Nutrient chapter

Fasting / abstention from energy intake

Fasting is a physiological state: the body shifts fuel use, keeps making glucose, produces and uses ketones, and changes hormone and nutrient-sensing signals. This chapter connects those steps to specific enzymes and nutrient dependencies, including magnesium, thiamine, riboflavin, niacin, biotin, choline and copper. Human fasting, cell-starvation experiments and refeeding retain their distinct settings. Open the preserved fasting source for the full readable pathway overview and discovery questions.

89 recorded mechanisms · 2 availability situations · 15 preserved sources. Draft and verified records are labeled separately.

Read recorded mechanisms Open recursive mind map

The mechanisms

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

Lipolysis increased approximately 2.5-fold over 60 hours.
Fasting / abstention from energy intake → Whole-body lipolytic flux source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Six men; isotope tracers and indirect calorimetry during a 60-hour fast.
limitations
Protocol-specific fluxes; no universal hour-by-hour threshold.
nutrient_topic
Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
plain_language
Stored fat supplied more circulating fuel.
primary_references
Fuel and energy metabolism in fasting humans. · 1994 · https://pubmed.ncbi.nlm.nih.gov/8017334/ · DOI 10.1093/ajcn/60.1.29
Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 24–30
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Six men; isotope tracers and indirect calorimetry during a 60-hour fast. · source_derived_draft · unverified_draft
## fast-lipolysis Stored fat supplied more circulating fuel. Lipolysis increased approximately 2.5-fold over 60 hours. Model: Six men; isotope tracers and indirect calorimetry during a 60-hour fast. Limitations: Protocol-specific fluxes; no universal hour-by-hour threshold. Evidence access: Primary abstract Fuel and energy metabolism in fasting humans. · 1994 · https://pubmed.ncbi.nlm.nih.gov/8017334/ · DOI 10.1093/ajcn/60.1.29
Complete structured claim and evidence
Intra-adipocyte fatty-acid re-esterification also increased approximately 2.5-fold.
Fasting / abstention from energy intake → Adipose fatty-acid re-esterification source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Six men; isotope tracers and indirect calorimetry during a 60-hour fast.
limitations
Protocol-specific fluxes; no universal hour-by-hour threshold.
nutrient_topic
Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
plain_language
Some released fat was recycled rather than burned.
primary_references
Fuel and energy metabolism in fasting humans. · 1994 · https://pubmed.ncbi.nlm.nih.gov/8017334/ · DOI 10.1093/ajcn/60.1.29
Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 32–38
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Six men; isotope tracers and indirect calorimetry during a 60-hour fast. · source_derived_draft · unverified_draft
## fast-reesterification Some released fat was recycled rather than burned. Intra-adipocyte fatty-acid re-esterification also increased approximately 2.5-fold. Model: Six men; isotope tracers and indirect calorimetry during a 60-hour fast. Limitations: Protocol-specific fluxes; no universal hour-by-hour threshold. Evidence access: Primary abstract Fuel and energy metabolism in fasting humans. · 1994 · https://pubmed.ncbi.nlm.nih.gov/8017334/ · DOI 10.1093/ajcn/60.1.29
Complete structured claim and evidence
Fat oxidation supplied about 75% of resting energy requirements at 60 hours.
Fasting / abstention from energy intake → Whole-body fat oxidation source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Six men; isotope tracers and indirect calorimetry during a 60-hour fast.
limitations
Protocol-specific fluxes; no universal hour-by-hour threshold.
nutrient_topic
Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
plain_language
Fuel use shifted toward fat.
primary_references
Fuel and energy metabolism in fasting humans. · 1994 · https://pubmed.ncbi.nlm.nih.gov/8017334/ · DOI 10.1093/ajcn/60.1.29
Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 40–46
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Six men; isotope tracers and indirect calorimetry during a 60-hour fast. · source_derived_draft · unverified_draft
## fast-fat-use Fuel use shifted toward fat. Fat oxidation supplied about 75% of resting energy requirements at 60 hours. Model: Six men; isotope tracers and indirect calorimetry during a 60-hour fast. Limitations: Protocol-specific fluxes; no universal hour-by-hour threshold. Evidence access: Primary abstract Fuel and energy metabolism in fasting humans. · 1994 · https://pubmed.ncbi.nlm.nih.gov/8017334/ · DOI 10.1093/ajcn/60.1.29
Complete structured claim and evidence
Glucose oxidation decreased approximately 85%.
Fasting / abstention from energy intake → Whole-body glucose oxidation source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Six men; isotope tracers and indirect calorimetry during a 60-hour fast.
limitations
Protocol-specific fluxes; no universal hour-by-hour threshold.
nutrient_topic
Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
plain_language
The body conserved glucose by burning less of it.
primary_references
Fuel and energy metabolism in fasting humans. · 1994 · https://pubmed.ncbi.nlm.nih.gov/8017334/ · DOI 10.1093/ajcn/60.1.29
Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 48–54
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Six men; isotope tracers and indirect calorimetry during a 60-hour fast. · source_derived_draft · unverified_draft
## fast-glucose-use The body conserved glucose by burning less of it. Glucose oxidation decreased approximately 85%. Model: Six men; isotope tracers and indirect calorimetry during a 60-hour fast. Limitations: Protocol-specific fluxes; no universal hour-by-hour threshold. Evidence access: Primary abstract Fuel and energy metabolism in fasting humans. · 1994 · https://pubmed.ncbi.nlm.nih.gov/8017334/ · DOI 10.1093/ajcn/60.1.29
Complete structured claim and evidence
Proteolysis and protein oxidation increased approximately 50%.
Fasting / abstention from energy intake → Whole-body protein oxidation source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Six men; isotope tracers and indirect calorimetry during a 60-hour fast.
limitations
Protocol-specific fluxes; no universal hour-by-hour threshold.
nutrient_topic
Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
plain_language
This protocol did not preserve all body protein.
primary_references
Fuel and energy metabolism in fasting humans. · 1994 · https://pubmed.ncbi.nlm.nih.gov/8017334/ · DOI 10.1093/ajcn/60.1.29
Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 56–62
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Six men; isotope tracers and indirect calorimetry during a 60-hour fast. · source_derived_draft · unverified_draft
## fast-protein-use This protocol did not preserve all body protein. Proteolysis and protein oxidation increased approximately 50%. Model: Six men; isotope tracers and indirect calorimetry during a 60-hour fast. Limitations: Protocol-specific fluxes; no universal hour-by-hour threshold. Evidence access: Primary abstract Fuel and energy metabolism in fasting humans. · 1994 · https://pubmed.ncbi.nlm.nih.gov/8017334/ · DOI 10.1093/ajcn/60.1.29
Complete structured claim and evidence
The estimated gluconeogenic fraction of glucose production increased from 36% overnight to 78% after 60 hours.
Fasting / abstention from energy intake → Hepatic gluconeogenic flux source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human stable-isotope study of fasting and hepatic UDP-glucose flux.
limitations
Tracer duration and glycogen cycling affect fractional estimates; a percentage is not an absolute production rate.
nutrient_topic
Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
plain_language
New glucose production increasingly replaced stored carbohydrate.
primary_references
Hepatic gluconeogenic fluxes and glycogen turnover during fasting in humans. A stable isotope study. · 1997 · https://pubmed.ncbi.nlm.nih.gov/9276749/ · DOI 10.1172/JCI119644
Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 64–70
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human stable-isotope study of fasting and hepatic UDP-glucose flux. · source_derived_draft · unverified_draft
## fast-gluconeogenesis New glucose production increasingly replaced stored carbohydrate. The estimated gluconeogenic fraction of glucose production increased from 36% overnight to 78% after 60 hours. Model: Human stable-isotope study of fasting and hepatic UDP-glucose flux. Limitations: Tracer duration and glycogen cycling affect fractional estimates; a percentage is not an absolute production rate. Evidence access: Primary abstract Hepatic gluconeogenic fluxes and glycogen turnover during fasting in humans. A stable isotope study. · 1997 · https://pubmed.ncbi.nlm.nih.gov/9276749/ · DOI 10.1172/JCI119644
Complete structured claim and evidence
At 60 hours, glycogen-derived plasma glucose flux of 0.32 mg/kg/min was balanced by 0.31 mg/kg/min retained gluconeogenic carbon.
Fasting / abstention from energy intake → Hepatic glycogen turnover source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human isotope model; 60-hour fast.
limitations
Does not support a fixed time when all glycogen becomes empty.
nutrient_topic
Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
plain_language
The liver still cycled carbon through glycogen.
primary_references
Hepatic gluconeogenic fluxes and glycogen turnover during fasting in humans. A stable isotope study. · 1997 · https://pubmed.ncbi.nlm.nih.gov/9276749/ · DOI 10.1172/JCI119644
Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 72–78
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human isotope model; 60-hour fast. · source_derived_draft · unverified_draft
## fast-glycogen-cycle The liver still cycled carbon through glycogen. At 60 hours, glycogen-derived plasma glucose flux of 0.32 mg/kg/min was balanced by 0.31 mg/kg/min retained gluconeogenic carbon. Model: Human isotope model; 60-hour fast. Limitations: Does not support a fixed time when all glycogen becomes empty. Evidence access: Primary abstract Hepatic gluconeogenic fluxes and glycogen turnover during fasting in humans. A stable isotope study. · 1997 · https://pubmed.ncbi.nlm.nih.gov/9276749/ · DOI 10.1172/JCI119644
Complete structured claim and evidence
Estimated renal contribution to whole-body glucose production increased from 5 ± 2% postabsorptively to 24 ± 3% after 60 hours.
Fasting / abstention from energy intake → Renal glucose production source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Healthy humans; renal/hepatic exchange and isotope measurements.
limitations
Study-specific estimates, not a universal organ split.
nutrient_topic
Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
plain_language
The kidney helped make glucose, alongside the liver.
primary_references
Contributions by kidney and liver to glucose production in the postabsorptive state and after 60 h of fasting. · 1999 · https://pubmed.ncbi.nlm.nih.gov/10334304/ · DOI 10.2337/diabetes.48.2.292
Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 80–86
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Healthy humans; renal/hepatic exchange and isotope measurements. · source_derived_draft · unverified_draft
## fast-kidney-glucose The kidney helped make glucose, alongside the liver. Estimated renal contribution to whole-body glucose production increased from 5 ± 2% postabsorptively to 24 ± 3% after 60 hours. Model: Healthy humans; renal/hepatic exchange and isotope measurements. Limitations: Study-specific estimates, not a universal organ split. Evidence access: Primary abstract Contributions by kidney and liver to glucose production in the postabsorptive state and after 60 h of fasting. · 1999 · https://pubmed.ncbi.nlm.nih.gov/10334304/ · DOI 10.2337/diabetes.48.2.292
Complete structured claim and evidence
Beta-hydroxybutyrate and acetoacetate became predominant cerebral fuels after prolonged starvation.
Fasting / abstention from energy intake → Cerebral ketone-body utilization source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Three obese patients; cerebral catheterization after 5–6 weeks of starvation.
limitations
This prolonged, small historical study does not establish a 16-hour switch.
nutrient_topic
Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
plain_language
The brain can use ketones while retaining a glucose requirement.
primary_references
Brain metabolism during fasting. · 1967 · https://pubmed.ncbi.nlm.nih.gov/6061736/ · DOI 10.1172/JCI105650
Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 88–94
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Three obese patients; cerebral catheterization after 5–6 weeks of starvation. · source_derived_draft · unverified_draft
## fast-brain-ketones The brain can use ketones while retaining a glucose requirement. Beta-hydroxybutyrate and acetoacetate became predominant cerebral fuels after prolonged starvation. Model: Three obese patients; cerebral catheterization after 5–6 weeks of starvation. Limitations: This prolonged, small historical study does not establish a 16-hour switch. Evidence access: Primary abstract Brain metabolism during fasting. · 1967 · https://pubmed.ncbi.nlm.nih.gov/6061736/ · DOI 10.1172/JCI105650
Complete structured claim and evidence
Somatostatin suppressed splanchnic glucose output by 50–100% for five hours after a 60-hour fast; the overnight-fast reduction was transient.
Somatostatin-induced combined insulin and glucagon suppression → Splanchnic glucose output source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Healthy humans; somatostatin, glucose infusion to maintain euglycemia, organ exchange measurements.
limitations
Insulin and glucagon were both suppressed. The experiment does not isolate glucagon alone.
nutrient_topic
Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
plain_language
Hormonal control changed with the fasting state.
primary_references
Role of basal glucagon levels in the regulation of splanchnic glucose output and ketogenesis in insulin-deficient humans. · 1984 · https://pubmed.ncbi.nlm.nih.gov/6146427/ · DOI 10.1111/j.1475-097x.1984.tb00117.x
Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 96–102
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Healthy humans; somatostatin, glucose infusion to maintain euglycemia, organ exchange measurements. · source_derived_draft · unverified_draft
## fast-hormone-withdrawal Hormonal control changed with the fasting state. Somatostatin suppressed splanchnic glucose output by 50–100% for five hours after a 60-hour fast; the overnight-fast reduction was transient. Model: Healthy humans; somatostatin, glucose infusion to maintain euglycemia, organ exchange measurements. Limitations: Insulin and glucagon were both suppressed. The experiment does not isolate glucagon alone. Evidence access: Primary abstract Role of basal glucagon levels in the regulation of splanchnic glucose output and ketogenesis in insulin-deficient humans. · 1984 · https://pubmed.ncbi.nlm.nih.gov/6146427/ · DOI 10.1111/j.1475-097x.1984.tb00117.x
Complete structured claim and evidence
Mitochondrial HMGCS2 catalyzes condensation of acetyl-CoA and acetoacetyl-CoA to form HMG-CoA.
Acetyl-CoA → (S)-3-Hydroxy-3-methylglutaryl-CoA source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human HMGCS1/HMGCS2 structures and catalytic reaction description.
limitations
The mitochondrial isoform is distinct from cytosolic HMGCS1 in sterol synthesis.
nutrient_topic
Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
plain_language
Two carbon-carrying molecules combine on the ketone-production route.
primary_references
Crystal structures of human HMG-CoA synthase isoforms provide insights into inherited ketogenesis disorders and inhibitor design. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20346956/ · DOI 10.1016/j.jmb.2010.03.034
Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 104–110
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human HMGCS1/HMGCS2 structures and catalytic reaction description. · source_derived_draft · unverified_draft
## fast-hmgcs2 Two carbon-carrying molecules combine on the ketone-production route. Mitochondrial HMGCS2 catalyzes condensation of acetyl-CoA and acetoacetyl-CoA to form HMG-CoA. Model: Human HMGCS1/HMGCS2 structures and catalytic reaction description. Limitations: The mitochondrial isoform is distinct from cytosolic HMGCS1 in sterol synthesis. Evidence access: Primary abstract Crystal structures of human HMG-CoA synthase isoforms provide insights into inherited ketogenesis disorders and inhibitor design. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20346956/ · DOI 10.1016/j.jmb.2010.03.034
Complete structured claim and evidence
Human HMGCL cleaves HMG-CoA to acetoacetate and acetyl-CoA.
(S)-3-Hydroxy-3-methylglutaryl-CoA → Acetoacetate source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract and indexed full-text introduction, PMC2924059
experimental_model
Human HMGCL structural study; reaction in primary introduction.
limitations
Mitochondrial pathway; net flux is not inferred from structure alone.
nutrient_topic
Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
plain_language
A second enzyme releases the first ketone body.
primary_references
Functional insights into human HMG-CoA lyase from structures of Acyl-CoA-containing ternary complexes. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20558737/ · DOI 10.1074/jbc.M110.139931
Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 112–118
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human HMGCL structural study; reaction in primary introduction. · source_derived_draft · unverified_draft
## fast-hmgcl A second enzyme releases the first ketone body. Human HMGCL cleaves HMG-CoA to acetoacetate and acetyl-CoA. Model: Human HMGCL structural study; reaction in primary introduction. Limitations: Mitochondrial pathway; net flux is not inferred from structure alone. Evidence access: Primary abstract and indexed full-text introduction, PMC2924059 Functional insights into human HMG-CoA lyase from structures of Acyl-CoA-containing ternary complexes. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20558737/ · DOI 10.1074/jbc.M110.139931
Complete structured claim and evidence
In HMGCL ternary structures Mg2+ coordinates His233, His235, Asp42, water and substrate/inhibitor oxygen atoms.
Mg2+ → Human HMG-CoA lyase / HMGCL source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human wild-type inhibitor complex and R41M substrate complex.
limitations
Structural dependence does not show that dietary magnesium limits ketosis in a replete person.
nutrient_topic
Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
plain_language
Magnesium participates directly in this ketone-producing enzyme.
primary_references
Functional insights into human HMG-CoA lyase from structures of Acyl-CoA-containing ternary complexes. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20558737/ · DOI 10.1074/jbc.M110.139931
Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 120–126
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human wild-type inhibitor complex and R41M substrate complex. · source_derived_draft · unverified_draft
## fast-hmgcl-magnesium Magnesium participates directly in this ketone-producing enzyme. In HMGCL ternary structures Mg2+ coordinates His233, His235, Asp42, water and substrate/inhibitor oxygen atoms. Model: Human wild-type inhibitor complex and R41M substrate complex. Limitations: Structural dependence does not show that dietary magnesium limits ketosis in a replete person. Evidence access: Primary abstract Functional insights into human HMG-CoA lyase from structures of Acyl-CoA-containing ternary complexes. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20558737/ · DOI 10.1074/jbc.M110.139931
Complete structured claim and evidence
BDH1 interconverts D-beta-hydroxybutyrate and acetoacetate using the NAD+/NADH redox pair.
D-(R)-beta-hydroxybutyrate → Acetoacetate source_derived_draftungraded
Experimental context and source evidence
evidence_access
Reactome curated reaction and its primary-study attribution
experimental_model
Curated human mitochondrial reaction R-HSA-73920; cites human-heart BDH1 work.
limitations
Reversible reaction; redox state and compartment determine net direction.
nutrient_topic
Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
plain_language
Ketone interconversion connects to niacin-derived redox chemistry.
primary_references
BDH1: D-beta-hydroxybutyrate + NAD+ ⇌ acetoacetate + NADH + H+ · 2003 · https://reactome.org/content/detail/R-HSA-73920
Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 128–134
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Curated human mitochondrial reaction R-HSA-73920; cites human-heart BDH1 work. · source_derived_draft · unverified_draft
## fast-bdh-reaction Ketone interconversion connects to niacin-derived redox chemistry. BDH1 interconverts D-beta-hydroxybutyrate and acetoacetate using the NAD+/NADH redox pair. Model: Curated human mitochondrial reaction R-HSA-73920; cites human-heart BDH1 work. Limitations: Reversible reaction; redox state and compartment determine net direction. Evidence access: Reactome curated reaction and its primary-study attribution BDH1: D-beta-hydroxybutyrate + NAD+ ⇌ acetoacetate + NADH + H+ · 2003 · https://reactome.org/content/detail/R-HSA-73920
Complete structured claim and evidence
Human-heart mitochondrial BDH1 was described as specifically requiring phosphatidylcholine for enzymic activity.
Phosphatidylcholine → Human mitochondrial D-beta-hydroxybutyrate dehydrogenase / BDH1 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Primary human-heart enzyme cloning and characterization.
limitations
Does not establish that supplemental choline increases ketone use.
nutrient_topic
Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
plain_language
A membrane lipid linked to choline supports a ketone enzyme.
primary_references
