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Literature summary for 1.1.99.1 extracted from

  • Salvi, F.; Gadda, G.
    Human choline dehydrogenase medical promises and biochemical challenges (2013), Arch. Biochem. Biophys., 537, 243-252 .
    View publication on PubMed

Application

Application Comment Organism
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 Rattus norvegicus
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 Homo sapiens

Cloned(Commentary)

Cloned (Comment) Organism
gene Chdh, phylogenetic tree Rattus norvegicus
gene CHDH, phylogenetic tree, recombinant expression in Escherichia coli Homo sapiens

Protein Variants

Protein Variants Comment Organism
L78X 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 Homo sapiens

General Stability

General Stability Organism
high instability of the enzyme once it is removed from the inner mitochondrial membrane Rattus norvegicus
high instability of the enzyme once it is removed from the inner mitochondrial membrane Homo sapiens

Localization

Localization Comment Organism GeneOntology No. Textmining
mitochondrial inner membrane a nuclear-encoded, membrane-located, mitochondrial enzyme Rattus norvegicus 5743
-
mitochondrial inner membrane a nuclear-encoded, membrane-located, mitochondrial enzyme. Human CHD is not an integral membrane protein, but associated to the membrane Homo sapiens 5743
-

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
choline + acceptor Rattus norvegicus
-
betaine aldehyde + reduced acceptor
-
r
choline + acceptor Homo sapiens
-
betaine aldehyde + reduced acceptor
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens Q8NE62
-
-
Rattus norvegicus Q6UPE0
-
-

Posttranslational Modification

Posttranslational Modification Comment Organism
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 Rattus norvegicus

Purification (Commentary)

Purification (Comment) Organism
from rat liver mitochondria, purification methods, overview Rattus norvegicus
recombinant enzyme from Escherichia coli Homo sapiens

Reaction

Reaction Comment Organism Reaction ID
choline + acceptor = betaine aldehyde + reduced acceptor ping–pong Bi–Bi steady state kinetic mechanism of partially purified rat CHD Rattus norvegicus

Source Tissue

Source Tissue Comment Organism Textmining
kidney
-
Rattus norvegicus
-
kidney
-
Homo sapiens
-
liver
-
Rattus norvegicus
-
liver
-
Homo sapiens
-
additional information CHD is predominantly active in the two main detoxifying organs liver and kidney Rattus norvegicus
-
additional information CHD is predominantly active in the two main detoxifying organs liver and kidney Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
choline + acceptor
-
Rattus norvegicus betaine aldehyde + reduced acceptor
-
r
choline + acceptor
-
Homo sapiens betaine aldehyde + reduced acceptor
-
?
additional information the enzyme is specific for choline or betaine aldehyde as substrate, substrate specificity, overview Rattus norvegicus ?
-
?

Subunits

Subunits Comment Organism
More structure homology modeling Rattus norvegicus
More structure homology modeling Homo sapiens

Synonyms

Synonyms Comment Organism
CHD
-
Rattus norvegicus
CHD
-
Homo sapiens
CHDH
-
Rattus norvegicus
CHDH
-
Homo sapiens

pH Range

pH Minimum pH Maximum Comment Organism
additional information
-
increase in the specific activity of the enzyme with choline at alkaline pH Rattus norvegicus

Cofactor

Cofactor Comment Organism Structure
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 Rattus norvegicus

General Information

General Information Comment Organism
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 Rattus norvegicus
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 Homo sapiens
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 Rattus norvegicus
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. Localization of Leu78 is relevant to the polymorphism rs12676 associated with male infertility and increased risk factor for breast cancer, on the surface of the enzyme Homo sapiens
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 Rattus norvegicus
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 Homo sapiens
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 Rattus norvegicus
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 Homo sapiens