Information on EC 1.13.11.63 - beta-carotene 15,15'-dioxygenase

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The expected taxonomic range for this enzyme is: Eukaryota, Bacteria

EC NUMBER
COMMENTARY hide
1.13.11.63
-
RECOMMENDED NAME
GeneOntology No.
beta-carotene 15,15'-dioxygenase
-
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
beta-carotene + O2 = 2 all-trans retinal
show the reaction diagram
beta-carotene + O2 = 2 all-trans-retinal
show the reaction diagram
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-
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
oxidation
reduction
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Metabolic pathways
-
-
retinol biosynthesis
-
-
Retinol metabolism
-
-
SYSTEMATIC NAME
IUBMB Comments
beta-carotene:oxygen 15,15'-dioxygenase (bond-cleaving)
Requires Fe2+. The enzyme cleaves beta-carotene symmetrically, producing two molecules of all-trans-retinal. Both atoms of the oxygen molecule are incorporated into the products [8]. The enzyme can also process beta-cryptoxanthin, 8'-apo-beta-carotenal, 4'-apo-beta-carotenal, alpha-carotene and gamma-carotene in decreasing order. The presence of at least one unsubstituted beta-ionone ring in a substrate greater than C(30) is mandatory [5]. A prokaryotic enzyme has been reported from the uncultured marine bacterium 66A03, where it is involved in the proteorhodopsin system, which uses retinal as its chromophore [6,7].
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
Domania subtryug
-
-
-
Manually annotated by BRENDA team
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
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
physiological function
-
crucial enzyme in development and metabolism that governs the de novo entry of vitamin A from plant-derived precursors
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
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
-
-
-
?
9,13-dicis-beta-carotene + O2
?
show the reaction diagram
-
-
-
?
9-13-dicis-beta-carotene + O2
?
show the reaction diagram
-
-
-
?
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
2 all-trans-retinal
show the reaction diagram
alpha-carotene + O2
2 retinal
show the reaction diagram
-
-
-
?
alpha-carotene + O2
?
show the reaction diagram
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
-
-
?
beta-apo-10'-carotenal + O2
?
show the reaction diagram
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
-
-
-
?
beta-apo-4'-carotenal + O2
?
show the reaction diagram
beta-apo-4'-carotenal + O2
retinal + ?
show the reaction diagram
-
one molecule retinal is formed
-
-
?
beta-apo-8'-carotenal + O2
?
show the reaction diagram
beta-apo-8'-carotenal + O2
retinal + ?
show the reaction diagram
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
11-cis-retinal + 13-cis-retinal + all-trans-retinal
show the reaction diagram
-
-
-
?
beta-carotene + O2
13-cis-retinal + all-trans-retinal
show the reaction diagram
-
-
-
-
?
beta-carotene + O2
2 all-trans-retinal
show the reaction diagram
beta-carotene + O2
2 retinal
show the reaction diagram
beta-carotene + O2
all-trans-retinal
show the reaction diagram
beta-carotene + O2
retinal
show the reaction diagram
beta-criptoxanthin + O2
retinal + ?
show the reaction diagram
-
one molecule retinal is formed
-
-
?
beta-cryptoxanthin + O2
2 retinal
show the reaction diagram
-
-
-
?
beta-cryptoxanthin + O2
?
show the reaction diagram
beta-cryptoxanthin + O2
retinal + (3R)-3-hydroxy-retinal
show the reaction diagram
-
-
-
-
?
beta-cryptoxanthin + O2
retinal + (3R)-3-hydroxyretinal
show the reaction diagram
-
-
-
-
?
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
2 all-trans-retinal
show the reaction diagram
-
-
-
-
?
gamma-carotene + O2
?
show the reaction diagram
gamma-carotene + O2
retinal + acycloretinal
show the reaction diagram
-
-
one molecule retinal is formed
-
?
lutein + O2
11-cis-3-hydroxy-retinal + all-trans-3-hydroxy-retinal + all-trans-3-hydroxy-alpha-retinal
show the reaction diagram
-
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39.9% 11-cis-3-hydroxy-retinal + 10.1% all-trans-3-hydroxy-retinal + 47.7% all-trans-3-hydroxy-alpha-retinal
-
?
lycopene + O2
2 acycloretinal
show the reaction diagram
-
-
-
?