Molecular cloning and characterization of (R)-3-hydroxybutyrate dehydrogenase from human heart. · 1992 · https://pubmed.ncbi.nlm.nih.gov/1639787/
Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 136–142
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Primary human-heart enzyme cloning and characterization. · source_derived_draft · unverified_draft
## fast-bdh-choline A membrane lipid linked to choline supports a ketone enzyme. Human-heart mitochondrial BDH1 was described as specifically requiring phosphatidylcholine for enzymic activity. Model: Primary human-heart enzyme cloning and characterization. Limitations: Does not establish that supplemental choline increases ketone use. Evidence access: Primary abstract Molecular cloning and characterization of (R)-3-hydroxybutyrate dehydrogenase from human heart. · 1992 · https://pubmed.ncbi.nlm.nih.gov/1639787/
Complete structured claim and evidence
OXCT1 transfers CoA from succinyl-CoA to acetoacetate, yielding acetoacetyl-CoA and succinate.
Acetoacetate → Acetoacetyl-CoA source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract and indexed full-text introduction, PMC3825524
experimental_model
Human SCOT structure; described ketolysis reaction.
limitations
Production of ketones and ability to use them are different capacities.
nutrient_topic
Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
plain_language
Using ketones requires a separate activation step.
primary_references
A structural mapping of mutations causing succinyl-CoA:3-ketoacid CoA transferase (SCOT) deficiency. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23420214/ · DOI 10.1007/s10545-013-9589-z
Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 144–150
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human SCOT structure; described ketolysis reaction. · source_derived_draft · unverified_draft
## fast-scot Using ketones requires a separate activation step. OXCT1 transfers CoA from succinyl-CoA to acetoacetate, yielding acetoacetyl-CoA and succinate. Model: Human SCOT structure; described ketolysis reaction. Limitations: Production of ketones and ability to use them are different capacities. Evidence access: Primary abstract and indexed full-text introduction, PMC3825524 A structural mapping of mutations causing succinyl-CoA:3-ketoacid CoA transferase (SCOT) deficiency. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23420214/ · DOI 10.1007/s10545-013-9589-z
Complete structured claim and evidence
G219E and G324E constructs had no detectable SCOT activity; patients had episodic ketoacidosis.
Human succinyl-CoA:3-ketoacid CoA transferase / OXCT1 → Ketoacidosis associated with SCOT deficiency source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Three SCOT-deficient patients and mutant expression in fibroblasts.
limitations
Rare genetic disease, not nutritional ketosis in healthy adults.
nutrient_topic
Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
plain_language
Ketones can accumulate when utilization machinery fails.
primary_references
Succinyl-CoA:3-ketoacid CoA transferase (SCOT): cloning of the human SCOT gene, tertiary structural modeling of the human SCOT monomer, and characterization of three pathogenic mutations. · 2000 · https://pubmed.ncbi.nlm.nih.gov/10964512/ · DOI 10.1006/geno.2000.6282
trigger_kind
machinery_impairment Imported condition classification; unverified.
Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 152–158
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Three SCOT-deficient patients and mutant expression in fibroblasts. · source_derived_draft · unverified_draft
## fast-scot-defect Ketones can accumulate when utilization machinery fails. G219E and G324E constructs had no detectable SCOT activity; patients had episodic ketoacidosis. Model: Three SCOT-deficient patients and mutant expression in fibroblasts. Limitations: Rare genetic disease, not nutritional ketosis in healthy adults. Evidence access: Primary abstract Succinyl-CoA:3-ketoacid CoA transferase (SCOT): cloning of the human SCOT gene, tertiary structural modeling of the human SCOT monomer, and characterization of three pathogenic mutations. · 2000 · https://pubmed.ncbi.nlm.nih.gov/10964512/ · DOI 10.1006/geno.2000.6282
Complete structured claim and evidence
Four patients with HMGCS2 or HMGCL deficiency had decompensation with hypoglycemia and absent urinary ketones.
Ketone-body production → Hypoglycemia with inadequate ketone availability source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Four-patient clinical, biochemical and molecular case series.
limitations
Distinct inherited defects; absence of urinary ketones is the reported observation.
nutrient_topic
Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
plain_language
Some bodies cannot make adequate backup fuel under lipolytic stress.
primary_references
Inborn Errors of Ketogenesis: Novel Variants, Clinical Presentation, and Follow-Up in a Series of Four Patients. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38567177/ · DOI 10.1055/s-0042-1749362
trigger_kind
machinery_impairment Imported condition classification; unverified.
Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 160–166
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Four-patient clinical, biochemical and molecular case series. · source_derived_draft · unverified_draft
## fast-synthesis-defects Some bodies cannot make adequate backup fuel under lipolytic stress. Four patients with HMGCS2 or HMGCL deficiency had decompensation with hypoglycemia and absent urinary ketones. Model: Four-patient clinical, biochemical and molecular case series. Limitations: Distinct inherited defects; absence of urinary ketones is the reported observation. Evidence access: Primary abstract Inborn Errors of Ketogenesis: Novel Variants, Clinical Presentation, and Follow-Up in a Series of Four Patients. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38567177/ · DOI 10.1055/s-0042-1749362
Complete structured claim and evidence
A post-bypass patient had fasting hypoglycemia, low BHB and high free fatty acids; carnitine replacement resolved fasting hypoglycemia.
L-Carnitine → Hypoglycemia with inadequate ketone availability source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Cachectic 69-year-old woman, 12 years after gastric bypass; supervised diagnostic fast.
limitations
Single case; impaired mitochondrial transport was inferred. This is not a general carnitine supplement recommendation.
nutrient_topic
Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
plain_language
Fat release was not enough when the next transport step appeared limited.
primary_references
Fasting hypoglycaemia secondary to carnitine deficiency: a late consequence of gastric bypass. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34281938/ · DOI 10.1136/bcr-2021-241703
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 168–174
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Cachectic 69-year-old woman, 12 years after gastric bypass; supervised diagnostic fast. · source_derived_draft · unverified_draft
## fast-carnitine-case Fat release was not enough when the next transport step appeared limited. A post-bypass patient had fasting hypoglycemia, low BHB and high free fatty acids; carnitine replacement resolved fasting hypoglycemia. Model: Cachectic 69-year-old woman, 12 years after gastric bypass; supervised diagnostic fast. Limitations: Single case; impaired mitochondrial transport was inferred. This is not a general carnitine supplement recommendation. Evidence access: Primary abstract Fasting hypoglycaemia secondary to carnitine deficiency: a late consequence of gastric bypass. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34281938/ · DOI 10.1136/bcr-2021-241703
Complete structured claim and evidence
Muscle PDK4 expression increased 13-fold, alongside greater inhibitory PDH phosphorylation.
Fasting / abstention from energy intake → Human pyruvate dehydrogenase kinase 4 / PDK4 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Thirteen adults; seven-day fast, muscle biopsies and exercise testing.
limitations
Co-occurrence supports the pathway interpretation but does not isolate causality.
nutrient_topic
Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
plain_language
Muscle reduced access from carbohydrate into oxidation.
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 176–182
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-pdk4 Muscle reduced access from carbohydrate into oxidation. Muscle PDK4 expression increased 13-fold, alongside greater inhibitory PDH phosphorylation. Model: Thirteen adults; seven-day fast, muscle biopsies and exercise testing. Limitations: Co-occurrence supports the pathway interpretation but does not isolate causality. 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
Complete structured claim and evidence
Measured muscle AMPK activity was unchanged.
Fasting / abstention from energy intake → Skeletal-muscle AMPK activity source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Peak oxygen uptake fell 13% and endurance declined; maximal strength was unchanged.
Fasting / abstention from energy intake → Exercise endurance capacity source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Thirteen adults; seven-day fast, muscle biopsies and exercise testing.
limitations
Measured lean-mass loss also includes water and glycogen; it is not all muscle protein.
nutrient_topic
Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
plain_language
Strength and endurance did not respond identically.
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 192–198
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-exercise Strength and endurance did not respond identically. Peak oxygen uptake fell 13% and endurance declined; maximal strength was unchanged. Model: Thirteen adults; seven-day fast, muscle biopsies and exercise testing. Limitations: Measured lean-mass loss also includes water and glycogen; it is not all muscle protein. 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
Complete structured claim and evidence
Muscle glycogen content was approximately halved.
Fasting / abstention from energy intake → Skeletal-muscle glycogen content source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Thirteen adults; seven-day fast, muscle biopsies and exercise testing.
limitations
This is muscle glycogen, not a measurement of hepatic glycogen.
nutrient_topic
Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
plain_language
Muscle retained some carbohydrate reserve.
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 200–206
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-glycogen-muscle Muscle retained some carbohydrate reserve. Muscle glycogen content was approximately halved. Model: Thirteen adults; seven-day fast, muscle biopsies and exercise testing. Limitations: This is muscle glycogen, not a measurement of hepatic glycogen. 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
Complete structured claim and evidence
Growth-hormone levels increased after 72 hours of fasting.
Fasting / abstention from energy intake → Human growth hormone source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Nine obese men; randomized crossover with overnight fast, 72-hour fast, and fast plus GH blockade.
limitations
Hormone concentration is not a direct measure of anabolic flux.
nutrient_topic
Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
plain_language
Fasting changed hormone signaling without proving muscle growth.
primary_references
Substrate Metabolism and Insulin Sensitivity During Fasting in Obese Human Subjects: Impact of GH Blockade. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28324055/ · DOI 10.1210/jc.2016-3835
Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 208–214
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Nine obese men; randomized crossover with overnight fast, 72-hour fast, and fast plus GH blockade. · source_derived_draft · unverified_draft
## fast-gh-rise Fasting changed hormone signaling without proving muscle growth. Growth-hormone levels increased after 72 hours of fasting. Model: Nine obese men; randomized crossover with overnight fast, 72-hour fast, and fast plus GH blockade. Limitations: Hormone concentration is not a direct measure of anabolic flux. Evidence access: Primary abstract Substrate Metabolism and Insulin Sensitivity During Fasting in Obese Human Subjects: Impact of GH Blockade. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28324055/ · DOI 10.1210/jc.2016-3835
Complete structured claim and evidence
GH blockade abolished fasting-induced insulin resistance, mainly through reduced endogenous glucose production.
Pegvisomant / growth-hormone receptor antagonist → Systemic insulin sensitivity source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Same nine-men protocol, hyperinsulinemic euglycemic clamp.
limitations
Acute adaptation during prolonged fasting differs from long-term diabetes outcomes.
nutrient_topic
Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
plain_language
A counterregulatory hormone helped explain glucose sparing in this experiment.
primary_references
Substrate Metabolism and Insulin Sensitivity During Fasting in Obese Human Subjects: Impact of GH Blockade. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28324055/ · DOI 10.1210/jc.2016-3835
Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 216–222
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Same nine-men protocol, hyperinsulinemic euglycemic clamp. · source_derived_draft · unverified_draft
## fast-gh-blockade A counterregulatory hormone helped explain glucose sparing in this experiment. GH blockade abolished fasting-induced insulin resistance, mainly through reduced endogenous glucose production. Model: Same nine-men protocol, hyperinsulinemic euglycemic clamp. Limitations: Acute adaptation during prolonged fasting differs from long-term diabetes outcomes. Evidence access: Primary abstract Substrate Metabolism and Insulin Sensitivity During Fasting in Obese Human Subjects: Impact of GH Blockade. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28324055/ · DOI 10.1210/jc.2016-3835
Complete structured claim and evidence
Adipose PDE3B transcript levels decreased after fasting, with and without GH blockade.
Fasting / abstention from energy intake → Human phosphodiesterase 3B / PDE3B source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full-text Results: Regulation of lipolysis, DOI 10.1210/jc.2016-3835
experimental_model
Nine obese men; adipose biopsy after 72-hour fast.
limitations
Transcript level is not direct PDE3B enzyme activity.
nutrient_topic
Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
plain_language
A molecular brake on fat release changed.
primary_references
Substrate Metabolism and Insulin Sensitivity During Fasting in Obese Human Subjects: Impact of GH Blockade. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28324055/ · DOI 10.1210/jc.2016-3835
Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 224–230
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Nine obese men; adipose biopsy after 72-hour fast. · source_derived_draft · unverified_draft
## fast-adipose-pde3b A molecular brake on fat release changed. Adipose PDE3B transcript levels decreased after fasting, with and without GH blockade. Model: Nine obese men; adipose biopsy after 72-hour fast. Limitations: Transcript level is not direct PDE3B enzyme activity. Evidence access: Primary full-text Results: Regulation of lipolysis, DOI 10.1210/jc.2016-3835 Substrate Metabolism and Insulin Sensitivity During Fasting in Obese Human Subjects: Impact of GH Blockade. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28324055/ · DOI 10.1210/jc.2016-3835
Complete structured claim and evidence
Adipose G0S2 transcript levels decreased after fasting, independent of GH blockade.
Fasting / abstention from energy intake → Human G0/G1 switch protein 2 / G0S2 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full-text Results: Regulation of lipolysis, DOI 10.1210/jc.2016-3835
experimental_model
Same human adipose biopsy study.
limitations
Expression alone does not establish which lipase step controlled whole-body flux.
nutrient_topic
Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
plain_language
A second fat-release regulator changed.
primary_references
Substrate Metabolism and Insulin Sensitivity During Fasting in Obese Human Subjects: Impact of GH Blockade. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28324055/ · DOI 10.1210/jc.2016-3835
Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 232–238
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Same human adipose biopsy study. · source_derived_draft · unverified_draft
## fast-adipose-g0s2 A second fat-release regulator changed. Adipose G0S2 transcript levels decreased after fasting, independent of GH blockade. Model: Same human adipose biopsy study. Limitations: Expression alone does not establish which lipase step controlled whole-body flux. Evidence access: Primary full-text Results: Regulation of lipolysis, DOI 10.1210/jc.2016-3835 Substrate Metabolism and Insulin Sensitivity During Fasting in Obese Human Subjects: Impact of GH Blockade. · 2017 · https://pubmed.ncbi.nlm.nih.gov/28324055/ · DOI 10.1210/jc.2016-3835
Complete structured claim and evidence
PPARalpha directly induced hepatic FGF21 in response to fasting or agonists.
Mouse peroxisome proliferator-activated receptor alpha / Ppara → Mouse fibroblast growth factor 21 / Fgf21 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Mouse fasting, agonist and FGF21 experiments.
limitations
Species-specific experimental evidence; not a human fasting timer.
nutrient_topic
Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
plain_language
A fat-sensing regulator activated an endocrine signal.
primary_references
Endocrine regulation of the fasting response by PPARalpha-mediated induction of fibroblast growth factor 21. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17550777/ · DOI 10.1016/j.cmet.2007.05.003
Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 240–246
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Mouse fasting, agonist and FGF21 experiments. · source_derived_draft · unverified_draft
## fast-mouse-fgf A fat-sensing regulator activated an endocrine signal. PPARalpha directly induced hepatic FGF21 in response to fasting or agonists. Model: Mouse fasting, agonist and FGF21 experiments. Limitations: Species-specific experimental evidence; not a human fasting timer. Evidence access: Primary abstract Endocrine regulation of the fasting response by PPARalpha-mediated induction of fibroblast growth factor 21. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17550777/ · DOI 10.1016/j.cmet.2007.05.003
Complete structured claim and evidence
FGF21 stimulated liver ketogenesis and white-adipose lipolysis.
Mouse fibroblast growth factor 21 / Fgf21 → Ketone-body production source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Mouse experiments.
limitations
Human timing differs; shared pathway labels retain mouse context.
nutrient_topic
Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
plain_language
The endocrine signal altered fuel mobilization.
primary_references
Endocrine regulation of the fasting response by PPARalpha-mediated induction of fibroblast growth factor 21. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17550777/ · DOI 10.1016/j.cmet.2007.05.003
Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 248–254
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Mouse experiments. · source_derived_draft · unverified_draft
## fast-mouse-ketones The endocrine signal altered fuel mobilization. FGF21 stimulated liver ketogenesis and white-adipose lipolysis. Model: Mouse experiments. Limitations: Human timing differs; shared pathway labels retain mouse context. Evidence access: Primary abstract Endocrine regulation of the fasting response by PPARalpha-mediated induction of fibroblast growth factor 21. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17550777/ · DOI 10.1016/j.cmet.2007.05.003
Complete structured claim and evidence
FGF21 reduced activity and promoted torpor.
Mouse fibroblast growth factor 21 / Fgf21 → Mouse torpor and reduced activity source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Mouse experiments.
limitations
Torpor in this model is not a demonstrated human fasting response.
nutrient_topic
Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
plain_language
Energy conservation involved behavior and temperature.
primary_references
Endocrine regulation of the fasting response by PPARalpha-mediated induction of fibroblast growth factor 21. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17550777/ · DOI 10.1016/j.cmet.2007.05.003
Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 256–262
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Mouse experiments. · source_derived_draft · unverified_draft
## fast-mouse-torpor Energy conservation involved behavior and temperature. FGF21 reduced activity and promoted torpor. Model: Mouse experiments. Limitations: Torpor in this model is not a demonstrated human fasting response. Evidence access: Primary abstract Endocrine regulation of the fasting response by PPARalpha-mediated induction of fibroblast growth factor 21. · 2007 · https://pubmed.ncbi.nlm.nih.gov/17550777/ · DOI 10.1016/j.cmet.2007.05.003
Complete structured claim and evidence
FGF21 reduced active hepatic STAT5 and expression of its target Igf1.
Mouse fibroblast growth factor 21 / Fgf21 → Mouse STAT5 transcription factors source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Mouse FGF21 exposure experiments.
limitations
Chronic experimental exposure is not an ordinary human overnight fast.
nutrient_topic
Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
plain_language
A starvation signal weakened growth-hormone action.
primary_references
Inhibition of growth hormone signaling by the fasting-induced hormone FGF21. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18585098/ · DOI 10.1016/j.cmet.2008.05.006
Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 264–270
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Mouse FGF21 exposure experiments. · source_derived_draft · unverified_draft
