrial Complex I for NAD+ and Aspartate Production and Determines Cancer Cell Sensitivity to Metformin. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27746050/ · DOI 10.1016/j.cmet.2016.09.006

trigger_kind

machinery_impairment Imported condition classification; unverified.

NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19) · lines 356–362

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human cancer-cell pharmacological inhibition and proliferation assay. · source_derived_draft · unverified_draft

## nad-plus-ldh-inhibition Blocking the backup redox route removes its rescue effect. The LDH inhibitor GSK2837808A partially inhibited pyruvate-to-lactate conversion and restored metformin sensitivity in pyruvate-containing cancer-cell medium. Model: Human cancer-cell pharmacological inhibition and proliferation assay. Limitations: Inhibitor results do not resolve individual LDH isoforms or establish a clinical combination. Evidence access: Primary full text Environment Dictates Dependence on Mitochondrial Complex I for NAD+ and Aspartate Production and Determines Cancer Cell Sensitivity to Metformin. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27746050/ · DOI 10.1016/j.cmet.2016.09.006

evidence_access

Primary full text

experimental_model

Human cancer-cell nutrient manipulation and NAD+/NADH measurements.

limitations

Reaction-level LDH activity is recorded without assigning an untested isoform.

nutrient_topic

NAD+ collection; molecular form, preparation, species, exposure and manipulation remain explicit. · NAD+

plain_language

An electron acceptor can restore NAD without making new NAD molecules.

primary_references

Environment Dictates Dependence on Mitochondrial Complex I for NAD+ and Aspartate Production and Determines Cancer Cell Sensitivity to Metformin. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27746050/ · DOI 10.1016/j.cmet.2016.09.006

NAD+: compartmental supply, consumption and cross-nutrient mechanisms (2026-09-19) · lines 348–354

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human cancer-cell nutrient manipulation and NAD+/NADH measurements. · source_derived_draft · unverified_draft

## nad-plus-ldh-redox An electron acceptor can restore NAD without making new NAD molecules. In the tested human A549 and HeLa cancer cells, net pyruvate-to-lactate conversion provided an alternative route to regenerate NAD+ from NADH during complex-I inhibition. Model: Human cancer-cell nutrient manipulation and NAD+/NADH measurements. Limitations: Reaction-level LDH activity is recorded without assigning an untested isoform. Evidence access: Primary full text Environment Dictates Dependence on Mitochondrial Complex I for NAD+ and Aspartate Production and Determines Cancer Cell Sensitivity to Metformin. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27746050/ · DOI 10.1016/j.cmet.2016.09.006

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Mouse tissue/urine metabolomics during combined genetic and dietary depletion.

limitations

Metabolite abundance alone is not complete pathway flux or a human diagnostic signature. Correction record: Author correction published 12 December 2025 (2026 issue), PMID 41388205, DOI 10.1038/s41586-025-09780-8: two incorrect day-3 muscle histology panels in Extended Data Fig. 2f,g duplicated day-7 panels and were replaced. The authors state that figure and paper conclusions were unaffected. This is a figure correction, not independent validation. https://www.nature.com/articles/s41586-025-09780-8

nutrient_topic

L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine

plain_language

The shortage affected how efficiently the animal retained and used fuel.

primary_references

Unravelling cysteine-deficiency-associated rapid weight loss. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40399674/ · DOI 10.1038/s41586-025-08996-y

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 316–322

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse tissue/urine metabolomics during combined genetic and dietary depletion. · source_derived_draft · unverified_draft

