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CDP Choline

Yasuhiro Horibata, Orly Elpeleg, Ayelet Eran, Yoshio Hirabayashi, David Savitzki, Galit Tal, Hanna Mandel, Hiroyuki Sugimoto
Ethanolamine phosphotransferase 1 (EPT1), also known as selenoprotein 1 (SELENOI), is an enzyme that transfers phosphoethanolamine from cytidine diphosphate (CDP)-ethanolamine to lipid acceptors to produce ethanolamine glycerophospholipids such as diacyl-linked phosphatidylethanolamine (PE) and ether-linked plasmalogen (plasmenyl-PE). However, to date there has been no analysis of the metabolomic consequence of the mutation of EPT1 on the concentration of ethanolamine glycerophospholipids in mammalian cells...
March 2, 2018: Journal of Lipid Research
Chitu Iulia, Tudosescu Ruxandra, Leasu-Branet Costin, Voinea Liliana-Mary
Citicoline is the generic name of cytidine-5'-diphosphocholine (CDP-choline), an endogenous compound that is able to increase the levels of neurotransmitters in the central nervous system by interacting with the synthesis of cellular membranes phospholipids, especially phosphatidylcholine. Exogenous Citicoline, administered by ingestion or injection, is hydrolyzed and dephosphorylated in order to form cytidine and choline, which resynthesize CDP-choline inside brain cells. It has proven neuroprotective effects in Alzheimer disease, stroke, and Parkinson's disease, as well as in glaucoma and amblyopia...
July 2017: Romanian Journal of Ophthalmology
Junzhi Wang, Cheng Zheng, Yang Cao, Zhuotao Tan, Dong Liu, Zhuopei Cheng, Hanjie Ying, Huanqing Niu
Salt accumulation often impedes cytidine diphosphate choline (CDP-choline)in vitro biosynthetic process. In this work a halotolerant in vitroenzymatic system was developed to solve this problem. It applies a halotolerant choline-phosphate cytidylyltransferase (CCT) obtained from rational design instructed by a unique stagey, which refers to one of the features of naturally occurring halophilic enzymes. By increasing acidic residues on protein surface where is most variable with respect to amino acid in the sequence alignment with other choline-phosphate cytidylyltransferase, the mutants were obtained...
February 1, 2018: Biotechnology Journal
Robert Aidelbaum, Alain Labelle, Ashley Baddeley, Verner Knott
Deficient sensory gating (SG) in schizophrenia is associated with functional outcome and offers a therapeutic target as it is linked to the altered function/expression of the α7 nicotinic acetylcholine receptors (nAChRs). This study analyzed the effects of citicoline (CDP-choline), a supplement with α7 nAChRs agonist properties, on SG in a sample of schizophrenia (SZ) patients. Using a randomized, placebo-controlled, double-blind design the dose-dependent (500 mg, 1000 mg, 2000 mg) and baseline-dependent (deficient versus normal suppressors) effects of CDP-choline on SG were examined using the P50 event-related potential (ERP) index of SG...
January 1, 2018: Journal of Psychopharmacology
Christopher R McMaster
The major phospholipid present in most eukaryotic membranes is phosphatidylcholine (PC), comprising ~ 50% of phospholipid content. PC metabolic pathways are highly conserved from yeast to humans. The main pathway for the synthesis of PC is the Kennedy (CDP-choline) pathway. In this pathway, choline is converted to phosphocholine by choline kinase, phosphocholine is metabolized to CDP-choline by the rate-determining enzyme for this pathway, CTP:phosphocholine cytidylyltransferase, and cholinephosphotransferase condenses CDP-choline with diacylglycerol to produce PC...
November 27, 2017: FEBS Letters
Yixiong Chen, Bing Li, Kai Cen, Yuzhen Lu, Siwei Zhang, Chengshu Wang
Phosphatidylcholine (PC) plays an important role in maintaining membrane integrity and functionality. In this study, two key genes (Mrpct and Mrpem) putatively involved in the cytidine diphosphate (CDP)-choline and phosphatidylethanolamine N-methyltransferase (PEMT) pathways for PC biosynthesis were characterized in the insect pathogenic fungus Metarhizium robertsii. The results indicated that disruption of Mrpct did not lead to any reduction of total PC content but impaired fungal virulence and increased cellular accumulation of triacylglycerol...
January 2018: Environmental Microbiology
Mabel Buelna-Chontal, Martha Franco, Luz Hernández-Esquivel, Natalia Pavón, José S Rodríguez-Zavala, Francisco Correa, Ricardo Jasso, Gregorio Pichardo-Ramos, José Santamaría, Héctor González-Pacheco, Virgilia Soto, Jorge L Díaz-Ruíz, Edmundo Chávez
Heavy metal ions are known to produce harmful alterations on kidney function. Specifically, the accumulation of Hg2+ in kidney tissue may induce renal failure. In this work, the protective effect of CDP-choline against the deleterious effects induced by Hg2+ on renal function was studied. CDP-choline administered ip at a dose of 125 mg/kg body weight prevented the damage induced by Hg2+ administration at a dose of 3 mg/kg body weight. The findings indicate that CDP-choline guards mitochondria against Hg2+ -toxicity by preserving their ability to retain matrix content, such as accumulated Ca2+ ...
