Information on EC 1.14.99.36 - beta-carotene 15,15'-monooxygenase

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The expected taxonomic range for this enzyme is: Coelomata

EC NUMBER
COMMENTARY
1.14.99.36
-
RECOMMENDED NAME
GeneOntology No.
beta-carotene 15,15'-monooxygenase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
15,15'-dihydroxy-beta-carotene + A = 2 all-trans-retinal + AH2
show the reaction diagram
(1c)
-
-
-
beta-carotene + O2 + AH2 = beta-carotene 15,15'-epoxide + H2O + A
show the reaction diagram
(1a)
-
-
-
beta-carotene + O2 = 2 all-trans retinal
show the reaction diagram
mechanism
-
beta-carotene + O2 = 2 all-trans retinal
show the reaction diagram
overall reaction
-
-
-
beta-carotene 15,15'-epoxide + H2O = 15,15'-dihydroxy-beta-carotene
show the reaction diagram
(1b)
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
oxidation
-
-
-
-
oxidation
-
-
oxidation
Q9VFS2
-
oxidation
-
-
redox reaction
-
-
-
-
reduction
-
-
-
-
reduction
-
-
reduction
Q9VFS2
-
reduction
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Metabolic pathways
-
-
retinol biosynthesis
-
-
Retinol metabolism
-
-
SYSTEMATIC NAME
IUBMB Comments
beta-carotene:oxygen 15,15'-oxidoreductase (bond-cleaving)
Requires bile salts and Fe(II). This animal enzyme catalyses the reaction in three stages, epoxidation of the 15,15'-double bond, hydration of the epoxide leading to ring opening, and oxidative cleavage of the diol formed. Thus only one atom of the dioxygen is incorporated into each retinal molecule. The nature of the acceptor listed in reactions (1a) and (1c) is assumed to be iron within the active site. Formerly classified in EC 1.13.11 as it had been thought to be a dioxygenase. cf. EC 1.13.11.63, beta-carotene 15,15'-dioxygenase.
SYNONYMS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
15,15'-carotenoid monooxygenase
-
-
15,15'-mono-oxygenase
-
-
BC-15,15'-oxygenase
Q9JJS6
-
BCM
-
gene name
BCM
Rattus norvegicus Zucker
-
gene name
-
BCMO
Q9HAY6
-
Bcmo1
H0VRY9
-
Bcmo1
-
-
Bcmo1
Q9I993
-
Bcmo1
Q9HAY6
gene name
Bcmo1
Q9JJS6
gene name
Bcmo1
Mus musculus C57/BL6/129 Sv
Q9JJS6
gene name
-
Bcmo1
G1SEP0
-
Bcmo1
C7C6F6
gene name
Bcmo1
Q91XT5
-
Bcmo1
-
-
BCO1
-
-
BCO1
Q9HAY6
-
BCO1
Q9JJS6
-
BCO2
C1L3B1
gene name
Bcox
-
-
Bcox
Q90WH4
-
beta,beta-carotene 15,15'-monooxygenase
Q9HAY6
-
beta,beta-carotene 15,15'-monooxygenase
Q9JJS6
-
beta,beta-carotene 15,15-monooxygenase 1
H0VRY9
-
beta,beta-carotene 15,15-monooxygenase 1
-
-
beta,beta-carotene 15,15-monooxygenase 1
Q9I993
-
beta,beta-carotene 15,15-monooxygenase 1
Q9HAY6
-
beta,beta-carotene 15,15-monooxygenase 1
Q9JJS6
-
beta,beta-carotene 15,15-monooxygenase 1
-
-
beta,beta-carotene 15,15-monooxygenase 1
G1SEP0
-
beta,beta-carotene 15,15-monooxygenase 1
Q91XT5
-
beta,beta-carotene oxygenase 1
-
-
beta,beta-carotene-15,15'-monooxygenase
Q9HAY6
-
beta,beta-carotene-15,15'-monooxygenase
Q9JJS6
-
beta,beta-carotene-15,15'-monooxygenase
Mus musculus C57/BL6/129 Sv
Q9JJS6
-
-
beta,beta-carotene-15,15'-oxygenase
-
-
beta,beta-carotene-15,15'-oxygenase
Q90WH4
-
beta-carotene 15,15' monooxygenase
-
-
beta-carotene 15,15' monooxygenase
Rattus norvegicus Zucker
-
-
-
beta-carotene 15,15'-dioxygenase
-
-
-
-
beta-carotene 15,15'-monooxygenase
Q9I993
-
beta-carotene 15,15'-monooxygenase
-
-
beta-carotene 15,15'-monooxygenase
Q9HAY6
-
beta-carotene 15,15'-monooxygenase
Q9JJS6
-
beta-carotene 15,15'-monooxygenase
-
-
beta-carotene 15,15'-monooxygenase 1
C7C6F6
-
beta-carotene 15,15'-monoxygenase
Q9HAY6
-
beta-carotene 15,15'-oxygenase
Q9HAY6
-
beta-carotene 15,15-monooxygenase
Q9HAY6
-
beta-carotene oxygenase 2
C1L3B1
-
beta-carotene-15,15'-monooxygenase
-
-
beta-carotene-15,15'-monooxygenase
Q9HAY6
-
beta-carotene-15,15'-monooxygenase
-
-
beta-carotene-15,15'-oxygenase
Q9JJS6
-
beta-CD
-
-
betaCDIOX
-
-
betaCO
-
-
carotene 15,15'-dioxygenase
-
-
-
-
carotene dioxygenase
-
-
-
-
carotenoid oxygenase
Q9VFS2
-
carotenoid oxygenase
-
-
CDO
-
-
-
-
CMO I
-
-
CMO1
Q9HAY6
-
CMO1
-
-
CMOI
Q9JJS6
-
EC 1.13.11.21
-
-
formerly
-
oxygenase, beta-carotene 15,15'-di-
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
37256-60-3
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
cattle
-
-
Manually annotated by BRENDA team
cattle with pigmented or non-pigmented, i.e. yellow or white, fat
-
-
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
Domania subtryug
-
-
-
Manually annotated by BRENDA team
gene Bcmo1
SwissProt
Manually annotated by BRENDA team
gene BCMO1; gene Bcmo1
SwissProt
Manually annotated by BRENDA team
gene cmo1
SwissProt
Manually annotated by BRENDA team
gene Bcmo1
-
-
Manually annotated by BRENDA team
gene Bcmo1
SwissProt
Manually annotated by BRENDA team
recombinant enzyme
SwissProt
Manually annotated by BRENDA team
Mus musculus C57/BL6/129 Sv
gene Bcmo1
SwissProt
Manually annotated by BRENDA team
no activity in Arabidopsis thaliana
-
-
-
Manually annotated by BRENDA team
no activity in Felis catus
intestine
-
-
Manually annotated by BRENDA team
no activity in Zea mays
-
-
-
Manually annotated by BRENDA team
gene bco2; gene BCO2
UniProt
Manually annotated by BRENDA team
gene bmco1; gene Bcmo1
UniProt
Manually annotated by BRENDA team
Goto-Kakizaki rat
-
-
Manually annotated by BRENDA team
male obese Zucker rats, gene BCM
-
-
Manually annotated by BRENDA team
male wistar rat
-
-
Manually annotated by BRENDA team
Rattus norvegicus Zucker
male obese Zucker rats, gene BCM
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
-
BCMO1 is a member of an evolutionary well-conserved family of carotenoid cleavage oxygenases
evolution
Mus musculus C57/BL6/129 Sv
-
BCMO1 is a member of an evolutionary well-conserved family of carotenoid cleavage oxygenases
-
malfunction
C1L3B1, C7C6F6
a nonsense mutation c.196C-T in the beta-carotene oxygenase 2 BCO2 gene is strongly associated with the yellow fat phenotype in sheep that is caused by accumulation of carotenoids in adipose tissue, a recessive trait. But animals homozygous for the mutation do not suffer from any negative health or development traits, pointing towards a minor role of BCO2 in vitamin A formation
malfunction
-
BCMO1 knock-out mice become vitamin A deficient despite expressing BCDO2. Hepatic BCDO2 expression is significantly elevated in BCMO1 KO mice compared with wild-type mice, leading to a significant increase in beta-apo-12'-carotenal or beta-apo-10'-carotenal concentration. BCMO1 KO mice reveal a large accumulation of beta-carotene in tissues (liver, lung, adipose tissue) of animals on a beta-carotene-enriched diet. Increased susceptibility of BCMO1 KO mice to diet induced obesity, coupled with increased expression of PPAR-gamma-induced genes. Knockout of BCMO1 alters serum lipid levels and leads to the development of liver steatosis in mice
malfunction
-
Bcmo1-/- mice show increased expression of Bcdo2 in adipocytes and beta-10'-apocarotenol accumulates as the major beta-carotene derivative. Bcmo1-/- mice have a lower average body weight than wild-type mice
malfunction
-
genetic disruption of BCO1 results in beta-carotene accumulation and vitamin A deficiency accompanied by a BCO2-dependent production of minor amounts of beta-apo-10'-carotenol, which can be esterified and transported by the same proteins as vitamin A but with a lower affinity and slower reaction kinetics. all-trans-Retinol treatment of vitamin A-deprived Bco1-/- mice decreases hepatic retinol-binding protein levels
malfunction
-
