Propionyl-CoA

evidence_access

Primary abstract

experimental_model

Primary prostate-cancer mechanistic study; exact construct and lysine site not resolved in accessed abstract.

limitations

Site identity is not guessed; clinical target engagement was not established.

nutrient_topic

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

plain_language

A breakdown product changed the stability of a lipid-regulating transcription factor.

primary_references

Isoleucine and valine promote prostate cancer progression via propionyl-CoA-mediated cholesterol metabolism. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42625032/ · DOI 10.1038/s42255-026-01583-z

L-Isoleucine: transport, translation, catabolism and cross-nutrient mechanisms (2026-09-19) · lines 506–512

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Primary prostate-cancer mechanistic study; exact construct and lysine site not resolved in accessed abstract. · source_derived_draft · unverified_draft

## isoleucine-prostate-srebp2 A breakdown product changed the stability of a lipid-regulating transcription factor. Propionyl-CoA-dependent site-specific lysine propionylation stabilized nuclear SREBP2 and increased its transcriptional activity in the reported prostate-cancer models. Model: Primary prostate-cancer mechanistic study; exact construct and lysine site not resolved in accessed abstract. Limitations: Site identity is not guessed; clinical target engagement was not established. Evidence access: Primary abstract Isoleucine and valine promote prostate cancer progression via propionyl-CoA-mediated cholesterol metabolism. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42625032/ · DOI 10.1038/s42255-026-01583-z

cross_nutrient

false

evidence_location

Full text Results; Figures 6-8 and isotope model

experimental_model

Differentiated mouse 3T3-L1 adipocytes

exposure

Parallel carbon-13 tracer and GC-MS fragment analysis

limitations

Mouse cell culture; isotope labeling and model assumptions do not establish human dietary carbon fractions.

nutrient_topic

Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)

organism

Mus musculus

plain_language

These mouse fat cells could divert the B12-pathway precursor into odd-chain fats.

primary_references

[crown-2015-bcaa-fatty-acids] Catabolism of Branched Chain Amino Acids Contributes Significantly to Synthesis of Odd-Chain and Even-Chain Fatty Acids in 3T3-L1 Adipocytes. (2015). https://pubmed.ncbi.nlm.nih.gov/26710334/ DOI: 10.1371/journal.pone.0145850

tissue_or_cell_type

Adipocytes

Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1244–1256

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Differentiated mouse 3T3-L1 adipocytes · source_derived_draft · unverified_draft

### propionyl-primes-odd-chain-fatty-acids Fatty-acid fragment labeling identified propionyl-CoA as the primer for odd-chain fatty-acid synthesis in 3T3-L1 adipocytes. Condition category: normal nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: These mouse fat cells could divert the B12-pathway precursor into odd-chain fats. organism: Mus musculus tissue_or_cell_type: Adipocytes experimental_model: Differentiated mouse 3T3-L1 adipocytes limitations: Mouse cell culture; isotope labeling and model assumptions do not establish human dietary carbon fractions. exposure: Parallel carbon-13 tracer and GC-MS fragment analysis cross_nutrient: false evidence_location: Full text Results; Figures 6-8 and isotope model [crown-2015-bcaa-fatty-acids] Catabolism of Branched Chain Amino Acids Contributes Significantly to Synthesis of Odd-Chain and Even-Chain Fatty Acids in 3T3-L1 Adipocytes. (2015). https://pubmed.ncbi.nlm.nih.gov/26710334/ DOI: 10.1371/journal.pone.0145850

evidence_access

Primary preprint full text; not peer reviewed

experimental_model

Mouse KPC2838c3/KPC6419c5 and human MIA-PaCa-2, Panc-1, HPAC and patient-derived cells.

limitations

Primary preprint, not peer reviewed; fractional tracer contribution is not absolute pathway flux.

nutrient_topic

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

plain_language

Cancer-cell carbon allocation favored one branch of the pathway.

primary_references

A nuclear branched-chain amino acid catabolism pathway controls histone propionylation in pancreatic cancer. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40568091/ · DOI 10.1101/2025.04.23.650241