## fast-mouse-stat5 A starvation signal weakened growth-hormone action. FGF21 reduced active hepatic STAT5 and expression of its target Igf1. Model: Mouse FGF21 exposure experiments. Limitations: Chronic experimental exposure is not an ordinary human overnight fast. Evidence access: Primary abstract Inhibition of growth hormone signaling by the fasting-induced hormone FGF21. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18585098/ · DOI 10.1016/j.cmet.2008.05.006
Complete structured claim and evidence
FGF21 induced hepatic IGFBP1 and SOCS2, regulators that blunt GH/IGF signaling.
Mouse fibroblast growth factor 21 / Fgf21 → Mouse IGF binding protein 1 / Igfbp1 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Mouse endocrine experiments.
limitations
No universal human growth-hormone response is inferred.
nutrient_topic
Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
plain_language
Additional regulators restrained growth signaling.
primary_references
Inhibition of growth hormone signaling by the fasting-induced hormone FGF21. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18585098/ · DOI 10.1016/j.cmet.2008.05.006
Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 272–278
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Mouse endocrine experiments. · source_derived_draft · unverified_draft
## fast-mouse-gh-brakes Additional regulators restrained growth signaling. FGF21 induced hepatic IGFBP1 and SOCS2, regulators that blunt GH/IGF signaling. Model: Mouse endocrine experiments. Limitations: No universal human growth-hormone response is inferred. Evidence access: Primary abstract Inhibition of growth hormone signaling by the fasting-induced hormone FGF21. · 2008 · https://pubmed.ncbi.nlm.nih.gov/18585098/ · DOI 10.1016/j.cmet.2008.05.006
Complete structured claim and evidence
FGF21 rose notably on days 7–10, after ketone concentrations had already increased.
Fasting / abstention from energy intake → Human fibroblast growth factor 21 / FGF21 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract; protocol checked in PMC4665770
experimental_model
Eleven volunteers; ten-day fast with daily multivitamin, 20 mEq potassium chloride and 200 mg allopurinol.
limitations
Small supported protocol; timing does not exclude every possible FGF21 contribution.
nutrient_topic
Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
plain_language
This hormone did not precede initial human ketogenesis.
primary_references
FGF21 and the late adaptive response to starvation in humans. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26529252/ · DOI 10.1172/JCI83349
Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 280–286
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Eleven volunteers; ten-day fast with daily multivitamin, 20 mEq potassium chloride and 200 mg allopurinol. · source_derived_draft · unverified_draft
## fast-human-fgf-delay This hormone did not precede initial human ketogenesis. FGF21 rose notably on days 7–10, after ketone concentrations had already increased. Model: Eleven volunteers; ten-day fast with daily multivitamin, 20 mEq potassium chloride and 200 mg allopurinol. Limitations: Small supported protocol; timing does not exclude every possible FGF21 contribution. Evidence access: Primary abstract; protocol checked in PMC4665770 FGF21 and the late adaptive response to starvation in humans. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26529252/ · DOI 10.1172/JCI83349
Complete structured claim and evidence
FGF21 induction was associated with decreased thermogenesis and adiponectin.
Human fibroblast growth factor 21 / FGF21 → Thermogenesis source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract; protocol checked in PMC4665770
experimental_model
Eleven volunteers; ten-day fast with daily multivitamin, 20 mEq potassium chloride and 200 mg allopurinol.
limitations
Association does not prove FGF21 caused either decrease.
nutrient_topic
Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
plain_language
Late starvation signaling accompanied energy conservation.
primary_references
FGF21 and the late adaptive response to starvation in humans. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26529252/ · DOI 10.1172/JCI83349
Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 288–294
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Eleven volunteers; ten-day fast with daily multivitamin, 20 mEq potassium chloride and 200 mg allopurinol. · source_derived_draft · unverified_draft
## fast-human-fgf-heat Late starvation signaling accompanied energy conservation. FGF21 induction was associated with decreased thermogenesis and adiponectin. Model: Eleven volunteers; ten-day fast with daily multivitamin, 20 mEq potassium chloride and 200 mg allopurinol. Limitations: Association does not prove FGF21 caused either decrease. Evidence access: Primary abstract; protocol checked in PMC4665770 FGF21 and the late adaptive response to starvation in humans. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26529252/ · DOI 10.1172/JCI83349
Complete structured claim and evidence
Under glucose starvation AMPK directly activated Ulk1 through Ser317 and Ser777 phosphorylation.
AMP-activated protein kinase complexes → Mouse autophagy initiating kinase / Ulk1 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Mammalian cell experiments with study Ulk1 constructs; mouse residue numbering.
limitations
Do not transfer residue numbers to human ULK1 or infer a fasting-hour threshold.
nutrient_topic
Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
plain_language
Energy stress can act on the autophagy-starting machinery.
primary_references
AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21258367/ · DOI 10.1038/ncb2152
Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 296–302
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Mammalian cell experiments with study Ulk1 constructs; mouse residue numbering. · source_derived_draft · unverified_draft
## fast-ampk-ulk Energy stress can act on the autophagy-starting machinery. Under glucose starvation AMPK directly activated Ulk1 through Ser317 and Ser777 phosphorylation. Model: Mammalian cell experiments with study Ulk1 constructs; mouse residue numbering. Limitations: Do not transfer residue numbers to human ULK1 or infer a fasting-hour threshold. Evidence access: Primary abstract AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21258367/ · DOI 10.1038/ncb2152
Complete structured claim and evidence
High mTOR activity phosphorylated Ulk1 Ser757 and disrupted its interaction with AMPK.
Mechanistic target of rapamycin complex 1 → Study-specific Ulk1–AMPK interaction source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Cellular kinase and autophagy assays; mouse Ulk1 numbering.
limitations
Specific signaling mechanism, not a whole-body autophagic-flux measurement.
nutrient_topic
Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
plain_language
Nutrient sufficiency can restrain this initiation route.
primary_references
AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21258367/ · DOI 10.1038/ncb2152
Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 304–310
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Cellular kinase and autophagy assays; mouse Ulk1 numbering. · source_derived_draft · unverified_draft
## fast-mtor-ulk Nutrient sufficiency can restrain this initiation route. High mTOR activity phosphorylated Ulk1 Ser757 and disrupted its interaction with AMPK. Model: Cellular kinase and autophagy assays; mouse Ulk1 numbering. Limitations: Specific signaling mechanism, not a whole-body autophagic-flux measurement. Evidence access: Primary abstract AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21258367/ · DOI 10.1038/ncb2152
Complete structured claim and evidence
Autophagy remained unimpaired in AMPK-deficient cells during amino-acid deprivation; ULK1 signaling and LC3B lipidation increased.
AMP-activated protein kinase complexes → Cellular autophagic flux, experimental context specified source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Several cultured cell lines under prolonged amino-acid withdrawal.
limitations
Different stress from glucose withdrawal; a universal AMPK-on/autophagy-on rule is unsupported.
nutrient_topic
Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
plain_language
Loss of this sensor did not shut down all autophagy.
primary_references
Unexpected roles for AMPK in the suppression of autophagy and the reactivation of MTORC1 signaling during prolonged amino acid deprivation. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38744665/ · DOI 10.1080/15548627.2024.2355074
Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 312–318
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Several cultured cell lines under prolonged amino-acid withdrawal. · source_derived_draft · unverified_draft
## fast-ampk-context Loss of this sensor did not shut down all autophagy. Autophagy remained unimpaired in AMPK-deficient cells during amino-acid deprivation; ULK1 signaling and LC3B lipidation increased. Model: Several cultured cell lines under prolonged amino-acid withdrawal. Limitations: Different stress from glucose withdrawal; a universal AMPK-on/autophagy-on rule is unsupported. Evidence access: Primary abstract Unexpected roles for AMPK in the suppression of autophagy and the reactivation of MTORC1 signaling during prolonged amino acid deprivation. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38744665/ · DOI 10.1080/15548627.2024.2355074
Complete structured claim and evidence
AMPK loss impaired mTORC1 reactivation during prolonged amino-acid deprivation and increased apoptosis.
AMP-activated protein kinase complexes → mTORC1 reactivation after prolonged amino-acid withdrawal source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Cultured nutrient-stressed cells.
limitations
Cell survival and autophagy readouts must be distinguished.
nutrient_topic
Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
plain_language
The same sensor can support recovery during persistent stress.
primary_references
Unexpected roles for AMPK in the suppression of autophagy and the reactivation of MTORC1 signaling during prolonged amino acid deprivation. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38744665/ · DOI 10.1080/15548627.2024.2355074
Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 320–326
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Cultured nutrient-stressed cells. · source_derived_draft · unverified_draft
## fast-ampk-reactivation The same sensor can support recovery during persistent stress. AMPK loss impaired mTORC1 reactivation during prolonged amino-acid deprivation and increased apoptosis. Model: Cultured nutrient-stressed cells. Limitations: Cell survival and autophagy readouts must be distinguished. Evidence access: Primary abstract Unexpected roles for AMPK in the suppression of autophagy and the reactivation of MTORC1 signaling during prolonged amino acid deprivation. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38744665/ · DOI 10.1080/15548627.2024.2355074
Complete structured claim and evidence
MCOLN1-dependent lysosomal calcium release activated calcineurin.
Human mucolipin-1 / MCOLN1 → Lysosomal calcium release source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Lysosomal signaling and starvation experiments in cultured cells.
limitations
Local calcium release is not equivalent to blood calcium or taking calcium.
nutrient_topic
Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
plain_language
A local calcium signal linked the lysosome to a phosphatase.
primary_references
Lysosomal calcium signalling regulates autophagy through calcineurin and TFEB. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25720963/ · DOI 10.1038/ncb3114
Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 328–334
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Lysosomal signaling and starvation experiments in cultured cells. · source_derived_draft · unverified_draft
## fast-lysosomal-calcium A local calcium signal linked the lysosome to a phosphatase. MCOLN1-dependent lysosomal calcium release activated calcineurin. Model: Lysosomal signaling and starvation experiments in cultured cells. Limitations: Local calcium release is not equivalent to blood calcium or taking calcium. Evidence access: Primary abstract Lysosomal calcium signalling regulates autophagy through calcineurin and TFEB. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25720963/ · DOI 10.1038/ncb3114
Complete structured claim and evidence
Calcineurin bound and dephosphorylated TFEB, promoting its nuclear translocation.
Calcineurin → Human transcription factor EB / TFEB source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Genetic and pharmacological perturbation of the calcineurin–TFEB pathway.
limitations
This establishes a regulatory route, not a fixed fasting schedule.
nutrient_topic
Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
plain_language
Removing phosphate marks let a regulator reach the nucleus.
primary_references
Lysosomal calcium signalling regulates autophagy through calcineurin and TFEB. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25720963/ · DOI 10.1038/ncb3114
Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 336–342
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Genetic and pharmacological perturbation of the calcineurin–TFEB pathway. · source_derived_draft · unverified_draft
## fast-tfeb-dephosphorylation Removing phosphate marks let a regulator reach the nucleus. Calcineurin bound and dephosphorylated TFEB, promoting its nuclear translocation. Model: Genetic and pharmacological perturbation of the calcineurin–TFEB pathway. Limitations: This establishes a regulatory route, not a fixed fasting schedule. Evidence access: Primary abstract Lysosomal calcium signalling regulates autophagy through calcineurin and TFEB. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25720963/ · DOI 10.1038/ncb3114
Complete structured claim and evidence
Autophagy and lysosomal biogenesis through TFEB required MCOLN1-mediated calcineurin activation.
Human transcription factor EB / TFEB → Lysosomal biogenesis source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Cellular starvation and mouse exercise experiments.
limitations
Lysosome abundance alone is not proof of increased degradation flux.
nutrient_topic
Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
plain_language
The signal helped build the cell’s recycling capacity.
primary_references
Lysosomal calcium signalling regulates autophagy through calcineurin and TFEB. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25720963/ · DOI 10.1038/ncb3114
Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 344–350
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Cellular starvation and mouse exercise experiments. · source_derived_draft · unverified_draft
## fast-tfeb-biogenesis The signal helped build the cell’s recycling capacity. Autophagy and lysosomal biogenesis through TFEB required MCOLN1-mediated calcineurin activation. Model: Cellular starvation and mouse exercise experiments. Limitations: Lysosome abundance alone is not proof of increased degradation flux. Evidence access: Primary abstract Lysosomal calcium signalling regulates autophagy through calcineurin and TFEB. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25720963/ · DOI 10.1038/ncb3114
Complete structured claim and evidence
D-beta-hydroxybutyrate activated human HM74a/HCAR2 and its mouse orthologue.
D-(R)-beta-hydroxybutyrate → Human hydroxycarboxylic acid receptor 2 / HCAR2 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human and mouse receptor pharmacology.
limitations
Shared receptor does not imply identical exposures or clinical effects.
nutrient_topic
Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
plain_language
A fasting-associated ketone uses a receptor also used by nicotinic acid.
primary_references
(D)-beta-Hydroxybutyrate inhibits adipocyte lipolysis via the nicotinic acid receptor PUMA-G. · 2005 · https://pubmed.ncbi.nlm.nih.gov/15929991/ · DOI 10.1074/jbc.C500213200
Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 352–358
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human and mouse receptor pharmacology. · source_derived_draft · unverified_draft
## fast-bhb-hcar2 A fasting-associated ketone uses a receptor also used by nicotinic acid. D-beta-hydroxybutyrate activated human HM74a/HCAR2 and its mouse orthologue. Model: Human and mouse receptor pharmacology. Limitations: Shared receptor does not imply identical exposures or clinical effects. Evidence access: Primary abstract (D)-beta-Hydroxybutyrate inhibits adipocyte lipolysis via the nicotinic acid receptor PUMA-G. · 2005 · https://pubmed.ncbi.nlm.nih.gov/15929991/ · DOI 10.1074/jbc.C500213200
Complete structured claim and evidence
D-beta-hydroxybutyrate inhibited mouse adipocyte lipolysis in an Hcar2-dependent manner.
D-(R)-beta-hydroxybutyrate → Mouse adipocyte lipolysis source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Mouse adipocyte experiments.
limitations
Whole-body ketone feedback was proposed; magnitude in human fasting was not established.
nutrient_topic
Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
plain_language
A ketone could feed back on its upstream fuel supply.
primary_references
(D)-beta-Hydroxybutyrate inhibits adipocyte lipolysis via the nicotinic acid receptor PUMA-G. · 2005 · https://pubmed.ncbi.nlm.nih.gov/15929991/ · DOI 10.1074/jbc.C500213200
Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 360–366
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Mouse adipocyte experiments. · source_derived_draft · unverified_draft
## fast-bhb-lipolysis-feedback A ketone could feed back on its upstream fuel supply. D-beta-hydroxybutyrate inhibited mouse adipocyte lipolysis in an Hcar2-dependent manner. Model: Mouse adipocyte experiments. Limitations: Whole-body ketone feedback was proposed; magnitude in human fasting was not established. Evidence access: Primary abstract (D)-beta-Hydroxybutyrate inhibits adipocyte lipolysis via the nicotinic acid receptor PUMA-G. · 2005 · https://pubmed.ncbi.nlm.nih.gov/15929991/ · DOI 10.1074/jbc.C500213200
Complete structured claim and evidence
BHB prevented potassium efflux in the tested NLRP3 activation experiments.
D-(R)-beta-hydroxybutyrate → Macrophage potassium efflux source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Stimulated innate immune cells; both BHB enantiomers were active.
limitations
Not evidence that BHB corrects systemic potassium deficiency.
nutrient_topic
Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
plain_language
A ketone altered an ion movement involved in inflammatory signaling.
primary_references
The ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome-mediated inflammatory disease. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25686106/ · DOI 10.1038/nm.3804
Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 368–374
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Stimulated innate immune cells; both BHB enantiomers were active. · source_derived_draft · unverified_draft
## fast-bhb-potassium A ketone altered an ion movement involved in inflammatory signaling. BHB prevented potassium efflux in the tested NLRP3 activation experiments. Model: Stimulated innate immune cells; both BHB enantiomers were active. Limitations: Not evidence that BHB corrects systemic potassium deficiency. Evidence access: Primary abstract The ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome-mediated inflammatory disease. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25686106/ · DOI 10.1038/nm.3804
Complete structured claim and evidence
BHB reduced ASC oligomerization and speck formation.
D-(R)-beta-hydroxybutyrate → ASC oligomerization and speck formation source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
NLRP3 activation models.
limitations
Effect did not require HCAR2, AMPK, autophagy or ketone oxidation.
nutrient_topic
Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
plain_language
The inflammatory complex assembled less effectively.
primary_references
The ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome-mediated inflammatory disease. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25686106/ · DOI 10.1038/nm.3804
Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 376–382
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · NLRP3 activation models. · source_derived_draft · unverified_draft
## fast-bhb-asc The inflammatory complex assembled less effectively. BHB reduced ASC oligomerization and speck formation. Model: NLRP3 activation models. Limitations: Effect did not require HCAR2, AMPK, autophagy or ketone oxidation. Evidence access: Primary abstract The ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome-mediated inflammatory disease. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25686106/ · DOI 10.1038/nm.3804
Complete structured claim and evidence
BHB reduced NLRP3-mediated IL-1beta and IL-18 production in human monocytes.
D-(R)-beta-hydroxybutyrate → Human monocyte IL-1beta and IL-18 production source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human monocyte experiments.
limitations
Not universal anti-inflammatory activity or a clinical fasting outcome.
nutrient_topic
Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
plain_language
The cellular signal changed selected cytokine outputs.
primary_references
The ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome-mediated inflammatory disease. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25686106/ · DOI 10.1038/nm.3804
Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 384–390
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human monocyte experiments. · source_derived_draft · unverified_draft
## fast-bhb-cytokines The cellular signal changed selected cytokine outputs. BHB reduced NLRP3-mediated IL-1beta and IL-18 production in human monocytes. Model: Human monocyte experiments. Limitations: Not universal anti-inflammatory activity or a clinical fasting outcome. Evidence access: Primary abstract The ketone metabolite β-hydroxybutyrate blocks NLRP3 inflammasome-mediated inflammatory disease. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25686106/ · DOI 10.1038/nm.3804
Complete structured claim and evidence