lack of CMOI in the developing tissues further exacerbates the severity of vitamin A deficiency and thus the embryonic malformations of retinol-binding protein-deficient mice, phenotypes, overview
malfunction
-
reduced BCMO1 expression in normal preneoplastic intestine of folate-deficient tumor-prone mice. A mouse model develops intestinal tumors after low dietary folate
malfunction
-
transfection of cells with BCMO1 siRNA inhibits BCMO1 expression, enhances cancer migration and invasion, and increases expression of MMP7 and MMP28
metabolism
-
Bcmo1 and retinal dehydrogenase 1 are key enzymes in the retinoid metabolism of inguinal white adipose tissue
metabolism
-
carotenoids and apo-carotenoids are converted to retinal by beta-carotene 15,15'-dioxygenase, BCDO, by beta-carotene 15,15'-monooxygenase, BCMO, and by apo-carotenoid 15,15'-oxygenase, ACO, EC 1.14.99.41
physiological function
-
beta-carotene cleavage oxygenase determines the beta-carotene content of the cell. Deletion of the cco1 gene, does not affect growth, morphology or pathogenicity
physiological function
-
enzyme deletion mutants show a significant increase in the total carotenoid content
physiological function
-
larvae of ninaB mutants show no photophobic behavior indicating that NinaB is essential for larval light perception. ninaB mutant flies exhibit impaired chromophore production and consequently lack visual pigments. Visual pigment production essentially depends on NinaB
physiological function
-
beta,beta-carotene 15,15'-monooxygenase-1, BCMO1, is a key enzyme in vitamin A metabolism in mammals. BCMO1 plays a significant physiological role in the local regulation of vitamin A and retinal in reproduction and development
physiological function
-
beta,beta-carotene 15,15'-monooxygenase-1, BCMO1, is a key enzyme in vitamin A metabolism in mammals. BCMO1 plays a significant physiological role in the local regulation of vitamin A and retinal in reproduction and development. Model of the putative mechanism for the regulation of BCMO1 by dietary fat and PPARgamma, overview
physiological function
-
carotenoid 15,15'-oxygenases produce retinal from carotenoids
physiological function
-
increased intestinal enzyme expression occurs in obesity and dyslipedemia and may affect the plasma retinol status, overview
physiological function
C1L3B1, C7C6F6
quantitatively important role for BCO2 in carotenoid degradation, which might indicate a broad enzyme specificity for carotenoids
physiological function
-
BCMO1 catalyzes the symmetric cleavage of carotenoids
physiological function
G1SEP0
BCMO1 catalyzes the symmetric cleavage of carotenoids
physiological function
Q91XT5
BCMO1 catalyzes the symmetric cleavage of carotenoids
physiological function
H0VRY9
BCMO1 catalyzes the symmetric cleavage of carotenoids
physiological function
-
BCMO1 catalyzes the symmetric cleavage of carotenoids. BCMO1 is implicated as a regulator of lipid metabolism. BCMO1 exerts an additional function on retinoid metabolism by influencing retinyl ester formation via modulation of lecithin:retinol acyltransferase activity, thus confirming the critical role of BCMO1 for embryonic retinoid metabolism
physiological function
-
BCMO1 catalyzes the symmetric cleavage of carotenoids. BCMO1 is the key enzyme for beta-carotene conversion into vitamin A. BCMO1-dependent decrease in PPAR-gamma target gene expression is observed during beta-carotene supplementation in inguinal white adipose tissue. The intestine-specific transcription factor intestine-specific homeobox in mouse intestine is an important regulator of BCMO1 expression. Activation of intestine-specific homeobox results in repression of SR-BI and BCMO1 expression thereby controlling beta-carotene absorption as well as vitamin A production
physiological function
-
BCMO1 is the major enzyme for vitamin A production
physiological function
-
beta,beta-carotene 15,15'-monooxygenase and its substrate beta-carotene modulate migration and invasion in colorectal carcinoma cells. Increased beta-carotene consumption is linked to antitumor effects. Retinoic acid reduces the invasiveness in cancer, through inhibition of matrix metalloproteinases
physiological function
-
beta,beta-carotene 15,15'-monooxygenase and its substrate beta-carotene modulate migration and invasion in colorectal carcinoma cells. Increased beta-carotene consumption is linked to antitumor effects. Retinoic acid reduces the migration and invasiveness in cancer, through inhibition of matrix metalloproteinase MMP28 expression, 5-aza-2'-deoxycytidine reduces LoVo cell invasiveness
physiological function
Q9HAY6
beta-carotene 15,15'-oxygenase (BCO1) produces vitamin A from carotenoids in food. BCO1 catalyzes the oxidative cleavage of the 15-15'-double bond of major dietary provitamin A carotenoids,beta-apocarotenals, and lycopene
physiological function
-
beta-carotene plays an important role in the control of body adiposity in mice. The enzyme is a critical molecular player for the regulation of peroxisome proliferator-activated receptor gamma activity in adipocytes
physiological function
-
beta-carotene-15,15'-oxygenase BCO1, but not beta-carotene-9',10'-oxygenase BCO2, is critical for retinoid homeostasis. In wild-type mice, beta-apo-10'-carotenol is converted to retinoids by BCO1
physiological function
Q9HAY6
cmo1 gene transcription may be subject to negative feedback by accumulation of its metabolic products in intestine and liver. Non-gastrointestinal CMO1 may be required for tissue-specific conversion of beta-carotene into vitamin A
physiological function
-
CMOI is expressed in embryonic tissues, suggesting that beta-carotene provides retinoids locally during development. CMOI exerts an additional function on retinoid metabolism by influencing retinyl ester formation via modulation of lecithin:retinol acyltransferase activity, at least in developing tissues
physiological function
Rattus norvegicus Zucker
-
increased intestinal enzyme expression occurs in obesity and dyslipedemia and may affect the plasma retinol status, overview
-
physiological function
Mus musculus C57/BL6/129 Sv
-
BCMO1 is the major enzyme for vitamin A production
-
metabolism
Q9HAY6
beta-carotene 15,15'-monooxygenase is a key enzyme in vitamin A metabolism
additional information
-
beta-carotene represses Ppar gamma and CCAAT/enhancer-binding protein alpha expression in mature adipocytes
additional information
-
transcriptional regulation, overview
additional information
Q9HAY6
beta-carotene treatment antagonizes peroxisome proliferator-activated receptor gamma activity in HEK-293 cells that stably express CMO1 wild-type, but not in cells that express the CMO1 mutant or vector alone having implications for local vitamin A synthesis in the lung, especially during systemic vitamin A insufficiency
additional information
-
dietary beta-carotene downregulates peroxisome proliferator-activated receptor gamma and peroxisome proliferator-activated receptor gamma target genes in adipose tissue of wild-type mice. Supplementation of beta-carotene alters gene expression profiles in wild-type but not in Bcmo1-/- mice
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
13-cis-beta-carotene + O2
retinal
show the reaction diagram
-
11.4% of the activity with all-trans-beta-carotene
-
-
?
3',4'-dehydro-18'-oxo-gamma-carotene + O2
?
show the reaction diagram
G1SEP0
-
-
-
?
9,13-dicis-beta-carotene + O2
?
show the reaction diagram
Q91XT5
-
-
-
?
9-13-dicis-beta-carotene + O2
?
show the reaction diagram
G1SEP0
-
-
-
?
alpha-carotene + ?
