Affinage

BCO1

Beta,beta-carotene 15,15'-dioxygenase · UniProt Q9HAY6

Length
547 aa
Mass
62.6 kDa
Annotated
2026-04-28
34 papers in source corpus 10 papers cited in narrative 10 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

BCO1 is the principal enzyme responsible for generating vitamin A (retinal) from dietary provitamin A carotenoids, thereby linking carotenoid intake to retinoid signaling, lipid metabolism, and cellular differentiation. It is a soluble, cytosolic, monomeric non-heme iron oxygenase that catalyzes oxidative cleavage of β-carotene at the central 15,15′ double bond with a kcat of ~8 s⁻¹ and also accepts α-carotene, β-cryptoxanthin, and lycopene as substrates, but not xanthophylls (PMID:24187135, PMID:23727499). In intestinal epithelial cells, BCO1 transcription is negatively regulated by the homeodomain factor ISX in a retinoic acid–dependent feedback loop, and its developmental induction involves thyroid hormone receptor α-1–driven chromatin remodeling at the promoter (PMID:18093975, PMID:23327966). The retinoids produced by BCO1 suppress PPARγ-driven adipogenesis in adipose tissue, activate RXR to inhibit macrophage foam cell formation, and are required for normal hepatic lipid homeostasis and myoblast differentiation (PMID:21673813, PMID:25629601, PMID:30006135, PMID:28625776).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 2007 High

    Identifying how intestinal BCO1 expression is controlled was critical; the discovery that ISX acts as a transcriptional repressor of BCO1 in intestinal epithelial cells established the existence of a vitamin A–dependent negative feedback circuit governing carotenoid absorption.

    Evidence ISX knockout mice with qRT-PCR and dietary vitamin A manipulation in mouse intestine

    PMID:18093975

    Open questions at the time
    • Direct ISX binding site on BCO1 promoter not mapped
    • Feedback loop not reconstituted in a cell-free or reporter system in this study
  2. 2011 High

    Whether BCO1-derived retinoids had metabolic consequences beyond vitamin A supply was unknown; demonstrating that BCO1 knockout abolishes β-carotene–mediated PPARγ suppression and increases adiposity established BCO1 as a metabolic regulator of lipogenesis.

    Evidence Bcmo1−/− vs. wild-type mice fed β-carotene, with microarray, qRT-PCR, Western blot, and metabolite profiling of white adipose tissue

    PMID:21673813

    Open questions at the time
    • Whether retinal or retinoic acid is the active species suppressing PPARγ was not resolved
    • Mechanism of PPARγ downregulation (direct vs. indirect) not determined
  3. 2012 Medium

    The epigenetic mechanism controlling BCO1 induction during development was unclear; ChIP analysis at the BCO1 locus showed sequential H3K4 methylation, TRα-1 recruitment, coactivator assembly, and histone acetylation during the suckling-to-weaning transition, establishing a chromatin-remodeling pathway for BCO1 activation.

    Evidence ChIP for H3K4me2/3, H3ac, TRα-1, SRC-1, CBP at BCO1 promoter/enhancer in rat jejunum across developmental stages

    PMID:23327966

    Open questions at the time
    • Functional requirement for TRα-1 binding not tested by mutation or knockout
    • Whether this mechanism operates in human intestine is unknown
  4. 2013 High

    Quantitative biochemical parameters and substrate scope of BCO1 had not been rigorously defined with purified human enzyme; in vitro reconstitution showed BCO1 is a cofactor-independent, soluble monomer with defined Michaelis-Menten kinetics and broader substrate specificity than expected, including lycopene cleavage.

    Evidence Purified recombinant human BCO1 from E. coli and Sf9 cells, kinetic assays, size-exclusion chromatography, subcellular fractionation of mouse liver

    PMID:23727499 PMID:24187135

    Open questions at the time
    • Structural basis for substrate selectivity (accepts lycopene but not lutein) not explained
    • No crystal structure of human BCO1
  5. 2014 Medium

    Whether BCO1 affects retinoid ester metabolism beyond its cleavage reaction was unknown; analysis of BCO1/LRAT single and double knockouts revealed BCO1 loss impairs both LRAT- and ARAT-dependent retinyl ester formation and alters broader lipid ester pools in a sex- and tissue-dependent manner.