The study reported direct class-I HDAC inhibition by D-beta-hydroxybutyrate, alongside increased histone acetylation in mouse tissues.
D-(R)-beta-hydroxybutyrate → Class I histone deacetylase activity source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Biochemical/cellular experiments; mouse fasting, calorie restriction or exogenous BHB.
limitations
Later direct testing challenged HDAC inhibition; see the linked research disagreement.
nutrient_topic
Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
plain_language
One study proposed a direct route from ketones to gene regulation.
primary_references
Suppression of oxidative stress by β-hydroxybutyrate, an endogenous histone deacetylase inhibitor. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23223453/ · DOI 10.1126/science.1227166
Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 392–398
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Biochemical/cellular experiments; mouse fasting, calorie restriction or exogenous BHB. · source_derived_draft · unverified_draft
## fast-hdac-positive One study proposed a direct route from ketones to gene regulation. The study reported direct class-I HDAC inhibition by D-beta-hydroxybutyrate, alongside increased histone acetylation in mouse tissues. Model: Biochemical/cellular experiments; mouse fasting, calorie restriction or exogenous BHB. Limitations: Later direct testing challenged HDAC inhibition; see the linked research disagreement. Evidence access: Primary abstract Suppression of oxidative stress by β-hydroxybutyrate, an endogenous histone deacetylase inhibitor. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23223453/ · DOI 10.1126/science.1227166
Complete structured claim and evidence
The later study detected no HDAC inhibition with 10 mM sodium R-BHB in its nuclear-extract assay; multiple cell models lacked histone hyperacetylation up to 40 mM.
D-(R)-beta-hydroxybutyrate → Class I histone deacetylase activity source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract and indexed full-text Figure 2/Discussion, PMC6346118
experimental_model
Nuclear-extract assay and HEK293, HMEC-1, rat and human myotube experiments.
limitations
Different preparations/readouts may matter; the discrepancy is unresolved. Concentrations are experimental, not target blood levels.
nutrient_topic
Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
plain_language
Another study did not reproduce the proposed direct effect.
primary_references
Prominent action of butyrate over β-hydroxybutyrate as histone deacetylase inhibitor, transcriptional modulator and anti-inflammatory molecule. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30679586/ · DOI 10.1038/s41598-018-36941-9
Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 400–406
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Nuclear-extract assay and HEK293, HMEC-1, rat and human myotube experiments. · source_derived_draft · unverified_draft
## fast-hdac-negative Another study did not reproduce the proposed direct effect. The later study detected no HDAC inhibition with 10 mM sodium R-BHB in its nuclear-extract assay; multiple cell models lacked histone hyperacetylation up to 40 mM. Model: Nuclear-extract assay and HEK293, HMEC-1, rat and human myotube experiments. Limitations: Different preparations/readouts may matter; the discrepancy is unresolved. Concentrations are experimental, not target blood levels. Evidence access: Primary abstract and indexed full-text Figure 2/Discussion, PMC6346118 Prominent action of butyrate over β-hydroxybutyrate as histone deacetylase inhibitor, transcriptional modulator and anti-inflammatory molecule. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30679586/ · DOI 10.1038/s41598-018-36941-9
Complete structured claim and evidence
R-beta-hydroxybutyrate increased histone beta-hydroxybutyrylation despite absent detectable HDAC inhibition.
D-(R)-beta-hydroxybutyrate → Histone lysine beta-hydroxybutyrylation source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Cultured-cell comparison with butyrate.
limitations
Beta-hydroxybutyrylation and acetylation are different modifications.
nutrient_topic
Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
plain_language
A distinct histone modification can occur without proving the proposed HDAC route.
primary_references
Prominent action of butyrate over β-hydroxybutyrate as histone deacetylase inhibitor, transcriptional modulator and anti-inflammatory molecule. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30679586/ · DOI 10.1038/s41598-018-36941-9
Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 408–414
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Cultured-cell comparison with butyrate. · source_derived_draft · unverified_draft
## fast-bhb-histone-mark A distinct histone modification can occur without proving the proposed HDAC route. R-beta-hydroxybutyrate increased histone beta-hydroxybutyrylation despite absent detectable HDAC inhibition. Model: Cultured-cell comparison with butyrate. Limitations: Beta-hydroxybutyrylation and acetylation are different modifications. Evidence access: Primary abstract Prominent action of butyrate over β-hydroxybutyrate as histone deacetylase inhibitor, transcriptional modulator and anti-inflammatory molecule. · 2019 · https://pubmed.ncbi.nlm.nih.gov/30679586/ · DOI 10.1038/s41598-018-36941-9
Complete structured claim and evidence
A seven-day fast changed more than 1,000 measured plasma proteins; broad changes became evident after about three days.
Fasting / abstention from energy intake → Plasma proteome changes during fasting source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Twelve volunteers; approximately 3,000 plasma proteins profiled.
limitations
Three days is not an autophagy-onset threshold. Proteogenomic disease predictions are not observed clinical outcomes.
nutrient_topic
Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
plain_language
Many circulating proteins adapted, on different schedules.
primary_references
Systemic proteome adaptions to 7-day complete caloric restriction in humans. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38429390/ · DOI 10.1038/s42255-024-01008-9
Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 416–422
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Twelve volunteers; approximately 3,000 plasma proteins profiled. · source_derived_draft · unverified_draft
## fast-proteome Many circulating proteins adapted, on different schedules. A seven-day fast changed more than 1,000 measured plasma proteins; broad changes became evident after about three days. Model: Twelve volunteers; approximately 3,000 plasma proteins profiled. Limitations: Three days is not an autophagy-onset threshold. Proteogenomic disease predictions are not observed clinical outcomes. Evidence access: Primary abstract Systemic proteome adaptions to 7-day complete caloric restriction in humans. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38429390/ · DOI 10.1038/s42255-024-01008-9
Complete structured claim and evidence
Five weeks of a six-hour early eating window improved insulin sensitivity without weight loss.
Early time-restricted feeding → Systemic insulin sensitivity source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Controlled crossover in men with prediabetes; dinner before 3 pm versus a 12-hour window.
limitations
Early circadian timing and fasting duration were changed together.
nutrient_topic
Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
plain_language
Meal timing can affect glucose control without a multi-day fast.
primary_references
Early Time-Restricted Feeding Improves Insulin Sensitivity, Blood Pressure, and Oxidative Stress Even without Weight Loss in Men with Prediabetes. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29754952/ · DOI 10.1016/j.cmet.2018.04.010
Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 424–430
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Controlled crossover in men with prediabetes; dinner before 3 pm versus a 12-hour window. · source_derived_draft · unverified_draft
## fast-early-window Meal timing can affect glucose control without a multi-day fast. Five weeks of a six-hour early eating window improved insulin sensitivity without weight loss. Model: Controlled crossover in men with prediabetes; dinner before 3 pm versus a 12-hour window. Limitations: Early circadian timing and fasting duration were changed together. Evidence access: Primary abstract Early Time-Restricted Feeding Improves Insulin Sensitivity, Blood Pressure, and Oxidative Stress Even without Weight Loss in Men with Prediabetes. · 2018 · https://pubmed.ncbi.nlm.nih.gov/29754952/ · DOI 10.1016/j.cmet.2018.04.010
Complete structured claim and evidence
CRP, hepcidin, midkine and IL-8 increased during prolonged fasting.
Fasting / abstention from energy intake → Acute inflammatory markers during prolonged fasting source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Twenty adults; supervised water fast averaging 9.8 days, then guided refeeding.
limitations
Not proof that every fast increases inflammation; cellular NLRP3 results measure something different.
nutrient_topic
Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
plain_language
Whole-body inflammatory measurements did not simply follow the anti-inflammatory ketone story.
primary_references
Prolonged fasting promotes systemic inflammation and platelet activation in humans: A medically supervised, water-only fasting and refeeding study. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40268190/ · DOI 10.1016/j.molmet.2025.102152
Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 432–438
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Twenty adults; supervised water fast averaging 9.8 days, then guided refeeding. · source_derived_draft · unverified_draft
## fast-inflammation Whole-body inflammatory measurements did not simply follow the anti-inflammatory ketone story. CRP, hepcidin, midkine and IL-8 increased during prolonged fasting. Model: Twenty adults; supervised water fast averaging 9.8 days, then guided refeeding. Limitations: Not proof that every fast increases inflammation; cellular NLRP3 results measure something different. Evidence access: Primary abstract Prolonged fasting promotes systemic inflammation and platelet activation in humans: A medically supervised, water-only fasting and refeeding study. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40268190/ · DOI 10.1016/j.molmet.2025.102152
Complete structured claim and evidence
Proteomic analyses and follow-up assays indicated platelet degranulation and complement/coagulation-associated changes.
Fasting / abstention from energy intake → Platelet degranulation and coagulation-associated readouts source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Same prolonged-fasting cohort.
limitations
Pathway readouts do not prove that participants developed thrombosis or cardiovascular disease.
nutrient_topic
Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
plain_language
The response included blood and vascular pathways.
primary_references
Prolonged fasting promotes systemic inflammation and platelet activation in humans: A medically supervised, water-only fasting and refeeding study. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40268190/ · DOI 10.1016/j.molmet.2025.102152
Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 440–446
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Same prolonged-fasting cohort. · source_derived_draft · unverified_draft
## fast-platelet-readouts The response included blood and vascular pathways. Proteomic analyses and follow-up assays indicated platelet degranulation and complement/coagulation-associated changes. Model: Same prolonged-fasting cohort. Limitations: Pathway readouts do not prove that participants developed thrombosis or cardiovascular disease. Evidence access: Primary abstract Prolonged fasting promotes systemic inflammation and platelet activation in humans: A medically supervised, water-only fasting and refeeding study. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40268190/ · DOI 10.1016/j.molmet.2025.102152
Complete structured claim and evidence
Urinary sodium excretion fell from 401 to 213 microequivalents/min without changes in GFR, renal blood flow or aldosterone.
Insulin → Renal sodium excretion source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Six water-loaded healthy subjects; 120-minute euglycemic insulin infusion, 98–193 microU/mL.
limitations
Insulin-clamp mechanism, not a fasting or refeeding-syndrome trial.
nutrient_topic
Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
plain_language
Insulin changed kidney sodium retention.
primary_references
The effect of insulin on renal handling of sodium, potassium, calcium, and phosphate in man. · 1975 · https://pubmed.ncbi.nlm.nih.gov/1120786/ · DOI 10.1172/JCI107996
Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 448–454
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Six water-loaded healthy subjects; 120-minute euglycemic insulin infusion, 98–193 microU/mL. · source_derived_draft · unverified_draft
## fast-insulin-sodium Insulin changed kidney sodium retention. Urinary sodium excretion fell from 401 to 213 microequivalents/min without changes in GFR, renal blood flow or aldosterone. Model: Six water-loaded healthy subjects; 120-minute euglycemic insulin infusion, 98–193 microU/mL. Limitations: Insulin-clamp mechanism, not a fasting or refeeding-syndrome trial. Evidence access: Primary abstract The effect of insulin on renal handling of sodium, potassium, calcium, and phosphate in man. · 1975 · https://pubmed.ncbi.nlm.nih.gov/1120786/ · DOI 10.1172/JCI107996
Complete structured claim and evidence
Urinary potassium excretion fell from 66 to 21 microequivalents/min while plasma potassium also decreased.
Insulin → Renal potassium excretion source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Six water-loaded healthy subjects; 120-minute euglycemic insulin infusion, 98–193 microU/mL.
limitations
Insulin-clamp mechanism, not a fasting or refeeding-syndrome trial.
nutrient_topic
Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
plain_language
Blood potassium and urinary loss changed together.
primary_references
The effect of insulin on renal handling of sodium, potassium, calcium, and phosphate in man. · 1975 · https://pubmed.ncbi.nlm.nih.gov/1120786/ · DOI 10.1172/JCI107996
Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 456–462
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Six water-loaded healthy subjects; 120-minute euglycemic insulin infusion, 98–193 microU/mL. · source_derived_draft · unverified_draft
## fast-insulin-potassium Blood potassium and urinary loss changed together. Urinary potassium excretion fell from 66 to 21 microequivalents/min while plasma potassium also decreased. Model: Six water-loaded healthy subjects; 120-minute euglycemic insulin infusion, 98–193 microU/mL. Limitations: Insulin-clamp mechanism, not a fasting or refeeding-syndrome trial. Evidence access: Primary abstract The effect of insulin on renal handling of sodium, potassium, calcium, and phosphate in man. · 1975 · https://pubmed.ncbi.nlm.nih.gov/1120786/ · DOI 10.1172/JCI107996
Complete structured claim and evidence
Urinary phosphate excretion fell from 504 to 230 micrograms/min, with a small plasma phosphate decrease.
Insulin → Renal phosphate excretion source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Six water-loaded healthy subjects; 120-minute euglycemic insulin infusion, 98–193 microU/mL.
limitations
Insulin-clamp mechanism, not a fasting or refeeding-syndrome trial.
nutrient_topic
Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
plain_language
Phosphate handling changed when insulin rose.
primary_references
The effect of insulin on renal handling of sodium, potassium, calcium, and phosphate in man. · 1975 · https://pubmed.ncbi.nlm.nih.gov/1120786/ · DOI 10.1172/JCI107996
Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 464–470
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Six water-loaded healthy subjects; 120-minute euglycemic insulin infusion, 98–193 microU/mL. · source_derived_draft · unverified_draft
## fast-insulin-phosphate Phosphate handling changed when insulin rose. Urinary phosphate excretion fell from 504 to 230 micrograms/min, with a small plasma phosphate decrease. Model: Six water-loaded healthy subjects; 120-minute euglycemic insulin infusion, 98–193 microU/mL. Limitations: Insulin-clamp mechanism, not a fasting or refeeding-syndrome trial. Evidence access: Primary abstract The effect of insulin on renal handling of sodium, potassium, calcium, and phosphate in man. · 1975 · https://pubmed.ncbi.nlm.nih.gov/1120786/ · DOI 10.1172/JCI107996
Complete structured claim and evidence
Urinary calcium excretion rose from 126 to 200 micrograms/min.
Insulin → Renal calcium excretion source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Six water-loaded healthy subjects; 120-minute euglycemic insulin infusion, 98–193 microU/mL.
limitations
Insulin-clamp mechanism, not a fasting or refeeding-syndrome trial.
nutrient_topic
Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
plain_language
Calcium did not follow the same urinary pattern as potassium and phosphate.
primary_references
The effect of insulin on renal handling of sodium, potassium, calcium, and phosphate in man. · 1975 · https://pubmed.ncbi.nlm.nih.gov/1120786/ · DOI 10.1172/JCI107996
Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 472–478
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Six water-loaded healthy subjects; 120-minute euglycemic insulin infusion, 98–193 microU/mL. · source_derived_draft · unverified_draft
## fast-insulin-calcium Calcium did not follow the same urinary pattern as potassium and phosphate. Urinary calcium excretion rose from 126 to 200 micrograms/min. Model: Six water-loaded healthy subjects; 120-minute euglycemic insulin infusion, 98–193 microU/mL. Limitations: Insulin-clamp mechanism, not a fasting or refeeding-syndrome trial. Evidence access: Primary abstract The effect of insulin on renal handling of sodium, potassium, calcium, and phosphate in man. · 1975 · https://pubmed.ncbi.nlm.nih.gov/1120786/ · DOI 10.1172/JCI107996
Complete structured claim and evidence
Direct copper interaction supported ULK1 kinase activity in the experimental system.
Copper → Human unc-51-like autophagy activating kinase ULK1 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/copper-research/32203415.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f248044309434e00cd35941d0e525a9c73a07e8d78eead20f7d7b6bdcb5f2915", "start_char": 0, "end_char": 1077, "text_sha256": "f248044309434e00cd35941d0e525a9c73a07e8d78eead20f7d7b6bdcb5f2915"}
experimental_model
Recombinant kinase assays, genetic perturbations and lung tumor models
exposure
Copper exposure, copper-binding mutations and Ctr1 deletion
limitations
Preclinical molecular evidence; not proof that copper supplementation improves autophagy in healthy people or that chelation improves cancer survival.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Human recombinant ULK1/ULK2 with complementary mouse systems
plain_language
Copper helps regulate one enzyme that starts cellular recycling.
primary_references
[copper-p32203415] Copper is an essential regulator of the autophagic kinases ULK1/2 to drive lung adenocarcinoma. (2020). https://pubmed.ncbi.nlm.nih.gov/32203415/ DOI: 10.1038/s41556-020-0481-4
tissue_or_cell_type
Autophagy signaling
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 1235–1246
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant kinase assays, genetic perturbations and lung tumor models · source_derived_draft · unverified_draft
### copper-cu-ulk1 Direct copper interaction supported ULK1 kinase activity in the experimental system. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: Copper helps regulate one enzyme that starts cellular recycling. organism: Human recombinant ULK1/ULK2 with complementary mouse systems tissue_or_cell_type: Autophagy signaling experimental_model: Recombinant kinase assays, genetic perturbations and lung tumor models limitations: Preclinical molecular evidence; not proof that copper supplementation improves autophagy in healthy people or that chelation improves cancer survival. exposure: Copper exposure, copper-binding mutations and Ctr1 deletion evidence_span: {"source_cache": "artifacts/copper-research/32203415.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f248044309434e00cd35941d0e525a9c73a07e8d78eead20f7d7b6bdcb5f2915", "start_char": 0, "end_char": 1077, "text_sha256": "f248044309434e00cd35941d0e525a9c73a07e8d78eead20f7d7b6bdcb5f2915"} [copper-p32203415] Copper is an essential regulator of the autophagic kinases ULK1/2 to drive lung adenocarcinoma. (2020). https://pubmed.ncbi.nlm.nih.gov/32203415/ DOI: 10.1038/s41556-020-0481-4
Complete structured claim and evidence
Copper-binding-disruptive ULK1 mutations reduced autophagy signaling and autophagosome formation in the tested cells.
Human unc-51-like autophagy activating kinase ULK1 → Autophagosome formation source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/copper-research/32203415.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f248044309434e00cd35941d0e525a9c73a07e8d78eead20f7d7b6bdcb5f2915", "start_char": 0, "end_char": 1077, "text_sha256": "f248044309434e00cd35941d0e525a9c73a07e8d78eead20f7d7b6bdcb5f2915"}
experimental_model
Recombinant kinase assays, genetic perturbations and lung tumor models
exposure
Copper exposure, copper-binding mutations and Ctr1 deletion
limitations
Preclinical molecular evidence; not proof that copper supplementation improves autophagy in healthy people or that chelation improves cancer survival.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Human recombinant ULK1/ULK2 with complementary mouse systems
plain_language
A binding defect interrupted the recycling pathway downstream.
primary_references
[copper-p32203415] Copper is an essential regulator of the autophagic kinases ULK1/2 to drive lung adenocarcinoma. (2020). https://pubmed.ncbi.nlm.nih.gov/32203415/ DOI: 10.1038/s41556-020-0481-4