L-Isoleucine: transport, translation, catabolism and cross-nutrient mechanisms (2026-09-19) · lines 474–480

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse KPC2838c3/KPC6419c5 and human MIA-PaCa-2, Panc-1, HPAC and patient-derived cells. · source_derived_draft · unverified_draft

## isoleucine-pancreatic-preprint-flux Cancer-cell carbon allocation favored one branch of the pathway. A pancreatic-cancer preprint traced isoleucine carbon prominently into propionyl-CoA in mouse KPC and human PDA cell lines, with smaller contributions to acetyl-CoA/succinyl-CoA in those assays. Model: Mouse KPC2838c3/KPC6419c5 and human MIA-PaCa-2, Panc-1, HPAC and patient-derived cells. Limitations: Primary preprint, not peer reviewed; fractional tracer contribution is not absolute pathway flux. Evidence access: Primary preprint full text; not peer reviewed A nuclear branched-chain amino acid catabolism pathway controls histone propionylation in pancreatic cancer. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40568091/ · DOI 10.1101/2025.04.23.650241

evidence_access

Primary abstract

experimental_model

Prostate-cancer cell and tumor models; detailed species/exposure unresolved in accessed abstract.

limitations

Not proof that dietary intake causes prostate cancer or that restriction treats patients.

nutrient_topic

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

plain_language

Two amino-acid branches converged on the same signaling metabolite.

primary_references

Isoleucine and valine promote prostate cancer progression via propionyl-CoA-mediated cholesterol metabolism. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42625032/ · DOI 10.1038/s42255-026-01583-z

L-Isoleucine: transport, translation, catabolism and cross-nutrient mechanisms (2026-09-19) · lines 498–504

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Prostate-cancer cell and tumor models; detailed species/exposure unresolved in accessed abstract. · source_derived_draft · unverified_draft

## isoleucine-prostate-carbon Two amino-acid branches converged on the same signaling metabolite. A 2026 prostate-cancer study identified isoleucine and valine catabolism as major sources of intracellular propionyl-CoA in its experimental models. Model: Prostate-cancer cell and tumor models; detailed species/exposure unresolved in accessed abstract. Limitations: Not proof that dietary intake causes prostate cancer or that restriction treats patients. Evidence access: Primary abstract Isoleucine and valine promote prostate cancer progression via propionyl-CoA-mediated cholesterol metabolism. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42625032/ · DOI 10.1038/s42255-026-01583-z

evidence_access

Primary abstract

experimental_model

Recombinant human CPT2 substrate panel.

limitations

No claim that every acylcarnitine originates from CPT2.

nutrient_topic

L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine

plain_language

The long-chain shuttle is not the same enzyme system as short-chain buffering.

primary_references

Carnitine palmitoyltransferase 2: New insights on the substrate specificity and implications for acylcarnitine profiling. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20538056/ · DOI 10.1016/j.bbadis.2010.06.002

L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 114–120

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Recombinant human CPT2 substrate panel. · source_derived_draft · unverified_draft

## l-carnitine-cpt2-specificity The long-chain shuttle is not the same enzyme system as short-chain buffering. Human CPT2 had activity with C8-C18 acyl-CoAs but virtually none with short-chain acyl-CoAs or branched-chain amino-acid oxidation intermediates. Model: Recombinant human CPT2 substrate panel. Limitations: No claim that every acylcarnitine originates from CPT2. Evidence access: Primary abstract Carnitine palmitoyltransferase 2: New insights on the substrate specificity and implications for acylcarnitine profiling. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20538056/ · DOI 10.1016/j.bbadis.2010.06.002

cross_nutrient

true

evidence_location

Full text Results; Figures 6-8 and isotope model

experimental_model

Differentiated mouse 3T3-L1 adipocytes

exposure

24-hour [U-13C]isoleucine tracing

limitations

Mouse cell culture; isotope labeling and model assumptions do not establish human dietary carbon fractions.

nutrient_topic

Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)

organism

Mus musculus

plain_language

Mouse fat-cell tracing identified isoleucine as another source of the B12-pathway precursor.