    Evidence BCO1−/−, LRAT−/−, and double-KO mice with retinoid and lipid mass spectrometry across embryonic and adult tissues

    PMID:25602705

    Open questions at the time
    • Whether BCO1 directly influences esterification enzymes or acts solely via retinoid substrate supply is unresolved
    • Sex-dependent mechanism not elucidated
  6. 2015 High

    BCO1's tissue expression pattern and distinct subcellular compartment relative to BCO2 was formally established by fractionation and immunohistochemistry, confirming cytosolic localization in hepatocytes, stellate cells, and intestinal epithelium.

    Evidence Subcellular fractionation of rat liver and immunohistochemistry of liver and intestine

    PMID:25575786

    Open questions at the time
    • Mechanisms retaining BCO1 in cytosol (no targeting signal) not studied
  7. 2015 Medium

    Whether BCO1 functions in immune cells was unexplored; demonstrating that macrophage BCO1 converts 9-cis β-carotene to 9-cis retinoic acid to activate RXR and inhibit foam cell formation extended BCO1's role to innate immunity and atherosclerosis protection.

    Evidence BCO1 activity assay in RAW264.7 lysates, RXR reporter assay, dietary 9-cis β-carotene feeding in mice

    PMID:25629601

    Open questions at the time
    • BCO1 knockout macrophages not directly tested
    • Relative contribution of 9-cis retinoic acid versus all-trans retinoids not dissected
  8. 2017 Medium

    BCO1's role in cell fate decisions outside adipose and immune contexts was not established; siRNA knockdown and RALDH inhibition in myoblasts showed BCO1-mediated retinal production is required for β-carotene's anti-proliferative and pro-differentiation effects.

    Evidence BCO1 siRNA and DEAB inhibitor in primary chicken myoblasts with BrdU incorporation, cell cycle, and differentiation index assays

    PMID:28625776

    Open questions at the time
    • Mammalian myoblast validation not performed
    • Downstream retinoid receptor mediating differentiation not identified
  9. 2018 Medium

    The combined hepatic consequences of losing both carotenoid oxygenases were unknown; BCO1/BCO2 double knockout caused steatosis with downregulation of the FXR/SIRT1 axis, linking carotenoid-derived retinoid supply to bile acid and lipid homeostasis pathways.

    Evidence BCO1/BCO2 double-knockout mice with hepatic lipid quantification, Western blot, RT-PCR, and miRNA profiling

    PMID:30006135

    Open questions at the time
    • Individual contributions of BCO1 vs. BCO2 to the phenotype not separated
    • Whether retinoid supplementation rescues steatosis not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • A high-resolution structure of human BCO1 and the structural determinants of its substrate selectivity (e.g., why it cleaves lycopene but not lutein) remain unresolved, as does the identity of the retinoid species and nuclear receptors mediating BCO1's sex-dependent effects on lipid metabolism across tissues.
  • No crystal or cryo-EM structure of human BCO1
  • Active-site determinants of substrate selectivity uncharacterized
  • Sex-dependent metabolic regulation mechanism unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016491 oxidoreductase activity 2 GO:0016787 hydrolase activity 2
Localization
GO:0005829 cytosol 2
Pathway
R-HSA-1430728 Metabolism 5 R-HSA-162582 Signal Transduction 2
Partners
CBPISXSRC1THRA

