Human AMP-activated protein kinase complexes

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Human Caco-2 cells; 40 mM ethanol challenge and AMPK perturbation.

limitations

Not evidence that butyrate makes alcohol exposure safe; AMPK subunit identity is not inferred from the accessed abstract.

nutrient_topic

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

plain_language

Reducing the signaling machinery removed the protective response.

primary_references

Short-chain fatty acids activate AMP-activated protein kinase and ameliorate ethanol-induced intestinal barrier dysfunction in Caco-2 cell monolayers. · 2013 · https://pubmed.ncbi.nlm.nih.gov/24132573/ · DOI 10.3945/jn.113.179549

trigger_kind

machinery_impairment Imported condition classification; unverified.

Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 294–300

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human Caco-2 cells; 40 mM ethanol challenge and AMPK perturbation. · source_derived_draft · unverified_draft

## butyrate-ampk-knockdown Reducing the signaling machinery removed the protective response. AMPK siRNA or compound C removed the barrier protection from SCFA pretreatment, including 2 mM butyrate, against ethanol in Caco-2 cells. Model: Human Caco-2 cells; 40 mM ethanol challenge and AMPK perturbation. Limitations: Not evidence that butyrate makes alcohol exposure safe; AMPK subunit identity is not inferred from the accessed abstract. Evidence access: Primary abstract Short-chain fatty acids activate AMP-activated protein kinase and ameliorate ethanol-induced intestinal barrier dysfunction in Caco-2 cell monolayers. · 2013 · https://pubmed.ncbi.nlm.nih.gov/24132573/ · DOI 10.3945/jn.113.179549

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Human-cell nutrient-withdrawal experiments with AMPK-pathway perturbation.

limitations

This is an adaptive response under culture deprivation, not evidence that chronic dietary deprivation is beneficial.

nutrient_topic

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

plain_language

The response to scarcity helped cells survive it.

primary_references

CARS senses cysteine deprivation to activate AMPK for cell survival. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34472622/ · DOI 10.15252/embj.2021108028

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 148–154

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human-cell nutrient-withdrawal experiments with AMPK-pathway perturbation. · source_derived_draft · unverified_draft

## l-cysteine-ampk-adaptation The response to scarcity helped cells survive it. Blocking AMPK activation increased cell death under cysteine-deficient conditions in the tested cultures. Model: Human-cell nutrient-withdrawal experiments with AMPK-pathway perturbation. Limitations: This is an adaptive response under culture deprivation, not evidence that chronic dietary deprivation is beneficial. Evidence access: Primary abstract CARS senses cysteine deprivation to activate AMPK for cell survival. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34472622/ · DOI 10.15252/embj.2021108028

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/mangiferin-research/29563875.fulltext.txt", "locator": "Primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1a48a1f92d67cd91638969bb1ec3cb9f18cb3cb4e29c7e5f2bacf627dda76415", "start_char": 33073, "end_char": 35334, "text_sha256": "166efaa83fd229a3e036a60bf4e23173a7b50a3044686fe1a324d6dc604354a9"}

experimental_model

KK-Ay mouse liver experiments and mechanistic HepG2 studies

exposure

Norathyriol in sodium-oleate lipid-loading model; micromolar range

limitations

Phosphorylation and expression are scoped to experiments; no established human fatty-liver therapy or direct SIRT1 ligand claim.

nutrient_topic

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

organism

Homo sapiens for HepG2 experiments; mouse findings separately scoped

plain_language

Removing an upstream component interrupted the response.

primary_references

[mangiferin-p29563875] Mangiferin Improves Hepatic Lipid Metabolism Mainly Through Its Metabolite-Norathyriol by Modulating SIRT-1/AMPK/SREBP-1c Signaling. (2018). https://pubmed.ncbi.nlm.nih.gov/29563875/ DOI: 10.3389/fphar.2018.00201

tissue_or_cell_type

HepG2 cells

trigger_kind

machinery_impairment Imported condition classification; unverified.