11-cis-retinal + all-trans-retinal + all-trans-alpha-retinal
show the reaction diagram
-
-
32.7% 11-cis-retinal + 17.3% all-trans-retinal + 50.0% all-trans-alpha-retinal
-
?
alpha-carotene + O2
retinal
show the reaction diagram
-
8.2% of the activity with all-trans-beta-carotene
-
-
?
alpha-carotene + O2
retinal + ?
show the reaction diagram
-
one molecule retinal is formed
-
-
?
alpha-carotene + O2
retinal + alpha-retinal
show the reaction diagram
-
one molecule retinal is formed
-
-
?
alpha-carotene + O2
2 all-trans-retinal
show the reaction diagram
-
-
-
-
?
alpha-carotene + O2
2 all-trans-retinal
show the reaction diagram
G1SEP0
-
-
-
?
alpha-carotene + O2
2 all-trans-retinal
show the reaction diagram
Q91XT5
-
-
-
?
alpha-carotene + O2
2 retinal
show the reaction diagram
Q9HAY6
-
-
-
?
apo-8'-carotene + O2
2 retinal
show the reaction diagram
Q9HAY6
-
-
-
?
beta-apo-10'-carotenal + O2
?
show the reaction diagram
G1SEP0
-
-
-
?
beta-apo-10'-carotenal + O2
?
show the reaction diagram
Q91XT5
-
-
-
?
beta-apo-10'-carotenol + O2
?
show the reaction diagram
-
beta-apo-10'-carotenol is the major long-chain beta-apocarotenoid in mouse liver
-
-
?
beta-apo-12'-carotenal + O2
?
show the reaction diagram
Q91XT5
-
-
-
?
beta-apo-4'-carotenal + O2
retinal + ?
show the reaction diagram
-
one molecule retinal is formed
-
-
?
beta-apo-4'-carotenal + O2
?
show the reaction diagram
-
-
-
-
?
beta-apo-4'-carotenal + O2
?
show the reaction diagram
G1SEP0
-
-
-
?
beta-apo-8'-carotenal + O2
?
show the reaction diagram
-
-
-
-
?
beta-apo-8'-carotenal + O2
?
show the reaction diagram
G1SEP0
-
-
-
?
beta-apo-8'-carotenal + O2
?
show the reaction diagram
Q91XT5
-
-
-
?
beta-apo-8'-carotenal + O2
retinal + ?
show the reaction diagram
-
one molecule retinal is formed
-
-
?
beta-carotene + ?
11-cis-retinal + all-trans-retinal
show the reaction diagram
-
-
41.2% 11-cis-retinal + 58.8% all-trans-retinal
-
?
beta-carotene + O2
retinal
show the reaction diagram
-
-
-
-
?
beta-carotene + O2
retinal
show the reaction diagram
-
-
-
?
beta-carotene + O2
retinal
show the reaction diagram
Q9JJS6
-
-
?
beta-carotene + O2
retinal
show the reaction diagram
-
-
-
-
?
beta-carotene + O2
retinal
show the reaction diagram
-
-
-
?
beta-carotene + O2
retinal
show the reaction diagram
-
-
-
-
?
beta-carotene + O2
retinal
show the reaction diagram
-
-
-
-
?
beta-carotene + O2
retinal
show the reaction diagram
Q90WH4
-
-
-
?
beta-carotene + O2
retinal
show the reaction diagram
-
-
-
-
?
beta-carotene + O2
retinal
show the reaction diagram
-
-
-
-
?
beta-carotene + O2
retinal
show the reaction diagram
-
conversion of the plant product beta-carotene into a product necessary for the growth and life of the animal organism
-
?
beta-carotene + O2
retinal
show the reaction diagram
Q9JJS6
crucial enzyme in development and metabolism that governs the de novo entry of vitamin A from plant-derived precursors, enzyme may play a critical role in gastrulation
-
-
?
beta-carotene + O2
retinal
show the reaction diagram
Q9HAY6
the enzyme catalyzes the first step in the synthesis of vitamin A from dietary carotenoids. May also play a role in peripheral vitamin A synthesis from plasma-borne provitamin A carotenoids
-
-
?
beta-carotene + O2
retinal
show the reaction diagram
-
the enzyme is responsible for providing vertebrates with vitamin A by catalyzing oxidative cleavage of beta-carotene at its central double bond to two molecules of retinal in intestinal cells
-
-
?
beta-carotene + O2
retinal
show the reaction diagram
Q9JJS6
enzyme may play a critical role in gastrulation
-
-
?
beta-carotene + O2
retinal
show the reaction diagram
Q9I993
key enzyme in the metabolism of beta,beta-carotene to vitamin A
-
-
?
beta-carotene + O2
retinal
show the reaction diagram
-
enzyme plays an important role in retinoid synthesis. BCDO may also be a candidate gene for retinal degenerative disease
-
-
?
beta-carotene + O2
retinal
show the reaction diagram
-
key enzyme in metabolism of provitamin A carotenoids to retinal
-
-
?
beta-carotene + O2
retinal
show the reaction diagram
-
the enzyme catalyzes the first step in conversion of dietary provitamin A carotenoids to vitamin A. The finding that the enzyme is expressed in all epithelia examined leads to the suggestion that BCO1 may be important for local synthesis of vitamin A, constituting a back-up pathway of vitamin A synthesis during times of insufficient dietary intake of vitamin A
-
-
?
beta-carotene + O2
retinal
show the reaction diagram
-
the enzyme catalyzes the first step of vitamin A biosynthesis from provitamin A carotenoids
-
-
?
beta-carotene + O2
retinal
show the reaction diagram
Q90WH4
the enzyme is essential for pattern formation and differentation during zebrafish embryogenesis
-
-
?
beta-carotene + O2
retinal
show the reaction diagram
-
two molecules retinal are formed
-
-
?
beta-carotene + O2
retinal
show the reaction diagram
-
two molecules retinal are formed
-
-
?
beta-carotene + O2
all-trans-retinal
show the reaction diagram
-
-
-
-
?
beta-carotene + O2
all-trans-retinal
show the reaction diagram
-
-
-
-
?
beta-carotene + O2
all-trans-retinal
show the reaction diagram
Q9JJS6
-
-
-
?
beta-carotene + O2
all-trans-retinal
show the reaction diagram
-
BCMO1 is a key enzyme in the pathway of retinoid synthesis from carotenoids, and is responsible for metabolically limiting the amount of intact beta-carotene that can be absorbed by mice from their diet, regulation of BCMO1 activity, overview
-
-
?
beta-carotene + O2
all-trans-retinal
show the reaction diagram
-
BCMO1 is a key enzyme in the pathway of retinoid synthesis from carotenoids, regulation of BCMO1 activity, overview
-
-
?
beta-carotene + O2
all-trans-retinal
show the reaction diagram
-
beta-carotene is stored in the fat
-
-
?
beta-carotene + O2
11-cis-retinal + 13-cis-retinal + all-trans-retinal
show the reaction diagram
Q9VFS2
-
-
-
?
beta-carotene + O2
13-cis-retinal + all-trans-retinal
show the reaction diagram
-
-
-
-
?
beta-carotene + O2
2 retinal
show the reaction diagram
-
-
-
-
?
beta-carotene + O2
2 retinal
show the reaction diagram
-
-
-
-
?
beta-carotene + O2
2 retinal
show the reaction diagram
-
-
-
-
?
beta-carotene + O2
2 retinal
show the reaction diagram
-
substrate binding structure, overview
-
-
?
beta-carotene + O2
2 retinal
show the reaction diagram
-
tyrosine Y235 and Y326 in mouse BCMO1 fix the position of the substrate on the two sides of the 15,15'-double bond most likely due to a mechanism implicating cation pi-stabilization
-
-
?
beta-carotene + O2
2 all-trans-retinal
show the reaction diagram
-
-
-
-
?
beta-carotene + O2
2 all-trans-retinal
show the reaction diagram
Q9JJS6
-
-
-
?
beta-carotene + O2
2 all-trans-retinal
show the reaction diagram
-
-
-
-
?
beta-carotene + O2
2 all-trans-retinal
show the reaction diagram
Q9HAY6
-
-
-
?
beta-carotene + O2
2 all-trans-retinal
show the reaction diagram
-
-
-
-
?
beta-carotene + O2
2 all-trans-retinal
show the reaction diagram
Q9HAY6
-
-
-
?
beta-carotene + O2
2 all-trans-retinal
show the reaction diagram
-
-
-
-
?
beta-carotene + O2
2 all-trans-retinal
show the reaction diagram
G1SEP0
-
-
-
?
beta-carotene + O2
2 all-trans-retinal
show the reaction diagram
Q91XT5
-
-
-
?
beta-carotene + O2
2 all-trans-retinal
show the reaction diagram
H0VRY9
-
-
-
?
beta-carotene + O2
2 all-trans-retinal
show the reaction diagram
-
BCMO1 cleaves at the central 15,15' position of the polyene chain producing two molecules of retinal
-
-
?
beta-carotene + O2
2 all-trans-retinal
show the reaction diagram
G1SEP0
BCMO1 cleaves at the central 15,15' position of the polyene chain producing two molecules of retinal
-
-
?
beta-carotene + O2
2 all-trans-retinal
show the reaction diagram
Q91XT5
BCMO1 cleaves at the central 15,15' position of the polyene chain producing two molecules of retinal
-
-
?
beta-carotene + O2
2 all-trans-retinal
show the reaction diagram
H0VRY9
BCMO1 cleaves at the central 15,15' position of the polyene chain producing two molecules of retinal
-
-
?
beta-carotene + O2
2 all-trans-retinal
show the reaction diagram
Mus musculus C57/BL6/129 Sv
Q9JJS6
-
-
-
?
beta-criptoxanthin + O2
retinal + ?
show the reaction diagram
-
one molecule retinal is formed
-
-
?
beta-cryptoxanthin + O2
?
show the reaction diagram
-
-
-
-
?
