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Information on EC 1.1.99.1 - choline dehydrogenase
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1.1.99.1 choline dehydrogenaseIUBMB 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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Word Map
The enzyme appears in viruses and cellular organisms
Synonyms
choline dehydrogenase, chdh, chodh, 
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
CHD
CHDH
ChoDH
choline dehydrogenase
choline oxidase
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choline-cytochrome c reductase
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choline:(acceptor) oxidoreductase
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dehydrogenase, choline
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oxidase, choline
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CHD
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-
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
choline + acceptor = betaine aldehyde + reduced acceptor
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-
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choline + acceptor = betaine aldehyde + reduced acceptor
pingpong BiBi steady state kinetic mechanism of partially purified rat CHD
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
oxidation
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-
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redox reaction
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-
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reduction
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-
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PATHWAY SOURCE
PATHWAYS
BRENDA
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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.
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CAS REGISTRY NUMBER
COMMENTARY
9028-67-5
identical with CAS Reg. No. of EC 1.1.3.17
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
choline + 2,6-dichlorophenolindophenol
betaine aldehyde + reduced 2,6-dichlorophenolindophenol
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-
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r
choline + acceptor + phenazine methosulfate
betaine aldehyde + ?
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?
choline + coenzyme Q1
betaine aldehyde + reduced coenzyme Q1
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mitochondrial oxidation of choline
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?
choline + p-benzoquinone
betaine aldehyde + reduced p-benzoquinone
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-
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r
choline + 2 acceptor + H2O
glycine-betaine + 2 reduced acceptor + H+
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four electron oxidation with betaine aldehyde as intermediate, provides glycine-betaine as compatible solute
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?
choline + 2 acceptor + H2O
glycine-betaine + 2 reduced acceptor + H+
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four electron oxidation with betaine aldehyde as intermediate
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?
choline + acceptor
betaine aldehyde + reduced acceptor
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electron acceptor: 2,6-dichlorophenolindophenol
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?
choline + acceptor
betaine aldehyde + reduced acceptor
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electron acceptor: phenazine methosulfate
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?
choline + acceptor
betaine aldehyde + reduced acceptor
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choline is the sole substrate
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?
choline + acceptor
betaine aldehyde + reduced acceptor
relation of plasma choline and betaine to cardiovascular risk factors, mitochondrial choline dehydrogenase pathway
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?
choline + acceptor
betaine aldehyde + reduced acceptor
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effects of food-deprivation on betaine accumulation and the levels of betaine synthesizing enzymes
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?
choline + acceptor
betaine aldehyde + reduced acceptor
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acceptor 3-(4,5-dimethylthiazolyl-2-)-2,5-diphenyltetrazolium bromide, particulate enzyme: 12.4% relative activity to phenazine methosulfate
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?
choline + acceptor
betaine aldehyde + reduced acceptor
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cytochrome c, particulate enzyme: 3.1% relative activity to phenazine methosulfate
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?
choline + acceptor
betaine aldehyde + reduced acceptor
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electron acceptor: 2,6-dichlorophenolindophenol
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?
choline + acceptor
betaine aldehyde + reduced acceptor
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acceptor ferricyanide, particulate enzyme: 112% relative activity to phenazine methosulfate
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?
choline + acceptor
betaine aldehyde + reduced acceptor
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acceptor 2,6-dichlorophenolindophenol, particulate enzyme: 3.2% relative activity to phenazine methosulfate
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?
choline + acceptor
betaine aldehyde + reduced acceptor
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acceptor: phenazine methosulfate, 100% relative activity
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?
choline + acceptor
betaine aldehyde + reduced acceptor
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electron acceptor: phenazine methosulfate
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?
choline + acceptor
betaine aldehyde + reduced acceptor
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electron acceptor: phenazine methosulfate
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?
choline + acceptor
betaine aldehyde + reduced acceptor
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electron acceptor: phenazine methosulfate
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?
choline + acceptor
betaine aldehyde + reduced acceptor
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acceptor 3-(4,5-dimethylthiazolyl-2-)-2,5-diphenyltetrazolium bromide, particulate enzyme: 12.4% relative activity to phenazine methosulfate
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?
choline + acceptor
betaine aldehyde + reduced acceptor
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cytochrome c, particulate enzyme: 3.1% relative activity to phenazine methosulfate
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?