Evidence

Reading pass · 10 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2013 Purified recombinant human BCO1 catalyzes oxidative cleavage of β-carotene at the central 15,15' double bond to yield retinal, with Vmax = 197.2 nmol retinal/mg BCO1/h, Km = 17.2 μM, and kcat/Km = 6098 M⁻¹ min⁻¹. BCO1 also cleaves α-carotene, β-cryptoxanthin, β-apo-8'-carotenal, and surprisingly lycopene (to acycloretinal), but not lutein, zeaxanthin, or 9-cis-β-carotene. In vitro enzymatic assay with purified recombinant protein expressed in E. coli, cobalt-affinity chromatography, Michaelis-Menten kinetics The Journal of biological chemistry High 24187135
2013 Human BCO1 is a soluble monomeric enzyme that does not require cofactors, displays Michaelis-Menten kinetics with KM = 14 μM for β-carotene and a turnover rate of ~8 molecules/second, and retains aqueous solubility confirmed in mouse liver and mammalian cells. Recombinant expression in Sf9 insect cells, purification without detergent, size/oligomeric state analysis, enzymatic activity assay, subcellular fractionation of mouse liver Archives of biochemistry and biophysics High 23727499
2015 BCO1 is a cytosolic protein in liver and intestine, localizing to hepatocytes, hepatic stellate cells, portal endothelial cells (liver), and duodenal mucosal epithelium (especially Brunner's glands), while BCO2 is mitochondrial — establishing distinct subcellular compartmentalization for the two carotenoid cleavage enzymes. Subcellular fractionation of rat liver, immunohistochemistry of liver and intestine sections Archives of biochemistry and biophysics High 25575786
2011 BCO1 (Bcmo1) enzymatic activity in adipocytes converts β-carotene into retinoids, which downregulate PPARγ mRNA and protein expression and reduce body adiposity; this effect is absent in Bcmo1⁻/⁻ mice despite β-apocarotenoid production by Bcdo2, demonstrating that retinoid production by Bcmo1 is mechanistically required to suppress PPARγ-driven lipogenesis. Bcmo1⁻/⁻ knockout mice vs. wild-type, dietary β-carotene supplementation, genome-wide microarray of inguinal WAT, quantitative RT-PCR and Western blot for PPARγ, metabolite profiling PloS one High 21673813
2007 The intestine-specific transcription factor ISX represses Bcmo1 expression in intestinal epithelial cells; Isx-deficient mice show drastically increased Bcmo1 mRNA in duodenum and jejunum, and Bcmo1 is not upregulated by mild vitamin A deficiency in the duodenum when ISX is absent, placing ISX as a negative regulator upstream of Bcmo1 in the intestinal vitamin A feedback circuit. ISX knockout (LacZ knock-in) mice, quantitative RT-PCR, vitamin A deficiency dietary manipulation, LacZ reporter expression mapping The Journal of biological chemistry High 18093975
2015 BCO1 activity in macrophages converts 9-cis β-carotene into 9-cis retinoic acid and other retinoids that activate the nuclear receptor RXR, thereby inhibiting macrophage foam cell formation; this is dependent on endogenous BCMO1 expression and activity demonstrated in RAW264.7 cells and peritoneal macrophages. BCMO1 activity assay in macrophage cell lysates, RXR reporter assay in hepa1-6 cells, ex vivo and in vivo foam cell formation with dietary algal 9-cis β-carotene in mice PloS one Medium 25629601
2014 Absence of BCO1 in embryos impairs both LRAT-mediated (lecithin-dependent) and ARAT-mediated (acyl CoA-dependent) retinyl ester synthesis, and also alters cholesterol ester and diacylglycerol ester pools; in adults, BCO1 influences retinyl ester formation in pancreas, lung, heart, and adipose in a sex-dependent manner, indicating a function beyond carotenoid cleavage. BCO1⁻/⁻, LRAT⁻/⁻, and LRAT⁻/⁻/BCO1⁻/⁻ mice; retinoid and lipid mass spectrometry; tissue-specific analysis at mid-gestation and adult stages Archives of biochemistry and biophysics Medium 25602705
2012 Induction of the BCMO1 gene during the suckling-weaning transition in rats is associated sequentially with histone H3 K4 di/tri-methylation and thyroid hormone receptor α-1 (TRα-1) binding to the BCMO1 promoter/enhancer, followed by coactivator (SRC-1, CBP) recruitment and histone H3 acetylation, establishing a chromatin-based epigenetic mechanism for BCMO1 transcriptional activation. Chromatin immunoprecipitation (ChIP) for H3K4me2/3, H3 acetylation, TRα-1, SRC-1, CBP at BCMO1 promoter; enzymatic activity assay; RT-PCR; developmental time-course in rat jejunum Journal of nutritional science and vitaminology Medium 23327966
2018 Ablation of both BCO1 and BCO2 in mice induces hepatic steatosis associated with downregulation of FXR, SHP, and SIRT1, and dysregulation of the FXR/miR-34a/SIRT1 pathway controlling lipogenesis and fatty acid β-oxidation, indicating that BCO1 (together with BCO2) is required for normal hepatic lipid and cholesterol homeostasis. BCO1/BCO2 double-knockout mice, hepatic lipid quantification, Western blot, RT-PCR, microRNA profiling, oxidative stress markers Archives of biochemistry and biophysics Medium 30006135
2017 BCO1 is expressed and active in chicken myoblasts; BCO1-mediated conversion of β-carotene to retinal (and subsequently retinoic acid via RALDH) is required for β-carotene's anti-proliferative and pro-differentiation effects, as inhibition of RALDH or siRNA knockdown of BCO1 abolishes these effects. BCO1 siRNA knockdown in primary chicken myoblasts, DEAB (RALDH inhibitor) treatment, BrdU incorporation assay, flow cytometry cell cycle analysis, differentiation index measurement Experimental cell research Medium 28625776