December 2017: Cell Biology International
Sergio A Pulido, Victoria H Nguyen, Juan F Alzate, David L Cedeño, Monika A Makurath, Amalia Ríos-Vásquez, Sandra M Duque-Benítez, Marjorie A Jones, Sara M Robledo, Jon A Friesen
The protozoan parasite Leishmania infantum is a causative agent of the disease visceral leishmaniasis, which can be fatal if not properly treated. Phosphatidylcholine (PC) and phosphatidylethanolamine (PE) biosynthesis pathways are attractive targets for new antileishmanial compounds since these Leishmania cell membrane phospholipids are important for parasite morphology and physiology. In this work we observed Leishmania synthesize PC and PE from extracellular choline and ethanolamine, respectively, suggesting the presence of CDP-choline and CDP-ethanolamine pathways...
November 2017: Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology
Helmut Trimmel, Marek Majdan, Andrea Wodak, Guenther Herzer, Daniel Csomor, Alexandra Brazinova
Goal-oriented management of traumatic brain injury (TBI) can save the lives and/or improve the long-term outcome of millions of affected patients worldwide. Additionally, enhancing quality of life will save enormous socio-economic costs; however, promising TBI treatment strategies with neuroprotective agents, such as citicoline (CDP-choline), lacked evidence or produced contradictory results in clinical trials. During a prehospital TBI project to optimize early TBI care within 14 Austrian trauma centers, data on 778 TBI patients were prospectively collected...
July 27, 2017: Wiener Klinische Wochenschrift
Melissa McDougall, Jaewoo Choi, Lisa Truong, Robert Tanguay, Maret G Traber
Vitamin E (α-tocopherol; VitE) is a lipophilic antioxidant required for normal embryonic development in vertebrates, but the long-term effects of embryonic VitE deficiency, and whether they are ameliorated by feeding VitE-adequate diets, remain unknown. We addressed these questions using a zebrafish (Danio rerio) model of developmental VitE deficiency followed by dietary remediation. Adult zebrafish maintained on VitE-deficient (E-) or sufficient (E+) diets were spawned to obtained E- and E+ embryos, respectively, which we evaluated up to 12 days post-fertilization (dpf)...
September 2017: Free Radical Biology & Medicine
Minwoo Lee, Bo Young Choi, Sang Won Suh
Choline alfoscerate (α-GPC) and Cytidine 5'-diphosphocholine (CDP-Choline) are both acetylcholine precursors and are considered to act as pro-cholinergic nootropic agents. Acetylcholine precursors have also recently found frequent use in the neurology clinic. Stroke and many types of dementia have been shown to respond favorably after treatment with these agents, not only in terms of cognitive dysfunction but also behavioral and psychological symptoms. The primary mechanisms of Acetylcholine precursors are the following: 1) Acetylcholine precursors themselves are used in the biosynthesis of acetylcholine and 2) byproducts like glycerophosphate have protective functions for neuronal phospholipids...
May 18, 2017: Current Neuropharmacology
Ariel B Ganz, Vanessa V Cohen, Camille C Swersky, Julie Stover, Gerardo A Vitiello, Jessica Lovesky, Jasmine C Chuang, Kelsey Shields, Vladislav G Fomin, Yusnier S Lopez, Sanjay Mohan, Anita Ganti, Bradley Carrier, Olga V Malysheva, Marie A Caudill
Single nucleotide polymorphisms (SNPs) in choline metabolizing genes are associated with disease risk and greater susceptibility to organ dysfunction under conditions of dietary choline restriction. However, the underlying metabolic signatures of these variants are not well characterized and it is unknown whether genotypic differences persist at recommended choline intakes. Thus, we sought to determine if common genetic risk factors alter choline dynamics in pregnant, lactating, and non-pregnant women consuming choline intakes meeting and exceeding current recommendations...
January 26, 2017: International Journal of Molecular Sciences
Miguel Ángel Vences-Guzmán, M Paula Goetting-Minesky, Ziqiang Guan, Santiago Castillo-Ramirez, Luz América Córdoba-Castro, Isabel M López-Lara, Otto Geiger, Christian Sohlenkamp, J Christopher Fenno
Treponema denticola synthesizes phosphatidylcholine through a licCA-dependent CDP-choline pathway identified only in the genus Treponema. However, the mechanism of conversion of CDP-choline to phosphatidylcholine remained unclear. We report here characterization of TDE0021 (herein designated cpt) encoding a 1,2-diacylglycerol choline phosphotransferase homologous to choline phosphotransferases that catalyze the final step of the highly conserved Kennedy pathway for phosphatidylcholine synthesis in eukaryotes...