tissue_or_cell_type
Autophagy signaling
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 1261–1272
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant kinase assays, genetic perturbations and lung tumor models · source_derived_draft · unverified_draft
### copper-ulk1-copper-autophagy Copper-binding-disruptive ULK1 mutations reduced autophagy signaling and autophagosome formation in the tested cells. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: A binding defect interrupted the recycling pathway downstream. organism: Human recombinant ULK1/ULK2 with complementary mouse systems tissue_or_cell_type: Autophagy signaling experimental_model: Recombinant kinase assays, genetic perturbations and lung tumor models limitations: Preclinical molecular evidence; not proof that copper supplementation improves autophagy in healthy people or that chelation improves cancer survival. exposure: Copper exposure, copper-binding mutations and Ctr1 deletion evidence_span: {"source_cache": "artifacts/copper-research/32203415.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f248044309434e00cd35941d0e525a9c73a07e8d78eead20f7d7b6bdcb5f2915", "start_char": 0, "end_char": 1077, "text_sha256": "f248044309434e00cd35941d0e525a9c73a07e8d78eead20f7d7b6bdcb5f2915"} [copper-p32203415] Copper is an essential regulator of the autophagic kinases ULK1/2 to drive lung adenocarcinoma. (2020). https://pubmed.ncbi.nlm.nih.gov/32203415/ DOI: 10.1038/s41556-020-0481-4
Complete structured claim and evidence
Copper-dependent PDE3B inhibition increased cAMP signaling and promoted lipolysis in 3T3-L1 adipocytes.
Mouse cGMP-inhibited phosphodiesterase Pde3b → Mouse adipocyte lipolysis source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/copper-research/27272565.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f8b7e13cc6ef608ddb589779fa85430ca530508013e710f380f4020c3f2632c7", "start_char": 0, "end_char": 1018, "text_sha256": "f8b7e13cc6ef608ddb589779fa85430ca530508013e710f380f4020c3f2632c7"}
experimental_model
Copper manipulation, purified Pde3b assays and adipocyte signaling
exposure
Copper perturbation and Pde3b cysteine mutations
limitations
This cellular signaling result is not a human weight-loss trial. Copper toxicity and systemic distribution are not captured by increasing one cell-culture signal.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Mouse proteins and 3T3-L1 adipocytes; Atp7b mutant mouse context
plain_language
The prolonged signal encouraged fat breakdown in these cells.
primary_references
[copper-p27272565] Copper regulates cyclic-AMP-dependent lipolysis. (2016). https://pubmed.ncbi.nlm.nih.gov/27272565/ DOI: 10.1038/nchembio.2098
tissue_or_cell_type
Adipocytes and purified enzyme
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 1209–1220
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Copper manipulation, purified Pde3b assays and adipocyte signaling · source_derived_draft · unverified_draft
### copper-pde3b-camp-lipolysis Copper-dependent PDE3B inhibition increased cAMP signaling and promoted lipolysis in 3T3-L1 adipocytes. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: The prolonged signal encouraged fat breakdown in these cells. organism: Mouse proteins and 3T3-L1 adipocytes; Atp7b mutant mouse context tissue_or_cell_type: Adipocytes and purified enzyme experimental_model: Copper manipulation, purified Pde3b assays and adipocyte signaling limitations: This cellular signaling result is not a human weight-loss trial. Copper toxicity and systemic distribution are not captured by increasing one cell-culture signal. exposure: Copper perturbation and Pde3b cysteine mutations evidence_span: {"source_cache": "artifacts/copper-research/27272565.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f8b7e13cc6ef608ddb589779fa85430ca530508013e710f380f4020c3f2632c7", "start_char": 0, "end_char": 1018, "text_sha256": "f8b7e13cc6ef608ddb589779fa85430ca530508013e710f380f4020c3f2632c7"} [copper-p27272565] Copper regulates cyclic-AMP-dependent lipolysis. (2016). https://pubmed.ncbi.nlm.nih.gov/27272565/ DOI: 10.1038/nchembio.2098
Complete structured claim and evidence
In the studied human ACC2 domain, phosphorylated Ser222 occupied the putative dimer interface, disrupting polymerization and explaining AMPK-mediated inactivation.
AMP-activated protein kinase complexes → Human acetyl-CoA carboxylase 2 / ACACB source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/biotin-research/19900410.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3d7161fb1a281c68bbe3b8d4738b26d5ed762ca2bea3d9621ee6c8946a7fa71c", "start_char": 0, "end_char": 870, "text_sha256": "3d7161fb1a281c68bbe3b8d4738b26d5ed762ca2bea3d9621ee6c8946a7fa71c"}
experimental_model
Crystal structures of the human ACC2 biotin-carboxylase domain after AMPK phosphorylation
exposure
Phosphorylation and soraphen A comparison
limitations
Domain structures explain a regulatory mechanism; the construct uses Ser222 numbering and must not be silently relabeled with another isoform numbering scheme.
nutrient_topic
Biotin research collection; topical membership is not evidence of a direct dietary effect. · Biotin
organism
Homo sapiens
plain_language
An energy-sensing kinase can switch ACC2 down even when biotin is available.
primary_references
[b7-p19900410] Molecular mechanism for the regulation of human ACC2 through phosphorylation by AMPK. (2010). https://pubmed.ncbi.nlm.nih.gov/19900410/ DOI: 10.1016/j.bbrc.2009.11.029
tissue_or_cell_type
Purified ACC2 domain
Biotin: carboxylases, recycling, deficiency and nutrient interactions (2026-09-17) · lines 702–713
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Crystal structures of the human ACC2 biotin-carboxylase domain after AMPK phosphorylation · source_derived_draft · unverified_draft
### b7-acc2-ampk In the studied human ACC2 domain, phosphorylated Ser222 occupied the putative dimer interface, disrupting polymerization and explaining AMPK-mediated inactivation. Condition category: normal nutrient_topic: Biotin research collection; topical membership is not evidence of a direct dietary effect. plain_language: An energy-sensing kinase can switch ACC2 down even when biotin is available. organism: Homo sapiens tissue_or_cell_type: Purified ACC2 domain experimental_model: Crystal structures of the human ACC2 biotin-carboxylase domain after AMPK phosphorylation limitations: Domain structures explain a regulatory mechanism; the construct uses Ser222 numbering and must not be silently relabeled with another isoform numbering scheme. exposure: Phosphorylation and soraphen A comparison evidence_span: {"source_cache": "artifacts/biotin-research/19900410.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3d7161fb1a281c68bbe3b8d4738b26d5ed762ca2bea3d9621ee6c8946a7fa71c", "start_char": 0, "end_char": 870, "text_sha256": "3d7161fb1a281c68bbe3b8d4738b26d5ed762ca2bea3d9621ee6c8946a7fa71c"} [b7-p19900410] Molecular mechanism for the regulation of human ACC2 through phosphorylation by AMPK. (2010). https://pubmed.ncbi.nlm.nih.gov/19900410/ DOI: 10.1016/j.bbrc.2009.11.029
Complete structured claim and evidence
Wild-type human CPT1B showed high-affinity malonyl-CoA binding and inhibition in recombinant mitochondrial assays.
Malonyl-CoA → Human carnitine palmitoyltransferase 1B / CPT1B source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/biotin-research/10651636.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e99728ef83700f17a810421385b71ea243576419df807dc4749b588beb01d400", "start_char": 0, "end_char": 1542, "text_sha256": "e99728ef83700f17a810421385b71ea243576419df807dc4749b588beb01d400"}
experimental_model
Human CPT1B wild type and N-terminal deletions expressed in yeast mitochondria
exposure
Malonyl-CoA binding and activity assays
limitations
Expression host is yeast; these data concern human CPT1B, not every CPT1 isoform or a biotin supplementation outcome.
nutrient_topic
Biotin research collection; topical membership is not evidence of a direct dietary effect. · Biotin
organism
Homo sapiens
plain_language
Malonyl-CoA links the carboxylase pathway to the carnitine-dependent fat-entry step.
primary_references
[b7-p10651636] The first 28 N-terminal amino acid residues of human heart muscle carnitine palmitoyltransferase I are essential for malonyl CoA sensitivity and high-affinity binding. (2000). https://pubmed.ncbi.nlm.nih.gov/10651636/ DOI: 10.1021/bi9918700
tissue_or_cell_type
Recombinant human muscle/heart CPT1B
Biotin: carboxylases, recycling, deficiency and nutrient interactions (2026-09-17) · lines 741–752
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human CPT1B wild type and N-terminal deletions expressed in yeast mitochondria · source_derived_draft · unverified_draft
### b7-malonyl-cpt1b Wild-type human CPT1B showed high-affinity malonyl-CoA binding and inhibition in recombinant mitochondrial assays. Condition category: normal nutrient_topic: Biotin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Malonyl-CoA links the carboxylase pathway to the carnitine-dependent fat-entry step. organism: Homo sapiens tissue_or_cell_type: Recombinant human muscle/heart CPT1B experimental_model: Human CPT1B wild type and N-terminal deletions expressed in yeast mitochondria limitations: Expression host is yeast; these data concern human CPT1B, not every CPT1 isoform or a biotin supplementation outcome. exposure: Malonyl-CoA binding and activity assays evidence_span: {"source_cache": "artifacts/biotin-research/10651636.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e99728ef83700f17a810421385b71ea243576419df807dc4749b588beb01d400", "start_char": 0, "end_char": 1542, "text_sha256": "e99728ef83700f17a810421385b71ea243576419df807dc4749b588beb01d400"} [b7-p10651636] The first 28 N-terminal amino acid residues of human heart muscle carnitine palmitoyltransferase I are essential for malonyl CoA sensitivity and high-affinity binding. (2000). https://pubmed.ncbi.nlm.nih.gov/10651636/ DOI: 10.1021/bi9918700
Complete structured claim and evidence
TPK1 activation transfers ATP-derived diphosphoryl to thiamine, yielding ThDP and AMP in a magnesium-dependent reaction.
ATP → Thiamine (vitamin B1) source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Mg-dependent ATP chemistry activates B1; it does not imply every later ThDP-binding event consumes ATP.
curation_note
Adds explicit phosphate-transfer/AMP-product detail to the existing magnesium collection.
evidence-scope
Recombinant enzyme
evidence_locator
Abstract
evidence_spans
[{"source_document": "artifacts/thiamine_transport_sources/sambon-2022-tpk1-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1689}]
experimental_model
Purified His-tagged human TPK1; ATP/Mg kinetics and mutagenesis.
limitations
Overall chemistry does not resolve substrate-binding order.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
B1 activation uses ATP and releases AMP; it is not an ATP-to-ADP single-phosphate step.
primary_references
[onozuka-2003-tpk1] Steady-state kinetics and mutational studies of recombinant human thiamin pyrophosphokinase (2003). https://pubmed.ncbi.nlm.nih.gov/12953792/ DOI: 10.3177/jnsv.49.156 [sambon-2022-tpk1] Product inhibition of mammalian thiamine pyrophosphokinase is an important mechanism for maintaining thiamine diphosphate homeostasis (2022). https://doi.org/10.1016/j.bbagen.2021.130071 DOI: 10.1016/j.bbagen.2021.130071
reaction
thiamine + ATP -> thiamine diphosphate + AMP
related_existing_claim_keys
["mg-tpk1-thiamine-to-thdp"]
tissue_or_cell_type
Recombinant enzyme
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 339–356
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified His-tagged human TPK1; ATP/Mg kinetics and mutagenesis. · source_derived_draft · unverified_draft
### b1-tpk1-atp-amp-stoichiometry TPK1 activation transfers ATP-derived diphosphoryl to thiamine, yielding ThDP and AMP in a magnesium-dependent reaction. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: B1 activation uses ATP and releases AMP; it is not an ATP-to-ADP single-phosphate step. organism: Homo sapiens tissue_or_cell_type: Recombinant enzyme experimental_model: Purified His-tagged human TPK1; ATP/Mg kinetics and mutagenesis. limitations: Overall chemistry does not resolve substrate-binding order. cross_nutrient: Mg-dependent ATP chemistry activates B1; it does not imply every later ThDP-binding event consumes ATP. reaction: thiamine + ATP -> thiamine diphosphate + AMP related_existing_claim_keys: ["mg-tpk1-thiamine-to-thdp"] curation_note: Adds explicit phosphate-transfer/AMP-product detail to the existing magnesium collection. evidence_spans: [{"source_document": "artifacts/thiamine_transport_sources/sambon-2022-tpk1-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1689}] evidence_locator: Abstract evidence-scope: Recombinant enzyme [onozuka-2003-tpk1] Steady-state kinetics and mutational studies of recombinant human thiamin pyrophosphokinase (2003). https://pubmed.ncbi.nlm.nih.gov/12953792/ DOI: 10.3177/jnsv.49.156 [sambon-2022-tpk1] Product inhibition of mammalian thiamine pyrophosphokinase is an important mechanism for maintaining thiamine diphosphate homeostasis (2022). https://doi.org/10.1016/j.bbagen.2021.130071 DOI: 10.1016/j.bbagen.2021.130071
Complete structured claim and evidence
Wild-type human PDH E1 structures show Mg coordinated at the ThDP diphosphate-binding site.
Mg2+ → Thiamine diphosphate source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Magnesium and thiamine-derived ThDP intersect at mitochondrial carbon metabolism; purified-enzyme responses do not measure whole-body energy supply.
experimental_model
Recombinant human wild-type and alphaV138M E1 structures and reconstituted PDH complex activity.
limitations
Structure supports binding geometry; no magnesium-deficiency intervention was performed.
nutrient_topic
Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
organism
Homo sapiens
plain_language
Magnesium helps position the B1-derived cofactor in the pyruvate-processing enzyme.
primary_references
[whitley-2018-pdh] Pyruvate dehydrogenase complex deficiency is linked to regulatory loop disorder in the αV138M variant of human pyruvate dehydrogenase (2018). https://pmc.ncbi.nlm.nih.gov/articles/PMC6109939/ DOI: 10.1074/jbc.RA118.003996
tissue_or_cell_type
Recombinant mitochondrial enzyme
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 613–623
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human wild-type and alphaV138M E1 structures and reconstituted PDH complex activity. · source_derived_draft · unverified_draft
### mg-pdh-e1-thdp-anchor Wild-type human PDH E1 structures show Mg coordinated at the ThDP diphosphate-binding site. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Magnesium helps position the B1-derived cofactor in the pyruvate-processing enzyme. organism: Homo sapiens tissue_or_cell_type: Recombinant mitochondrial enzyme experimental_model: Recombinant human wild-type and alphaV138M E1 structures and reconstituted PDH complex activity. limitations: Structure supports binding geometry; no magnesium-deficiency intervention was performed. cross_nutrient: Magnesium and thiamine-derived ThDP intersect at mitochondrial carbon metabolism; purified-enzyme responses do not measure whole-body energy supply. [whitley-2018-pdh] Pyruvate dehydrogenase complex deficiency is linked to regulatory loop disorder in the αV138M variant of human pyruvate dehydrogenase (2018). https://pmc.ncbi.nlm.nih.gov/articles/PMC6109939/ DOI: 10.1074/jbc.RA118.003996
Complete structured claim and evidence
Human PDH E1 forms a covalent lactyl-ThDP intermediate from pyruvate and decarboxylates it, retaining the two-carbon fragment on ThDP.
Human pyruvate dehydrogenase E1 → Pyruvate source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Patient muscle PDH activity was deficient without added ThDP but normal or near-normal under cofactor-supplemented assay conditions.
Thiamine diphosphate → Pyruvate dehydrogenase complex activity source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence-scope
Muscle and blood
evidence_locator
Figure 3; Table 1
evidence_spans
[{"source_document": "artifacts/thiamine_transport_sources/PMC3234371.txt", "start_char": 12774, "end_char": 13380}]
experimental_model
Five patients from three families; muscle/blood chemistry and enzyme assays.
limitations
Ex vivo cofactor rescue does not establish oral ThDP delivery or clinical efficacy.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
Supplying cofactor directly to the assay exposed an activation problem upstream of PDH.
primary_references
[mayr-2011-tpk1-deficiency] Thiamine pyrophosphokinase deficiency in encephalopathic children with defects in the pyruvate oxidation pathway (2011). https://pmc.ncbi.nlm.nih.gov/articles/PMC3234371/ DOI: 10.1016/j.ajhg.2011.11.007
tissue_or_cell_type
Muscle and blood
trigger_kind
machinery_impairment Imported condition classification; unverified.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 402–414
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Five patients from three families; muscle/blood chemistry and enzyme assays. · source_derived_draft · unverified_draft
### b1-tpk1-deficiency-pdh-assay-rescue Patient muscle PDH activity was deficient without added ThDP but normal or near-normal under cofactor-supplemented assay conditions. Condition category: machinery_impairment nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Supplying cofactor directly to the assay exposed an activation problem upstream of PDH. organism: Homo sapiens tissue_or_cell_type: Muscle and blood experimental_model: Five patients from three families; muscle/blood chemistry and enzyme assays. limitations: Ex vivo cofactor rescue does not establish oral ThDP delivery or clinical efficacy. evidence_locator: Figure 3; Table 1 evidence_spans: [{"source_document": "artifacts/thiamine_transport_sources/PMC3234371.txt", "start_char": 12774, "end_char": 13380}] evidence-scope: Muscle and blood [mayr-2011-tpk1-deficiency] Thiamine pyrophosphokinase deficiency in encephalopathic children with defects in the pyruvate oxidation pathway (2011). https://pmc.ncbi.nlm.nih.gov/articles/PMC3234371/ DOI: 10.1016/j.ajhg.2011.11.007
Complete structured claim and evidence
The LIAS Arg249His patient had depleted protein-bound lipoyl signal and reduced PDH activity/pyruvate oxidation in investigated muscle and fibroblast preparations.
LIAS Arg249His → Human pyruvate dehydrogenase complex source_derived_draftungraded
Experimental context and source evidence
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
Complete structured claim and evidence
Refeeding syndrome occurred in three cohort participants; two had received vitamin B/C preparations before nutrition support.
Thiamine (vitamin B1) → Electrolyte and fluid disorder during refeeding source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
B1 repletion and K/P/Mg management address different requirements.
experimental_model
Prospective cohort and individual case histories.
exposure
Study-specific exposure described in the model; no regimen inferred beyond the accessed evidence.
limitations
No claim that thiamine caused the syndrome, that supplementation failed biologically, or that glucose should be withheld in an emergency.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
Providing vitamins did not by itself prevent every electrolyte and fluid complication.
primary_references
[b1-rio2013] Occurrence of refeeding syndrome in adults started on artificial nutrition support: prospective cohort study (2013). https://pubmed.ncbi.nlm.nih.gov/23315514/ DOI: 10.1136/bmjopen-2012-002173
tissue_or_cell_type
Whole-body clinical nutrition
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1733–1744
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Prospective cohort and individual case histories. · source_derived_draft · unverified_draft
### b1-refeeding-vitamins-not-complete-rescue Refeeding syndrome occurred in three cohort participants; two had received vitamin B/C preparations before nutrition support. Condition category: nutrient_deficiency nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Providing vitamins did not by itself prevent every electrolyte and fluid complication. organism: Homo sapiens tissue_or_cell_type: Whole-body clinical nutrition experimental_model: Prospective cohort and individual case histories. limitations: No claim that thiamine caused the syndrome, that supplementation failed biologically, or that glucose should be withheld in an emergency. cross_nutrient: B1 repletion and K/P/Mg management address different requirements. exposure: Study-specific exposure described in the model; no regimen inferred beyond the accessed evidence. [b1-rio2013] Occurrence of refeeding syndrome in adults started on artificial nutrition support: prospective cohort study (2013). https://pubmed.ncbi.nlm.nih.gov/23315514/ DOI: 10.1136/bmjopen-2012-002173
Complete structured claim and evidence
Low baseline serum magnesium was associated with subsequent refeeding syndrome in the cohort.
Serum magnesium concentration → Electrolyte and fluid disorder during refeeding source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
experimental_model
Three syndrome events among 243 adults.
exposure
Study-specific exposure described in the model; no regimen inferred beyond the accessed evidence.
limitations
Too few events for robust multivariable regression; association does not identify a universal causal bottleneck.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Homo sapiens
plain_language
A mineral shortage was a risk signal alongside poor prior intake.
primary_references
[b1-rio2013] Occurrence of refeeding syndrome in adults started on artificial nutrition support: prospective cohort study (2013). https://pubmed.ncbi.nlm.nih.gov/23315514/ DOI: 10.1136/bmjopen-2012-002173
tissue_or_cell_type
Serum and clinical course
trigger_kind
biomarker_context Imported condition classification; unverified.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1746–1756
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Three syndrome events among 243 adults. · source_derived_draft · unverified_draft