zeaxanthin + O2
(3R)-11-cis-3-hydroxyretinal + (3R)-all-trans-3-hydroxyretinal
show the reaction diagram
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
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
2 all-trans-retinal
show the reaction diagram
beta-carotene + O2
2 retinal
show the reaction diagram
beta-carotene + O2
all-trans-retinal
show the reaction diagram
beta-carotene + O2
retinal
show the reaction diagram
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
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-
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
-
recombinant BCMO1 does not require cofactors
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1,1'-biphenyl
-
-
1,10-phenanthroline
13-cis-retinal
-
-
15,15'-Dehydro-beta-apo-10'-carotenol
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inhibits reaction with beta-apo-10'-carotenol
2,2'-dipyridyl
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
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at 0.245%
4-chloromercuribenzoate
4-hydroxymercuribenzoate
8-hydroxyquinoline
-
-
9-cis retinoic acid
-
suppresses the upregulation by vitamin A deficiency
9-cis-retinal
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-
all-trans retinal
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all-trans retinoic acid
-
suppresses the upregulation by vitamin A deficiency
apo-8'-carotenal
-
-
astaxanthin
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competitive
beta-carotene
-
-
butylated hydroxyanisole
-
moderate inhibition
canthaxanthin
-
mixed inhibition
curcumin
-
moderate inhibition
desferrioxamine
-
noncompetitive inhibitor
Diphenylamine
-
non-competitive inhibition
hexaethylene glycol monooctyl ether
-
at 0.195-0.78%
iodoacetamide
lutein
-
competitive
luteolin
-
remarkable noncompetitive inhibition
lycopene
-
competitive
N-ethylmaleimide
n-octyl-beta-D-thioglucopyranoside
-
at 0.56%
n-propyl gallate
-
moderate inhibition
Na-arsenite
-
-
nordihydroguaiaretic acid
-
moderate inhibition
o-Iodosobenzoate
-
-
o-phenanthroline
p-hydroxymercuribenzoate
-
-
phenanthrene
-
-
Phenanthroline
-
2% residual activity
phloretin
-
remarkable noncompetitive inhibition
quercetin
-
remarkable noncompetitive inhibition
retinyl acetate
-
-
Rhamnetin
-
remarkable noncompetitive inhibition
sodium arsenide
-
-
Sodium glycocholate
-
-
tetraethylene glycol monooctyl ether
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at 0.125-0.5%
zeaxanthin
-
non-competitive
additional information
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1-S-octyl-beta-D-thioglucopyranoside
-
detergent required, maximal activity at 1% w/v
2-mercaptoethanol
apo-12'-carotenal
-
-
glycocholate
-
plus lecithin, stimulates
hexadecyl trimethyl ammonium bromide
-
stimulates
lecithin
linoleic acid
-
stimulates
lysolecithin
-
lysolecithin, stimulates
monoolein
-
significant stimulation
octyl beta-glucoside
-
detergent required
oleyl acid phosphate
-
stimulates
palmitic acid
-
stimulates
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
-
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0092
10'-apo-beta-carotenal
-
-
0.0035
13-cis-beta-carotene
-
-
0.0077 - 0.0085
8'-apo-beta-carotenal
0.0057
all-trans-beta-carotene
-
-
0.0062 - 0.37
alpha-carotene
0.067
beta-apo-10'-carotenol
-
-
-
0.147
beta-apo-4'-carotenal
-
pH 8.0, 40°C
0.18
beta-apo-4'carotenal
-
-
0.19
beta-apo-8'carotenal
-
-
0.00052 - 0.215
beta-carotene
0.0067 - 0.29
beta-cryptoxanthin
0.382 - 0.69
gamma-carotene
additional information
additional information
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.001 - 0.0083
alpha-carotene
0.01 - 0.015
beta-apo-4'-carotenal
0.0183
beta-apo-8'-carotenal
Gallus gallus
-
-
0.0001 - 8.5
beta-carotene
0.013 - 0.668
beta-cryptoxanthin
0.0003 - 0.0082
gamma-carotene
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.06
alpha-carotene
uncultured marine bacterium
-
pH 8.0, 40°C
3878
0.07
beta-apo-4'-carotenal
uncultured marine bacterium
-
pH 8.0, 40°C
8731
1.62
beta-carotene
uncultured marine bacterium
-
pH 8.0, 40°C
858
0.47
beta-cryptoxanthin
uncultured marine bacterium
-
pH 8.0, 40°C
3892
0.01
gamma-carotene
uncultured marine bacterium
-
pH 8.0, 40°C
8104
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
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 hide
LITERATURE
0.0022
purified recombinant His6-tagged enzyme, pH and temperature not specified in the publication
0.01
-
crude extract
0.16
-
purification step His-Trap HP
0.32
-
purification step Resource Q
0.51
-
pH 9.0, 36°C
1.97
-
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.5 - 8
-
-
7.5
-
assay at
7.5 - 8
7.6
-
activity assay
7.8 - 8.2
-
-
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7 - 9
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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 hide
LITERATURE
28
-
activity assay
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