choline + acceptor
betaine aldehyde + reduced acceptor
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acceptor ferricyanide, particulate enzyme: 112% relative activity to phenazine methosulfate
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?
choline + acceptor
betaine aldehyde + reduced acceptor
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acceptor 2,6-dichlorophenolindophenol, particulate enzyme: 3.2% relative activity to phenazine methosulfate
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?
choline + acceptor
betaine aldehyde + reduced acceptor
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acceptor: phenazine methosulfate, 100% relative activity
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?
choline + acceptor
betaine aldehyde + reduced acceptor
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?
choline + acceptor
betaine aldehyde + reduced acceptor
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electron acceptor: phenazine methosulfate
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?
choline + acceptor
betaine aldehyde + reduced acceptor
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acceptor: ubiquinone-2
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?
choline + acceptor
betaine aldehyde + reduced acceptor
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the enzyme can use only choline and betaine aldehyde
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r
choline + acceptor
betaine aldehyde + reduced acceptor
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acceptor O2: 73% relative activity to phenazine methosulfate
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?
choline + acceptor
betaine aldehyde + reduced acceptor
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electron acceptor: 2,6-dichlorophenolindophenol
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?
choline + acceptor
betaine aldehyde + reduced acceptor
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acceptor 2,6-dichlorophenolindophenol: 27% relative activity to phenazine methosulfate
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?
choline + acceptor
betaine aldehyde + reduced acceptor
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absolute requirement for an electron acceptor other than O2
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r
choline + acceptor
betaine aldehyde + reduced acceptor
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reverse reaction at 5.2% of forward reaction
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r
choline + acceptor
betaine aldehyde + reduced acceptor
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cytochrome c, ferricyanide, methylene blue and 2,6-dichlorophenolindophenol show no direct reaction with the enzyme
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?
choline + acceptor
betaine aldehyde + reduced acceptor
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acceptor methylene blue: 4% relative activity to phenazine methosulfate
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?
choline + acceptor
betaine aldehyde + reduced acceptor
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coenzyme Q, primary electron acceptor in vivo
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r
choline + acceptor
betaine aldehyde + reduced acceptor
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acceptor cytochrome c: 63% relative activity to phenazine methosulfate
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?
choline + acceptor
betaine aldehyde + reduced acceptor
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acceptor: phenazine methosulfate, 100% relative activity
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?
choline + acceptor
betaine aldehyde + reduced acceptor
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electron acceptor: phenazine methosulfate
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?
choline + acceptor
betaine aldehyde + reduced acceptor
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electron acceptor: phenazine methosulfate
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?
choline + acceptor
betaine aldehyde + reduced acceptor
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electron acceptor: phenazine methosulfate
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r
choline + acceptor
betaine aldehyde + reduced acceptor
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not: 2-dimethylaminoethanol, monoethanolamine
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r
choline + acceptor
betaine aldehyde + reduced acceptor
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electron acceptor: p-benzoquinone
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?
choline + acceptor
betaine aldehyde + reduced acceptor
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acceptor ferricyanide: 42% relative activity to phenazine methosulfate
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?
choline + acceptor
betaine aldehyde + reduced acceptor
connects choline to the respiratory chain
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?
choline + phenazine methosulfate
betaine aldehyde + reduced phenazine methosulfate
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-
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?
choline + phenazine methosulfate
betaine aldehyde + reduced phenazine methosulfate
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?
choline + phenazine methosulfate
betaine aldehyde + reduced phenazine methosulfate
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?
choline + phenazine methosulfate
betaine aldehyde + reduced phenazine methosulfate
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r
choline + phenazine methosulfate
betaine aldehyde + reduced phenazine methosulfate
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r
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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?
additional information
?
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the enzyme is specific for choline or betaine aldehyde as substrate, substrate specificity, overview
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?
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
choline + 2 acceptor + H2O
glycine-betaine + 2 reduced acceptor + H+
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four electron oxidation with betaine aldehyde as intermediate, provides glycine-betaine as compatible solute
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?
choline + coenzyme Q1
betaine aldehyde + reduced coenzyme Q1
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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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?
choline + acceptor
betaine aldehyde + reduced acceptor
connects choline to the respiratory chain
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?