beta-cryptoxanthin + O2
?
show the reaction diagram
-
-
-
-
?
beta-cryptoxanthin + O2
?
show the reaction diagram
G1SEP0
-
-
-
?
beta-cryptoxanthin + O2
?
show the reaction diagram
Q91XT5
-
-
-
?
beta-cryptoxanthin + O2
retinal + (3R)-3-hydroxy-retinal
show the reaction diagram
-
-
-
-
?
beta-cryptoxanthin + O2
2 retinal
show the reaction diagram
Q9HAY6
-
-
-
?
cryptoxanthin + O2
11-cis-retinal + all-trans-retinal + 11-cis-3-hydroxy-retinal + all-trans-3-hydroxy-retinal
show the reaction diagram
-
-
4.2% 11-cis-retinal + 45.8% all-trans-retinal + 35.1% 11-cis-3-hydroxy-retinal + 14.9% all-trans-3-hydroxy-retinal
-
?
gamma-carotene + O2
retinal + acycloretinal
show the reaction diagram
-
-
one molecule retinal is formed
-
?
gamma-carotene + O2
2 all-trans-retinal
show the reaction diagram
-
-
-
-
?
lutein + O2
11-cis-3-hydroxy-retinal + all-trans-3-hydroxy-retinal + all-trans-3-hydroxy-alpha-retinal
show the reaction diagram
-
-
39.9% 11-cis-3-hydroxy-retinal + 10.1% all-trans-3-hydroxy-retinal + 47.7% all-trans-3-hydroxy-alpha-retinal
-
?
zeaxanthin + O2
(3R)-11-cis-3-hydroxyretinal + (3R)-all-trans-3-hydroxyretinal
show the reaction diagram
-
-
-
-
?
zeaxanthin + O2
(3R)-11-cis-3-hydroxyretinal + (3R)-all-trans-3-hydroxyretinal
show the reaction diagram
-
-
41.5% 11-cis-3-hydroxy-retinal + 58.5% all-trans-3-hydroxy-retinal
-
?
lycopene + O2
2 acycloretinal
show the reaction diagram
Q9HAY6
-
-
-
?
additional information
?
-
-
catalyses the first step in the conversion of dietary provitamin A carotenoids to vitamin A in the small intestine
-
-
-
additional information
?
-
-
beta-carotene but not all-trans-retinol is converted to all-trans-retinoic acid in mature adipocytes
-
-
-
additional information
?
-
-
BCMO is also active with alpha-carotene, beta-apo-8'-carotenal, and beta-apo-4'-carotenal. The hydrophobicity of residue 108 specifically affects the affinity of beta-carotene 15,15'-monooxygenase for substrates with two ionone rings. Residue 108 may be related to the indirect interaction with the second ionone ring of the substrates with two ionone rings, comparison with apo-carotenoid 15,15'-oxygenase, EC 1.14.99.41, overview
-
-
-
additional information
?
-
-
25-hydroxycholesterol is a secondary autoxidation product derived from 3beta-hydroxy-cholest-5-ene-25-hydroperoxide, a hydroperoxide identified in air-aged cholesterol
-
-
-
additional information
?
-
Q9HAY6
shorter beta-apocarotenals, i.e. beta-apo-10-carotenal, beta-apo-12'-carotenal, and beta-apo-14'-carotenal, do not show Michaelis-Menten behavior under the conditions tested. No activity with lutein, zeaxanthin, and 9-cis-beta-carotene. Purified recombinant BCO1 cleaves beta-carotene solely at the central 15-15' bond
-
-
-
additional information
?
-
-
substrate specificity for BCMO1, overview
-
-
-
additional information
?
-
-
substrate specificity for BCMO1, overview. BCMO1 requires at least one unsubstituted beta-ionone ring for the cleavage of carotenoid substrates, but also the presence and position of methyl groups on the polyene chain are important. Therefore, activity is limited mainly to alpha- and beta-carotene, beta-apo-carotenals and beta-cryptoxanthin
-
-
-
additional information
?
-
Q91XT5
substrate specificity for BCMO1, overview. BCMO1 requires at least one unsubstituted beta-ionone ring for the cleavage of carotenoid substrates, but also the presence and position of methyl groups on the polyene chain are important. Therefore, activity is limited mainly to alpha- and beta-carotene, beta-apo-carotenals and beta-cryptoxanthin. Specificity of BCMO1 towards substrates decreased in the order: beta-carotene, beta-cryptoxanthin, beta-apo-8'-carotenal, beta-apo-4'-carotenal, alpha-carotene, gamma-carotene
-
-
-
additional information
?
-
-
substrate specificity for BCMO1, overview. BCMO1 requires at least one unsubstituted beta-ionone ring for the cleavage of carotenoid substrates, but also the presence and position of methyl groups on the polyene chain are important. Therefore, activity is limited mainly to alpha- and beta-carotene, beta-apo-carotenals and beta-cryptoxanthin. Specificity of BCMO1 towards substrates decreases in the order: beta-carotene, beta-cryptoxanthin, beta-apo-8'-carotenal, beta-apo-4'-carotenal, alpha-carotene, gamma-carotene
-
-
-
additional information
?
-
G1SEP0
substrate specificity for BCMO1, overview. BCMO1 requires at least one unsubstituted beta-ionone ring for the cleavage of carotenoid substrates, but also the presence and position of methyl groups on the polyene chain are important. Therefore, activity is limited mainly to alpha- and beta-carotene, beta-apo-carotenals and beta-cryptoxanthin. Specificity of BCMO1 towards substrates decreases in the order: beta-carotene, beta-cryptoxanthin, beta-apo-8'-carotenal, beta-apo-4'-carotenal, alpha-carotene, gamma-carotene
-
-
-
additional information
?
-
H0VRY9
substrate specificity for BCMO1, overview. BCMO1 requires at least one unsubstituted beta-ionone ring for the cleavage of carotenoid substrates, but also the presence and position of methyl groups on the polyene chain are important. Therefore, activity is limited mainly to alpha- and beta-carotene, beta-apo-carotenals and beta-cryptoxanthin. Specificity of BCMO1 towards substrates decreases in the order: beta-carotene, beta-cryptoxanthin, beta-apo-8'-carotenal, beta-apo-4'-carotenal, alpha-carotene, gamma-carotene
-
-
-
additional information
?
-
-
symmetric cleavage by BCO1 yields retinoids, i.e. beta-15'-apocarotenoids, C20
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
beta-apo-10'-carotenol + O2
?
show the reaction diagram
-
beta-apo-10'-carotenol is the major long-chain beta-apocarotenoid in mouse liver
-
-
?
beta-carotene + O2
retinal
show the reaction diagram
-
-
-
-
?
beta-carotene + O2
retinal
show the reaction diagram
-
-
-
-
?
beta-carotene + O2
retinal
show the reaction diagram
-
-
-
-
?
beta-carotene + O2
retinal
show the reaction diagram
-
-
-
-
?
beta-carotene + O2
retinal
show the reaction diagram
-
conversion of the plant product beta-carotene into a product necessary for the growth and life of the animal organism
-
?
beta-carotene + O2
retinal
show the reaction diagram
Q9JJS6
crucial enzyme in development and metabolism that governs the de novo entry of vitamin A from plant-derived precursors, enzyme may play a critical role in gastrulation
-
-
?
beta-carotene + O2
retinal
show the reaction diagram
Q9HAY6
the enzyme catalyzes the first step in the synthesis of vitamin A from dietary carotenoids. May also play a role in peripheral vitamin A synthesis from plasma-borne provitamin A carotenoids
-
-
?
beta-carotene + O2
retinal
show the reaction diagram
-
the enzyme is responsible for providing vertebrates with vitamin A by catalyzing oxidative cleavage of beta-carotene at its central double bond to two molecules of retinal in intestinal cells
-
-
?
beta-carotene + O2
retinal
show the reaction diagram
Q9JJS6
enzyme may play a critical role in gastrulation
-
-
?
beta-carotene + O2
retinal
show the reaction diagram
Q9I993
key enzyme in the metabolism of beta,beta-carotene to vitamin A
-
-
?
beta-carotene + O2
retinal
show the reaction diagram
-
enzyme plays an important role in retinoid synthesis. BCDO may also be a candidate gene for retinal degenerative disease
-
-
?
beta-carotene + O2
retinal
show the reaction diagram
-
key enzyme in metabolism of provitamin A carotenoids to retinal
-
-
?
beta-carotene + O2
retinal
show the reaction diagram
-
the enzyme catalyzes the first step in conversion of dietary provitamin A carotenoids to vitamin A. The finding that the enzyme is expressed in all epithelia examined leads to the suggestion that BCO1 may be important for local synthesis of vitamin A, constituting a back-up pathway of vitamin A synthesis during times of insufficient dietary intake of vitamin A
-
-
?
beta-carotene + O2
retinal
show the reaction diagram
-
the enzyme catalyzes the first step of vitamin A biosynthesis from provitamin A carotenoids
-
-
?