primary_references

[crown-2015-bcaa-fatty-acids] Catabolism of Branched Chain Amino Acids Contributes Significantly to Synthesis of Odd-Chain and Even-Chain Fatty Acids in 3T3-L1 Adipocytes. (2015). https://pubmed.ncbi.nlm.nih.gov/26710334/ DOI: 10.1371/journal.pone.0145850

tissue_or_cell_type

Adipocytes

Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1230–1242

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Differentiated mouse 3T3-L1 adipocytes · source_derived_draft · unverified_draft

### isoleucine-propionyl-coa-lipogenesis Carbon-13 isoleucine supplied lipogenic propionyl-CoA in cultured 3T3-L1 adipocytes. Condition category: normal nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Mouse fat-cell tracing identified isoleucine as another source of the B12-pathway precursor. organism: Mus musculus tissue_or_cell_type: Adipocytes experimental_model: Differentiated mouse 3T3-L1 adipocytes limitations: Mouse cell culture; isotope labeling and model assumptions do not establish human dietary carbon fractions. exposure: 24-hour [U-13C]isoleucine tracing cross_nutrient: true evidence_location: Full text Results; Figures 6-8 and isotope model [crown-2015-bcaa-fatty-acids] Catabolism of Branched Chain Amino Acids Contributes Significantly to Synthesis of Odd-Chain and Even-Chain Fatty Acids in 3T3-L1 Adipocytes. (2015). https://pubmed.ncbi.nlm.nih.gov/26710334/ DOI: 10.1371/journal.pone.0145850

availability_state

machinery_impairment Imported condition classification; unverified.

cross_nutrient

false

evidence_location

Full text Results: vitamin B12 supplementation; Figure 4g-u

experimental_model

Differentiating ECHDC1-knockout mouse L929 adipocytes (Figure 4g-u)

exposure

ECHDC1 knockout; 2.5 micromolar supplementary B12 during differentiation

limitations

Whole-cell LC-MS pools; no compartment or epimer resolution and no direct pathway flux measurement.

nutrient_topic

Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)

organism

Mus musculus

plain_language

In the same mouse-cell experiment, B12 also lowered the upstream propionyl-CoA pool. The cells had ECHDC1 deleted.

primary_references

[dewulf-2019-l929-b12] The synthesis of branched-chain fatty acids is limited by enzymatic decarboxylation of ethyl- and methylmalonyl-CoA. (2019). https://pubmed.ncbi.nlm.nih.gov/31416829/ DOI: 10.1042/bcj20190500

tissue_or_cell_type

Adipocytes

trigger_kind

machinery_impairment Imported condition classification; unverified.

Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1272–1284

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Differentiating ECHDC1-knockout mouse L929 adipocytes (Figure 4g-u) · source_derived_draft · unverified_draft

### l929-b12-lowers-propionyl-pool B12 supplementation lowered the measured propionyl-CoA pool approximately fourfold in differentiating ECHDC1-knockout L929 adipocytes. Condition category: machinery_impairment nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: In the same mouse-cell experiment, B12 also lowered the upstream propionyl-CoA pool. The cells had ECHDC1 deleted. organism: Mus musculus tissue_or_cell_type: Adipocytes experimental_model: Differentiating ECHDC1-knockout mouse L929 adipocytes (Figure 4g-u) limitations: Whole-cell LC-MS pools; no compartment or epimer resolution and no direct pathway flux measurement. exposure: ECHDC1 knockout; 2.5 micromolar supplementary B12 during differentiation cross_nutrient: false evidence_location: Full text Results: vitamin B12 supplementation; Figure 4g-u [dewulf-2019-l929-b12] The synthesis of branched-chain fatty acids is limited by enzymatic decarboxylation of ethyl- and methylmalonyl-CoA. (2019). https://pubmed.ncbi.nlm.nih.gov/31416829/ DOI: 10.1042/bcj20190500

cross_nutrient

true

evidence_location

Indexed primary abstract; Full text Methods 2.6 and Results 3.6; Figure 5

experimental_model

Human fibroblast PCC and coupled-pathway assays

exposure

Propionyl-CoA, ATP and bicarbonate in enzyme pathway

limitations

Pathway assignment combines human PCC characterization with coupled assays; it is not a simultaneous dietary biotin/B12 intervention.