March 2017: Molecular Microbiology
Parker S Woods, Lauren M Doolittle, Lucia E Rosas, Lisa M Joseph, Edward P Calomeni, Ian C Davis
Alveolar type II (ATII) epithelial cells are the primary site of influenza virus replication in the distal lung. Development of acute respiratory distress syndrome in influenza-infected mice correlates with significant alterations in ATII cell function. However, the impact of infection on ATII cell surfactant lipid metabolism has not been explored. C57BL/6 mice were inoculated intranasally with influenza A/WSN/33 (H1N1) virus (10,000 plaque-forming units/mouse) or mock-infected with virus diluent. ATII cells were isolated by a standard lung digestion protocol at 2 and 6 days postinfection...
December 1, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
Sandi A Kwee, Miles M Sato, Yu Kuang, Adrian Franke, Laurie Custer, Kyle Miyazaki, Linda L Wong
PURPOSE: [(18)F]fluorocholine PET/CT can detect hepatocellular carcinoma (HCC) based on imaging the initial steps of phosphatidylcholine synthesis. To relate the diagnostic performance of [(18)F]fluorocholine positron emission tomography (PET)/x-ray computed tomography (CT) to the phospholipid composition of liver tumors, radiopathologic correspondence was performed in patients with early-stage liver cancer who had undergone [(18)F]fluorocholine PET/CT before tumor resection. PROCEDURES: Tumor and adjacent liver were profiled by liquid chromatography mass spectrometry, quantifying phosphatidylcholine species by mass-to-charge ratio...
June 2017: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
Xi Chen, Heng Qiu, Chao Wang, Yu Yuan, Jennifer Tickner, Jiake Xu, Jun Zou
Choline, a hydrophilic cation, has versatile physiological roles throughout the body, including cholinergic neurotransmission, memory consolidation and membrane biosynthesis and metabolism. Choline kinases possess enzyme activity that catalyses the conversion of choline to phosphocholine, which is further converted to cytidine diphosphate-coline (CDP-choline) in the biosynthesis of phosphatidylcholine (PC). PC is a major constituent of the phospholipid bilayer which constitutes the eukaryotic cell membrane, and regulates cell signal transduction...
February 2017: Cytokine & Growth Factor Reviews
Yingmiao Liu, Junzhi Wang, Chongmao Xu, Yong Chen, Junjie Yang, Dong Liu, Huanqing Niu, Yu Jiang, Sheng Yang, Hanjie Ying
Cytidine diphosphate choline (CDP-choline) has been applied for treating acute craniocerebral injury and allowing recovery of consciousness after brain surgery. In this study, an acetate kinase (ACK)/acetyl phosphate system was used to supply ATP and combined with Escherichia coli-overexpressed CMP kinase (CMK), NDP kinase (NDK), choline phosphate cytidylyltransferase (CCT), and choline kinase (CKI) to produce CDP-choline from CMP and choline chloride. Within 1 h, 49 mM CDP-choline was produced, for a molar yield of 89...
February 2017: Applied Microbiology and Biotechnology
Alexei Gorelik, Leonhard X Heinz, Katalin Illes, Giulio Superti-Furga, Bhushan Nagar
The enzyme acid sphingomyelinase-like phosphodiesterase 3B (SMPDL3B) was shown to act as a negative regulator of innate immune signaling, affecting cellular lipid composition and membrane fluidity. Furthermore, several reports identified this enzyme as an off target of the therapeutic antibody rituximab, with implications in kidney disorders. However, structural information for this protein is lacking. Here we present the high resolution crystal structure of murine SMPDL3B, which reveals a substrate binding site strikingly different from its paralogs...
November 11, 2016: Journal of Biological Chemistry
Joseph W Brewer, Viktoriya Solodushko, Ileana Aragon, Robert A Barrington
In activated B cells, increased production of phosphatidylcholine (PtdCho), the most abundant cellular phospholipid, is handled primarily by the CDP-choline pathway. B cell-specific deletion of CTP:phosphocholine cytidylyltransferase α (CCTα), the rate-limiting enzyme in the CDP-choline pathway, led to augmented IgM secretion and reduced IgG production, suggesting that PtdCho synthesis is required for germinal center reactions. To specifically assess whether PtdCho influences B cell fate during germinal center responses, we examined immune responses in mice whereby PtdCho synthesis is disrupted in B cells that have undergone class switch recombination to IgG1 (referred to as either Cγ1wt/wt , Cγ1Cre/wt or Cγ1Cre/Cre based on Cre copy number)...
December 2016: Cellular Immunology
Mun-Teng Wong, Steve S Chen
UNLABELLED: Hepatitis C virus (HCV) infection reorganizes cellular membranes to create an active viral replication site named the membranous web (MW). The role that human choline kinase-α (hCKα) plays in HCV replication remains elusive. Here, we first showed that hCKα activity, not the CDP-choline pathway, promoted viral RNA replication. Confocal microscopy and subcellular fractionation of HCV-infected cells revealed that a small fraction of hCKα colocalized with the viral replication complex (RC) on the endoplasmic reticulum (ER) and that HCV infection increased hCKα localization to the ER...
October 15, 2016: Journal of Virology
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