45
-
14% of maximum activity
50
-
66% of maximum activity
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
immunostaining of CMO1 in the A549 cells, overview
Manually annotated by BRENDA team
-
human kidney cell line
Manually annotated by BRENDA team
-
of skin squamous epithelium
Manually annotated by BRENDA team
-
predominantly expressed in ocellus photoreceptor cells of the larva
Manually annotated by BRENDA team
-
cells comprising the exocrine gland
Manually annotated by BRENDA team
-
glandular cells
Manually annotated by BRENDA team
-
enzyme is highly expressed in retinal pigment epithelium
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
additional information
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
32000
-
2 * 32000, SDS-PAGE
50000
-
gel filtration
57800
-
theoretical
61210
-
theoretical, plus hexahistidine tag
62000
-
theoretical
63400
-
theoretical, His-tagged protein
63702
x * 63702, His-tagged enzyme, sequence calculation
63859
-
x * 63859, calculated, x * 63000, SDS-PAGE; x * 63859, calculation from nucleotide sequence
64686
-
x * 64686, calculated, x * 65000, SDS-PAGE
230000
-
gel filtration
240000
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
homotetramer
-
4 * 60000
monomer
tetramer
-
-
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 hide
LITERATURE
35
-
half-life 17.6 min
40
-
half-life 15 min
45
-
half-life 12.5 min
64
-
55 seconds, complete inactivation of intestinal enzyme
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
carotenoids stabilize the enzyme during the isolation from small intestinal mucosa
-
liver enzyme may be frozen and thawed repeatedly without loss of activity
-
loss of activity during concentration by ultrafiltration or (NH4)2SO4 precipitation as well as during dialysis
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20°C, 40% glycerol and presence of protease inhibitors, enzyme purified by metal affinity chromatography is stable for several weeks
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
by affinity chromatography
-
by His-Trap HP affinity and Resource Q ion exchange chromatography
-
native and recombinant protein
-
native enzyme partially from Stellate cell cytosol
-
partial
recombinant BCO1 with a C-terminal polyhistidine tag from Escherichia coli strain BL21-Gold(DE3) by cobalt affinity chromatography
recombinant enzyme
-
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
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
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 in Escherichia coli
expression in Escherichia coli and in CHO cells
-
expression in Escherichia coli; expression in Escherichia coli
-
expression of BCO1 with a C-terminal polyhistidine tag in Escherichia coli strain BL21-Gold(DE3)
for expression in Escherichia coli cells, genetically engineered to produce beta-carotene
from intestinal cDNA library
-
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
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 vector pET-24a+ for expression in Escherichia coli ER2566 cells
-
into the vector pET-24b+ for expression in Escherichia coli ER2566 cells
-
into the vectors pCRII TOPO and pBAD-TOPO for expression in Escherichia coli XL1-blue cells
-
quantitative reverse-transcriptase PCR enzyme expression analysis
-
real-time quantitative RT-PCR enzyme expression analysis
tissue-specific quantitative RT-PCR expression analysis
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
mRNA is abundant at embryonic day 7, with lower expression at embryonic days 11, 13, and 15
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
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
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
N329T
-
naturally occuring polymorphism
R228C
-
naturally occuring polymorphism
R267S
-
naturally occuring polymorphism, the mutation does not show any effect on BCMO1 activity in vitro and in vivo
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
T382P
-
naturally occuring polymorphism
Y236S
-
naturally occuring polymorphism
D52A
more than 50% loss of activity
D52A/E140A
no enzymatic activity
E140A
more than 50% loss of activity
E314A
little reduction in enzymatic activity
E405A
no enzymatic activity
E450A
little reduction in enzymatic activity
E457A
about 80% loss of activity
E469A
about 50% decrease in activity, cells are bleached when left growing overnight
H172A
no enzymatic activity
H174A
little reduction in enzymatic activity
H237A
no enzymatic activity
H308A
no enzymatic activity
H309A
little reduction in enzymatic activity
H49A
little reduction in enzymatic activity
H514A
no enzymatic activity
H58A
little reduction in enzymatic activity
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
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
diagnostics
genotyping AI rams for c.196C-T can be used in selection against the yellow fat trait
medicine
synthesis