Human propionyl-CoA carboxylase / PCC

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

Six alpha and six beta subunits form the working complex.

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 624–635

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-assembly Human PCC cryo-EM supported an alpha6-beta6 assembly similar to the bacterial holoenzyme architecture. Condition category: normal nutrient_topic: Biotin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Six alpha and six beta subunits form the working complex. 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

cross_nutrient

true

evidence_location

Indexed primary abstract

experimental_model

Partially purified human fibroblast PCC

exposure

Control fibroblast enzyme fraction

limitations

Biotin content in an enzyme preparation; does not establish whole-body biotin thresholds.

nutrient_topic

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

organism

Homo sapiens

plain_language

Human fibroblast PCC carried biotin, a different vitamin required upstream of the B12-dependent step.

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

tissue_or_cell_type

Fibroblasts

Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1145–1157

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Partially purified human fibroblast PCC · source_derived_draft · unverified_draft

### human-pcc-biotin PCC partially purified from control human fibroblasts contained biotin. Condition category: normal nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Human fibroblast PCC carried biotin, a different vitamin required upstream of the B12-dependent step. organism: Homo sapiens tissue_or_cell_type: Fibroblasts experimental_model: Partially purified human fibroblast PCC limitations: Biotin content in an enzyme preparation; does not establish whole-body biotin thresholds. exposure: Control fibroblast enzyme fraction cross_nutrient: true evidence_location: Indexed primary abstract [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

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

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 alpha subunit handles biotin loading with the carboxyl group and carries that group onward.

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 598–609

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-pcca PCCA contains the biotin-carboxylase and biotin-carrier domains of human PCC. Condition category: normal nutrient_topic: Biotin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The alpha subunit handles biotin loading with the carboxyl group and carries that group onward. 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_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"}

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

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/biotin-research/10590022.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bbdc1b8fa77a6935ced529e847093935cf4c8c9e056470e81aa3473968b980c5", "start_char": 0, "end_char": 1628, "text_sha256": "bbdc1b8fa77a6935ced529e847093935cf4c8c9e056470e81aa3473968b980c5"}

experimental_model

Kinetics of seven human HLCS variants, patient cells and clinical response comparison

exposure

Genetic variants and biotin supplementation

limitations

Biotin responsiveness varied with residual enzyme capacity. Genotype effects must not be equated with ordinary dietary biotin deficiency.

nutrient_topic

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

organism

Homo sapiens

plain_language

An enzyme with very little remaining capacity may respond less, even when more biotin is supplied.

primary_references

[b7-p10590022] Relationship between kinetic properties of mutant enzyme and biochemical and clinical responsiveness to biotin in holocarboxylase synthetase deficiency. (1999). https://pubmed.ncbi.nlm.nih.gov/10590022/ DOI: 10.1203/00006450-199912000-00004

tissue_or_cell_type

Purified variants and cultured patient cells

trigger_kind

machinery_impairment Imported condition classification; unverified.

Biotin: carboxylases, recycling, deficiency and nutrient interactions (2026-09-17) · lines 520–531

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Kinetics of seven human HLCS variants, patient cells and clinical response comparison · source_derived_draft · unverified_draft

### b7-hlcs-vmax-response Lower residual HLCS Vmax correlated with poorer PCC and clinical responses to biotin in the studied variants and patients; non-Km variants could also respond. Condition category: machinery_impairment nutrient_topic: Biotin research collection; topical membership is not evidence of a direct dietary effect. plain_language: An enzyme with very little remaining capacity may respond less, even when more biotin is supplied. organism: Homo sapiens tissue_or_cell_type: Purified variants and cultured patient cells experimental_model: Kinetics of seven human HLCS variants, patient cells and clinical response comparison limitations: Biotin responsiveness varied with residual enzyme capacity. Genotype effects must not be equated with ordinary dietary biotin deficiency. exposure: Genetic variants and biotin supplementation evidence_span: {"source_cache": "artifacts/biotin-research/10590022.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bbdc1b8fa77a6935ced529e847093935cf4c8c9e056470e81aa3473968b980c5", "start_char": 0, "end_char": 1628, "text_sha256": "bbdc1b8fa77a6935ced529e847093935cf4c8c9e056470e81aa3473968b980c5"} [b7-p10590022] Relationship between kinetic properties of mutant enzyme and biochemical and clinical responsiveness to biotin in holocarboxylase synthetase deficiency. (1999). https://pubmed.ncbi.nlm.nih.gov/10590022/ DOI: 10.1203/00006450-199912000-00004

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

true

evidence_location

Primary abstract and indexed Results: PCC activity

experimental_model

Seven healthy adults

exposure

28-day egg-white-rich biotin-depletion diet

limitations

Lymphocyte enzyme activity; no concurrent B12 intervention or systemic pathway flux measurement.

nutrient_topic

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

organism

Homo sapiens

plain_language

In this small depletion study, low biotin weakened a human enzyme upstream of B12-dependent metabolism.

primary_references

[stratton-2006-biotin] Lymphocyte propionyl-CoA carboxylase and its activation by biotin are sensitive indicators of marginal biotin deficiency in humans. (2006). https://pubmed.ncbi.nlm.nih.gov/16895887/ DOI: 10.1093/ajcn/84.1.384

tissue_or_cell_type

Peripheral blood lymphocytes

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1202–1214

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

### biotin-depletion-lowers-pcc In seven adults, 28-day egg-white-induced biotin depletion reduced mean lymphocyte PCC activity to 23% of baseline. Condition category: nutrient_deficiency nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: In this small depletion study, low biotin weakened a human enzyme upstream of B12-dependent metabolism. organism: Homo sapiens tissue_or_cell_type: Peripheral blood lymphocytes experimental_model: Seven healthy adults limitations: Lymphocyte enzyme activity; no concurrent B12 intervention or systemic pathway flux measurement. exposure: 28-day egg-white-rich biotin-depletion diet cross_nutrient: true evidence_location: Primary abstract and indexed Results: PCC activity [stratton-2006-biotin] Lymphocyte propionyl-CoA carboxylase and its activation by biotin are sensitive indicators of marginal biotin deficiency in humans. (2006). https://pubmed.ncbi.nlm.nih.gov/16895887/ DOI: 10.1093/ajcn/84.1.384