## l-cysteine-depletion-carbon-loss The shortage affected how efficiently the animal retained and used fuel. Cysteine-depleted Cse-null mice excreted more intermediary metabolites, including pyruvate, citrate, 2-oxoglutarate and orotate, with altered hepatic glycolytic and TCA-cycle metabolism. Model: Mouse tissue/urine metabolomics during combined genetic and dietary depletion. Limitations: Metabolite abundance alone is not complete pathway flux or a human diagnostic signature. Correction record: Author correction published 12 December 2025 (2026 issue), PMID 41388205, DOI 10.1038/s41586-025-09780-8: two incorrect day-3 muscle histology panels in Extended Data Fig. 2f,g duplicated day-7 panels and were replaced. The authors state that figure and paper conclusions were unaffected. This is a figure correction, not independent validation. https://www.nature.com/articles/s41586-025-09780-8 Evidence access: Primary full text Unravelling cysteine-deficiency-associated rapid weight loss. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40399674/ · DOI 10.1038/s41586-025-08996-y

evidence_access

Primary abstract and primary figure descriptions

experimental_model

Purified human MPST structure and kinetics at pH 7.4.

limitations

The upstream cysteine transamination is pathway context; this experiment does not identify its dominant human tissue isoenzyme.

nutrient_topic

L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine

plain_language

A cysteine-derived intermediate hands sulfur to an enzyme before it reaches another acceptor.

primary_references

Structure and kinetic analysis of H2S production by human mercaptopyruvate sulfurtransferase. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23698001/ · DOI 10.1074/jbc.M113.466177

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 452–458

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified human MPST structure and kinetics at pH 7.4. · source_derived_draft · unverified_draft

## l-cysteine-mpst-sulfur-transfer A cysteine-derived intermediate hands sulfur to an enzyme before it reaches another acceptor. Human MPST transfers sulfur from 3-mercaptopyruvate to its active-site Cys248, releasing pyruvate and forming an enzyme-bound persulfide. Model: Purified human MPST structure and kinetics at pH 7.4. Limitations: The upstream cysteine transamination is pathway context; this experiment does not identify its dominant human tissue isoenzyme. Evidence access: Primary abstract and primary figure descriptions Structure and kinetic analysis of H2S production by human mercaptopyruvate sulfurtransferase. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23698001/ · DOI 10.1074/jbc.M113.466177

evidence_access

Primary abstract

experimental_model

Rat hepatocytes; simultaneous synthase and phosphorylase activation.

limitations

Context-dependent null result, not an unexplained contradiction.

nutrient_topic

Lithium collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Lithium

plain_language

Changing the starting substrate changed the outcome.

primary_references

Lithium restores glycogen synthesis from glucose in hepatocytes from diabetic rats. · 1993 · https://pubmed.ncbi.nlm.nih.gov/8460950/ · DOI 10.1006/abbi.1993.1164

Lithium: metal-sensitive enzymes, transport 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 · Rat hepatocytes; simultaneous synthase and phosphorylase activation. · source_derived_draft · unverified_draft

## lithium-glycogen-substrate-null Changing the starting substrate changed the outcome. LiCl did not increase glycogen accumulation with lactate and pyruvate in the same hepatocyte study. Model: Rat hepatocytes; simultaneous synthase and phosphorylase activation. Limitations: Context-dependent null result, not an unexplained contradiction. Evidence access: Primary abstract Lithium restores glycogen synthesis from glucose in hepatocytes from diabetic rats. · 1993 · https://pubmed.ncbi.nlm.nih.gov/8460950/ · DOI 10.1006/abbi.1993.1164

evidence_span

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experimental_model

CRISPR SUOX/GOT1/GOT2 perturbations and sulfur-metabolite assays

exposure

Cysteine-sulfinate and H2S pathway experiments

limitations

Cell-specific contributions; a higher concentration is not a direct measurement of pathway flux.

nutrient_topic

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

organism

Homo sapiens

plain_language

The B6-linked transaminase route can feed sulfur into SUOX.

primary_references

[mo-p33271457] The role of glutamate oxaloacetate transaminases in sulfite biosynthesis and H₂S metabolism. (2021). https://pubmed.ncbi.nlm.nih.gov/33271457/ DOI: 10.1016/j.redox.2020.101800

tissue_or_cell_type

HEK293T cells

Molybdenum: cofactor assembly, sulfur metabolism and nutrient interactions (2026-09-17) · lines 690–701

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · CRISPR SUOX/GOT1/GOT2 perturbations and sulfur-metabolite assays · source_derived_draft · unverified_draft

