1.1.99.1: choline dehydrogenase
This is an abbreviated version!
For detailed information about choline dehydrogenase, go to the full flat file.
Reaction
Synonyms
Cdh, CHD, CHDH, ChoDH, choline dehydrogenase, choline oxidase, choline-cytochrome c reductase, choline:(acceptor) oxidoreductase, dehydrogenase, choline, oxidase, choline
ECTree
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General Information
General Information on EC 1.1.99.1 - choline dehydrogenase
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evolution
malfunction
metabolism
physiological function
additional information
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
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
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deletion of choline dehydrogenase results in diminished sperm motility with abnormal mitochondrial morphology, but does not affect fetal viability or alter growth or liver, kidney, or muscle function. Loss of choline dehydrogenase activity results in decreased testicular betaine and increased choline and phosphocholine concentrations. Mitochondrial changes are also detected in liver, kidney, heart, and testis tissues. Chdh-deficient mice have increased plasma total homocysteine
malfunction
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mutant sperm produced by men who are show polymorphisms rs12676 have 40% and 73% lower ATP concentrations, respectively, in their sperm than controls. Variation rs12676 is associated with decreased CHDH protein in sperm and hepatocytes. A second single-nucleotide polymorphism located in the coding region of IL17BR, rs1025689, is linked to altered sperm motility characteristics and changes in choline metabolite concentrations in sperm
malfunction
downregulation of CHDH expression abolishes the colocalization of MAP1LC3B/LC3B (LC3) with mitochondria
malfunction
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
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
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
in Escherichia coli, the biosynthetic pathway for the production of glycine betaine from choline involves choline dehydrogenase (betA), betaine aldehyde dehydrogenase (betB), a putative regulator (betI) and a choline transporter (betT), the genes are clustered in the bet operon
metabolism
in Escherichia coli, the biosynthetic pathway for the production of glycine betaine from choline involves choline dehydrogenase (betA), catalyzing the first step of the biosynthetic pathway, and betaine aldehyde dehydrogenase (betB), a putative regulator (betI) and a choline transporter (betT), the genes are clustered in the bet operon
metabolism
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in Escherichia coli, the biosynthetic pathway for the production of glycine betaine from choline involves choline dehydrogenase (betA), betaine aldehyde dehydrogenase (betB), a putative regulator (betI) and a choline transporter (betT), the genes are clustered in the bet operon
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in SN4741 dopaminergic cells, CHDH plays a role during mitophagy triggered by 1-methyl-4-phenylpyridinium (MPPC), a Parkinsonism-causing reagent. Like CCCP, treatment with MPPC induces a significant level (30.0%) of colocalization of MAP1LC3B/LC3B (LC3) with mitochondria in SN4741 cells. CHDH is essential in the mitophagy of SN4741 dopaminergic neurons following exposure to MPPC
physiological function
pivotal role of CHDH in mitophagy. CHDH is required for mitophagy in which CHDH interacts with SQSTM1, a mitophagic adaptor molecule, and subsequently facilitates the recruitment of MAP1LC3B/LC3B (LC3) into the mitochondria. CHDH is not a substrate of PARK2 but interacts with SQSTM1 independently of PARK2 to recruit SQSTM1 into depolarized mitochondria. The FB1 domain of CHDH is exposed to the cytosol and is required for the interaction with SQSTM1, and overexpression of the FB1 domain only in cytosol reduces CCCP-induced mitochondrial degradation via competitive interaction with SQSTM1. CHDH is required for PARK2-mediated mitophagy for the recruitment of SQSTM1 and LC3 onto the mitochondria for cargo recognition. CHDH overexpression enhances CCCP-induced clearance of mitochondria. But the expression level of CHDH does not affect the stability of PINK1 protein, although CCCP treatment stabilizes PINK1 in mitochondria. Mitophagic activity of CHDH is independent of CDH enzyme activity
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
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
CHDH appears to have a mitochondria-targeting sequence at its N-terminus (residues 1 to 38) and 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)
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
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
additional information
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rapid turnover of choline when administered as a drug, about 50% of injected choline are directly eliminated via liver and kidney. Structure homology modeling