### b1-refeeding-low-mg-association Low baseline serum magnesium was associated with subsequent refeeding syndrome in the cohort. Condition category: biomarker_context nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A mineral shortage was a risk signal alongside poor prior intake. organism: Homo sapiens tissue_or_cell_type: Serum and clinical course experimental_model: Three syndrome events among 243 adults. limitations: Too few events for robust multivariable regression; association does not identify a universal causal bottleneck. exposure: Study-specific exposure described in the model; no regimen inferred beyond the accessed evidence. [b1-rio2013] Occurrence of refeeding syndrome in adults started on artificial nutrition support: prospective cohort study (2013). https://pubmed.ncbi.nlm.nih.gov/23315514/ DOI: 10.1136/bmjopen-2012-002173
Complete structured claim and evidence
Days alive after ICU discharge did not differ significantly: 44.8 versus 39.9 days, estimated difference 4.9 days (95% CI −2.3 to 13.6), p=0.19.
Protocolized caloric restriction during ICU refeeding-syndrome management → Days alive after ICU discharge over 60 days in the refeeding trial source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/phosphorus-research/26597128.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0324ddb02d92a61886682e682350e42356a4596c93e3ff60d23860163c6c1aa6", "start_char": 0, "end_char": 2574, "text_sha256": "0324ddb02d92a61886682e682350e42356a4596c93e3ff60d23860163c6c1aa6"}
experimental_model
Multicenter randomized clinical management trial
exposure
Protocolized caloric restriction versus continued standard feeding during electrolyte replacement; 60-day follow-up
limitations
Management-strategy trial, not isolated phosphate supplementation. Primary composite endpoint was nonsignificant; component results must retain that context.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Human
plain_language
The trial’s primary composite outcome was not statistically significant.
primary_references
[phosphorus-p26597128] Restricted versus continued standard caloric intake during the management of refeeding syndrome in critically ill adults: a randomised, parallel-group, multicentre, single-blind controlled trial. (2015). https://pubmed.ncbi.nlm.nih.gov/26597128/ DOI: 10.1016/s2213-2600(15)00418-x
tissue_or_cell_type
339 critically ill adults developing refeeding syndrome within 72 hours of nutrition
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 1154–1165
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Multicenter randomized clinical management trial · source_derived_draft · unverified_draft
### phosphorus-refeeding-primary Days alive after ICU discharge did not differ significantly: 44.8 versus 39.9 days, estimated difference 4.9 days (95% CI −2.3 to 13.6), p=0.19. Condition category: normal nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: The trial’s primary composite outcome was not statistically significant. organism: Human tissue_or_cell_type: 339 critically ill adults developing refeeding syndrome within 72 hours of nutrition experimental_model: Multicenter randomized clinical management trial limitations: Management-strategy trial, not isolated phosphate supplementation. Primary composite endpoint was nonsignificant; component results must retain that context. exposure: Protocolized caloric restriction versus continued standard feeding during electrolyte replacement; 60-day follow-up evidence_span: {"source_cache": "artifacts/phosphorus-research/26597128.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0324ddb02d92a61886682e682350e42356a4596c93e3ff60d23860163c6c1aa6", "start_char": 0, "end_char": 2574, "text_sha256": "0324ddb02d92a61886682e682350e42356a4596c93e3ff60d23860163c6c1aa6"} [phosphorus-p26597128] Restricted versus continued standard caloric intake during the management of refeeding syndrome in critically ill adults: a randomised, parallel-group, multicentre, single-blind controlled trial. (2015). https://pubmed.ncbi.nlm.nih.gov/26597128/ DOI: 10.1016/s2213-2600(15)00418-x
Complete structured claim and evidence
A component analysis found 149/164 participants alive at day 60 with restriction versus 128/163 with standard feeding, p=0.002.
Protocolized caloric restriction during ICU refeeding-syndrome management → Day-60 survival in the ICU refeeding trial source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/phosphorus-research/26597128.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0324ddb02d92a61886682e682350e42356a4596c93e3ff60d23860163c6c1aa6", "start_char": 0, "end_char": 2574, "text_sha256": "0324ddb02d92a61886682e682350e42356a4596c93e3ff60d23860163c6c1aa6"}
experimental_model
Multicenter randomized clinical management trial
exposure
Protocolized caloric restriction versus continued standard feeding during electrolyte replacement; 60-day follow-up
limitations
Management-strategy trial, not isolated phosphate supplementation. Primary composite endpoint was nonsignificant; component results must retain that context.
nutrient_topic
Phosphorus research collection; topical membership is not evidence of a direct dietary effect. · Phosphorus
organism
Human
plain_language
The survival component favored the supervised strategy, while the primary composite remained nonsignificant.
primary_references
[phosphorus-p26597128] Restricted versus continued standard caloric intake during the management of refeeding syndrome in critically ill adults: a randomised, parallel-group, multicentre, single-blind controlled trial. (2015). https://pubmed.ncbi.nlm.nih.gov/26597128/ DOI: 10.1016/s2213-2600(15)00418-x
tissue_or_cell_type
339 critically ill adults developing refeeding syndrome within 72 hours of nutrition
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17) · lines 1167–1178
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Multicenter randomized clinical management trial · source_derived_draft · unverified_draft
### phosphorus-refeeding-survival A component analysis found 149/164 participants alive at day 60 with restriction versus 128/163 with standard feeding, p=0.002. Condition category: normal nutrient_topic: Phosphorus research collection; topical membership is not evidence of a direct dietary effect. plain_language: The survival component favored the supervised strategy, while the primary composite remained nonsignificant. organism: Human tissue_or_cell_type: 339 critically ill adults developing refeeding syndrome within 72 hours of nutrition experimental_model: Multicenter randomized clinical management trial limitations: Management-strategy trial, not isolated phosphate supplementation. Primary composite endpoint was nonsignificant; component results must retain that context. exposure: Protocolized caloric restriction versus continued standard feeding during electrolyte replacement; 60-day follow-up evidence_span: {"source_cache": "artifacts/phosphorus-research/26597128.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0324ddb02d92a61886682e682350e42356a4596c93e3ff60d23860163c6c1aa6", "start_char": 0, "end_char": 2574, "text_sha256": "0324ddb02d92a61886682e682350e42356a4596c93e3ff60d23860163c6c1aa6"} [phosphorus-p26597128] Restricted versus continued standard caloric intake during the management of refeeding syndrome in critically ill adults: a randomised, parallel-group, multicentre, single-blind controlled trial. (2015). https://pubmed.ncbi.nlm.nih.gov/26597128/ DOI: 10.1016/s2213-2600(15)00418-x
Complete structured claim and evidence
Human PC catalyzes two-step pyruvate carboxylation to oxaloacetate.
Human pyruvate carboxylase / PC → Pyruvate source_derived_draftungraded
Experimental context and source evidence
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"}
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
Complete structured claim and evidence
Human MCAD and ETF form an electron-transfer complex in which a recognition loop anchors binding while the ETF FAD domain samples electron-transfer-compatible conformations.
Human medium-chain acyl-CoA dehydrogenase / ACADM → Human electron transfer flavoprotein / ETF source_derived_draftungraded
Experimental context and source evidence
evidence_spans
[{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMID15159392", "locator": "metadata.abstractText", "paragraph_index": 0, "char_start": 0, "char_end": 1430, "evidence_access": "primary-abstract"}]
experimental_model
Human ETF-MCAD complex crystallography and solution interfacial mutagenesis.
exposure
No nutrient intervention; structural or biochemical characterization.
limitations
Primary abstract supports mechanism; no inference about clinical MCAD supplementation response.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
Fatty-acid oxidation hands electrons from MCAD to a distinct ETF carrier.
primary_references
[toogood-2004-etf-mcad] Extensive domain motion and electron transfer in the human electron transferring flavoprotein.medium chain Acyl-CoA dehydrogenase complex (2004). https://pubmed.ncbi.nlm.nih.gov/15159392/ DOI: 10.1074/jbc.m404884200
tissue_or_cell_type
Recombinant human protein complex
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 741–752
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human ETF-MCAD complex crystallography and solution interfacial mutagenesis. · source_derived_draft · unverified_draft
### b2-met-mcad-etf-electron-transfer Human MCAD and ETF form an electron-transfer complex in which a recognition loop anchors binding while the ETF FAD domain samples electron-transfer-compatible conformations. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Fatty-acid oxidation hands electrons from MCAD to a distinct ETF carrier. organism: Homo sapiens tissue_or_cell_type: Recombinant human protein complex experimental_model: Human ETF-MCAD complex crystallography and solution interfacial mutagenesis. limitations: Primary abstract supports mechanism; no inference about clinical MCAD supplementation response. exposure: No nutrient intervention; structural or biochemical characterization. evidence_spans: [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMID15159392", "locator": "metadata.abstractText", "paragraph_index": 0, "char_start": 0, "char_end": 1430, "evidence_access": "primary-abstract"}] [toogood-2004-etf-mcad] Extensive domain motion and electron transfer in the human electron transferring flavoprotein.medium chain Acyl-CoA dehydrogenase complex (2004). https://pubmed.ncbi.nlm.nih.gov/15159392/ DOI: 10.1074/jbc.m404884200
Complete structured claim and evidence
Human mitochondrial acetoacetyl-CoA thiolase ACAT1/T2, a homotetramer, uses coenzyme A to cleave acetoacetyl-CoA into two acetyl-CoA molecules.
Acetoacetyl-CoA → Acetyl-CoA source_derived_draftungraded
Experimental context and source evidence
experimental_model
Purified recombinant human ACAT1/T2 enzyme kinetics and crystal structures
limitations
Thiolase chemistry is reversible and shared with ketone metabolism. These experiments do not measure lysine-specific flux. ACAT1 here denotes acetyl-CoA acetyltransferase, not cholesterol acyltransferase SOAT1.
organism
Homo sapiens
plain_language
The four-carbon intermediate is split into two acetyl-CoA molecules.
primary_references
[haapalainen2007] Crystallographic and kinetic studies of human mitochondrial acetoacetyl-CoA thiolase: the importance of potassium and chloride ions for its structure and function (2007). https://pubmed.ncbi.nlm.nih.gov/17371050/ DOI: 10.1021/bi6026192
tissue_or_cell_type
Mitochondrial matrix enzyme; recombinant protein study
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 377–385
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified recombinant human ACAT1/T2 enzyme kinetics and crystal structures · source_derived_draft · unverified_draft
### acat1-acetoacetyl-coa-thiolysis Human mitochondrial acetoacetyl-CoA thiolase ACAT1/T2, a homotetramer, uses coenzyme A to cleave acetoacetyl-CoA into two acetyl-CoA molecules. Plain language: The four-carbon intermediate is split into two acetyl-CoA molecules. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Mitochondrial matrix enzyme; recombinant protein study experimental_model: Purified recombinant human ACAT1/T2 enzyme kinetics and crystal structures limitations: Thiolase chemistry is reversible and shared with ketone metabolism. These experiments do not measure lysine-specific flux. ACAT1 here denotes acetyl-CoA acetyltransferase, not cholesterol acyltransferase SOAT1. [haapalainen2007] Crystallographic and kinetic studies of human mitochondrial acetoacetyl-CoA thiolase: the importance of potassium and chloride ions for its structure and function (2007). https://pubmed.ncbi.nlm.nih.gov/17371050/ DOI: 10.1021/bi6026192
Complete structured claim and evidence
Nicotinic-acid activation of GPR109A/HCAR2 in the human cell-line assay lowered cAMP through a pertussis-toxin-sensitive pathway.
Human hydroxycarboxylic acid receptor 2 / HCAR2 → Intracellular cyclic AMP content source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Nicotinic acid (agonist); Cyclic adenosine monophosphate (measured_signal)
evidence_span
{"source_cache": "artifacts/niacin-clinical-sources/walters2009.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "2eb822534ed0c8ea9f71ec67288c302e4e375ed9e86cfe70b28f21ae65ffbd4b", "start_char": 0, "end_char": 1537, "text_sha256": "2eb822534ed0c8ea9f71ec67288c302e4e375ed9e86cfe70b28f21ae65ffbd4b"}
experimental_model
Human cell-line nicotinic-acid receptor signaling assay
exposure
Nicotinic-acid stimulation and beta-arrestin perturbation
limitations
Pharmacological receptor signaling, not an essential effect of every B3 precursor. Cell signaling and mouse physiology are distinct arms. Reduced fatty acids or flushing does not establish cardiovascular benefit.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Homo sapiens
plain_language
Nicotinic acid can act as a receptor signal as well as a vitamin precursor, switching down a cellular signaling molecule.
primary_references
[nia-clin-walters2009] beta-Arrestin1 mediates nicotinic acid-induced flushing, but not its antilipolytic effect, in mice. (2009). https://pubmed.ncbi.nlm.nih.gov/19349687/ DOI: 10.1172/jci36806
tissue_or_cell_type
Cultured human cells
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 1291–1303
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human cell-line nicotinic-acid receptor signaling assay · source_derived_draft · unverified_draft
### nia-clin-hcar2-camp Nicotinic-acid activation of GPR109A/HCAR2 in the human cell-line assay lowered cAMP through a pertussis-toxin-sensitive pathway. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Nicotinic acid can act as a receptor signal as well as a vitamin precursor, switching down a cellular signaling molecule. organism: Homo sapiens tissue_or_cell_type: Cultured human cells experimental_model: Human cell-line nicotinic-acid receptor signaling assay limitations: Pharmacological receptor signaling, not an essential effect of every B3 precursor. Cell signaling and mouse physiology are distinct arms. Reduced fatty acids or flushing does not establish cardiovascular benefit. exposure: Nicotinic-acid stimulation and beta-arrestin perturbation cross_nutrient: Nicotinic acid (agonist); Cyclic adenosine monophosphate (measured_signal) evidence_span: {"source_cache": "artifacts/niacin-clinical-sources/walters2009.abstract.txt", "locator": "Indexed primary abstract", "file_sha256": "2eb822534ed0c8ea9f71ec67288c302e4e375ed9e86cfe70b28f21ae65ffbd4b", "start_char": 0, "end_char": 1537, "text_sha256": "2eb822534ed0c8ea9f71ec67288c302e4e375ed9e86cfe70b28f21ae65ffbd4b"} [nia-clin-walters2009] beta-Arrestin1 mediates nicotinic acid-induced flushing, but not its antilipolytic effect, in mice. (2009). https://pubmed.ncbi.nlm.nih.gov/19349687/ DOI: 10.1172/jci36806
Complete structured claim and evidence
Human PANK3 catalyzes ATP-dependent conversion of pantothenate to 4′-phosphopantothenate.
Human pantothenate kinase 3 / PANK3 → Pantothenate (vitamin B5) source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
experimental_model
Purified recombinant human PANK3, crystallography and biochemical ligand-binding/heterodimer experiments
exposure
In-vitro biochemical exposure; concentrations not extracted.
limitations
Abstract-level structural and biochemical findings; no diet or Mg-repletion experiment. Substrate concentrations not established here.
nutrient_topic
Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. · Pantothenate (vitamin B5)
organism
Homo sapiens
plain_language
PANK3 starts vitamin B5 activation by adding phosphate.
primary_references
[b5-bio-pank3allosteric] Allosteric Regulation of Mammalian Pantothenate Kinase. (2016). https://pubmed.ncbi.nlm.nih.gov/27555321/ DOI: 10.1074/jbc.m116.748061
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 483–494
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified recombinant human PANK3, crystallography and biochemical ligand-binding/heterodimer experiments · source_derived_draft · unverified_draft
### b5-bio-pank3-phosphorylation Human PANK3 catalyzes ATP-dependent conversion of pantothenate to 4′-phosphopantothenate. Condition category: normal nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: PANK3 starts vitamin B5 activation by adding phosphate. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Purified recombinant human PANK3, crystallography and biochemical ligand-binding/heterodimer experiments limitations: Abstract-level structural and biochemical findings; no diet or Mg-repletion experiment. Substrate concentrations not established here. exposure: In-vitro biochemical exposure; concentrations not extracted. cross_nutrient: true [b5-bio-pank3allosteric] Allosteric Regulation of Mammalian Pantothenate Kinase. (2016). https://pubmed.ncbi.nlm.nih.gov/27555321/ DOI: 10.1074/jbc.m116.748061
Complete structured claim and evidence
Purified human PPCS, PPCDC and bifunctional CoA synthase reconstituted CoA synthesis from phosphopantothenate in vitro.
4-Phosphopantothenate → Coenzyme A source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Provides the B5-derived CoA partner required by PDH, OGDH, BCKDH and OADH; simultaneous B1/B5 depletion was not tested.
evidence
[{"paper_key": "daugherty-2002-coa", "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
Reconstituted human enzyme pathway.
limitations
Cross-pathway connection is biochemical integration, not a tested clinical supplementation interaction.
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
Vitamin B5 supplies a separate carrier used after B1-dependent decarboxylation. The experiment starts with phosphorylated B5, so it does not test absorption or the first phosphorylation step.
primary_references
[daugherty-2002-coa] Complete reconstitution of the human coenzyme A biosynthetic pathway via comparative genomics (2002). https://pubmed.ncbi.nlm.nih.gov/11923312/ DOI: 10.1074/jbc.m201708200
tissue_or_cell_type
Purified recombinant enzymes
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 731–743
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Reconstituted human enzyme pathway. · source_derived_draft · unverified_draft
### b1-coa-b5-downstream-biosynthesis Purified human PPCS, PPCDC and bifunctional CoA synthase reconstituted CoA synthesis from phosphopantothenate in vitro. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin B5 supplies a separate carrier used after B1-dependent decarboxylation. The experiment starts with phosphorylated B5, so it does not test absorption or the first phosphorylation step. organism: Homo sapiens tissue_or_cell_type: Purified recombinant enzymes experimental_model: Reconstituted human enzyme pathway. limitations: Cross-pathway connection is biochemical integration, not a tested clinical supplementation interaction. evidence: [{"paper_key": "daugherty-2002-coa", "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: Provides the B5-derived CoA partner required by PDH, OGDH, BCKDH and OADH; simultaneous B1/B5 depletion was not tested. nutrient: Thiamine (vitamin B1) [daugherty-2002-coa] Complete reconstitution of the human coenzyme A biosynthetic pathway via comparative genomics (2002). https://pubmed.ncbi.nlm.nih.gov/11923312/ DOI: 10.1074/jbc.m201708200
Complete structured claim and evidence
A labeled cofactor-analogue experiment supported direct participation of the PLP phosphate group in glycogen phosphorylase glucosyl transfer.
PLP → Rabbit skeletal-muscle glycogen phosphorylase source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
PLP-phosphate chemistry supports glycogen metabolism.
experimental_model
Rabbit muscle phosphorylase reconstituted with synthetic cofactor analogue
exposure
Synthetic pyridoxal-diphospho-glucose analogue reconstitution
limitations
Mechanistic analogue evidence; not a demonstration of muscle glycogen failure in human B6 deficiency.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Oryctolagus cuniculus
plain_language
The phosphate portion of active B6 helps this carbohydrate reaction.
primary_references
[b6-phosphorylase-1982] Catalytic mechanism of glycogen phosphorylase: pyridoxal(5')diphospho(1)-alpha-D-glucose as a transition-state analogue. (1982). https://pmc.ncbi.nlm.nih.gov/articles/PMC346497/ DOI: 10.1073/pnas.79.12.3716
tissue_or_cell_type
Rabbit skeletal-muscle protein
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 860–871
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rabbit muscle phosphorylase reconstituted with synthetic cofactor analogue · source_derived_draft · unverified_draft
### b6-met-rabbit-phosphorylase-phosphate A labeled cofactor-analogue experiment supported direct participation of the PLP phosphate group in glycogen phosphorylase glucosyl transfer. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The phosphate portion of active B6 helps this carbohydrate reaction. organism: Oryctolagus cuniculus tissue_or_cell_type: Rabbit skeletal-muscle protein experimental_model: Rabbit muscle phosphorylase reconstituted with synthetic cofactor analogue limitations: Mechanistic analogue evidence; not a demonstration of muscle glycogen failure in human B6 deficiency. cross_nutrient: PLP-phosphate chemistry supports glycogen metabolism. exposure: Synthetic pyridoxal-diphospho-glucose analogue reconstitution [b6-phosphorylase-1982] Catalytic mechanism of glycogen phosphorylase: pyridoxal(5')diphospho(1)-alpha-D-glucose as a transition-state analogue. (1982). https://pmc.ncbi.nlm.nih.gov/articles/PMC346497/ DOI: 10.1073/pnas.79.12.3716
Complete structured claim and evidence