Source papers

Stage 0 corpus · 34 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 Beta-carotene reduces body adiposity of mice via BCMO1. PloS one 126 21673813
2013 Substrate specificity of purified recombinant human β-carotene 15,15'-oxygenase (BCO1). The Journal of biological chemistry 88 24187135
2010 Molecular and dietary regulation of beta,beta-carotene 15,15'-monooxygenase 1 (BCMO1). Archives of biochemistry and biophysics 76 20599666
2007 Isx participates in the maintenance of vitamin A metabolism by regulation of beta-carotene 15,15'-monooxygenase (Bcmo1) expression. The Journal of biological chemistry 76 18093975
2011 Importance of β,β-carotene 15,15'-monooxygenase 1 (BCMO1) and β,β-carotene 9',10'-dioxygenase 2 (BCDO2) in nutrition and health. Molecular nutrition & food research 52 22147584
2015 Cellular localization of β-carotene 15,15' oxygenase-1 (BCO1) and β-carotene 9',10' oxygenase-2 (BCO2) in rat liver and intestine. Archives of biochemistry and biophysics 47 25575786
2018 Ablation of carotenoid cleavage enzymes (BCO1 and BCO2) induced hepatic steatosis by altering the farnesoid X receptor/miR-34a/sirtuin 1 pathway. Archives of biochemistry and biophysics 29 30006135
2015 The inhibition of macrophage foam cell formation by 9-cis β-carotene is driven by BCMO1 activity. PloS one 27 25629601
2013 Single nucleotide polymorphisms in CETP, SLC46A1, SLC19A1, CD36, BCMO1, APOA5, and ABCA1 are significant predictors of plasma HDL in healthy adults. Lipids in health and disease 27 23656756
2016 Common SNP rs6564851 in the BCO1 Gene Affects the Circulating Levels of β-Carotene and the Daily Intake of Carotenoids in Healthy Japanese Women. PloS one 25 28005968
2013 Characterization of human β,β-carotene-15,15'-monooxygenase (BCMO1) as a soluble monomeric enzyme. Archives of biochemistry and biophysics 25 23727499
2010 Knockout of the Bcmo1 gene results in an inflammatory response in female lung, which is suppressed by dietary beta-carotene. Cellular and molecular life sciences : CMLS 25 20372966
2018 Dietary patterns, BCMO1 polymorphisms, and primary lung cancer risk in a Han Chinese population: a case-control study in Southeast China. BMC cancer 18 29673335
2015 Tissue- and sex-specific effects of β-carotene 15,15' oxygenase (BCO1) on retinoid and lipid metabolism in adult and developing mice. Archives of biochemistry and biophysics 16 25602705
2017 Beta-carotene preferentially regulates chicken myoblast proliferation withdrawal and differentiation commitment via BCO1 activity and retinoic acid production. Experimental cell research 14 28625776
2010 Downregulation of Fzd6 and Cthrc1 and upregulation of olfactory receptors and protocadherins by dietary beta-carotene in lungs of Bcmo1-/- mice. Carcinogenesis 14 20472610
2018 The preliminary association study of ADIPOQ, RBP4, and BCMO1 variants with polycystic ovary syndrome and with biochemical characteristics in a cohort of Polish women. Advances in medical sciences 13 29428584
2014 The relationship between BCMO1 gene variants and macular pigment optical density in persons with and without age-related macular degeneration. PloS one 10 24586510