nutrient_topic

Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)

organism

Homo sapiens

plain_language

Biotin-dependent PCC makes the precursor that must be rearranged before human MMUT can use B12 on it.

primary_references

[hsia-1979-pcc] Human propionyl CoA carboxylase: some properties of the partially purified enzyme in fibroblasts from controls and patients with propionic acidemia. (1979). https://pubmed.ncbi.nlm.nih.gov/481943/ DOI: 10.1203/00006450-197906000-00005 [heuberger-2019-mcee] Genetic, structural, and functional analysis of pathogenic variations causing methylmalonyl-CoA epimerase deficiency. (2019). https://pubmed.ncbi.nlm.nih.gov/30682498/ DOI: 10.1016/j.bbadis.2019.01.021

tissue_or_cell_type

Fibroblasts

Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1159–1172

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human fibroblast PCC and coupled-pathway assays · source_derived_draft · unverified_draft

### pcc-carboxylation-upstream-b12 Human PCC supplies (S)-methylmalonyl-CoA by propionyl-CoA carboxylation upstream of the MCEE-MMUT sequence examined in fibroblast assays. Condition category: normal nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Biotin-dependent PCC makes the precursor that must be rearranged before human MMUT can use B12 on it. organism: Homo sapiens tissue_or_cell_type: Fibroblasts experimental_model: Human fibroblast PCC and coupled-pathway assays limitations: Pathway assignment combines human PCC characterization with coupled assays; it is not a simultaneous dietary biotin/B12 intervention. exposure: Propionyl-CoA, ATP and bicarbonate in enzyme pathway cross_nutrient: true evidence_location: Indexed primary abstract; Full text Methods 2.6 and Results 3.6; Figure 5 [hsia-1979-pcc] Human propionyl CoA carboxylase: some properties of the partially purified enzyme in fibroblasts from controls and patients with propionic acidemia. (1979). https://pubmed.ncbi.nlm.nih.gov/481943/ DOI: 10.1203/00006450-197906000-00005 [heuberger-2019-mcee] Genetic, structural, and functional analysis of pathogenic variations causing methylmalonyl-CoA epimerase deficiency. (2019). https://pubmed.ncbi.nlm.nih.gov/30682498/ DOI: 10.1016/j.bbadis.2019.01.021

cross_nutrient

true

evidence_location

Full text Results; Figures 6-8 and isotope model

experimental_model

Differentiated mouse 3T3-L1 adipocytes

exposure

24-hour [U-13C]valine tracing

limitations

Mouse cell culture; isotope labeling and model assumptions do not establish human dietary carbon fractions.

nutrient_topic

Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)

organism

Mus musculus

plain_language

Mouse fat-cell tracing placed valine carbon into the precursor that can enter B12-dependent metabolism or odd-chain fat synthesis.

primary_references

[crown-2015-bcaa-fatty-acids] Catabolism of Branched Chain Amino Acids Contributes Significantly to Synthesis of Odd-Chain and Even-Chain Fatty Acids in 3T3-L1 Adipocytes. (2015). https://pubmed.ncbi.nlm.nih.gov/26710334/ DOI: 10.1371/journal.pone.0145850

tissue_or_cell_type

Adipocytes

Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1216–1228

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Differentiated mouse 3T3-L1 adipocytes · source_derived_draft · unverified_draft

### valine-propionyl-coa-lipogenesis Carbon-13 valine supplied the lipogenic propionyl-CoA precursor in cultured 3T3-L1 adipocytes. Condition category: normal nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Mouse fat-cell tracing placed valine carbon into the precursor that can enter B12-dependent metabolism or odd-chain fat synthesis. organism: Mus musculus tissue_or_cell_type: Adipocytes experimental_model: Differentiated mouse 3T3-L1 adipocytes limitations: Mouse cell culture; isotope labeling and model assumptions do not establish human dietary carbon fractions. exposure: 24-hour [U-13C]valine tracing cross_nutrient: true evidence_location: Full text Results; Figures 6-8 and isotope model [crown-2015-bcaa-fatty-acids] Catabolism of Branched Chain Amino Acids Contributes Significantly to Synthesis of Odd-Chain and Even-Chain Fatty Acids in 3T3-L1 Adipocytes. (2015). https://pubmed.ncbi.nlm.nih.gov/26710334/ DOI: 10.1371/journal.pone.0145850

evidence_access

Primary abstract

experimental_model

E. coli operon analysis, mutants, enzyme assays and culture-supernatant NMR.

limitations

This is not a human enzyme reaction or a measurement of net propionate production in the human gut.