Mangiferin: metabolism, signaling and nutrient connections (2026-09-17) · lines 497–508

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · KK-Ay mouse liver experiments and mechanistic HepG2 studies · source_derived_draft · unverified_draft

### mangiferin-lkb1-ampk LKB1 knockdown prevented the norathyriol-associated increase in AMPK phosphorylation. Condition category: machinery_impairment nutrient_topic: Mangiferin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Removing an upstream component interrupted the response. organism: Homo sapiens for HepG2 experiments; mouse findings separately scoped tissue_or_cell_type: HepG2 cells experimental_model: KK-Ay mouse liver experiments and mechanistic HepG2 studies limitations: Phosphorylation and expression are scoped to experiments; no established human fatty-liver therapy or direct SIRT1 ligand claim. exposure: Norathyriol in sodium-oleate lipid-loading model; micromolar range evidence_span: {"source_cache": "artifacts/mangiferin-research/29563875.fulltext.txt", "locator": "Primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1a48a1f92d67cd91638969bb1ec3cb9f18cb3cb4e29c7e5f2bacf627dda76415", "start_char": 33073, "end_char": 35334, "text_sha256": "166efaa83fd229a3e036a60bf4e23173a7b50a3044686fe1a324d6dc604354a9"} [mangiferin-p29563875] Mangiferin Improves Hepatic Lipid Metabolism Mainly Through Its Metabolite-Norathyriol by Modulating SIRT-1/AMPK/SREBP-1c Signaling. (2018). https://pubmed.ncbi.nlm.nih.gov/29563875/ DOI: 10.3389/fphar.2018.00201

evidence_access

Primary full text

experimental_model

HEK293 expression and phosphorylation assays; the paper labels the construct site S485.

limitations

Construct site numbering is retained without silently mapping it to a human endogenous isoform. No universal AMPK inhibition across all tissues.

nutrient_topic

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

plain_language

Changing the inhibitory phosphorylation site interrupted the measured drug interaction.

primary_references

Microbial Imidazole Propionate Affects Responses to Metformin through p38γ-Dependent Inhibitory AMPK Phosphorylation. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32783890/ · DOI 10.1016/j.cmet.2020.07.012

L-Histidine: supply, catabolism, histamine, receptors and cross-nutrient mechanisms (2026-09-19) · lines 330–336

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · HEK293 expression and phosphorylation assays; the paper labels the construct site S485. · source_derived_draft · unverified_draft

## histidine-imp-ampk Changing the inhibitory phosphorylation site interrupted the measured drug interaction. In HEK293 cells, imidazole propionate suppressed metformin-induced AMPK activation; expression of the study-labeled AMPK S485A mutant prevented suppression of activating T172 phosphorylation. Model: HEK293 expression and phosphorylation assays; the paper labels the construct site S485. Limitations: Construct site numbering is retained without silently mapping it to a human endogenous isoform. No universal AMPK inhibition across all tissues. Evidence access: Primary full text Microbial Imidazole Propionate Affects Responses to Metformin through p38γ-Dependent Inhibitory AMPK Phosphorylation. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32783890/ · DOI 10.1016/j.cmet.2020.07.012

acting_entity

s-allylcysteine

dose

Not specified in accessed abstract

duration

Not specified in accessed abstract

evidence_access

Primary abstract

experimental_comparison

SAC addition; pathway inhibitor comparisons

experimental_model

Free-fatty-acid-treated HepG2 cells

interpretation_status

Source-derived research curation; not independent primary verification

limitations

Phosphorylation does not establish direct AMPK binding.

nutrient_topic

S-allylcysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · S-allyl-L-cysteine / SAC

organism

Homo sapiens

plain_language

Energy-regulation signaling changed after exposure.

primary_references

[23465592] S-allyl cysteine attenuates free fatty acid-induced lipogenesis in human HepG2 cells through activation of the AMP-activated protein kinase-dependent pathway. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23465592/ · DOI 10.1016/j.jnutbio.2012.12.006

route

Cell culture

tissue_or_cell_type

Free-fatty-acid-treated HepG2 cells

S-allylcysteine: sulfur signaling, redox responses and cross-nutrient mechanisms (2026-09-20) · lines 185–192

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Free-fatty-acid-treated HepG2 cells · source_derived_draft · unverified_draft