beta-carotene + O2
retinal
show the reaction diagram
Q90WH4
the enzyme is essential for pattern formation and differentation during zebrafish embryogenesis
-
-
?
beta-carotene + O2
retinal
show the reaction diagram
-
two molecules retinal are formed
-
-
?
beta-carotene + O2
retinal
show the reaction diagram
-
two molecules retinal are formed
-
-
?
beta-carotene + O2
all-trans-retinal
show the reaction diagram
-
BCMO1 is a key enzyme in the pathway of retinoid synthesis from carotenoids, and is responsible for metabolically limiting the amount of intact beta-carotene that can be absorbed by mice from their diet, regulation of BCMO1 activity, overview
-
-
?
beta-carotene + O2
all-trans-retinal
show the reaction diagram
-
BCMO1 is a key enzyme in the pathway of retinoid synthesis from carotenoids, regulation of BCMO1 activity, overview
-
-
?
beta-carotene + O2
all-trans-retinal
show the reaction diagram
-
beta-carotene is stored in the fat
-
-
?
beta-carotene + O2
2 retinal
show the reaction diagram
-
-
-
-
?
beta-carotene + O2
2 retinal
show the reaction diagram
-
-
-
-
?
beta-carotene + O2
2 retinal
show the reaction diagram
-
-
-
-
?
beta-carotene + O2
2 retinal
show the reaction diagram
-
-
-
-
?
beta-carotene + O2
2 all-trans-retinal
show the reaction diagram
-
-
-
-
?
beta-carotene + O2
2 all-trans-retinal
show the reaction diagram
Q9JJS6
-
-
-
?
beta-carotene + O2
2 all-trans-retinal
show the reaction diagram
-
-
-
-
?
beta-carotene + O2
2 all-trans-retinal
show the reaction diagram
Q9HAY6
-
-
-
?
beta-carotene + O2
2 all-trans-retinal
show the reaction diagram
-
-
-
-
?
beta-carotene + O2
2 all-trans-retinal
show the reaction diagram
Q9HAY6
-
-
-
?
beta-carotene + O2
2 all-trans-retinal
show the reaction diagram
-
-
-
-
?
beta-carotene + O2
2 all-trans-retinal
show the reaction diagram
G1SEP0
-
-
-
?
beta-carotene + O2
2 all-trans-retinal
show the reaction diagram
Q91XT5
-
-
-
?
beta-carotene + O2
2 all-trans-retinal
show the reaction diagram
H0VRY9
-
-
-
?
beta-carotene + O2
2 all-trans-retinal
show the reaction diagram
Mus musculus C57/BL6/129 Sv
Q9JJS6
-
-
-
?
additional information
?
-
-
beta-carotene but not all-trans-retinol is converted to all-trans-retinoic acid in mature adipocytes
-
-
-
additional information
?
-
-
25-hydroxycholesterol is a secondary autoxidation product derived from 3beta-hydroxy-cholest-5-ene-25-hydroperoxide, a hydroperoxide identified in air-aged cholesterol
-
-
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
-
recombinant BCMO1 does not require cofactors
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Fe2+
-
activates; maximal activation, 5.8fold, at 1 mM
Fe2+
-
activates
Fe2+
-
the enzyme is a non-heme iron oxygenase
Fe2+
H0VRY9
the enzyme requires Fe2+ as an essential cofactor that binds to four conserved histidine residues in the active centre
Fe2+
-
the enzyme requires Fe2+ as an essential cofactor that binds to four conserved histidine residues in the active centre
Fe2+
-
the enzyme requires Fe2+ as an essential cofactor that binds to four conserved histidine residues in the active centre. Fe2+ is coordinated by the four histidines, water and molecular oxygen forming an octahedral arrangement with cation-pi stabilisation by Y235 and Y326 in the BCMO1 active site
Fe2+
G1SEP0
the enzyme requires Fe2+ as an essential cofactor that binds to four conserved histidine residues in the active centre
Fe2+
Q91XT5
the enzyme requires Fe2+ as an essential cofactor that binds to four conserved histidine residues in the active centre
Iron
-
the iron-dependent enzyme is sensitive to copper status in vivo
Iron
Q9JJS6
required
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1,1'-biphenyl
-
-
1,10-phenanthroline
-
-
1,10-phenanthroline
-
-
1,10-phenanthroline
-
-
1,10-phenanthroline
-
-
13-cis-retinal
-
-
15,15'-Dehydro-beta-apo-10'-carotenol
-
inhibits reaction with beta-apo-10'-carotenol
2,2'-dipyridyl
-
-
2,2'-dipyridyl
-
-
2,2'-dipyridyl
-
-
2,2'-dipyridyl
-
slight inhibition
2,6-di-tert-butyl-4-methylphenol
-
0.001 mM, strong mixed-type inhibition
3,5-di-tert-butyltoluene
-
-
3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate
-
at 0.245%
8-hydroxyquinoline
-
-
9-cis retinoic acid
-
suppresses the upregulation by vitamin A deficiency
9-cis-retinal
-
-
all-trans retinal
-
-
all-trans retinoic acid
-
suppresses the upregulation by vitamin A deficiency
apo-8'-carotenal
-
-
-
astaxanthin
-
competitive
beta-carotene
-
-
butylated hydroxyanisole
-
moderate inhibition
canthaxanthin
-
mixed inhibition
curcumin
-
moderate inhibition
Desferrioxamine
-
noncompetitive inhibitor
Diphenylamine
-
non-competitive inhibition
EDTA
-
0.02 mM, very slight inhibition
EDTA
-
slight inhibition
Fe2+
-
4 mM, 60% inhibition
fenretinide
-
selectively inhibits the anti-adipogenic effects of beta,beta-carotene via inhibition of BCMO
hexaethylene glycol monooctyl ether
-
at 0.195-0.78%
-
iodoacetate
-
-
lutein
-
competitive
luteolin
-
remarkable noncompetitive inhibition
n-octyl-beta-D-thioglucopyranoside
-
at 0.56%
n-propyl gallate
-
moderate inhibition
Na-arsenite
-
-
nordihydroguaiaretic acid
-
moderate inhibition
o-Iodosobenzoate
-
-
p-hydroxymercuribenzoate
-
-
PCMB
-
reversed by glutathione
PCMB
-
-
phenanthrene
-
-
phloretin
-
remarkable noncompetitive inhibition
quercetin
-
remarkable noncompetitive inhibition
retinyl acetate
-
-
Rhamnetin
-
remarkable noncompetitive inhibition
SDS
-
required for maximal activity
sodium arsenide
-
-
Sodium glycocholate
-
-
tetraethylene glycol monooctyl ether
-
at 0.125-0.5%
-
zeaxanthin
-
non-competitive
lycopene
-
competitive
additional information
-
catechol structure of the ring B and a planar flavone structure are essential for inhibition
-
additional information
-
no inhibition by cyanide
-
additional information
-
influence of different types of fats on intestinal and hepatic BCMO1 activity, overview
-
additional information
-
no inhibition by EDTA
-
additional information
-
addition of detergents fails to increase BCMO1 enzymatic activity, but short chain aliphatic detergents such as C8E4 and C8E6 decrease enzymatic activity probably by interacting with the substrate binding site
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1-S-octyl-beta-D-thioglucopyranoside
-
detergent required, maximal activity at 1% w/v
apo-12'-carotenal
-
-
glycocholate
-
plus lecithin, stimulates
GSH
-
activates
GSH
-
stimulates
GSH
-
thiol-dependent enzyme
GSH
-
-
hexadecyl trimethyl ammonium bromide
-
stimulates
lecithin
-
plus glycocholate, stimulates
lecithin
-
egg or plant lecithin stimulates
linoleic acid
-
stimulates
lysolecithin
-
lysolecithin, stimulates
octyl beta-glucoside
-
detergent required
oleyl acid phosphate
-
stimulates
palmitic acid
-
stimulates
SDS
-
2-6 mg, stimulates
SDS
-
stimulates
SDS
-
detergent required, low activation
Sodium cholate
-
detergent required
sodium dodecyl phosphate
-
stimulates
Sodium glycocholate
-
optimum concentration is 6 mM
sphingomyelin
-
stimulates
Triton X-100
-
detergent required
Tween 20
-
stimulates
Tween 40
-
stimulates
Tween 80
-
stimulates
type I cellular retinol-binding protein
-
i.e. RBP1, RBP1, but not RBP2, is required for the transport of water-insoluble substrates of retinoid pathway enzymes, e.g. of BCMO1, into the cell, and acts as an intracellular sensor of retinoid status that, when present as apo-RBP1, stimulates BCMO1 activity and the conversion of carotenoids to retinoids
-
monoolein
-
significant stimulation
additional information
-
the enzyme is completely inactive in absence of any added bile salt or detergent
-
additional information
-
maximal reaction by addition of an appropriate combination of detergent and bile salt, SDS, and egg lecithin
-
additional information
-
influence of different types of fats on intestinal and hepatic BCMO1 activity, overview
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0092
10'-apo-beta-carotenal
-
-
0.0035
13-cis-beta-carotene
-
-
0.0077
8'-apo-beta-carotenal
-
-
0.0085
8'-apo-beta-carotenal
-
-
0.0057
all-trans-beta-carotene
-
-
0.0062
alpha-carotene
-
-
0.02213
alpha-carotene
-
-
0.37
alpha-carotene
-
-
0.0095
beta,beta-carotene
-
-
0.067
beta-apo-10'-carotenol
-
-
-
0.18