nutrient_topic

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

plain_language

Microbes have a separate route for fermenting threonine carbon.

primary_references

Novel keto acid formate-lyase and propionate kinase enzymes are components of an anaerobic pathway in Escherichia coli that degrades L-threonine to propionate. · 1998 · https://pubmed.ncbi.nlm.nih.gov/9484901/ · DOI 10.1046/j.1365-2958.1998.00696.x

L-Threonine: translation, intestinal barrier, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 426–432

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · E. coli operon analysis, mutants, enzyme assays and culture-supernatant NMR. · source_derived_draft · unverified_draft

## l-threonine-microbial-ketoacid Microbes have a separate route for fermenting threonine carbon. E. coli mutant and enzyme studies showed TdcE conversion of threonine-derived 2-ketobutyrate into propionyl-CoA during anaerobic growth. Model: E. coli operon analysis, mutants, enzyme assays and culture-supernatant NMR. Limitations: This is not a human enzyme reaction or a measurement of net propionate production in the human gut. Evidence access: Primary abstract Novel keto acid formate-lyase and propionate kinase enzymes are components of an anaerobic pathway in Escherichia coli that degrades L-threonine to propionate. · 1998 · https://pubmed.ncbi.nlm.nih.gov/9484901/ · DOI 10.1046/j.1365-2958.1998.00696.x

evidence_span

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experimental_model

Bacterial PCC crystallography and separate 15-angstrom human PCC cryo-EM reconstruction

exposure

Structural analysis

limitations

Atomic bacterial positions are not high-resolution human measurements. Human cryo-EM establishes the overall assembly at lower resolution.

nutrient_topic

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

organism

Homo sapiens; bacterial PCC comparison

plain_language

The beta subunit performs the transfer onto the carbon substrate.

primary_references

[b7-p20725044] Crystal structure of the alpha(6)beta(6) holoenzyme of propionyl-coenzyme A carboxylase. (2010). https://pubmed.ncbi.nlm.nih.gov/20725044/ DOI: 10.1038/nature09302

tissue_or_cell_type

Purified PCC complexes

Biotin: carboxylases, recycling, deficiency and nutrient interactions (2026-09-17) · lines 611–622

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Bacterial PCC crystallography and separate 15-angstrom human PCC cryo-EM reconstruction · source_derived_draft · unverified_draft

### b7-pcc-pccb PCCB provides the carboxyltransferase activity of human PCC. Condition category: normal nutrient_topic: Biotin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The beta subunit performs the transfer onto the carbon substrate. organism: Homo sapiens; bacterial PCC comparison tissue_or_cell_type: Purified PCC complexes experimental_model: Bacterial PCC crystallography and separate 15-angstrom human PCC cryo-EM reconstruction limitations: Atomic bacterial positions are not high-resolution human measurements. Human cryo-EM establishes the overall assembly at lower resolution. exposure: Structural analysis evidence_span: {"source_cache": "artifacts/biotin-research/20725044.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "825bf28b9f35a8d45f8d08d883fa200bd430336b0558db035ce4fd1c5ef19053", "start_char": 0, "end_char": 1921, "text_sha256": "825bf28b9f35a8d45f8d08d883fa200bd430336b0558db035ce4fd1c5ef19053"} [b7-p20725044] Crystal structure of the alpha(6)beta(6) holoenzyme of propionyl-coenzyme A carboxylase. (2010). https://pubmed.ncbi.nlm.nih.gov/20725044/ DOI: 10.1038/nature09302

evidence_access

Primary abstract

experimental_model

Purified human T2 structural/kinetic study; established product chemistry.