## s-allylcysteine-ampk Energy-regulation signaling changed after exposure. Adding SAC increased AMPK phosphorylation in fatty-acid-treated human HepG2 cells. Model: Free-fatty-acid-treated HepG2 cells Limitations: Phosphorylation does not establish direct AMPK binding. Evidence access: Primary abstract [23465592] S-allyl cysteine attenuates free fatty acid-induced lipogenesis in human HepG2 cells through activation of the AMP-activated protein kinase-dependent pathway. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23465592/ · DOI 10.1016/j.jnutbio.2012.12.006 Structured context: {"organism": "Homo sapiens", "tissue_or_cell_type": "Free-fatty-acid-treated HepG2 cells", "dose": "Not specified in accessed abstract", "duration": "Not specified in accessed abstract", "route": "Cell culture", "experimental_comparison": "SAC addition; pathway inhibitor comparisons", "acting_entity": "s-allylcysteine", "interpretation_status": "Source-derived research curation; not independent primary verification"}

evidence_access

Primary abstract

experimental_model

Human Caco-2 calcium-switch model.

limitations

This does not show that dietary calcium or magnesium supplementation improves the response.

nutrient_topic

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

plain_language

Calcium signaling helped connect butyrate to barrier repair.

primary_references

Sodium Butyrate Promotes Reassembly of Tight Junctions in Caco-2 Monolayers Involving Inhibition of MLCK/MLC2 Pathway and Phosphorylation of PKCβ2. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27735862/ · DOI 10.3390/ijms17101696

Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 270–276

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human Caco-2 calcium-switch model. · source_derived_draft · unverified_draft

## butyrate-calcium-soce Calcium signaling helped connect butyrate to barrier repair. Sodium butyrate promoted store-operated calcium entry and activated the CaMKK-beta/AMPK pathway during Caco-2 tight-junction reassembly, without the change being explained by ATP concentration. Model: Human Caco-2 calcium-switch model. Limitations: This does not show that dietary calcium or magnesium supplementation improves the response. Evidence access: Primary abstract Sodium Butyrate Promotes Reassembly of Tight Junctions in Caco-2 Monolayers Involving Inhibition of MLCK/MLC2 Pathway and Phosphorylation of PKCβ2. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27735862/ · DOI 10.3390/ijms17101696

evidence_access

Primary abstract

experimental_model

Human Caco-2 monolayers; calcium-switch and permeability assays.

limitations

Compound C is not uniquely specific for AMPK; this is a culture mechanism, not proven treatment of human intestinal permeability.

nutrient_topic

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

plain_language

An energy-sensing pathway contributed to barrier assembly.

primary_references

Butyrate enhances the intestinal barrier by facilitating tight junction assembly via activation of AMP-activated protein kinase in Caco-2 cell monolayers. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19625695/ · DOI 10.3945/jn.109.104638

Butyrate: microbial production, fuel use, signaling and nutrient interactions (2026-09-19) · lines 262–268

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human Caco-2 monolayers; calcium-switch and permeability assays. · source_derived_draft · unverified_draft

## butyrate-tight-junction-ampk An energy-sensing pathway contributed to barrier assembly. Butyrate increased AMPK activity and accelerated tight-junction assembly in human Caco-2 monolayers; compound C abolished the improvement in electrical resistance. Model: Human Caco-2 monolayers; calcium-switch and permeability assays. Limitations: Compound C is not uniquely specific for AMPK; this is a culture mechanism, not proven treatment of human intestinal permeability. Evidence access: Primary abstract Butyrate enhances the intestinal barrier by facilitating tight junction assembly via activation of AMP-activated protein kinase in Caco-2 cell monolayers. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19625695/ · DOI 10.3945/jn.109.104638

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary full text

experimental_model

HeLa experiments selected to avoid myogenesis confounding; 50 micromolar resveratrol.

limitations

RNAi does not make all tissue responses Epac1-dependent.

nutrient_topic

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

plain_language

A cAMP effector is a tested dependency.

primary_references

Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22304913/ · DOI 10.1016/j.cell.2012.01.017

trigger_kind

machinery_impairment Imported condition classification; unverified.

