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CDP Choline

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...
December 23, 2016: 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...
October 27, 2016: 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...
October 8, 2016: 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 Cγ1(wt/wt), Cγ1(Cre/wt) or Cγ1(Cre/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
James P Brault, Jon A Friesen
The cytidylyltransferases are a family of enzymes that utilize cytidine 5'-triphosphate (CTP) to synthesize molecules that are typically precursors to membrane phospholipids. The most extensively studied cytidylyltransferase is CTP:phosphocholine cytidylyltransferase (CCT), which catalyzes conversion of phosphocholine and CTP to cytidine diphosphocholine (CDP-choline), a step critical for synthesis of the membrane phospholipid phosphatidylcholine (PC). The current method used to determine catalytic activity of CCT measures production of radiolabeled CDP-choline from (14)C-labeled phosphocholine...
October 1, 2016: Analytical Biochemistry
Konstantin Gavriljuk, Jonas Schartner, Hans Seidel, Clarissa Dickhut, Rene P Zahedi, Christian Hedberg, Carsten Kötting, Klaus Gerwert
The intracellular pathogen Legionella pneumophila infects lung macrophages and injects numerous effector proteins into the host cell to establish a vacuole for proliferation. The necessary interference with vesicular trafficking of the host is achieved by modulation of the function of Rab GTPases. The effector protein AnkX chemically modifies Rab1b and Rab35 by covalent phosphocholination of serine or threonine residues using CDP-choline as a donor. So far, the phosphoryl transfer mechanism and the relevance of observed autophosphocholination of AnkX remained disputable...
August 9, 2016: Biochemistry
Ariel B Ganz, Kelsey Shields, Vlad G Fomin, Yusnier S Lopez, Sanjay Mohan, Jessica Lovesky, Jasmine C Chuang, Anita Ganti, Bradley Carrier, Jian Yan, Siraphat Taeswuan, Vanessa V Cohen, Camille C Swersky, Julie A Stover, Gerardo A Vitiello, Olga V Malysheva, Erika Mudrak, Marie A Caudill
Although single nucleotide polymorphisms (SNPs) in folate-mediated pathways predict susceptibility to choline deficiency during severe choline deprivation, it is unknown if effects persist at recommended intakes. Thus, we used stable isotope liquid chromatography-mass spectrometry (LC-MS) methodology to examine the impact of candidate SNPs on choline metabolism in a long-term, randomized, controlled feeding trial among pregnant, lactating, and nonpregnant (NP) women consuming 480 or 930 mg/d choline (22% as choline-d9, with d9 indicating a deuterated trimethyl amine group) and meeting folate-intake recommendations...
October 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Jay S Kirkwood, Cristobal L Miranda, Gerd Bobe, Claudia S Maier, Jan F Stevens
The differentiation of precursor cells into mature adipocytes (adipogenesis) has been an area of increased focus, spurred by a rise in obesity rates. Though our understanding of adipogenesis and its regulation at the cellular level is growing, many questions remain, especially regarding the regulation of the metabolome. The 3T3-L1 cell line is the most well characterized cellular model of adipogenesis. Using a time course metabolomics approach, we show that the 3T3-L1 preadipocyte metabolome is greatly altered during the first 48 hours of differentiation, where cells go through about two rounds of cell division, a process known as mitotic clonal expansion...
2016: PloS One
Naoki Sato, Natsumi Mori, Takashi Hirashima, Takashi Moriyama
Phosphatidylcholine (PC) is an almost ubiquitous phospholipid in eukaryotic algae and plants but is not found in a few species, for example Chlamydomonas reinhardtii. We recently found that some species of the genus Chlamydomonas possess PC. In the universal pathway, PC is synthesized de novo by methylation of phosphatidylethanolamine (PE) or transfer of phosphocholine from cytidine diphosphate (CDP)-choline to diacylglycerol. Phosphocholine, the direct precursor to CDP-choline, is synthesized either by methylation of phosphoethanolamine or phosphorylation of choline...