limitations

ACAT1 here is acetyl-CoA acetyltransferase, not the cholesterol-esterifying SOAT1 enzyme sometimes called ACAT.

nutrient_topic

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

plain_language

One carbon skeleton feeds both an acetyl branch and a propionyl branch.

primary_references

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

L-Isoleucine: transport, translation, catabolism and cross-nutrient mechanisms (2026-09-19) · lines 226–232

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified human T2 structural/kinetic study; established product chemistry. · source_derived_draft · unverified_draft

## isoleucine-acat1-split One carbon skeleton feeds both an acetyl branch and a propionyl branch. Human mitochondrial ACAT1/T2 degraded 2-methylacetoacetyl-CoA by CoA-dependent thiolysis, yielding the isoleucine-branch acetyl-CoA and propionyl-CoA products. Model: Purified human T2 structural/kinetic study; established product chemistry. Limitations: ACAT1 here is acetyl-CoA acetyltransferase, not the cholesterol-esterifying SOAT1 enzyme sometimes called ACAT. Evidence access: Primary abstract 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

evidence_access

Primary abstract

experimental_model

SILEC-SF fractionation/tracing; specific cell lines and exposure not resolved in accessed abstract.

limitations

Not a claim that all tissues use the same carbon source or that oral isoleucine controls human gene expression.

nutrient_topic

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

plain_language

An amino-acid carbon skeleton can reach a chromatin modification.

primary_references

Quantitative subcellular acyl-CoA analysis reveals distinct nuclear metabolism and isoleucine-dependent histone propionylation. · 2022 · https://pubmed.ncbi.nlm.nih.gov/34856123/ · DOI 10.1016/j.molcel.2021.11.006

L-Isoleucine: transport, translation, catabolism and cross-nutrient mechanisms (2026-09-19) · lines 466–472

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · SILEC-SF fractionation/tracing; specific cell lines and exposure not resolved in accessed abstract. · source_derived_draft · unverified_draft

## isoleucine-nuclear-propionyl An amino-acid carbon skeleton can reach a chromatin modification. Isotope tracing and controlled subcellular acyl-CoA measurement identified isoleucine as a major source of nuclear propionyl-CoA and histone propionyl groups in the tested cells. Model: SILEC-SF fractionation/tracing; specific cell lines and exposure not resolved in accessed abstract. Limitations: Not a claim that all tissues use the same carbon source or that oral isoleucine controls human gene expression. Evidence access: Primary abstract Quantitative subcellular acyl-CoA analysis reveals distinct nuclear metabolism and isoleucine-dependent histone propionylation. · 2022 · https://pubmed.ncbi.nlm.nih.gov/34856123/ · DOI 10.1016/j.molcel.2021.11.006

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_access

Primary preprint full text; not peer reviewed

experimental_model

Engineered mouse KPC PDA cells; nuclear-exclusion/localization experiments.

limitations

Preprint and compartment-engineering result; not established as a general nuclear pathway in healthy human tissue.

nutrient_topic

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

plain_language

The location of an enzyme complex influenced which cellular process used its products.

primary_references

A nuclear branched-chain amino acid catabolism pathway controls histone propionylation in pancreatic cancer. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40568091/ · DOI 10.1101/2025.04.23.650241

trigger_kind

machinery_impairment Imported condition classification; unverified.

L-Isoleucine: transport, translation, catabolism and cross-nutrient mechanisms (2026-09-19) · lines 490–496

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Engineered mouse KPC PDA cells; nuclear-exclusion/localization experiments. · source_derived_draft · unverified_draft

## isoleucine-pancreatic-preprint-nuclear The location of an enzyme complex influenced which cellular process used its products. The preprint reported that excluding BCKDH machinery from nuclei suppressed histone propionylation and associated gene-expression responses in PDA models. Model: Engineered mouse KPC PDA cells; nuclear-exclusion/localization experiments. Limitations: Preprint and compartment-engineering result; not established as a general nuclear pathway in healthy human tissue. Evidence access: Primary preprint full text; not peer reviewed A nuclear branched-chain amino acid catabolism pathway controls histone propionylation in pancreatic cancer. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40568091/ · DOI 10.1101/2025.04.23.650241

