Information on EC 1.1.99.1 - choline dehydrogenase

for references in articles please use BRENDA:EC1.1.99.1
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The expected taxonomic range for this enzyme is: Eukaryota, Bacteria

EC NUMBER
COMMENTARY hide
1.1.99.1
-
RECOMMENDED NAME
GeneOntology No.
choline dehydrogenase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
choline + acceptor = betaine aldehyde + reduced acceptor
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
oxidation
-
-
-
-
redox reaction
-
-
-
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reduction
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-
-
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PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
choline degradation I
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glycine betaine biosynthesis I (Gram-negative bacteria)
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glycine betaine biosynthesis
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Glycine, serine and threonine metabolism
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Metabolic pathways
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SYSTEMATIC NAME
IUBMB Comments
choline:acceptor 1-oxidoreductase
A quinoprotein. In many bacteria, plants and animals, the osmoprotectant betaine is synthesized using different enzymes to catalyse the conversion of (1) choline into betaine aldehyde and (2) betaine aldehyde into betaine. In plants, the first reaction is catalysed by EC 1.14.15.7, choline monooxygenase, whereas in animals and many bacteria, it is catalysed by either membrane-bound choline dehydrogenase (EC 1.1.99.1) or soluble choline oxidase (EC 1.1.3.17) [4]. The enzyme involved in the second step, EC 1.2.1.8, betaine-aldehyde dehydrogenase, appears to be the same in plants, animals and bacteria.
CAS REGISTRY NUMBER
COMMENTARY hide
9028-67-5
identical with CAS Reg. No. of EC 1.1.3.17
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
isolated from a finfish, gene betA
UniProt
Manually annotated by BRENDA team
halophil
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
A-16 strain
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-
Manually annotated by BRENDA team
C10 strain
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-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
malfunction
metabolism
physiological function
additional information
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
betaine aldehyde + phenazine methosulfate
glycine-betaine + ?
show the reaction diagram
-
-
-
-
?
choline + 2 acceptor + H2O
glycine-betaine + 2 reduced acceptor + H+
show the reaction diagram
choline + acceptor
betaine aldehyde + reduced acceptor
show the reaction diagram
choline + acceptor + phenazine methosulfate
betaine aldehyde + ?
show the reaction diagram
-
-
-
-
?
choline + coenzyme Q1
betaine aldehyde + reduced coenzyme Q1
show the reaction diagram
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mitochondrial oxidation of choline
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choline + phenazine methosulfate
betaine aldehyde + reduced phenazine methosulfate
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
choline + 2 acceptor + H2O
glycine-betaine + 2 reduced acceptor + H+
show the reaction diagram
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four electron oxidation with betaine aldehyde as intermediate, provides glycine-betaine as compatible solute
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-
?
choline + acceptor
betaine aldehyde + reduced acceptor
show the reaction diagram
choline + coenzyme Q1
betaine aldehyde + reduced coenzyme Q1
show the reaction diagram
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mitochondrial oxidation of choline
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-
additional information
?
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the enzyme is responsible for the two-step choline oxidation to betaine together with the betaine-homocysteine methyltransferase
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-
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
coenzyme Q
-
primary electron acceptor in vivo
phenazine methosulfate
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pyrroloquinoline quinone
additional information
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
iron sulfur cluster
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-
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2-Dimethylaminoethanol
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AgNO3
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1 mM causes 100% inhibition
Benzyltrimethylammonium chloride
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slight
Betaine aldehyde
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choline dehydrogenase activity
Betaine hydrochloride
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slight
CuSO4
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1 mM causes 100% inhibition
dimethylglycine
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slight
DL-3-hydroxybutyrate
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at 16.7 mM acts as weak inhibitor
DL-Carnitine hydrochloride
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slight
glycine
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slight
HgCl2
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1 mM causes 100% inhibition
iodoacetic acid
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-
KCN
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1 mM inhibits
Mercuric acetate
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-
MnCl2
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1 mM causes 100% inhibition
Monoethanolamine
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NaCN
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1 mM inhibits
p-chloromercuribenzoate
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-
Phenyltriethylammonium iodide
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slight
Semicarbazide
Tetra-n-butylammonium iodide
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slight
Tetra-n-propylammonium iodide
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slight
Tetraethylammonium iodide
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slight
Tetramethylammonium iodide
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slight
Triethylbenzylammonium iodide
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slight
additional information
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the enzyme expression is not affected by methionine or choline intake in liver, overview
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
coenzyme Q
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primary electron acceptor in vivo
pyrroloquinoline quinone
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as prosthetic group
additional information
-
the enzyme expression is not affected by methionine or choline intake in liver, overview
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1
2,6-dichlorophenol-indophenol
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at 10 mM choline
3.1
Betaine aldehyde
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at 1 mM phenazine methosulfate
1.7 - 7
choline
0.83
p-benzoquinone
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at 10 mM choline
0.14 - 1.1
phenazine methosulfate
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1
2-Dimethylaminoethanol
-
inhibits the enzyme competitively
3.3
Betaine aldehyde
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inhibits the oxidation of choline competitively
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.041
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enzyme from rat liver mitochondria
0.047
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recombinant enzyme from yeast mitochondria
1.8
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purified enzyme, pH 7.0, 25C
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.6 - 8.2
