Information on EC 1.1.1.105 - all-trans-retinol dehydrogenase (NAD+)

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

EC NUMBER
COMMENTARY hide
1.1.1.105
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RECOMMENDED NAME
GeneOntology No.
all-trans-retinol dehydrogenase (NAD+)
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
all-trans-retinol-[cellular-retinol-binding-protein] + NAD+ = all-trans-retinal-[cellular-retinol-binding-protein] + NADH + H+
show the reaction diagram
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
oxidation
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redox reaction
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reduction
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
retinoate biosynthesis I
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Retinol metabolism
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Metabolic pathways
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SYSTEMATIC NAME
IUBMB Comments
all-trans retinol:NAD+ oxidoreductase
The enzyme recognizes all-trans-retinol and all-trans-retinal as substrates and exhibits a strong preference for NAD+/NADH as cofactors. Recognizes the substrate both in free form and when bound to cellular-retinol-binding-protein (CRBP1), but has higher affinity for the bound form [2]. No activity with 11-cis-retinol or 11-cis-retinal (cf. EC 1.1.1.315, 11-cis retinol dehydrogenase). Also active with 3alpha-hydroxysteroids [2].
CAS REGISTRY NUMBER
COMMENTARY hide
9033-53-8
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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Manually annotated by BRENDA team
isoforms 1 and 2
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Manually annotated by BRENDA team
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Manually annotated by BRENDA team
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UniProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
malfunction
metabolism
physiological function
additional information
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N-ethylmaleimide does not affect the catalytic action of RDH1, but interferes with its approach to holo-CRBP1, interrupting retinol transfer. The membrane context of RDH affects function
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-retinol + NAD+
13-cis-retinal + NADH + H+
show the reaction diagram
3,4-didehydroretinol + NAD+
3,4-didehydroretinal + NADH
show the reaction diagram
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60% of the efficiency against all-trans-retinol
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-
?
5alpha-androstan-3alpha-ol-17-one + NAD+
? + NADH
show the reaction diagram
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-
-
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9-cis-retinol + NAD+
9-cis-retinal + NADH + H+
show the reaction diagram
higher activity with all-trans-retinol versus 9-cis-retinol
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-
?
all-trans retinal + NADH + H+
all-trans-retinol + NAD+
show the reaction diagram
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oxidative activity is below the detection limit
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r
all-trans-retinal + NAD(P)H + H+
all-trans-retinol + NAD(P)+
show the reaction diagram
all-trans-retinal + NADH + H+
all-trans-retinol + NAD+
show the reaction diagram
all-trans-retinaldehyde + NADH + H+
?
show the reaction diagram
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-
-
?
all-trans-retinol + NAD+
all-trans-retinal + NADH
show the reaction diagram
all-trans-retinol + NAD+
all-trans-retinal + NADH + H+
show the reaction diagram
all-trans-retinol + NADP+
all-trans-retinal + NADPH + H+
show the reaction diagram
exhibits a strong preference for NAD+/NADH as cofactors. Activity with NAD+ is about 10fold higher than activity in presence of NADP+
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r
all-trans-retinol-[cellular-retinol-binding-protein] + NAD+
all-trans-retinal-[cellular-retinol-binding-protein] + NADH + H+
show the reaction diagram
androsterone + NAD+
? + NADH
show the reaction diagram
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-
-
-
?
retinal + NAD(P)H
retinol + NAD(P)+
show the reaction diagram
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-
ir
retinal + NADH
retinol + NAD+
show the reaction diagram
retinal + NADH + H+
retinol + NAD+
show the reaction diagram
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-
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r
retinal + NADPH + H+
retinol + NADP+
show the reaction diagram
retinol + NAD+
retinal + NADH
show the reaction diagram
retinol + NADP+
retinal + NADPH
show the reaction diagram
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-
-
-
?
retinol bound to cellular retinol binding protein + NAD+
retinal bound to cellular retinol binding protein + NADH
show the reaction diagram
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additional information
?