Resveratrol: metabolites, target selectivity and cross-nutrient mechanisms (2026-09-19) · lines 238–244

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · HeLa experiments selected to avoid myogenesis confounding; 50 micromolar resveratrol. · source_derived_draft · unverified_draft

## resveratrol-epac-loss A cAMP effector is a tested dependency. Epac1 siRNA, unlike PKA catalytic-subunit siRNA, blocked resveratrol-induced AMPK/ACC phosphorylation in human HeLa cells. Model: HeLa experiments selected to avoid myogenesis confounding; 50 micromolar resveratrol. Limitations: RNAi does not make all tissue responses Epac1-dependent. Evidence access: Primary full text Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22304913/ · DOI 10.1016/j.cell.2012.01.017

evidence_access

Primary abstract

experimental_model

Randomized double-blind crossover; resVida preparation.

limitations

HOMA is not a clamp; no increase in mitochondrial content and no long-term disease outcome were demonstrated.

nutrient_topic

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

plain_language

A small controlled human study found several metabolic changes.

primary_references

Calorie restriction-like effects of 30 days of resveratrol supplementation on energy metabolism and metabolic profile in obese humans. · 2011 · https://pubmed.ncbi.nlm.nih.gov/22055504/ · DOI 10.1016/j.cmet.2011.10.002

Resveratrol: metabolites, target selectivity and cross-nutrient mechanisms (2026-09-19) · lines 454–460

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Randomized double-blind crossover; resVida preparation. · source_derived_draft · unverified_draft

## resveratrol-human-metabolic-positive A small controlled human study found several metabolic changes. In 11 obese men, 150 mg/day resveratrol for 30 days increased muscle AMPK activation and SIRT1/PGC-1alpha protein, improved fatty-acid-supported mitochondrial respiration and reduced liver fat and selected metabolic markers. Model: Randomized double-blind crossover; resVida preparation. Limitations: HOMA is not a clamp; no increase in mitochondrial content and no long-term disease outcome were demonstrated. Evidence access: Primary abstract Calorie restriction-like effects of 30 days of resveratrol supplementation on energy metabolism and metabolic profile in obese humans. · 2011 · https://pubmed.ncbi.nlm.nih.gov/22055504/ · DOI 10.1016/j.cmet.2011.10.002

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Pharmacological AMPK-pathway perturbation.

limitations

Compound C has off-target activity; this is not equivalent to AMPK-specific genetic proof.

nutrient_topic

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

plain_language

A kinase-pathway inhibitor also weakened the response.

primary_references

Activation of reactive oxygen species/AMP activated protein kinase signaling mediates fisetin-induced apoptosis in multiple myeloma U266 cells. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22261340/ · DOI 10.1016/j.canlet.2012.01.008

trigger_kind

machinery_impairment Imported condition classification; unverified.

Fisetin: metabolism, cell-state responses 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 · Pharmacological AMPK-pathway perturbation. · source_derived_draft · unverified_draft

## fisetin-u266-ampk-inhibitor A kinase-pathway inhibitor also weakened the response. Compound C blocked fisetin-induced apoptosis in human U266 cells. Model: Pharmacological AMPK-pathway perturbation. Limitations: Compound C has off-target activity; this is not equivalent to AMPK-specific genetic proof. Evidence access: Primary abstract Activation of reactive oxygen species/AMP activated protein kinase signaling mediates fisetin-induced apoptosis in multiple myeloma U266 cells. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22261340/ · DOI 10.1016/j.canlet.2012.01.008

evidence_access

Primary abstract

experimental_model

Human tumor cell culture.

limitations

Different from protection of nonmalignant cells; not an established cancer therapy.

nutrient_topic

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

plain_language

A pro-oxidant response can contribute to cell killing.

primary_references

Activation of reactive oxygen species/AMP activated protein kinase signaling mediates fisetin-induced apoptosis in multiple myeloma U266 cells. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22261340/ · DOI 10.1016/j.canlet.2012.01.008

Fisetin: metabolism, cell-state responses 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 · Human tumor cell culture. · source_derived_draft · unverified_draft

## fisetin-u266-ros A pro-oxidant response can contribute to cell killing. Fisetin increased ROS and AMPK-associated signaling in human U266 myeloma cells undergoing apoptosis. Model: Human tumor cell culture. Limitations: Different from protection of nonmalignant cells; not an established cancer therapy. Evidence access: Primary abstract Activation of reactive oxygen species/AMP activated protein kinase signaling mediates fisetin-induced apoptosis in multiple myeloma U266 cells. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22261340/ · DOI 10.1016/j.canlet.2012.01.008

evidence_span

{"source_cache": "artifacts/metformin-research/12086935.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a7807ae8af1c0f438eeff1dd4106d0198681e72f0333f0556786b9151b0df680", "start_char": 0, "end_char": 1474, "text_sha256": "a7807ae8af1c0f438eeff1dd4106d0198681e72f0333f0556786b9151b0df680"}

experimental_model

Ten weeks of metformin in people with type 2 diabetes with muscle biopsies

exposure

Therapeutic metformin doses for 10 weeks

limitations

A human tissue measurement at therapeutic dose. It is an association within a treatment study, not a demonstration that AMPK causes the glucose disposal change.