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crude enzyme extract
8
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assay at
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.5 - 10
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about 50% of activity maximum at pH 7.5 and pH 10.0
additional information
-
increase in the specific activity of the enzyme with choline at alkaline pH
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
-
assay at
pI VALUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5.45
sequence calculation
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
choline and betaine levels
Manually annotated by BRENDA team
dopaminergic cells
Manually annotated by BRENDA team
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highest activity
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
60000 - 70000
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gel filtration
62000
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? * 62000, SDS-PAGE
66000
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1 * 66000, SDS-PAGE
145000
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calculated from density gradient profiles and comparison with catalase
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
monomer
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
proteolytic modification
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CHD contains an N-terminal cleavable mitochondrial targeting presequence of 34 amino acids and two cleavage sites may be present for recognition and processing by mitochondrial processing protease and inner membrane protease, mature CHD begins with amino acid 35
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
8 - 9.5
-
10 min, 37C, stable
389888
additional information
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-
389888
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
35
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10 min, pH 8.3, 10% loss of activity
37
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10 min, pH 8.0-9.5, stable
40
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10 min, pH 8.3, 50% loss of activity
50
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10 min, pH 8.3, 100% loss of activity
60
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3 min, pH 7, 63% inactivation
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
25 cycles of freezing/thawing cause 40% loss of activity
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detergents, e.g. Brij 58, Triton X-100, cholate, deoxycholate or beta-octylglucoside stabilize
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glycerol, 30%, stabilizes partially purified enzyme
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high instability of the enzyme once it is removed from the inner mitochondrial membrane
repeated freezing and thawing: rapid loss of activity
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-15C, 50% loss of activity, 1 month
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-15C, pH 7.4 as mitochondrial acetone powder, 20% loss of activity after 6 days
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-15C, pH 7.4 in extracts, 13% loss of activity after 6 days
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-20C , stable
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-20C, phosphate buffer, pH 7.0, 2 M sorbitol, 20% glycerol
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-20C, stable, partially purified enzyme
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5C, pH 7.4, complete loss of activity, partially purified enzyme, 5-6 days
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Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
from rat liver mitochondria, purification methods, overview
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partial, using Triton-treatment, chloroform-treatment and column chromatography on Sepharose 6B
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recombinant enzyme from Escherichia coli
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recombnant enzyme from Escherichia coli strain M15 by ammonium sulfate fractionation and anion exchange chromatography
using 0.5% Brij 58 treatment, column chromatography on DEAE-cellulose and gel filtration on Toyopearl HW-60S
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using column chromatography of the chemically modified enzyme with 5,5'-dithiobis(2-nitrobenzoic acid) on DEAE-Sepharose CL-6B and choline-Sepharose 4B with C3-spacer, subsequent release of the thionitrobenzoate with dithiothreitol, and a second column chromatography on DEAE-Sepharose CL-6B in the presence of 0.1% Triton X-100
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using column chromatography on thio-hexyl and on an anion exchanger
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli OrigamiB(DE3)pLysS
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expressed in Saccharomyces cerevisiae INVSC2as GFP fusion protein
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gene betA, DNA and amino acid sequence determination and analysis, sequence comparisons, expression in Escherichia coli strain JM109
gene betA, DNA and amino acid sequence determination and analysis, sequence comparisons, expression in Escherichia coli strain M15/pREP4, subcloning in strain JM109
gene Chdh, DNA and amino acid sequence determination and analysis, polymorphism rs12676 genotyping, overview
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gene Chdh, phylogenetic tree
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gene CHDH, phylogenetic tree, recombinant expression in Escherichia coli
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gene CHDH, recombinant expression of wild-type and truncated mutant enzymes, enzyme overexpression in HeLa cells
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transformed with the chimeric betA gene from Escherichia coli to betaine-producing tobacco
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
liver samples from Chdh-deficient mice have 37% of the CHDH activity measured in wild type samples
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
G233T
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naturally occuring mutation, identificatin of polymorphism rs12676, a non-synonymous SNP located in the CHDH coding region, which is associated with altered sperm motility patterns and dysmorphic mitochondrial structure in sperm, and is associated with increased susceptibility to dietary choline deficiency and risk of breast cancer, phenotye, overview
L78X
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localization of Leu78, which is relevant to the polymorphism rs12676 associated with male infertility and increased risk factor for breast cancer, on the surface of the enzyme. Such a replacement of a hydrophobic residue with a positively charge one would locally alter the polarity of the enzyme surface, perhaps decreasing the stability of the enzyme
additional information
-
construction of a series of CHDH deletion mutants in HeLa cells. Overexpression of the CHDH-RDDELTA or CHDHFB2DELTA mutants induces colocalization of GFP-LC3 with Mito-RFP as effectively as wild-type CHDH, but the CHDH-FB1DELTA mutant fails to do so. Knockdown of CHDH expression impairs CCCP-induced mitophagy and PARK2/parkin-mediated clearance of mitochondria in mammalian cells, including HeLa cells. Conversely, overexpression of CHDH accelerates PARK2-mediated mitophagy. Overexpression of the FB1 domain only in cytosol reduces CCCP-induced mitochondrial degradation via competitive interaction with SQSTM1
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
diagnostics
medicine
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population-based study, relation of plasma choline and betaine to smoking, physical activity, BMI, percent body fat, waist circumference, blood pressure, serum lipids and glucose
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