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_access

Primary preprint full text; not peer reviewed

experimental_model

Mouse KPC and human PDA cell assays; combined Ile/Val removal, twenty-four hours.

limitations

Preprint; deprivation of two amino acids cannot be attributed exclusively to one.

nutrient_topic

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

plain_language

Restoring one carbon product did not replace essential amino-acid supply.

primary_references

A nuclear branched-chain amino acid catabolism pathway controls histone propionylation in pancreatic cancer. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40568091/ · DOI 10.1101/2025.04.23.650241

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

L-Isoleucine: transport, translation, catabolism and cross-nutrient mechanisms (2026-09-19) · lines 482–488

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse KPC and human PDA cell assays; combined Ile/Val removal, twenty-four hours. · source_derived_draft · unverified_draft

## isoleucine-pancreatic-preprint-rescue Restoring one carbon product did not replace essential amino-acid supply. In the preprint, propionate rescued propionyl-CoA and selected histone propionylation after combined isoleucine/valine deprivation, but did not restore proliferation. Model: Mouse KPC and human PDA cell assays; combined Ile/Val removal, twenty-four hours. Limitations: Preprint; deprivation of two amino acids cannot be attributed exclusively to one. Evidence access: Primary preprint full text; not peer reviewed A nuclear branched-chain amino acid catabolism pathway controls histone propionylation in pancreatic cancer. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40568091/ · DOI 10.1101/2025.04.23.650241

evidence_access

Primary abstract

experimental_model

Prostate-cancer experimental models.

limitations

Does not imply a testosterone-boosting effect of supplements or a human dietary cancer treatment.

nutrient_topic

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

plain_language

The pathway linked amino-acid carbon handling to lipid and hormone-related tumor adaptation.

primary_references

Isoleucine and valine promote prostate cancer progression via propionyl-CoA-mediated cholesterol metabolism. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42625032/ · DOI 10.1038/s42255-026-01583-z

L-Isoleucine: transport, translation, catabolism and cross-nutrient mechanisms (2026-09-19) · lines 514–520

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Prostate-cancer experimental models. · source_derived_draft · unverified_draft

## isoleucine-prostate-cholesterol The pathway linked amino-acid carbon handling to lipid and hormone-related tumor adaptation. The reported SREBP2 activation promoted cholesterol biosynthesis and supported de novo androgen production and androgen-receptor signaling under metabolic/androgen-deprivation stress. Model: Prostate-cancer experimental models. Limitations: Does not imply a testosterone-boosting effect of supplements or a human dietary cancer treatment. Evidence access: Primary abstract Isoleucine and valine promote prostate cancer progression via propionyl-CoA-mediated cholesterol metabolism. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42625032/ · DOI 10.1038/s42255-026-01583-z

evidence_access

Primary abstract

experimental_model

Small human metabolic intervention; three healthy comparison subjects excreted mainly acetylcarnitine.

limitations

Restoration of mitochondrial free CoA was a proposed mechanism, not directly measured.

nutrient_topic

L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine

plain_language

Acyl-group disposal can consume and export carnitine.

primary_references

L-carnitine enhances excretion of propionyl coenzyme A as propionylcarnitine in propionic acidemia. · 1984 · https://pubmed.ncbi.nlm.nih.gov/6725560/ · DOI 10.1172/JCI111387

L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 250–256

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Small human metabolic intervention; three healthy comparison subjects excreted mainly acetylcarnitine. · source_derived_draft · unverified_draft

## l-carnitine-organic-acid-export Acyl-group disposal can consume and export carnitine. Giving L-carnitine to three patients with propionic acidemia increased urinary propionylcarnitine, verified by mass spectrometry. Model: Small human metabolic intervention; three healthy comparison subjects excreted mainly acetylcarnitine. Limitations: Restoration of mitochondrial free CoA was a proposed mechanism, not directly measured. Evidence access: Primary abstract L-carnitine enhances excretion of propionyl coenzyme A as propionylcarnitine in propionic acidemia. · 1984 · https://pubmed.ncbi.nlm.nih.gov/6725560/ · DOI 10.1172/JCI111387