### mo-got1-sulfite GOT1 was the principal contributor to cysteine-sulfinate conversion to sulfite and pyruvate in the studied human-cell system. Condition category: normal nutrient_topic: Molybdenum research collection; topical membership is not evidence of a direct dietary effect. plain_language: The B6-linked transaminase route can feed sulfur into SUOX. organism: Homo sapiens tissue_or_cell_type: HEK293T cells experimental_model: CRISPR SUOX/GOT1/GOT2 perturbations and sulfur-metabolite assays limitations: Cell-specific contributions; a higher concentration is not a direct measurement of pathway flux. exposure: Cysteine-sulfinate and H2S pathway experiments evidence_span: {"source_cache": "artifacts/molybdenum-research/33271457.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "619710a31160db0927e01193e458277773ebe5e5423629e7dab58888ab6bc617", "start_char": 0, "end_char": 1479, "text_sha256": "619710a31160db0927e01193e458277773ebe5e5423629e7dab58888ab6bc617"} [mo-p33271457] The role of glutamate oxaloacetate transaminases in sulfite biosynthesis and H₂S metabolism. (2021). https://pubmed.ncbi.nlm.nih.gov/33271457/ DOI: 10.1016/j.redox.2020.101800

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

Human Jurkat-centered genetic and metabolic experiments.

limitations

Pyruvate is not a universally effective rescue for every respiratory or transaminase defect.

nutrient_topic

L-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Aspartate

plain_language

Providing an electron acceptor did not bypass the need for functioning synthesis machinery.

primary_references

An Essential Role of the Mitochondrial Electron Transport Chain in Cell Proliferation Is to Enable Aspartate Synthesis. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26232224/ · DOI 10.1016/j.cell.2015.07.016

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 58–64

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human Jurkat-centered genetic and metabolic experiments. · source_derived_draft · unverified_draft

## l-aspartate-pyruvate-got1-gate Providing an electron acceptor did not bypass the need for functioning synthesis machinery. GOT1 loss prevented pyruvate from rescuing aspartate synthesis and proliferation during ETC dysfunction. Model: Human Jurkat-centered genetic and metabolic experiments. Limitations: Pyruvate is not a universally effective rescue for every respiratory or transaminase defect. Evidence access: Primary full text An Essential Role of the Mitochondrial Electron Transport Chain in Cell Proliferation Is to Enable Aspartate Synthesis. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26232224/ · DOI 10.1016/j.cell.2015.07.016

evidence_access

Primary abstract and primary figure descriptions

experimental_model

Proliferating-cell perturbation and tracer study, including human NSCLC models.

limitations

Substrate availability in cell models is not evidence for benefits of oral L-aspartate.

nutrient_topic

L-Aspartate collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Aspartate

plain_language

Aspartate demand for building material can compete with its participation in redox transfer.

primary_references

Aspartate availability drives differential engagement of the malate-aspartate shuttle. · 2026 · https://pubmed.ncbi.nlm.nih.gov/41759528/ · DOI 10.1016/j.molcel.2026.02.004

L-Aspartate: redox transfer, nitrogen partitioning and cross-nutrient mechanisms (2026-09-19) · lines 226–232

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Proliferating-cell perturbation and tracer study, including human NSCLC models. · source_derived_draft · unverified_draft

## l-aspartate-shuttle-aspartate-availability Aspartate demand for building material can compete with its participation in redox transfer. Increasing aspartate availability enhanced malate–aspartate shuttle use and mitochondrial metabolism of glucose-derived pyruvate in proliferating cell experiments. Model: Proliferating-cell perturbation and tracer study, including human NSCLC models. Limitations: Substrate availability in cell models is not evidence for benefits of oral L-aspartate. Evidence access: Primary abstract and primary figure descriptions Aspartate availability drives differential engagement of the malate-aspartate shuttle. · 2026 · https://pubmed.ncbi.nlm.nih.gov/41759528/ · DOI 10.1016/j.molcel.2026.02.004