beta-apo-4'carotenal
-
-
0.19
beta-apo-8'carotenal
-
-
0.00052 - 0.0059
beta-carotene
-
pH 7.7, 37C
0.0009
beta-carotene
Q9JJS6
mutant E140A, pH 8.0, 37C
0.0012
beta-carotene
Q9JJS6
wild-type, pH 8.0, 37C
0.0013 - 0.0056
beta-carotene
-
pH 7.8-8.2, 37C
0.0016
beta-carotene
-
-
0.0023
beta-carotene
Q9JJS6
mutant E450A, pH 8.0, 37C
0.0027
beta-carotene
Q9JJS6
mutant H58A, pH 8.0, 37C
0.0033
beta-carotene
-
intestinal enzyme
0.0033
beta-carotene
-
-
0.0033
beta-carotene
Q9JJS6
mutant E314A, pH 8.0, 37C
0.0047
beta-carotene
Q9JJS6
mutant D52A, pH 8.0, 37C
0.006 - 0.031
beta-carotene
-
pH 7.5-8.0, 37C, recombinant enzyme
0.006
beta-carotene
-
pH 7.5-8.0, 37C, recombinant enzyme
0.0071
beta-carotene
-
-
0.0104
beta-carotene
-
-
0.0123
beta-carotene
-
mutant R267S
0.0137 - 0.0148
beta-carotene
-
recombinant enzyme, pH 7.5, temperature not specified in the publication
0.0172
beta-carotene
Q9HAY6
recombinant His6-tagged enzyme, pH and temperature not specified in the publication
0.0179
beta-carotene
-
mutant R267S
0.0183
beta-carotene
-
wild-type
0.0195
beta-carotene
-
R267S/R267S double mutant
0.026
beta-carotene
-
-
0.026
beta-carotene
-
pH 7.5-8.0, 37C, recombinant enzyme
0.028
beta-carotene
-
T381L mutant
0.03
beta-carotene
-
pH 8.0, 37C, recombinant wild-type enzyme
0.031
beta-carotene
-
wild-type
0.088
beta-carotene
-
pH 8.0, 37C, recombinant mutant K108L
0.215
beta-carotene
-
pH 8.0, 37C, recombinant mutant K108F
0.0067
beta-cryptoxanthin
-
-
0.03
beta-cryptoxanthin
-
-
0.29
beta-cryptoxanthin
-
-
0.69
gamma-carotene
-
-
additional information
additional information
-
Michaelis-Menten kinetics of wild-type enzyme and mutants K108L and K108F with beta-carotene and beta-apo-8'-carotenal, overview
-
additional information
additional information
-
Michaelis-Menten kinetics, overview
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00817
alpha-carotene
-
-
0.0083
alpha-carotene
-
-
0.015
beta-apo-4'-carotenal
-
-
0.0183
beta-apo-8'-carotenal
-
-
0.0001
beta-carotene
-
-
0.00867
beta-carotene
-
-
0.011
beta-carotene
-
-
0.0275
beta-carotene
-
-
0.0395
beta-carotene
-
pH 8.0, 37C, recombinant mutant K108L
0.04
beta-carotene
-
pH 8.0, 37C, recombinant mutant K108F
0.046
beta-carotene
-
pH 8.0, 37C, recombinant wild-type enzyme
7.5 - 8.5
beta-carotene
-
recombinant enzyme, pH 7.5, temperature not specified in the publication
0.0333
beta-cryptoxanthin
-
-
0.668
beta-cryptoxanthin
-
-
0.0082
gamma-carotene
-
-
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.1016
beta-carotene
Q9HAY6
recombinant His6-tagged enzyme, pH and temperature not specified in the publication
858
0.17
beta-carotene
-
pH 8.0, 37C, recombinant mutant K108F
858
0.45
beta-carotene
-
pH 8.0, 37C, recombinant mutant K108L
858
1.52
beta-carotene
-
pH 8.0, 37C, recombinant wild-type enzyme
858
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00079
2,6-di-tert-butyl-4-methylcatechol
-
-
-
0.1187
3,5-di-tert-butyltoluene
-
-
0.0474
butylated hydroxyanisole
-
-
0.0016
canthaxanthin
-
-
0.0169
curcumin
-
-
0.0133
luteolin
-
-
0.0099
phloretin
-
-
0.0058
Rhamnetin
-
-
0.0078
zeaxanthin
-
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.000036
-
-
0.001
-
R267S/A379V double mutant
0.0022
Q9HAY6
purified recombinant His6-tagged enzyme, pH and temperature not specified in the publication
0.0023
-
wild-type
0.01
-
crude extract
0.16
-
purification step His-Trap HP
0.32
-
purification step Resource Q
0.51
-
pH 9.0, 36C
1.97
-
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.5
-
activity assay
7.5
-
assay at
7.6
-
activity assay
7.7
-
assay at
7.8 - 8.2
-
-
7.8
-
reaction with beta-apo-10'-carotenol
8
-
activity assay
8
-
activity assay
8
-
activity assay
8
-
assay at
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7 - 8.5
-
pH 7.0: about 60% of maximal activity, pH 8.5: about 75% of maximal activity
7 - 9
-
pH 7.0: about 50% of maximal activity, pH 9.0: about 35% of maximal activity, reaction with beta-apo-10'-carotenol
8.5
-
70% of maximum activity
10
-
70% of maximum activity
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
28
-
activity assay
28
-
activity assay
37
-
assay at
37
-
activity assay
37
-
activity assay
37
-
activity assay
37
-
assay at
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
25
-
22% of maximum activity
45
-
14% of maximum activity
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
a preadipocyte cell line
Manually annotated by BRENDA team
Q9HAY6
immunostaining of CMO1 in the A549 cells, overview
Manually annotated by BRENDA team
-
human kidney cell line
Manually annotated by BRENDA team
Rattus norvegicus Zucker
-
-
-
Manually annotated by BRENDA team
-
steroidogenic cells
Manually annotated by BRENDA team
-
lower levels
Manually annotated by BRENDA team
-
intestinal cell line Caco-2/subclone TC7
Manually annotated by BRENDA team
-
when TC7 cells are maintained in serum-free medium, activity is increased 8.2fold after 19 days of postconfluence
Manually annotated by BRENDA team
-
for cloning of full-length BCMO1, RNA is isolated from Caco-2/TC7 cells
Manually annotated by BRENDA team
-
lower levels
Manually annotated by BRENDA team
-
glandular cell
Manually annotated by BRENDA team
-
in epithelial cells of the mucosa, quantitative RT-PCR expression analysis, and in situ hybridization
Manually annotated by BRENDA team
-
mRNA is abundant at embryonic day 7, with lower expression at embryonic days 11, 13 and 15
Manually annotated by BRENDA team
-
of several tissues including stomach, intestine, colon, prostate glands, and endometrium
Manually annotated by BRENDA team
-
expression is eye-dependent
Manually annotated by BRENDA team
Clarias batrachus, Domania subtryug
-
mucosa
Manually annotated by BRENDA team
-
high levels of BCO mRNA, highest level in jejunum
Manually annotated by BRENDA team
-
pylorus to the lower ileum
Manually annotated by BRENDA team
-
activity is 20-30% greater in vitamin-A deficient animals than in the controls
Manually annotated by BRENDA team
-
activity detected in two subclones of Caco-2, PF11 and TC7. When TC7 cells are maintained in serum-free medium, activity is increased 8.2fold after 19 days of postconfluence. No activity detected in IPEC-1, HepG2, HL60, Wurzburg, or parent Caco-2, PF11 and TC7
Manually annotated by BRENDA team
-
highest expression in duodenum, mRNA level in ileum is markedly low
Manually annotated by BRENDA team
-
activity of enzyme in intestinal mucosa is higher after feeding with oleic acid or eicosapentanoic acid than with linoleic acid
Manually annotated by BRENDA team
-
high expression, expression in small intestine is increased by vitamin A deficiency. Upregulation is suppressed by all-trans retinoic acid or 9-cis retinoic acid
Manually annotated by BRENDA team
Rattus norvegicus Zucker
-
-
-
Manually annotated by BRENDA team
-
of the squamous epithelium of skin
Manually annotated by BRENDA team
-
of skin squamous epithelium
Manually annotated by BRENDA team
-
low expression
Manually annotated by BRENDA team
-
high levels of BCO mRNA
Manually annotated by BRENDA team
-
only marginal activity
Manually annotated by BRENDA team
-
elevated levels of mRNA
Manually annotated by BRENDA team
-
high level, in distal and proximal tubular structures
Manually annotated by BRENDA team
-
high levels of BCO mRNA
Manually annotated by BRENDA team
-
expression is increased by feeding animals with a PPARalpha/gamma agonist
Manually annotated by BRENDA team
-
parenchymal cell
Manually annotated by BRENDA team
-
high expression, expression is suppressed by all-trans retinoic acid
Manually annotated by BRENDA team
-
diffuse distribution in the lobules, quantitative RT-PCR expression analysis and in situ hybridization
Manually annotated by BRENDA team
-
elevated levels of mRNA
Manually annotated by BRENDA team
Mus musculus C57/BL6/129 Sv
-
-
-
Manually annotated by BRENDA team
-
high expression, expression is increased by vitamin A deficiency. Upregulation is suppressed by all-trans retinoic acid or 9-cis retinoic acid
Manually annotated by BRENDA team
-
elevated levels of mRNA
Manually annotated by BRENDA team
-
of stomach
Manually annotated by BRENDA team
-
predominantly expressed in ocellus photoreceptor cells of the larva