BBOX1 hydroxylates gamma-butyrobetaine to L-carnitine using oxygen, 2-oxoglutarate and ferrous iron.
gamma-Butyrobetaine → L-Carnitine source_derived_draftungraded
Experimental context and source evidence
experimental_model
Human cDNA expression and human tissue activity assays
limitations
Do not generalize full carnitine-synthesis capacity to every tissue.
organism
Homo sapiens
plain_language
BBOX1 completes carnitine synthesis.
primary_references
[vaz1998] Carnitine biosynthesis: identification of the cDNA encoding human gamma-butyrobetaine hydroxylase (1998). https://pubmed.ncbi.nlm.nih.gov/9753662/ DOI: 10.1006/bbrc.1998.9343 [rebouche1980] Tissue distribution of carnitine biosynthetic enzymes in man (1980). https://pubmed.ncbi.nlm.nih.gov/6770910/ DOI: 10.1016/0304-4165(80)90133-6
tissue_or_cell_type
Kidney, liver and brain; abundance differs
L-Lysine: mechanism-first literature curation (2026-09-17) · lines 207–216
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human cDNA expression and human tissue activity assays · source_derived_draft · unverified_draft
### bbox1-carnitine-formation BBOX1 hydroxylates gamma-butyrobetaine to L-carnitine using oxygen, 2-oxoglutarate and ferrous iron. Plain language: BBOX1 completes carnitine synthesis. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Kidney, liver and brain; abundance differs experimental_model: Human cDNA expression and human tissue activity assays limitations: Do not generalize full carnitine-synthesis capacity to every tissue. [vaz1998] Carnitine biosynthesis: identification of the cDNA encoding human gamma-butyrobetaine hydroxylase (1998). https://pubmed.ncbi.nlm.nih.gov/9753662/ DOI: 10.1006/bbrc.1998.9343 [rebouche1980] Tissue distribution of carnitine biosynthetic enzymes in man (1980). https://pubmed.ncbi.nlm.nih.gov/6770910/ DOI: 10.1016/0304-4165(80)90133-6
Complete structured claim and evidence
Arginine bound CASTOR1 with an approximate dissociation constant of 30 micromolar.
L-Arginine → Human cellular arginine sensor CASTOR1 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Mammalian-cell signaling experiments and biochemical CASTOR1 binding.
limitations
Binding constant is not a human deficiency threshold.
nutrient_topic
L-Arginine collection; tissue, species, dose and formulation distinctions retained. · L-Arginine
plain_language
Arginine is a signal as well as a reaction substrate.
primary_references
The CASTOR Proteins Are Arginine Sensors for the mTORC1 Pathway. · 2016 · https://pubmed.ncbi.nlm.nih.gov/26972053/ · DOI 10.1016/j.cell.2016.02.035
L-Arginine: transport, metabolic branches, nutrient interactions, availability and discovery questions (2026-09-18) · lines 174–180
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Mammalian-cell signaling experiments and biochemical CASTOR1 binding. · source_derived_draft · unverified_draft
## arg-castor-binding Arginine is a signal as well as a reaction substrate. Arginine bound CASTOR1 with an approximate dissociation constant of 30 micromolar. Model: Mammalian-cell signaling experiments and biochemical CASTOR1 binding. Limitations: Binding constant is not a human deficiency threshold. Evidence access: Primary abstract The CASTOR Proteins Are Arginine Sensors for the mTORC1 Pathway. · 2016 · https://pubmed.ncbi.nlm.nih.gov/26972053/ · DOI 10.1016/j.cell.2016.02.035
Complete structured claim and evidence
Arginine binding disrupted the CASTOR1–GATOR2 complex; arginine-binding capacity was needed for pathway activation.
L-Arginine → Human CASTOR1–GATOR2 complex source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Mammalian-cell signaling experiments and biochemical CASTOR1 binding.
limitations
Do not equate pathway activation with guaranteed muscle growth.
nutrient_topic
L-Arginine collection; tissue, species, dose and formulation distinctions retained. · L-Arginine
plain_language
Binding releases a brake on nutrient signaling.
primary_references
The CASTOR Proteins Are Arginine Sensors for the mTORC1 Pathway. · 2016 · https://pubmed.ncbi.nlm.nih.gov/26972053/ · DOI 10.1016/j.cell.2016.02.035
L-Arginine: transport, metabolic branches, nutrient interactions, availability and discovery questions (2026-09-18) · lines 182–188
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Mammalian-cell signaling experiments and biochemical CASTOR1 binding. · source_derived_draft · unverified_draft
## arg-castor-release Binding releases a brake on nutrient signaling. Arginine binding disrupted the CASTOR1–GATOR2 complex; arginine-binding capacity was needed for pathway activation. Model: Mammalian-cell signaling experiments and biochemical CASTOR1 binding. Limitations: Do not equate pathway activation with guaranteed muscle growth. Evidence access: Primary abstract The CASTOR Proteins Are Arginine Sensors for the mTORC1 Pathway. · 2016 · https://pubmed.ncbi.nlm.nih.gov/26972053/ · DOI 10.1016/j.cell.2016.02.035
Complete structured claim and evidence
CASTOR1 was required for arginine deprivation to inhibit mTORC1.
Human cellular arginine sensor CASTOR1 → Mechanistic target of rapamycin complex 1 source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Mammalian-cell signaling experiments and biochemical CASTOR1 binding.
limitations
Experimental starvation response; no universal dietary cutoff.
nutrient_topic
L-Arginine collection; tissue, species, dose and formulation distinctions retained. · L-Arginine
plain_language
Low arginine is sensed through specific machinery.
primary_references
The CASTOR Proteins Are Arginine Sensors for the mTORC1 Pathway. · 2016 · https://pubmed.ncbi.nlm.nih.gov/26972053/ · DOI 10.1016/j.cell.2016.02.035
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
L-Arginine: transport, metabolic branches, nutrient interactions, availability and discovery questions (2026-09-18) · lines 190–196
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Mammalian-cell signaling experiments and biochemical CASTOR1 binding. · source_derived_draft · unverified_draft
## arg-castor-starvation Low arginine is sensed through specific machinery. CASTOR1 was required for arginine deprivation to inhibit mTORC1. Model: Mammalian-cell signaling experiments and biochemical CASTOR1 binding. Limitations: Experimental starvation response; no universal dietary cutoff. Evidence access: Primary abstract The CASTOR Proteins Are Arginine Sensors for the mTORC1 Pathway. · 2016 · https://pubmed.ncbi.nlm.nih.gov/26972053/ · DOI 10.1016/j.cell.2016.02.035
Complete structured claim and evidence
SLC38A9 mediated arginine-regulated export of essential amino acids, including leucine, from lysosomes.
Human lysosomal amino acid transporter SLC38A9 → Leucine export from lysosomes source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Lysosomal transport and mammalian-cell experiments.
limitations
This is a compartment-specific mechanism, not a demonstrated arginine–leucine supplement synergy.
nutrient_topic
L-Arginine collection; tissue, species, dose and formulation distinctions retained. · L-Arginine
plain_language
Arginine sensing helps make another amino acid available to the cell.
primary_references
mTORC1 Activator SLC38A9 Is Required to Efflux Essential Amino Acids from Lysosomes and Use Protein as a Nutrient. · 2017 · https://pubmed.ncbi.nlm.nih.gov/29053970/ · DOI 10.1016/j.cell.2017.09.046
L-Arginine: transport, metabolic branches, nutrient interactions, availability and discovery questions (2026-09-18) · lines 206–212
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Lysosomal transport and mammalian-cell experiments. · source_derived_draft · unverified_draft
## arg-lysosome-leucine Arginine sensing helps make another amino acid available to the cell. SLC38A9 mediated arginine-regulated export of essential amino acids, including leucine, from lysosomes. Model: Lysosomal transport and mammalian-cell experiments. Limitations: This is a compartment-specific mechanism, not a demonstrated arginine–leucine supplement synergy. Evidence access: Primary abstract mTORC1 Activator SLC38A9 Is Required to Efflux Essential Amino Acids from Lysosomes and Use Protein as a Nutrient. · 2017 · https://pubmed.ncbi.nlm.nih.gov/29053970/ · DOI 10.1016/j.cell.2017.09.046
Complete structured claim and evidence
Leucine generated by lysosomal proteolysis required SLC38A9 for export and subsequent mTORC1 activation.
Human lysosomal amino acid transporter SLC38A9 → mTORC1 activation from lysosomally degraded protein source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Cellular proteolysis and mTORC1 experiments.
limitations
Not evidence that a high blood arginine level guarantees lysosomal amino-acid release.
nutrient_topic
L-Arginine collection; tissue, species, dose and formulation distinctions retained. · L-Arginine
plain_language
Stored or ingested protein must be released from the lysosome before its amino acids can signal.
primary_references
mTORC1 Activator SLC38A9 Is Required to Efflux Essential Amino Acids from Lysosomes and Use Protein as a Nutrient. · 2017 · https://pubmed.ncbi.nlm.nih.gov/29053970/ · DOI 10.1016/j.cell.2017.09.046
L-Arginine: transport, metabolic branches, nutrient interactions, availability and discovery questions (2026-09-18) · lines 214–220
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Cellular proteolysis and mTORC1 experiments. · source_derived_draft · unverified_draft
## arg-lysosome-growth Stored or ingested protein must be released from the lysosome before its amino acids can signal. Leucine generated by lysosomal proteolysis required SLC38A9 for export and subsequent mTORC1 activation. Model: Cellular proteolysis and mTORC1 experiments. Limitations: Not evidence that a high blood arginine level guarantees lysosomal amino-acid release. Evidence access: Primary abstract mTORC1 Activator SLC38A9 Is Required to Efflux Essential Amino Acids from Lysosomes and Use Protein as a Nutrient. · 2017 · https://pubmed.ncbi.nlm.nih.gov/29053970/ · DOI 10.1016/j.cell.2017.09.046
Complete structured claim and evidence
Fasting achlorhydric participants absorbed substantially less calcium from carbonate than from citrate.
Calcium carbonate → Intestinal calcium absorption source_derived_draftungraded
Experimental context and source evidence
experimental_model
11 achlorhydric patients and nine controls; 250 mg calcium isotope tests.
exposure
Fasting achlorhydric mean fractions: carbonate 0.042, citrate 0.452; normal subjects showed no significant formulation difference.
limitations
Not evidence that carbonate always fails or citrate always outperforms it.
nutrient_topic
Calcium research collection; topical membership is not evidence of a direct dietary effect. · Calcium
organism
Homo sapiens
plain_language
Low stomach acid can change how a calcium preparation is absorbed.
primary_references
[cal-clin-recker1985] Calcium absorption and achlorhydria (1985). https://pubmed.ncbi.nlm.nih.gov/4000241/ DOI: 10.1056/NEJM198507113130202
tissue_or_cell_type
Human clinical or absorption endpoint
Calcium: mechanism-first literature curation (2026-09-17) · lines 1164–1174
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 11 achlorhydric patients and nine controls; 250 mg calcium isotope tests. · source_derived_draft · unverified_draft
### cal-carbonate-fasting-achlorhydria Fasting achlorhydric participants absorbed substantially less calcium from carbonate than from citrate. Condition category: normal nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Low stomach acid can change how a calcium preparation is absorbed. organism: Homo sapiens tissue_or_cell_type: Human clinical or absorption endpoint experimental_model: 11 achlorhydric patients and nine controls; 250 mg calcium isotope tests. limitations: Not evidence that carbonate always fails or citrate always outperforms it. exposure: Fasting achlorhydric mean fractions: carbonate 0.042, citrate 0.452; normal subjects showed no significant formulation difference. [cal-clin-recker1985] Calcium absorption and achlorhydria (1985). https://pubmed.ncbi.nlm.nih.gov/4000241/ DOI: 10.1056/NEJM198507113130202
Complete structured claim and evidence
Calcium carbonate given with a normal breakfast showed normal absorption in the achlorhydric participants.
Calcium carbonate → Intestinal calcium absorption source_derived_draftungraded
Experimental context and source evidence
experimental_model
Meal comparison in the achlorhydria absorption study.
limitations
Small study; the meal experiment did not isolate a molecular rescue mechanism.
nutrient_topic
Calcium research collection; topical membership is not evidence of a direct dietary effect. · Calcium
organism
Homo sapiens
plain_language
The meal changed the result seen during fasting.
primary_references
[cal-clin-recker1985] Calcium absorption and achlorhydria (1985). https://pubmed.ncbi.nlm.nih.gov/4000241/ DOI: 10.1056/NEJM198507113130202
tissue_or_cell_type
Human clinical or absorption endpoint
Calcium: mechanism-first literature curation (2026-09-17) · lines 1176–1185
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Meal comparison in the achlorhydria absorption study. · source_derived_draft · unverified_draft
### cal-carbonate-meal-achlorhydria Calcium carbonate given with a normal breakfast showed normal absorption in the achlorhydric participants. Condition category: normal nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The meal changed the result seen during fasting. organism: Homo sapiens tissue_or_cell_type: Human clinical or absorption endpoint experimental_model: Meal comparison in the achlorhydria absorption study. limitations: Small study; the meal experiment did not isolate a molecular rescue mechanism. [cal-clin-recker1985] Calcium absorption and achlorhydria (1985). https://pubmed.ncbi.nlm.nih.gov/4000241/ DOI: 10.1056/NEJM198507113130202
Complete structured claim and evidence
Fasting-water zinc absorption was 59%, 58% and 34% at ferrous Fe:Zn molar ratios of 1:1, 2.5:1 and 25:1 respectively; inhibition was significant at the highest ratio.
Ferrous iron → Intestinal zinc absorption source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Zinc(II) ion (absorbed_nutrient_ion); Iron (coadministered_nutrient); L-Ascorbate (coadministered_ligand)
evidence_location
Indexed primary abstract.
evidence_span
{"source_cache": "artifacts/zinc-clinical-sources/sandstrom1985.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "aa462f6a961ec4190690f8def1be1f5e54491574698b131992161a989103ca76", "utf8_bytes": 1044}
experimental_model
Human 65Zn tracer study with whole-body counting after two weeks
exposure
Ferrous iron with ascorbic acid; Fe:Zn molar ratios 1:1, 2.5:1 and 25:1, in fasting water or a meal; histidine and iron-preloading comparisons.
limitations
Meal matrix, iron ratio and ligand differed. Absolute administered amounts and sample sizes were not verified in the indexed abstract; no universal spacing rule follows.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Homo sapiens
plain_language
The high iron-to-zinc ratio reduced zinc uptake in the fasting solution.
primary_references
[zn-clin-sandstrom1985] Oral iron, dietary ligands and zinc absorption. (1985). https://pubmed.ncbi.nlm.nih.gov/3973750/ DOI: 10.1093/jn/115.3.411
tissue_or_cell_type
Intestinal absorption
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 1226–1239
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human 65Zn tracer study with whole-body counting after two weeks · source_derived_draft · unverified_draft
### zn-clin-iron-fasting Fasting-water zinc absorption was 59%, 58% and 34% at ferrous Fe:Zn molar ratios of 1:1, 2.5:1 and 25:1 respectively; inhibition was significant at the highest ratio. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: The high iron-to-zinc ratio reduced zinc uptake in the fasting solution. organism: Homo sapiens tissue_or_cell_type: Intestinal absorption experimental_model: Human 65Zn tracer study with whole-body counting after two weeks limitations: Meal matrix, iron ratio and ligand differed. Absolute administered amounts and sample sizes were not verified in the indexed abstract; no universal spacing rule follows. exposure: Ferrous iron with ascorbic acid; Fe:Zn molar ratios 1:1, 2.5:1 and 25:1, in fasting water or a meal; histidine and iron-preloading comparisons. cross_nutrient: Zinc(II) ion (absorbed_nutrient_ion); Iron (coadministered_nutrient); L-Ascorbate (coadministered_ligand) evidence_location: Indexed primary abstract. evidence_span: {"source_cache": "artifacts/zinc-clinical-sources/sandstrom1985.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "aa462f6a961ec4190690f8def1be1f5e54491574698b131992161a989103ca76", "utf8_bytes": 1044} [zn-clin-sandstrom1985] Oral iron, dietary ligands and zinc absorption. (1985). https://pubmed.ncbi.nlm.nih.gov/3973750/ DOI: 10.1093/jn/115.3.411
Complete structured claim and evidence
When the corresponding iron-to-zinc ratios were administered with a meal, zinc absorption was 25%, 23% and 22%, without the inhibitory iron effect detected in fasting water. Two weeks of iron preloading also did not alter zinc absorption from water.
Ferrous iron → Intestinal zinc absorption source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Zinc(II) ion (absorbed_nutrient_ion); Iron (dietary_context)
evidence_location
Indexed primary abstract.
evidence_span
{"source_cache": "artifacts/zinc-clinical-sources/sandstrom1985.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "aa462f6a961ec4190690f8def1be1f5e54491574698b131992161a989103ca76", "utf8_bytes": 1044}
experimental_model
Human 65Zn tracer study with whole-body counting after two weeks
exposure
Ferrous iron with ascorbic acid; Fe:Zn molar ratios 1:1, 2.5:1 and 25:1, in fasting water or a meal; histidine and iron-preloading comparisons.
limitations
Meal matrix, iron ratio and ligand differed. Absolute administered amounts and sample sizes were not verified in the indexed abstract; no universal spacing rule follows.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Homo sapiens
plain_language
The fasting-solution result did not carry over to the tested meal.
primary_references
[zn-clin-sandstrom1985] Oral iron, dietary ligands and zinc absorption. (1985). https://pubmed.ncbi.nlm.nih.gov/3973750/ DOI: 10.1093/jn/115.3.411
tissue_or_cell_type
Intestinal absorption
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 1241–1254
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human 65Zn tracer study with whole-body counting after two weeks · source_derived_draft · unverified_draft
### zn-clin-iron-meal When the corresponding iron-to-zinc ratios were administered with a meal, zinc absorption was 25%, 23% and 22%, without the inhibitory iron effect detected in fasting water. Two weeks of iron preloading also did not alter zinc absorption from water. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: The fasting-solution result did not carry over to the tested meal. organism: Homo sapiens tissue_or_cell_type: Intestinal absorption experimental_model: Human 65Zn tracer study with whole-body counting after two weeks limitations: Meal matrix, iron ratio and ligand differed. Absolute administered amounts and sample sizes were not verified in the indexed abstract; no universal spacing rule follows. exposure: Ferrous iron with ascorbic acid; Fe:Zn molar ratios 1:1, 2.5:1 and 25:1, in fasting water or a meal; histidine and iron-preloading comparisons. cross_nutrient: Zinc(II) ion (absorbed_nutrient_ion); Iron (dietary_context) evidence_location: Indexed primary abstract. evidence_span: {"source_cache": "artifacts/zinc-clinical-sources/sandstrom1985.abstract.txt", "locator": "Primary indexed abstract; complete local file", "file_sha256": "aa462f6a961ec4190690f8def1be1f5e54491574698b131992161a989103ca76", "utf8_bytes": 1044} [zn-clin-sandstrom1985] Oral iron, dietary ligands and zinc absorption. (1985). https://pubmed.ncbi.nlm.nih.gov/3973750/ DOI: 10.1093/jn/115.3.411
Complete structured claim and evidence
In a 30-person crossover study, fasting produced more than 3.5-fold higher free-EGCG peak concentrations than fed administration.
Polyphenon E green tea catechin mixture → Free EGCG plasma exposure source_derived_draftungraded
Experimental context and source evidence
experimental_model
Polyphenon E providing 400, 800 or 1200 mg EGCG; 10 subjects per dose group.
limitations
Mixture and high experimental doses; greater exposure is not a recommendation to take extracts fasting. Nausea was most frequent at 1200 mg fasting.
nutrient_topic
EGCG collection; comparator and shared-pathway records retain their actual intervention. · Epigallocatechin-3-gallate (EGCG)
plain_language
Food changed how much free EGCG reached the blood.
primary_references
Effects of dosing condition on the oral bioavailability of green tea catechins after single-dose administration of Polyphenon E in healthy individuals. · 2005 · https://pubmed.ncbi.nlm.nih.gov/15958649/ · DOI 10.1158/1078-0432.ccr-04-2549
EGCG: receptor signaling, metabolism, nutrient interactions and discovery questions (2026-09-18) · lines 460–466
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Polyphenon E providing 400, 800 or 1200 mg EGCG; 10 subjects per dose group. · source_derived_draft · unverified_draft
## egcg-fasting Food changed how much free EGCG reached the blood. In a 30-person crossover study, fasting produced more than 3.5-fold higher free-EGCG peak concentrations than fed administration. Model: Polyphenon E providing 400, 800 or 1200 mg EGCG; 10 subjects per dose group. Limitations: Mixture and high experimental doses; greater exposure is not a recommendation to take extracts fasting. Nausea was most frequent at 1200 mg fasting. Evidence access: primary abstract. Effects of dosing condition on the oral bioavailability of green tea catechins after single-dose administration of Polyphenon E in healthy individuals. · 2005 · https://pubmed.ncbi.nlm.nih.gov/15958649/ · DOI 10.1158/1078-0432.ccr-04-2549
Complete structured claim and evidence