2014 Nutrigenetics of carotenoid metabolism in the chicken: a polymorphism at the β,β-carotene 15,15'-mono-oxygenase 1 (BCMO1) locus affects the response to dietary β-carotene. The British journal of nutrition 8 24642187
2014 Hesperidin increases intestinal β,β-carotene 15-15' mono-oxygenase 1 (BCMO1) activity in Mongolian gerbils (Meriones unguiculatus) fed with β-carotene-free diet. Food chemistry 8 24767085
2020 SNP rs6564851 in the BCO1 Gene Is Associated with Varying Provitamin a Plasma Concentrations but Not with Retinol Concentrations among Adolescents from Rural Ghana. Nutrients 7 32560166
2019 Polymorphisms in PCSK9, LDLR, BCMO1, SLC12A3, and KCNJ1 are Associated with Serum Lipid Profile in Chinese Han Population. International journal of environmental research and public health 6 31480784
2014 The Effect of BCMO1 Gene Variants on Macular Pigment Optical Density in Young Healthy Caucasians. Frontiers in nutrition 5 25988124
2023 β-Cryptoxanthin Attenuates Cigarette-Smoke-Induced Lung Lesions in the Absence of Carotenoid Cleavage Enzymes (BCO1/BCO2) in Mice. Molecules (Basel, Switzerland) 4 36771049
2021 ALDH2, ADCY3 and BCMO1 polymorphisms and lifestyle-induced traits are jointly associated with CAD risk in Chinese Han people. Gene 4 34481002
2019 Carotenoid metabolic (BCO1) polymorphisms and personal behaviors modify the risk of coronary atherosclerosis: a nested case-control study in Han Chinese with dyslipidaemia (2013-2016). Asia Pacific journal of clinical nutrition 4 30896431
2023 The BCO2 Genotype and the Expression of BCO1, BCO2, LRAT, and TTPA Genes in the Adipose Tissue and Brain of Rabbits Fed a Diet with Marigold Flower Extract. International journal of molecular sciences 3 36768627
2022 Structural and Functional Analysis of Nonheme Iron Enzymes BCMO-1 and BCMO-2 from Caenorhabditis elegans. Frontiers in molecular biosciences 3 35223999
2012 Organ specificity of beta-carotene induced lung gene-expression changes in Bcmo1-/- mice. Molecular nutrition & food research 3 23203725
2025 Single-cell transcriptomics reveals the regulation of bco1 and bco2 genes in the carotenoid metabolism of koi carp. International journal of biological macromolecules 1 41043743
2024 LncRNA (BCO1-AS) regulate inflammatory responses in bacterial infection through caspase-1 in turbot (Scophthalmus maximus). International journal of biological macromolecules 1 39208888
2022 A Computer Simulation Insight into the Formation of Apocarotenoids: Study of the Carotenoid Oxygenases BCO1 and BCO2 and Their Interaction with Putative Substrates. Molecules (Basel, Switzerland) 1 36431912
2014 Decidual β-carotene-15,15'-oxygenase-1 and 2 (BCMO1,2) expression is increased in nitrofen model of congenital diaphragmatic hernia. Pediatric surgery international 1 25344780
2012 Induction of the BCMO1 gene during the suckling-weaning transition in rats is associated with histone H3 K4 methylation and subsequent coactivator binding and histone H3 acetylation to the gene. Journal of nutritional science and vitaminology 1 23327966