nutrient_topic

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

organism

Human

plain_language

At the dose people take, the energy sensor is measurably more active in human muscle.

primary_references

[metformin-p12086935] Metformin increases AMP-activated protein kinase activity in skeletal muscle of subjects with type 2 diabetes. (2002). https://pubmed.ncbi.nlm.nih.gov/12086935/ DOI: 10.2337/diabetes.51.7.2074

tissue_or_cell_type

Skeletal muscle

Metformin: transport, molecular targets, gut mechanisms and nutrient interactions (2026-09-19) · lines 736–747

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Ten weeks of metformin in people with type 2 diabetes with muscle biopsies · source_derived_draft · unverified_draft

### metformin-human-muscle-ampk Ten weeks of metformin significantly increased skeletal-muscle AMPK alpha2 activity with increased Thr172 phosphorylation and decreased acetyl-CoA carboxylase-2 activity in people with type 2 diabetes. 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: At the dose people take, the energy sensor is measurably more active in human muscle. organism: Human tissue_or_cell_type: Skeletal muscle experimental_model: Ten weeks of metformin in people with type 2 diabetes with muscle biopsies limitations: A human tissue measurement at therapeutic dose. It is an association within a treatment study, not a demonstration that AMPK causes the glucose disposal change. exposure: Therapeutic metformin doses for 10 weeks evidence_span: {"source_cache": "artifacts/metformin-research/12086935.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a7807ae8af1c0f438eeff1dd4106d0198681e72f0333f0556786b9151b0df680", "start_char": 0, "end_char": 1474, "text_sha256": "a7807ae8af1c0f438eeff1dd4106d0198681e72f0333f0556786b9151b0df680"} [metformin-p12086935] Metformin increases AMP-activated protein kinase activity in skeletal muscle of subjects with type 2 diabetes. (2002). https://pubmed.ncbi.nlm.nih.gov/12086935/ DOI: 10.2337/diabetes.51.7.2074

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_access

Primary abstract and indexed primary figure descriptions

experimental_model

Human 293T and cancer-cell experimental program.

limitations

CaMKK2 identity does not by itself show dietary calcium depletion or calcium-supplement rescue.

nutrient_topic

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

plain_language

The sensing protein helped bring a kinase and its target together.

primary_references

CARS senses cysteine deprivation to activate AMPK for cell survival. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34472622/ · DOI 10.15252/embj.2021108028

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 140–146

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human 293T and cancer-cell experimental program. · source_derived_draft · unverified_draft

## l-cysteine-cars-camkk2-bridge The sensing protein helped bring a kinase and its target together. Under cysteine-deficient conditions, CARS promoted AMPK association with CaMKK2 and CaMKK2-dependent AMPK phosphorylation. Model: Human 293T and cancer-cell experimental program. Limitations: CaMKK2 identity does not by itself show dietary calcium depletion or calcium-supplement rescue. Evidence access: Primary abstract and indexed primary figure descriptions CARS senses cysteine deprivation to activate AMPK for cell survival. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34472622/ · DOI 10.15252/embj.2021108028

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_access

Primary abstract and indexed primary figure descriptions

experimental_model

Human 293T-centered cell and binding experiments; extracellular cystine withdrawal or 0–200 micromolar titration for eight hours.

limitations

Medium cystine manipulation changes intracellular cysteine; do not relabel it as a controlled human dietary intake.

nutrient_topic

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

plain_language

A protein-synthesis enzyme also helped sense the availability of its amino acid.

primary_references

CARS senses cysteine deprivation to activate AMPK for cell survival. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34472622/ · DOI 10.15252/embj.2021108028

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 132–138

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human 293T-centered cell and binding experiments; extracellular cystine withdrawal or 0–200 micromolar titration for eight hours. · source_derived_draft · unverified_draft