Manually annotated by BRENDA team
-
low levels of BCO mRNA
Manually annotated by BRENDA team
-
lower levels
Manually annotated by BRENDA team
-
steroidogenic cells
Manually annotated by BRENDA team
-
cell that make up exocrine glands
Manually annotated by BRENDA team
-
cells comprising the exocrine gland
Manually annotated by BRENDA team
-
glandular cell
Manually annotated by BRENDA team
-
glandular cells
Manually annotated by BRENDA team
-
low levels of BCO mRNA
Manually annotated by BRENDA team
-
enzyme is highly expressed in retinal pigment epithelium
Manually annotated by BRENDA team
-
low levels of BCO mRNA
Manually annotated by BRENDA team
-
keratinocytes of the squamous epithelium
Manually annotated by BRENDA team
-
high enzyme expression
Manually annotated by BRENDA team
Mus musculus C57/BL6/129 Sv
-
high enzyme expression
-
Manually annotated by BRENDA team
-
mucosa, glandular cells
Manually annotated by BRENDA team
-
mucosal and glandular cells
Manually annotated by BRENDA team
-
low expression
Manually annotated by BRENDA team
-
low levels of BCO mRNA
Manually annotated by BRENDA team
-
steroidogenic cells
Manually annotated by BRENDA team
-
Leydig and Sertoli cells
Manually annotated by BRENDA team
additional information
-
no expression in lung
Manually annotated by BRENDA team
additional information
-
no activity is detected in adult stomach tissue
Manually annotated by BRENDA team
additional information
-
enzyme activity is similar in the duodenum, but pigmented animals have higher enzyme activity in the liver, eevnthough not high enough to prevent the storage of beta-carotene in adipose tissues
Manually annotated by BRENDA team
additional information
-
BCMO1 expression in the exocrine portion of the pancreas, epidermis of the skin, and ciliary body pigment epithelia and RPE of the eye
Manually annotated by BRENDA team
additional information
-
quantitative reverse-transcriptase PCR enzyme expression analysis
Manually annotated by BRENDA team
additional information
Q9HAY6
real-time quantitative RT-PCR enzyme expression analysis
Manually annotated by BRENDA team
additional information
-
tissue levels of all-trans-retinoic acid in wild-type and enzyme-deficient mice, real-time RT-PCR enzyme expression analysis, overview
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
BCMO1 is soluble and its enzymatic activity is not dependent on a membrane-like environment
-
Manually annotated by BRENDA team
Mus musculus C57/BL6/129 Sv
-
-
-
Manually annotated by BRENDA team
additional information
-
determination of BCMO1 subcellular localization in mouse liver, overview
-
Manually annotated by BRENDA team
additional information
Mus musculus C57/BL6/129 Sv
-
determination of BCMO1 subcellular localization in mouse liver, overview
-
-
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
50000
-
gel filtration
438230
57800
-
theoretical
700967
60000
-
determined by SDS-PAGE
696908
60000
-
recombinant enzyme with C-terminal TEV-, His6- and 1D4-tags, gel filtration
726818
61210
-
theoretical, plus hexahistidine tag
696908
62000
-
theoretical
696901
62000
-
determined by SDS-PAGE and Western Blot analysis
697854
63000
-
determined by SDS-PAGE
696914
63400
-
theoretical, His-tagged protein
696914
63400
-
theoretical
697854
64000
-
determined by SDS-PAGE and Western Blot analysis
700967
65000
-
determined by SDS-PAGE
696901
230000
-
gel filtration
438228
240000
-
determined by gel filtration
696908
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
-
x * 63000, SDS-PAGE
?
-
x * 64000, SDS-PAGE
?
-
x * 63859, calculation from nucleotide sequence
?
-
x * 64686, calculated, x * 65000, SDS-PAGE
?
-
x * 100000-20000
?
-
x * 100000-200000
?
-
x * 240000, recombinant enzyme
?
-
x * 63000, recombinant enzyme
?
-
x * 64000, recombinant enzyme
?
Q9HAY6
x * 63702, His-tagged enzyme, sequence calculation
homotetramer
-
4 * 60000
monomer
-
-
monomer
-
1 x 65200, recombinant enzyme with C-terminal TEV-, His6- and 1D4-tags, SDS-PAGE
tetramer
-
-
monomer
Mus musculus C57/BL6/129 Sv
-
-
-
additional information
-
BCMO three-dimensional structure, with entrance of active tunnel and the hydrophobic patch, including Pro101, Cys102, Ile105, Phe106, Lys108, Leu258, Thr262, and Tyr264, modelling, overview
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
52
-
3 min, no effect
438235
64
-
55 seconds, complete inactivation of intestinal enzyme
438226
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
loss of activity during concentration by ultrafiltration or (NH4)2SO4 precipitation as well as during dialysis
-
carotenoids stabilize the enzyme during the isolation from small intestinal mucosa
-
liver enzyme may be frozen and thawed repeatedly without loss of activity
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20C, as (NH4)2SO4 precipitate, 25-55%, for one month without considerable loss in activity
-
-20C, 40% glycerol and presence of protease inhibitors, enzyme purified by metal affinity chromatography is stable for several weeks
Q9JJS6
-20C, as (NH4)2SO4 precipitate, 25-55%, for one month without considerable loss in activity
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
by affinity chromatography
-
by His-Trap HP affinity and Resource Q ion exchange chromatography
-
affinity purified via the His-tag
-
recombinant BCO1 with a C-terminal polyhistidine tag from Escherichia coli strain BL21-Gold(DE3) by cobalt affinity chromatography
Q9HAY6
recombinant enzyme from Escherichia coli by affinity and anion exchange chromatography
-
recombinant enzyme with C-terminal TEV-, His6- and 1D4-tags from Spodoptera frugiperda Sf9 cells by Co2+ affinity chromatography and gel filtration in absence of detergent
-
recombinant His-tagged enzyme from Escherichia coli by nickel affinity chromatography
-
using a His-Trap HP affinity chromatography column
-
using a HiTrap Chelating HP column
-
native enzyme partially from Stellate cell cytosol
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
tissue-specific quantitative RT-PCR expression analysis
-
-
Q90WH4
for expression in Escherichia coli cells, genetically engineered to produce beta-carotene
Q9VFS2
into the vectors pCRII TOPO and pBAD-TOPO for expression in Escherichia coli XL1-blue cells
-
expression in Escherichia coli and in CHO cells
-
into the vector pET-24a+ for expression in Escherichia coli ER2566 cells
-
baculovurus expressed
-
BCMO gene, DNA and mino acid sequence determination and analysis, expression in Escherichia coli strain ER2566
-
EST library screening, DNA and amino acid sequence determination and analysis, expression of His-tagged enzyme in Escherichia coli
-
expression by an baculovirus/Spodoptera frugiperda 9 insect cell system
-
expression of BCO1 with a C-terminal polyhistidine tag in Escherichia coli strain BL21-Gold(DE3)
Q9HAY6
gene BCMO1, expression of enzyme with C-terminal C-terminal TEV-, His6- and 1D4-tags in Spodoptera frugiperda Sf9 cells using the baculovirus transfection method
-
identification of ligand binding sites on the bcmo1 promoter, transcriptional regulation, overview
-
into a Flag fusion-modified mammalian expression vector pcDNA3 and into the bacterial vectors pET-15b and pGEX-4T2
-
into the pCR Blunt vector and subsequently into the pTrcHis vector for sequencing and expression in Escherichia coli cells
-
into the vector pET-24b+ for expression in Escherichia coli ER2566 cells
-
quantitative reverse-transcriptase PCR enzyme expression analysis
-
real-time quantitative RT-PCR enzyme expression analysis
Q9HAY6
expression in Escherichia coli
-
for expression in Escherichia coli cells, genetically engineered to produce beta-carotene
-
gene bcmo1, quantitative real time PCR expression analysis. The murine Bcmo1 promoter contains a DR1-type peroxisome proliferator-response element that binds Ppargamma/Rxr heterodimers. Recombinant expression of Bcmo1 in Escherichia coli
-
real-time RT-PCR enzyme expression analysis
-
the proximal promoter of the mouse Bcm gene contains a PPRE site that specifically binds PPARgamma and regulates transcriptional expression of Bcm. This element is functional in vitro and confers peroxisome proliferator responsiveness, using specific PPARgamma and RXR agonists