August 2016: Plant Journal: for Cell and Molecular Biology
Sing Mei Lim, Kit Yeung, Lionel Trésaugues, Teo Hsiang Ling, Pär Nordlund
UNLABELLED: Human sphingomyelinase phosphodiesterase like 3a (SMPDL3a) is a secreted enzyme that shares a conserved catalytic domain with human acid sphingomyelinase (aSMase), the enzyme carrying mutations causative of Niemann-Pick disease. We have solved the structure of SMPDL3a revealing a calcineurin-like fold. A dimetal site, glycosylation pattern and a disulfide bond network are likely to be conserved also in human aSMase. We show that the binuclear site of SMPDL3a is occupied by two Zn(2+) ions and that excess Zn(2+) leads to inhibition of enzyme activity through binding to additional sites...
March 2016: FEBS Journal
Luce Farine, Moritz Niemann, André Schneider, Peter Bütikofer
Phosphatidylethanolamine (PE) and phosphatidylcholine (PC) are among the most abundant phospholipids in biological membranes. In many eukaryotes, the CDP-ethanolamine and CDP-choline branches of the Kennedy pathway represent major and often essential routes for the production of PE and PC, with ethanolamine and choline/ethanolamine phosphotransferases (EPT and CEPT, respectively) catalysing the last reactions in the respective pathways. Although the site of PE and PC synthesis is commonly known to be the endoplasmic reticulum (ER), detailed information on the localization of the different phosphotransferases is lacking...
2015: Scientific Reports
Luciana Paoletti, Pablo Domizi, Hebe Marcucci, Aneley Montaner, Dario Krapf, Gabriela Salvador, Claudia Banchio
Neuronal differentiation plays a key role during embryogenesis. However, based on the capacity of neuronal stem cells to either generate or regenerate neurons and because differentiation stops aberrant neuroblasts proliferation, neuronal differentiation is crucial during neuropathological conditions. Although phosphatidylcholine (PtdCho) has been proposed as an important molecule for neurite growth and neuronal regeneration, the identity of the molecular target has remained elusive. This study originally describes that lysophosphatidylcholine (LPtdCho), either exogenously supplied or generated by the imbalance of PtdCho metabolism through the enzymatic action of cytosolic phospholipase A2, acts as a neurotrophic-like factor...
November 14, 2015: Molecular Neurobiology
Elif Basaran Gundogdu, Ahmet Bekar, Mesut Turkyilmaz, Abdullah Gumus, Ilker Mustafa Kafa, Mehmet Cansev
BACKGROUND: CDP-choline (cytidine-5'-diphosphocholine) improves functional recovery, promotes nerve regeneration, and decreases perineural scarring in rat peripheral nerve injury. The aim of the present study was to investigate the mechanism of action of CDP-choline with regard to matrix metalloproteinase (MMP) activity in the rat-transected sciatic nerve injury model. MATERIALS AND METHODS: Male Wistar rats were randomized into Sham, Saline, and CDP-choline groups...
February 2016: Journal of Surgical Research
Jochen Frederick Hernekamp, Sissi Xi Hu, Volker Jürgen Schmidt, Julian Vogelpohl, Ulrich Kneser, Thomas Kremer
PURPOSE: The cholinergic anti-inflammatory pathway may play an important role in early burn edema. Therefore, we evaluated the influence of cdp-choline on early systemic burn edema and leukocyte activation in shock in rat mesenteries after burn plasma transfer. METHODS: Burn plasma harvested from donor rats 4 hours after thermal injury (30% total body surface area, 100°C water, 12 seconds) was administered intravenously to healthy animals during 2 hours of intravital microscopy...
October 2015: Annals of Plastic Surgery
Keshuai Li, Rolf Erik Olsen, Mari-Ann Østensen, Dag Altin, Elin Kjørsvik, Yngvar Olsen
The dietary requirement of phospholipid (PL) of fish larvae has been suggested to originate in an inefficient ability for de novo biosynthesis of PL based on dietary triacylglycerol (TAG). The main objective of the present study was to investigate whether cod larvae could synthesis PL from sn-2-monoacylglycerol (2-MAG) and glycerol precursors. A tube feeding method was used to deliver equal molar aliquots of 2-oleoyl-[1,2,3-(3)H]glycerol and [U-(14)C] glycerol together with bovine serum albumin (BSA) bound 16:0 (palmitic acid) and 22:6n-3 (docosahexaenoic acid, DHA), with or without choline chloride to the foregut of anesthetized cod larvae and thereafter monitoring the metabolism of these components in the larvae through 4 h following injection...
February 2016: Fish Physiology and Biochemistry
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