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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
13-cis-retinol + NAD+
13-cis-retinal + NADH + H+
show the reaction diagram
O75452
RoDH-4 can potentially contribute to the biosynthesis of two powerful modulators of gene expression: retinoic acid from retinol and dihydrotestosterone from 3alpha-androstane-diol
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-
?
all-trans-retinal + NAD(P)H + H+
all-trans-retinol + NAD(P)+
show the reaction diagram
O55240
RDH5 has only a minor in vivo all-trans RDH activity
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?
all-trans-retinol + NAD+
all-trans-retinal + NADH
show the reaction diagram
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RoDH-4 is capable of contributing to the oxidation of retinol to retinaldehyde for retinoic acid biosynthesis in the cellular context
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-
?
all-trans-retinol + NAD+
all-trans-retinal + NADH + H+
show the reaction diagram
all-trans-retinol-[cellular-retinol-binding-protein] + NAD+
all-trans-retinal-[cellular-retinol-binding-protein] + NADH + H+
show the reaction diagram
retinal + NAD(P)H
retinol + NAD(P)+
show the reaction diagram
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-
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ir
retinal + NADH
retinol + NAD+
show the reaction diagram
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?
additional information
?
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
NAD(P)H
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NADP+
NADPH
additional information
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no significant activity with NADPH
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INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
13-cis-retinoic acid
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3,4-didehydroretinoic acid
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3,4-didehydroretinol
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cellular retinol binding protein
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free form without retinol
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Chloral hydrate
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imidazole
; increasing the amount of imidazole in the reaction mixture with purified RDH-E2 from 25 to 225mM significantly decreases RDH-E2 activity
Lubrol Px
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SKF525A
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moderately
Sodium deoxycholate
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Triton X-100
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additional information
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
BigCHAP
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10-20% stimulation
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0022
9-cis-retinol
pH 8, 37C
0.0087 - 0.57
all-trans-retinal
0.0011 - 0.0041
all-trans-retinol
0.0002
androsterone
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pH 7.3, 37C
0.00024 - 0.036
NAD+
0.098 - 0.224
NADH
0.027
NADP+
wild type enzyme, in 100 mM sodium phosphate, pH 7.4
0.0015
NADPH
wild type enzyme, in 100 mM sodium phosphate, pH 7.4
0.12
retinol
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0.0027
retinol bound to cellular retinol binding protein
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pH 7.3, 37C
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additional information
additional information
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possible Michaelis-Menten relationship between RDH10 and holo-CRBP1
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.02
all-trans-retinol
Homo sapiens
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37C
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00021 - 0.0011
13-cis-retinoic acid
0.0035 - 0.0069
3,4-didehydroretinoic acid
0.0022 - 0.0025
3,4-didehydroretinol
0.00003
cellular retinol binding protein
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pH 7.3, 37C
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.00025
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per mg of microsome, isoform 1
0.0014
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per mg of microsome, isoform 2
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6
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reduction of retinal
7.4
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assay at
additional information
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maximal activity at physiological pH
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.5 - 8
pH 7.5: 54% of maximal activity, pH 8: maximal activity
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
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assay at
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
mRNA expression
Manually annotated by BRENDA team
strong mRNA expression
Manually annotated by BRENDA team
mRNA expression
Manually annotated by BRENDA team
mRNA expression
Manually annotated by BRENDA team
strong mRNA expression
Manually annotated by BRENDA team
mRNA expression
Manually annotated by BRENDA team
strong mRNA expression
Manually annotated by BRENDA team
mRNA expression
Manually annotated by BRENDA team
mRNA expression
Manually annotated by BRENDA team
mRNA expression
Manually annotated by BRENDA team
