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Information on EC 1.1.99.1 - choline dehydrogenase and Organism(s) Rattus norvegicus and UniProt Accession Q6UPE0

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IUBMB Comments
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) . 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.
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Rattus norvegicus
UNIPROT: Q6UPE0
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The taxonomic range for the selected organisms is: Rattus norvegicus
The enzyme appears in selected viruses and cellular organisms
Synonyms
choline dehydrogenase, chdh, chodh, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
CHD
-
-
-
-
choline dehydrogenase
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-
choline oxidase
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-
-
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choline-cytochrome c reductase
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-
-
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choline:(acceptor) oxidoreductase
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-
-
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dehydrogenase, choline
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-
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oxidase, choline
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-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
choline + acceptor = betaine aldehyde + reduced acceptor
show the reaction diagram
ping–pong Bi–Bi steady state kinetic mechanism of partially purified rat CHD
choline + acceptor = betaine aldehyde + reduced acceptor
show the reaction diagram
mechanism
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
redox reaction
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-
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oxidation
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reduction
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PATHWAY SOURCE
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
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
choline + acceptor
betaine aldehyde + reduced acceptor
show the reaction diagram
choline + 2,6-dichlorophenolindophenol
betaine aldehyde + reduced 2,6-dichlorophenolindophenol
show the reaction diagram
-
-
-
-
r
choline + acceptor
betaine aldehyde + reduced acceptor
show the reaction diagram
choline + coenzyme Q1
betaine aldehyde + reduced coenzyme Q1
show the reaction diagram
-
mitochondrial oxidation of choline
-
?
choline + p-benzoquinone
betaine aldehyde + reduced p-benzoquinone
show the reaction diagram
-
-
-
-
r
choline + phenazine methosulfate
betaine aldehyde + reduced phenazine methosulfate
show the reaction diagram
-
-
-
-
r
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
choline + acceptor
betaine aldehyde + reduced acceptor
show the reaction diagram
choline + coenzyme Q1
betaine aldehyde + reduced coenzyme Q1
show the reaction diagram
-
mitochondrial oxidation of choline
-
?
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
additional information
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
iron sulfur cluster
-
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2-Dimethylaminoethanol
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Betaine aldehyde
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choline dehydrogenase activity
DL-3-hydroxybutyrate
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at 16.7 mM acts as weak inhibitor
Monoethanolamine
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Semicarbazide
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-
additional information
-
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
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-dichlorophenolindophenol
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at 10 mM choline
3.1
Betaine aldehyde
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at 1 mM phenazine methosulfate
7
choline
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electron acceptor: phenazine methosulfate
0.83
p-benzoquinone
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at 10 mM choline
0.18 - 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
-
inhibits the oxidation of choline competitively
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.041
enzyme from rat liver mitochondria
0.047
recombinant enzyme from yeast mitochondria
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.6 - 8.2
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crude enzyme extract
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
increase in the specific activity of the enzyme with choline at alkaline pH
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
SwissProt
Manually annotated by BRENDA team
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
additional information
CHD is predominantly active in the two main detoxifying organs liver and kidney
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
a nuclear-encoded, membrane-located, mitochondrial enzyme
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
the enzyme belongs to the glucose-methanol-choline (GMC) enzyme oxidoreductase enzyme superfamily, members of the family contain a glycine box. Other members of the family all use FAD as cofactor, overall structures and active sites of members of the GMC oxidoreductase enzyme superfamily, overview
malfunction