## l-cysteine-cars-sensing A protein-synthesis enzyme also helped sense the availability of its amino acid. Cysteine scarcity promoted CARS association with AMPK gamma-2, whereas cysteine inhibited this association in the reported experiments. Model: Human 293T-centered cell and binding experiments; extracellular cystine withdrawal or 0–200 micromolar titration for eight hours. Limitations: Medium cystine manipulation changes intracellular cysteine; do not relabel it as a controlled human dietary intake. Evidence access: Primary abstract and indexed primary figure descriptions CARS senses cysteine deprivation to activate AMPK for cell survival. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34472622/ · DOI 10.15252/embj.2021108028

evidence_access

Primary abstract

experimental_model

Thirteen adults; seven-day fast, muscle biopsies and exercise testing.

limitations

Not proof that AMPK is unchanged in every tissue or at every time point.

nutrient_topic

Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake

plain_language

A popular fasting signal did not rise in this tissue and protocol.

primary_references

Effects of seven days' fasting on physical performance and metabolic adaptation during exercise in humans. · 2025 · https://pubmed.ncbi.nlm.nih.gov/39747857/ · DOI 10.1038/s41467-024-55418-0

Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 184–190

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Thirteen adults; seven-day fast, muscle biopsies and exercise testing. · source_derived_draft · unverified_draft

## fast-muscle-ampk A popular fasting signal did not rise in this tissue and protocol. Measured muscle AMPK activity was unchanged. Model: Thirteen adults; seven-day fast, muscle biopsies and exercise testing. Limitations: Not proof that AMPK is unchanged in every tissue or at every time point. Evidence access: Primary abstract Effects of seven days' fasting on physical performance and metabolic adaptation during exercise in humans. · 2025 · https://pubmed.ncbi.nlm.nih.gov/39747857/ · DOI 10.1038/s41467-024-55418-0

acting_entity

s-allylcysteine

dose

Not specified in accessed abstract

duration

Not specified in accessed abstract

evidence_access

Primary abstract

experimental_comparison

SAC addition; pathway inhibitor comparisons

experimental_model

Free-fatty-acid-treated HepG2 cells

interpretation_status

Source-derived research curation; not independent primary verification

limitations

Abstract does not specify CaMKK isoform, inhibitor selectivity or direct SIRT1 activation. No NAD or calcium depletion is demonstrated.

nutrient_topic

S-allylcysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · S-allyl-L-cysteine / SAC

organism

Homo sapiens

plain_language

Upstream pathway perturbations identify dependencies to investigate.

primary_references

[23465592] S-allyl cysteine attenuates free fatty acid-induced lipogenesis in human HepG2 cells through activation of the AMP-activated protein kinase-dependent pathway. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23465592/ · DOI 10.1016/j.jnutbio.2012.12.006

route

Cell culture

tissue_or_cell_type

Free-fatty-acid-treated HepG2 cells

S-allylcysteine: sulfur signaling, redox responses and cross-nutrient mechanisms (2026-09-20) · lines 212–219

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Free-fatty-acid-treated HepG2 cells · source_derived_draft · unverified_draft

## s-allylcysteine-upstream-kinase Upstream pathway perturbations identify dependencies to investigate. Pharmacological inhibitor experiments implicated CaMKK and SIRT1 in SAC-associated AMPK signaling. Model: Free-fatty-acid-treated HepG2 cells Limitations: Abstract does not specify CaMKK isoform, inhibitor selectivity or direct SIRT1 activation. No NAD or calcium depletion is demonstrated. Evidence access: Primary abstract [23465592] S-allyl cysteine attenuates free fatty acid-induced lipogenesis in human HepG2 cells through activation of the AMP-activated protein kinase-dependent pathway. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23465592/ · DOI 10.1016/j.jnutbio.2012.12.006 Structured context: {"organism": "Homo sapiens", "tissue_or_cell_type": "Free-fatty-acid-treated HepG2 cells", "dose": "Not specified in accessed abstract", "duration": "Not specified in accessed abstract", "route": "Cell culture", "experimental_comparison": "SAC addition; pathway inhibitor comparisons", "acting_entity": "s-allylcysteine", "interpretation_status": "Source-derived research curation; not independent primary verification"}