additional information
RDH1 has widespread and intense mRNA expression in tissues of embryonic and adult mice
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
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cytoplasmic or lumenal facing, RDH1. An N-terminal signaling sequence of 22 residues anchors RDH1 in the endoplasmic reticulum projecting into the cytoplasm
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
35000
calculated from amino acid sequence
40000
SDS-PAGE
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
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x * 36000, SDS-PAGE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
no glycoprotein
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
gel-filtration of RDH-E2 preparation to remove imidazole results in significant loss of activity (about 90%) despite nearly complete recovery of the protein suggesting that RDH-E2 is sensitive to desalting
repeated freezing and thawing strikingly affects activity
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the enzyme is sensitive to desalting
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
4C, reconstitution of enzyme into proteoliposomes, stable for at least 4 months
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
Ni2+-NTA resin column chromatography; recombinant enzyme
preparation of RoDH-4 contains a minor contaminating protein band. Therefore, the exact concentration of RoDH-4 is determined based on the calibration curve constructed from several concentrations of BSA loaded on to the same SDS/PAGE gel
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RDH1 activity during purification is maintained only with phosphotidylcholine
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solubilized enzyme is extremely unstabel and loses almost 80% of initial activity even at partially purified stage, purification uses resistance of enzyme to proteolysis at 4C in the presence of 1% Triton
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
both isoforms 1 and 2, expression in COS-7 cell with N-terminal His-tag
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cloning of Rdh7
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expressed in COS-1 cells
expressed in HEK-293T cells
expressed in Sf9 insect cells and in HEK-293 cells; RDH-E2 is expressed in Sf9 insect cells as a fusion to the C-terminal His6-tag
expression in CHO-K1 cells
expression of His6-tagged RDH10 in Spodoptera frugiperda Sf9 insect cell membranes
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RDH8 gene is located on 19p13, DNA and amino acid sequence determination and analysis, RDH8 genotping and phenotyping in Han Chinese population
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recombinant RoDH-4, expressed in microsomes of Sf9 insect cells
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retinol dehydrogenase 4
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
C201R
the loss of function mutant is associated with severe loss of retinal functionand early onset severe retinal dystrophy
DELTAM1-Y13
truncated RoDH-4 that lacks the first thirteen amino acids of the N-terminal segment is partially active and exhibits the apparent Km value for androsterone similar to that of the wild-type enzyme, truncated mutant behaves as an integral membrane protein
DELTAS295-L317
removal of 23 N-terminal hydrophobic amino acids results in significant loss of activity and a 14fold increase in the apparent Km value, truncated mutant behaves as an integral membrane protein
DELTAY291-L317
removal of the C-terminal 27 amino acid segment results in about 600fold increase in the apparent Km value, truncated mutant behaves as an integral membrane protein
G43A/G47A/G49A
the triple mutation completely abolishes the enzymatic activity of RDH10 without affecting its protein level
K214A
the mutation completely abolishes the enzymatic activity of RDH10 without affecting its protein level
K214R
the mutation completely abolishes the enzymatic activity of RDH10 without affecting its protein level
N169A
the mutation completely abolishes the enzymatic activity of RDH10 without affecting its protein level
N169D
the mutation completely abolishes the enzymatic activity of RDH10 without affecting its protein level
S197A
mutant retains significant enzymatic activities, although lower than that of wild type enzyme
S197C
the mutation completely abolishes the enzymatic activity of RDH10 without affecting its protein level
S197G
mutant retains significant enzymatic activities, although lower than that of wild type enzyme
S197T
the mutation completely abolishes the enzymatic activity of RDH10 without affecting its protein level
S197V
the mutation completely abolishes the enzymatic activity of RDH10 without affecting its protein level
Y210A
the mutation completely abolishes the enzymatic activity of RDH10 without affecting its protein level
Y210F
the mutation completely abolishes the enzymatic activity of RDH10 without affecting its protein level
L3R/L5R/R16Q/R19Q/R21Q
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RDH1 mutant, deleting the positive charges from the C-terminal end of the leader, and inserting two arginine residues near the N-terminus of the signaling sequence causes 95% inversion from cytoplasmic to luminal, the mutant faces the lumen
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
mutations in RDH12 are associated with Leber congenital amaurosis