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_access

Primary abstract

experimental_model

Two PA and two MMA cases; plasma, urine and selected muscle measurements.

limitations

Export-driven tissue depletion is the authors' mechanism; these inherited conditions are not synonymous with dietary B12 deficiency.

nutrient_topic

L-Carnitine collection; isomer, preparation, species, exposure and manipulation remain explicit. · L-Carnitine

plain_language

A metabolic block can tie up carnitine and lead to its loss in urine.

primary_references

Propionylcarnitine excretion in propionic and methylmalonic acidurias: a cause of carnitine deficiency. · 1984 · https://pubmed.ncbi.nlm.nih.gov/6723070/ · DOI 10.1016/0009-8981(84)90187-6

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

L-Carnitine: synthesis, acyl-group transport, fuel selection and nutrient interactions (2026-09-19) · lines 258–264

AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Two PA and two MMA cases; plasma, urine and selected muscle measurements. · source_derived_draft · unverified_draft

## l-carnitine-organic-acid-loss A metabolic block can tie up carnitine and lead to its loss in urine. Four patients with propionic or methylmalonic aciduria had low plasma free carnitine and elevated short-chain acylcarnitine excretion; muscle carnitine was low in two biopsied patients. Model: Two PA and two MMA cases; plasma, urine and selected muscle measurements. Limitations: Export-driven tissue depletion is the authors' mechanism; these inherited conditions are not synonymous with dietary B12 deficiency. Evidence access: Primary abstract Propionylcarnitine excretion in propionic and methylmalonic acidurias: a cause of carnitine deficiency. · 1984 · https://pubmed.ncbi.nlm.nih.gov/6723070/ · DOI 10.1016/0009-8981(84)90187-6

evidence_access

Primary abstract

experimental_model

Purified-enzyme comparison; source species is not specified in the accessible abstract.

limitations

This is not recorded as direct human enzyme evidence or an exclusive BCKDH route. Correction record: PubMed indexes an erratum in Biochemical Journal 1987;242(3):935. The notice text was inaccessible during this curation; its specific scope and impact remain unverified. The purified-enzyme findings are retained provisionally with this flag, and the abstract does not identify the source species. https://pubmed.ncbi.nlm.nih.gov/3800905/

nutrient_topic

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

plain_language

More than one ketoacid complex can handle this carbon skeleton in vitro.

primary_references

Oxidative decarboxylation of 4-methylthio-2-oxobutyrate by branched-chain 2-oxo acid dehydrogenase complex. · 1986 · https://pubmed.ncbi.nlm.nih.gov/3800905/ · DOI 10.1042/bj2370621

L-Threonine: translation, intestinal barrier, metabolism and cross-nutrient mechanisms (2026-09-19) · lines 306–312

AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified-enzyme comparison; source species is not specified in the accessible abstract. · source_derived_draft · unverified_draft

## l-threonine-ketoacid-oxidation More than one ketoacid complex can handle this carbon skeleton in vitro. Purified BCOADC oxidized 2-oxobutyrate with a reported Km of 18 micromolar; purified PDC also accepted it, whereas OGDH did not. Model: Purified-enzyme comparison; source species is not specified in the accessible abstract. Limitations: This is not recorded as direct human enzyme evidence or an exclusive BCKDH route. Correction record: PubMed indexes an erratum in Biochemical Journal 1987;242(3):935. The notice text was inaccessible during this curation; its specific scope and impact remain unverified. The purified-enzyme findings are retained provisionally with this flag, and the abstract does not identify the source species. https://pubmed.ncbi.nlm.nih.gov/3800905/ Evidence access: Primary abstract Oxidative decarboxylation of 4-methylthio-2-oxobutyrate by branched-chain 2-oxo acid dehydrogenase complex. · 1986 · https://pubmed.ncbi.nlm.nih.gov/3800905/ · DOI 10.1042/bj2370621