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
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the enzyme requires no readily dissociable coenzyme for activity
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additional information
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the enzyme requires no readily dissociable coenzyme for activity
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additional information
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FAD and pyrroloquinoline quinone has no effect on activity
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additional information
the enzyme has 3 functional domains, named FAD/NAD(P)-binding domain 1 (FB1, residues 39 to 326), FAD-linked reductase domain (RD, residues 333 to 515) and FAD/NAD(P)-binding domain 2 (FB2, residues 511 to 574)
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additional information
oxygen is not the preferred electron acceptor even though the enzyme is able to utilize it. Phenazine methosulfate can act as artificial cofactor. Cytochrome c and ferricyanide give poor activity
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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
LITERATURE
IMAGE
additional information
-
the enzyme expression is not affected by methionine or choline intake in liver, overview
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DISEASE
TITLE OF PUBLICATION
LINK TO PUBMED
Alzheimer Disease
Organelle-specific autophagy in inflammatory diseases: a potential therapeutic target underlying the quality control of multiple organelles.
Amyotrophic Lateral Sclerosis
Organelle-specific autophagy in inflammatory diseases: a potential therapeutic target underlying the quality control of multiple organelles.
Breast Neoplasms
Choline dehydrogenase polymorphism rs12676 is a functional variation and is associated with changes in human sperm cell function.
Breast Neoplasms
Dietary choline and betaine intake, choline-metabolising genetic polymorphisms and breast cancer risk: a case-control study in China.
Breast Neoplasms
The HOXB13:IL17BR expression index is a prognostic factor in early-stage breast cancer.
Breast Neoplasms
The Prognostic Biomarkers HOXB13, IL17BR, and CHDH Are Regulated by Estrogen in Breast Cancer.
Choline Deficiency
Choline dehydrogenase polymorphism rs12676 is a functional variation and is associated with changes in human sperm cell function.
Choline Deficiency
Common genetic polymorphisms affect the human requirement for the nutrient choline.
Coronary Artery Disease
Cystathionine beta-synthase 844Ins68 polymorphism is not associated with the levels of homocysteine and cysteine in an Indian population.
Endometriosis
Polymorphic variants of folate and choline metabolism genes and the risk of endometriosis-associated infertility.
Fetal Death
Polymorphic variants of genes involved in choline pathway and the risk of intrauterine fetal death.
Frontotemporal Dementia
Organelle-specific autophagy in inflammatory diseases: a potential therapeutic target underlying the quality control of multiple organelles.
Hyperhomocysteinemia
Single nucleotide polymorphisms in homocysteine metabolism pathway genes: association of CHDH A119C and MTHFR C677T with hyperhomocysteinemia.
Hypernatremia
Renal inner medullary choline dehydrogenase activity: characterization and modulation.
Metabolic Syndrome
Divergent associations of plasma choline and betaine with components of metabolic syndrome in middle age and elderly men and women.
Neoplasms
The HOXB13:IL17BR expression index is a prognostic factor in early-stage breast cancer.
Neoplasms
The Prognostic Biomarkers HOXB13, IL17BR, and CHDH Are Regulated by Estrogen in Breast Cancer.
Obesity
CHDH-PNPLA3 Gene-Gene Interactions Predict Insulin Resistance in Children with Obesity.
Parkinson Disease
Organelle-specific autophagy in inflammatory diseases: a potential therapeutic target underlying the quality control of multiple organelles.
Pulmonary Disease, Chronic Obstructive
Organelle-specific autophagy in inflammatory diseases: a potential therapeutic target underlying the quality control of multiple organelles.
Squamous Cell Carcinoma of Head and Neck
A Metabolic Gene Signature to Predict Overall Survival in Head and Neck Squamous Cell Carcinoma.
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
population-based study, unfavorable cardiovascular risk factor profile associated with high choline and low betaine concentrations, choline and betaine associated in opposite directions with key components of metabolic syndrome, disruption of mitochondrial choline dehydrogenase pathway
additional information
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population-based study, unfavorable cardiovascular risk factor profile associated with high choline and low betaine concentrations, choline and betaine associated in opposite directions with key components of metabolic syndrome, disruption of mitochondrial choline dehydrogenase pathway
additional information
-
effects of food deprivation on betaine accumulation, betaine of marginal importance as an intracellular osmolyte in this species
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
increase in the specific activity of the enzyme with choline at alkaline pH
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
CHDH transcripts and protein are found in oocytes. CHDH becomes highly active during oocyte meiotic maturation and is inactive after fertilization. Endogenous betaine is present at low levels in germinal vesicle stage mouse oocytes before ovulation and reaches high levels in the mature, ovulated egg
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