-
gene bcmo1, DNA and amino acid sequence determination and analysis; gene bco2, DNA and amino acid sequence determination and analysis of wild-type and mutant enzymes, genotyping, overview
C1L3B1, C7C6F6
from intestinal cDNA library
-
gene BCM, quantitative expression analysis, overview
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
all-trans-retinal does not affect liver bcmo1 expression
-
all-trans-retinal at 0.001 mM suppresses bcmo1 expression
-
exposure to beta-carotene suppresses CMO1 expression at both mRNA and protein levels. beta-Carotene, but not all-trans retinoic acid, decreases CMO1 promoter activity in a time- and dosage-dependent manner. This beta-carotene-mediated inhibition of CMO1 expression results from decreased binding of peroxisome proliferator-activated receptor gamma and retinoid X receptor alpha in the CMO1 promoter
Q9HAY6
beta-carotene and all-trans-retinal at 10-100 nM induces bcmo1 expression
-
Isx, intestine specific homeobox, participates in the maintenance of vitamin A by regulating Bcmo1 expression in the intestine
-
Bcmo1 expression is induced during adipocyte differentiation
-
severe vitamin A deficiency markedly decreases intestine-specific transcription factor intestine-specific homeobox expression accompanied by an increase in BCMO1 expression in duodenum and jejunum
-
BCM gene expression in the liver and intestines of puromycin aminonucleoside-treated rats is decreased
-
all-trans-retinal suppresses liver, lung and testis bcmo1 expression, and 9-cis-retinal in lung and testis, in vitamin A-deficient rats
-
BCM gene expression in the kidney of puromycin aminonucleoside-treated rats is increased
-
intestinal BCM gene expresssion is increased in obese and dyslipedemic rats
-
chronic alcohol intake significantly upregulates hepatic BCMO1 expression in rats, possibly mediated via PPAR-gamma
Q91XT5
intestinal BCM gene expresssion is increased in obese and dyslipedemic rats
Rattus norvegicus Zucker
-
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
A379V
-
single nucleotide polymorphism, allele frequency 24%, recombinant mutant
A379V
-
naturally occuring polymorphism, the mutation causes 33% reduced BCMO1 activity compared to wild-type in vitro and 32% reduced conversion of beta-carotene after a pharmacological dose in female volunteers
K108F
-
site-directed mutagenesis, the mutant shows highly decreased affinity for substrates with ionone rings at both ends, such as alpha-carotene, beta-carotene, and beta-cryptoxanthin, and a 7.2fold increased Km for beta-carotene compared to the wild-type enzyme. But the mutation has little effect on the affinity of the enzyme for substrates with one ionone ring and one open-chain end, such as beta-apo-4'-carotenal and beta-apo-8'-carotenal
N329T
-
naturally occuring polymorphism
R228C
-
naturally occuring polymorphism
R267S
-
single nucleotide polymorphism, allele frequency 42%, recombinant mutant
R267S
-
naturally occuring polymorphism, the mutation does not show any effect on BCMO1 activity in vitro and in vivo
R267S/A379V
-
recombinant double mutant, reveals a reduced catalytic activity by 57%
R267S/A379V
-
naturally occuring polymorphism, the mutation causes 57% reduced BCMO1 activity compared to wild-type in vitro and 69% reduced conversion of beta-carotene after a pharmacological dose in female volunteers
R537K
-
naturally occuring polymorphism
T170M
-
naturally occuring polymorphism, the mutant shows 90% reduced BCMO1 activity compared to wild-type in vitro causing hypercarotenemia and hypovitaminose A
T381L
-
mutant, shows 1.5fold higher catalytic efficiency for beta-carotene and 1.7fold higher retinal production than the wild-type
T381L
-
naturally occuring polymorphism, the mutant shows 75% increased BCMO1 activity compared to wild-type in vitro
T382P
-
naturally occuring polymorphism
Y236S
-
naturally occuring polymorphism
D52A
Q9JJS6
more than 50% loss of activity
D52A/E140A
Q9JJS6
no enzymatic activity
E140A
Q9JJS6
more than 50% loss of activity
E314A
Q9JJS6
little reduction in enzymatic activity
E405A
Q9JJS6
no enzymatic activity
E450A
Q9JJS6
little reduction in enzymatic activity
E457A
Q9JJS6
about 80% loss of activity
E469A
Q9JJS6
about 50% decrease in activity, cells are bleached when left growing overnight
H172A
Q9JJS6
no enzymatic activity
H174A
Q9JJS6
little reduction in enzymatic activity
H237A
Q9JJS6
no enzymatic activity
H308A
Q9JJS6
no enzymatic activity
H309A
Q9JJS6
little reduction in enzymatic activity
H49A
Q9JJS6
little reduction in enzymatic activity
H514A
Q9JJS6
no enzymatic activity
additional information
-
targeted knockdown of enzyme results in microphthalmia at larval stages. Photoreceptors in the central retina show shortened outer segments, and electron dense debris in their intermembranal space. The number of phagosomes is increased and cell death is frequently observed in the outer nuclear layer. The number of Mller cells is significantly reduced in the inner nuclear layer
K108L
-
site-directed mutagenesis, the mutant shows highly decreased affinity for substrates with ionone rings at both ends, such as alpha-carotene, beta-carotene, and beta-cryptoxanthin, and a 2.9fold increased Km for beta-carotene compared to the wild-type enzyme. But the mutation has little effect on the affinity of the enzyme for substrates with one ionone ring and one open-chain end, such as beta-apo-4'-carotenal and beta-apo-8'-carotenal
additional information
-
LoVo cells are transfected with either BCMO1 siRNA or scrambled siRNA. BCMO1 siRNA knockdown increases migration and invasion in LoVo cells and increased the expression of MMP7 and MMP28
H58A
Q9JJS6
little reduction in enzymatic activity
additional information
-
phenotype of enzyme-deficient mice, beta-carotene conversion is blocked in BCMO1-deficient mice, comparison of plasma retinol and liver retinyl esters of wild-type, heterozygous and homozygous BCMO1-deficient mice, overview
additional information
-
mutations in any of the four conserved histidine residues His172, His237, His308 and His514 or Glu405 result in the total loss of BCMO1 activity
additional information
-
subjection of wild type, Bco1-/-, Bco2-/-, and Bco1-/-/Bco2-/- double knock-out mice to a controlled diet providing beta-carotene as the sole source for apocarotenoid production
Renatured/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
reconstitution of recombinant Bcmo1 from Escherichia coli in micelles formed by n-octyl-beta-D-thioglucopyranoside
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
analysis
-
BCMO function in mammalian cells is analyzed by a retinoic acid receptor assay, which responds to the metabolic conversion of beta-carotene to retinoic acid in vivo, this tool can be used to screen more active BCMO for the industrial and pharmacological purpose of retinal production from beta-carotene
synthesis
-
production of retinal from beta-carotene using recombinant enzyme. The optimum pH, temperature, substrate and detergent concentrations, and enzyme amount for effective retinal production are 9.0, 37C, 200 mg per ml beta-carotene, 5% w/v Tween 40, and 0.2 U per ml enzyme, respectively. Under optimum conditions, the recombinant enzyme produces 72 mg per ml retinal in a 15 h reaction time, with a conversion yield of 36% w/w
synthesis
-
stepwise cleavage by BCO2, i.e. beta-carotene-9',10'-oxygenase, and BCO1 with beta-apo-10'-carotenol as an intermediate can provide a mechanism to tailor asymmetric carotenoids such as beta-cryptoxanthin for vitamin A production
diagnostics
C1L3B1, C7C6F6
genotyping AI rams for c.196C-T can be used in selection against the yellow fat trait
medicine
-
Modulation of intestinal beta-carotene uptake and its conversion to vitamin A using specific fatty acids. Improved absorption and metabolism of beta-carotene by feeding mixed micelles with oleic acid or eicosapentanoic acid compared with linoleic acid
medicine
-
BCM gene expression in the liver and intestine might affect retinol levels in type 2 diabetes
medicine
-
changes in the metabolism of retinol and beta-carotene might have an important role in the protection against the development of nephrosis