Availability and dependencies

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

Ketone-use machinery fails in SCOT deficiency

Condition: machinery_impairment · Pathogenic OXCT1 variants impair ketone utilization.

Normal role: Available substrate and intact production, transport and utilization machinery support the fasting fuel transition.

Recorded consequence: G219E and G324E constructs had no detectable SCOT activity; patients had episodic ketoacidosis.

Scope: Mechanism failure relevant to fasting; fasting is the physiological-state collection, not a deficient nutrient.

Ketone-production machinery fails under lipolytic stress

Condition: machinery_impairment · Inherited HMGCS2 or HMGCL defects.

Normal role: Available substrate and intact production, transport and utilization machinery support the fasting fuel transition.

Recorded consequence: Four patients with HMGCS2 or HMGCL deficiency had decompensation with hypoglycemia and absent urinary ketones.

Scope: Mechanism failure relevant to fasting; fasting is the physiological-state collection, not a deficient nutrient.

The sources

Every document behind this chapter is preserved word for word. Open one to read it in full with its recorded conflicts marked in place.

Biotin: carboxylases, recycling, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Calcium: mechanism-first literature curation (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
EGCG: receptor signaling, metabolism, nutrient interactions and discovery questions (2026-09-18)AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · unverified_draftRead preserved source
Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18)AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · unverified_draftRead preserved source
L-Arginine: transport, metabolic branches, nutrient interactions, availability and discovery questions (2026-09-18)AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · unverified_draftRead preserved source
L-Lysine: mechanism-first literature curation (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Phosphorus: metabolism, signaling and nutrient connections (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source

Recorded disagreements

Where two sources say different things, both are kept and the difference is explained. You can discuss a disagreement or propose a mechanism that might account for it.

Does beta-hydroxybutyrate directly inhibit HDACs?The 2013 primary study reports direct class-I HDAC inhibition by D-beta-hydroxybutyrate. The 2019 primary study explicitly challenges this interpretation after failing to detect inhibition in its HDAC assay or histone hyperacetylation in several cell models. This is a published mechanistic disagreement, not a correction to an earlier ledger draft.Read the recorded disagreement

Open questions in this collection

Questions the curators could not answer from the sources in front of them, kept here with the reason each one is still open. These are gaps in this collection, not findings or proof that no one has studied them.

Chapters are assembled from supplied drafts and curated literature summaries. Statements remain unverified against the primary studies, and the ledger is not medical advice.

Evidence, AI assistance and curation standards

Fasting / abstention from energy intake

The mechanisms

Lipolysis increased approximately 2.5-fold over 60 hours.

Intra-adipocyte fatty-acid re-esterification also increased approximately 2.5-fold.

Fat oxidation supplied about 75% of resting energy requirements at 60 hours.

Glucose oxidation decreased approximately 85%.

Proteolysis and protein oxidation increased approximately 50%.

The estimated gluconeogenic fraction of glucose production increased from 36% overnight to 78% after 60 hours.

At 60 hours, glycogen-derived plasma glucose flux of 0.32 mg/kg/min was balanced by 0.31 mg/kg/min retained gluconeogenic carbon.

Estimated renal contribution to whole-body glucose production increased from 5 ± 2% postabsorptively to 24 ± 3% after 60 hours.

Beta-hydroxybutyrate and acetoacetate became predominant cerebral fuels after prolonged starvation.

Somatostatin suppressed splanchnic glucose output by 50–100% for five hours after a 60-hour fast; the overnight-fast reduction was transient.

Mitochondrial HMGCS2 catalyzes condensation of acetyl-CoA and acetoacetyl-CoA to form HMG-CoA.

Human HMGCL cleaves HMG-CoA to acetoacetate and acetyl-CoA.

In HMGCL ternary structures Mg2+ coordinates His233, His235, Asp42, water and substrate/inhibitor oxygen atoms.

BDH1 interconverts D-beta-hydroxybutyrate and acetoacetate using the NAD+/NADH redox pair.

Human-heart mitochondrial BDH1 was described as specifically requiring phosphatidylcholine for enzymic activity.

OXCT1 transfers CoA from succinyl-CoA to acetoacetate, yielding acetoacetyl-CoA and succinate.

G219E and G324E constructs had no detectable SCOT activity; patients had episodic ketoacidosis.

Four patients with HMGCS2 or HMGCL deficiency had decompensation with hypoglycemia and absent urinary ketones.

A post-bypass patient had fasting hypoglycemia, low BHB and high free fatty acids; carnitine replacement resolved fasting hypoglycemia.

Muscle PDK4 expression increased 13-fold, alongside greater inhibitory PDH phosphorylation.

Measured muscle AMPK activity was unchanged.

Peak oxygen uptake fell 13% and endurance declined; maximal strength was unchanged.

Muscle glycogen content was approximately halved.

Growth-hormone levels increased after 72 hours of fasting.

GH blockade abolished fasting-induced insulin resistance, mainly through reduced endogenous glucose production.

Adipose PDE3B transcript levels decreased after fasting, with and without GH blockade.

Adipose G0S2 transcript levels decreased after fasting, independent of GH blockade.

PPARalpha directly induced hepatic FGF21 in response to fasting or agonists.

FGF21 stimulated liver ketogenesis and white-adipose lipolysis.

FGF21 reduced activity and promoted torpor.

FGF21 reduced active hepatic STAT5 and expression of its target Igf1.

FGF21 induced hepatic IGFBP1 and SOCS2, regulators that blunt GH/IGF signaling.

FGF21 rose notably on days 7–10, after ketone concentrations had already increased.

FGF21 induction was associated with decreased thermogenesis and adiponectin.

Under glucose starvation AMPK directly activated Ulk1 through Ser317 and Ser777 phosphorylation.

High mTOR activity phosphorylated Ulk1 Ser757 and disrupted its interaction with AMPK.

Autophagy remained unimpaired in AMPK-deficient cells during amino-acid deprivation; ULK1 signaling and LC3B lipidation increased.

AMPK loss impaired mTORC1 reactivation during prolonged amino-acid deprivation and increased apoptosis.

MCOLN1-dependent lysosomal calcium release activated calcineurin.

Calcineurin bound and dephosphorylated TFEB, promoting its nuclear translocation.

Autophagy and lysosomal biogenesis through TFEB required MCOLN1-mediated calcineurin activation.

D-beta-hydroxybutyrate activated human HM74a/HCAR2 and its mouse orthologue.

D-beta-hydroxybutyrate inhibited mouse adipocyte lipolysis in an Hcar2-dependent manner.

BHB prevented potassium efflux in the tested NLRP3 activation experiments.

BHB reduced ASC oligomerization and speck formation.

BHB reduced NLRP3-mediated IL-1beta and IL-18 production in human monocytes.

The study reported direct class-I HDAC inhibition by D-beta-hydroxybutyrate, alongside increased histone acetylation in mouse tissues.

The later study detected no HDAC inhibition with 10 mM sodium R-BHB in its nuclear-extract assay; multiple cell models lacked histone hyperacetylation up to 40 mM.

R-beta-hydroxybutyrate increased histone beta-hydroxybutyrylation despite absent detectable HDAC inhibition.

A seven-day fast changed more than 1,000 measured plasma proteins; broad changes became evident after about three days.

Five weeks of a six-hour early eating window improved insulin sensitivity without weight loss.

CRP, hepcidin, midkine and IL-8 increased during prolonged fasting.

Proteomic analyses and follow-up assays indicated platelet degranulation and complement/coagulation-associated changes.

Urinary sodium excretion fell from 401 to 213 microequivalents/min without changes in GFR, renal blood flow or aldosterone.

Urinary potassium excretion fell from 66 to 21 microequivalents/min while plasma potassium also decreased.

Urinary phosphate excretion fell from 504 to 230 micrograms/min, with a small plasma phosphate decrease.

Urinary calcium excretion rose from 126 to 200 micrograms/min.

Direct copper interaction supported ULK1 kinase activity in the experimental system.

Copper-binding-disruptive ULK1 mutations reduced autophagy signaling and autophagosome formation in the tested cells.

Copper-dependent PDE3B inhibition increased cAMP signaling and promoted lipolysis in 3T3-L1 adipocytes.

In the studied human ACC2 domain, phosphorylated Ser222 occupied the putative dimer interface, disrupting polymerization and explaining AMPK-mediated inactivation.

Wild-type human CPT1B showed high-affinity malonyl-CoA binding and inhibition in recombinant mitochondrial assays.

TPK1 activation transfers ATP-derived diphosphoryl to thiamine, yielding ThDP and AMP in a magnesium-dependent reaction.

Wild-type human PDH E1 structures show Mg coordinated at the ThDP diphosphate-binding site.

Human PDH E1 forms a covalent lactyl-ThDP intermediate from pyruvate and decarboxylates it, retaining the two-carbon fragment on ThDP.

Patient muscle PDH activity was deficient without added ThDP but normal or near-normal under cofactor-supplemented assay conditions.

The LIAS Arg249His patient had depleted protein-bound lipoyl signal and reduced PDH activity/pyruvate oxidation in investigated muscle and fibroblast preparations.

Refeeding syndrome occurred in three cohort participants; two had received vitamin B/C preparations before nutrition support.

Low baseline serum magnesium was associated with subsequent refeeding syndrome in the cohort.

Days alive after ICU discharge did not differ significantly: 44.8 versus 39.9 days, estimated difference 4.9 days (95% CI −2.3 to 13.6), p=0.19.

A component analysis found 149/164 participants alive at day 60 with restriction versus 128/163 with standard feeding, p=0.002.

Human PC catalyzes two-step pyruvate carboxylation to oxaloacetate.

Human MCAD and ETF form an electron-transfer complex in which a recognition loop anchors binding while the ETF FAD domain samples electron-transfer-compatible conformations.

Human mitochondrial acetoacetyl-CoA thiolase ACAT1/T2, a homotetramer, uses coenzyme A to cleave acetoacetyl-CoA into two acetyl-CoA molecules.

Nicotinic-acid activation of GPR109A/HCAR2 in the human cell-line assay lowered cAMP through a pertussis-toxin-sensitive pathway.

Human PANK3 catalyzes ATP-dependent conversion of pantothenate to 4′-phosphopantothenate.

Purified human PPCS, PPCDC and bifunctional CoA synthase reconstituted CoA synthesis from phosphopantothenate in vitro.

A labeled cofactor-analogue experiment supported direct participation of the PLP phosphate group in glycogen phosphorylase glucosyl transfer.