the enzyme is associated with male infertility. Absence of CHD enzyme activity causes diminished sperm motility, and mitochondrial alterations are described in testis as well as liver, kidney and heart. Impairments in human CHD activity are associated with homocysteinuria, an accumulation of homocysteine that represents an independent risk factor for cardiovascular diseases. It exists a correlation between high concentrations of choline, low concentrations of glycine betaine in blood and a high-risk profile for cardiovascular disease. Choline deficiency the brain may degrade the membrane phospholipids of the neurons in order to recycle choline for the production of acetylcholine. Choline is involved in the global hypomethylation of hepatic DNA of rats fed a low choline diet, different rate of development of the hippocampus in the fetal brains of rodent models in the case of low and high maternal choline intake. The folate content in the liver of choline deficient rats decreases by 31% compared to control rats
physiological function
the enzyme oxidizes choline. The regulation of the concentration of choline in tissues and blood is very important as choline plays key roles in different pathways. Choline is involved in the epigenetic regulation of gene expression through DNA methylation, in the biosynthesis of lipoproteins and membrane phospholipids and in the biosynthesis of the neurotransmitter acetylcholine. It is therefore important for the integrity of cell membranes, lipid metabolism and nerve function. Choline is considered an important nutrient for fetal and brain development, and choline is a constituent of phospholipids involved in signal transduction, such as phosphatidylcholine and plasmalogen, and of the phospholipid platelet activating factor. The metabolism of choline is also interrelated with the metabolism of folate. CHD is important for the catabolic utilization of choline when the latter is administered as a pharmacological agent, because choline is involved in the stimulation of cholinergic neuronal activity and in restoring phosphatidylcholine levels in the neuronal membrane, thus displaying a neuroprotective action relevant for diseases such as memory and cognitive deficits. CHD, predominantly active in the two main detoxifying organs liver and kidney, determines the half-life of choline in blood. The metabolic oxidation of choline is related to the risk of developing breast cancer
additional information
rapid turnover of choline when administered as a drug, about 50% of injected choline are directly eliminated via liver and kidney. Structure homology modeling
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
CHDH_RAT
599
0
66389
Swiss-Prot
Mitochondrion (Reliability: 1)
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
structure homology modeling
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
proteolytic modification
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
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
60
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3 min, pH 7, 63% inactivation
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
high instability of the enzyme once it is removed from the inner mitochondrial membrane
25 cycles of freezing/thawing cause 40% loss of activity
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glycerol, 30%, stabilizes partially purified enzyme
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repeated freezing and thawing: rapid loss of activity
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-15°C, 50% loss of activity, 1 month
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-15°C, pH 7.4 as mitochondrial acetone powder, 20% loss of activity after 6 days
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-15°C, pH 7.4 in extracts, 13% loss of activity after 6 days
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-20°C, stable, partially purified enzyme
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
from rat liver mitochondria, purification methods, overview
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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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expressed in Saccharomyces cerevisiae INVSC2as GFP fusion protein
gene Chdh, phylogenetic tree
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
diagnostics
study of prognostic biomarkers for breast cancer identifies the expression of CHD among three human genes controlled by estrogens, and shows that this is a strong predictor of the outcome of treatment with tamoxifen in early-stage (ER)-positive breast cancer patients
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Rendina, G.; Singer, T.P.
Studies on choline dehydrogenase
J. Biol. Chem.
234
1605-1610
1959
Rattus norvegicus
Manually annotated by BRENDA team
Barrett, M.C.; Dawson, A.P.
The reaction of choline dehydrogenase with some electron acceptors
Biochem. J.
151
677-683
1975
Rattus norvegicus
Manually annotated by BRENDA team
Tsuge, H.; Nakano, Y.; Onishi, H.; Futamura, Y.; Ohashi, K.
A novel purification and some properties of rat liver mitochondrial choline dehydrogenase
Biochim. Biophys. Acta
614
274-284
1980
Rattus norvegicus
Manually annotated by BRENDA team
Huang, S.; Lin, Q.
Functional expression and processing of rat choline dehydrogenase precursor
Biochem. Biophys. Res. Commun.
309
344-350
2003
Rattus norvegicus (Q6UPE0)
Manually annotated by BRENDA team
Slow, S.; Garrow, T.A.
Liver choline dehydrogenase and kidney betaine-homocysteine methyltransferase expression are not affected by methionine or choline intake in growing rats
J. Nutr.
136
2279-2283
2006
Rattus norvegicus
Manually annotated by BRENDA team
Clow, K.A.; Treberg, J.R.; Brosnan, M.E.; Brosnan, J.T.
Elevated tissue betaine contents in developing rats are due to dietary betaine, not to synthesis
J. Nutr.
138
1641-1646
2008
Rattus norvegicus
Manually annotated by BRENDA team
Salvi, F.; Gadda, G.
Human choline dehydrogenase medical promises and biochemical challenges
Arch. Biochem. Biophys.
537
243-252
2013
Homo sapiens (Q8NE62), Homo sapiens, Rattus norvegicus (Q6UPE0)
Manually annotated by BRENDA team