Top Publications

  1. ncbi Antibodies against cyclic citrullinated peptide and IgA rheumatoid factor predict the development of rheumatoid arthritis
    Solbritt Rantapaa-Dahlqvist
    Umea Universitet, Umea, Sweden
    Arthritis Rheum 48:2741-9. 2003
  2. pmc Induction of osteoclastogenesis and bone loss by human autoantibodies against citrullinated vimentin
    Ulrike Harre
    Department of Internal Medicine 3, University of Erlangen Nuremberg, Erlangen, Germany
    J Clin Invest 122:1791-802. 2012
  3. ncbi Autoimmunity to specific citrullinated proteins gives the first clues to the etiology of rheumatoid arthritis
    Natalia Wegner
    The Kennedy Institute of Rheumatology, Imperial College London, London, UK
    Immunol Rev 233:34-54. 2010
  4. ncbi Immunity to citrullinated proteins in rheumatoid arthritis
    Lars Klareskog
    Rheumatology Unit, Department of Medicine, Karolinska Institutet Karolinska University Hospital, SE 171 76, Stockholm, Sweden
    Annu Rev Immunol 26:651-75. 2008
  5. ncbi Citrullination: a posttranslational modification in health and disease
    Bence György
    Department of Genetics, Cell and Immunobiology, Semmelweis University, Budapest, Hungary
    Int J Biochem Cell Biol 38:1662-77. 2006
  6. ncbi Specific autoantibodies precede the symptoms of rheumatoid arthritis: a study of serial measurements in blood donors
    Markus M J Nielen
    Jan van Breemen Institute, Amsterdam, The Netherlands
    Arthritis Rheum 50:380-6. 2004
  7. pmc Inhibitors and inactivators of protein arginine deiminase 4: functional and structural characterization
    Yuan Luo
    Department of Chemistry and Biochemistry, University of South Carolina, 631 Sumter Street, Columbia, South Carolina 29208, USA
    Biochemistry 45:11727-36. 2006
  8. ncbi Response of Th17 cells to a citrullinated arthritogenic aggrecan peptide in patients with rheumatoid arthritis
    Alexei von Delwig
    Newcastle University, Newcastle upon Tyne, UK
    Arthritis Rheum 62:143-9. 2010
  9. pmc Autoantibody systems in rheumatoid arthritis: specificity, sensitivity and diagnostic value
    Martinus A M van Boekel
    Department of Biochemistry, University of Nijmegen, PO Box 9101, 6500 HB Nijmegen, The Netherlands
    Arthritis Res 4:87-93. 2002
  10. ncbi Antibodies to citrullinated alpha-enolase peptide 1 are specific for rheumatoid arthritis and cross-react with bacterial enolase
    Karin Lundberg
    Kennedy Institute of Rheumatology, Imperial College London, London, UK
    Arthritis Rheum 58:3009-19. 2008

Detail Information

Publications299 found, 100 shown here

  1. ncbi Antibodies against cyclic citrullinated peptide and IgA rheumatoid factor predict the development of rheumatoid arthritis
    Solbritt Rantapaa-Dahlqvist
    Umea Universitet, Umea, Sweden
    Arthritis Rheum 48:2741-9. 2003
  2. pmc Induction of osteoclastogenesis and bone loss by human autoantibodies against citrullinated vimentin
    Ulrike Harre
    Department of Internal Medicine 3, University of Erlangen Nuremberg, Erlangen, Germany
    J Clin Invest 122:1791-802. 2012
    ..Our data thus suggest that autoantibody formation in response to citrullinated vimentin directly induces bone loss, providing a link between the adaptive immune system and bone...
  3. ncbi Autoimmunity to specific citrullinated proteins gives the first clues to the etiology of rheumatoid arthritis
    Natalia Wegner
    The Kennedy Institute of Rheumatology, Imperial College London, London, UK
    Immunol Rev 233:34-54. 2010
    ..Thus, both smoking and Porphyromonas gingivalis are attractive etiological agents for further investigation into the gene/environment/autoimmunity triad of RA...
  4. ncbi Immunity to citrullinated proteins in rheumatoid arthritis
    Lars Klareskog
    Rheumatology Unit, Department of Medicine, Karolinska Institutet Karolinska University Hospital, SE 171 76, Stockholm, Sweden
    Annu Rev Immunol 26:651-75. 2008
    ..e., to peptides posttranslationally modified by the conversion of arginine to citrulline, are specific serological markers for rheumatoid arthritis (RA)...
  5. ncbi Citrullination: a posttranslational modification in health and disease
    Bence György
    Department of Genetics, Cell and Immunobiology, Semmelweis University, Budapest, Hungary
    Int J Biochem Cell Biol 38:1662-77. 2006
    ..Introduction of citrulline dramatically changes the structure and function of proteins...
  6. ncbi Specific autoantibodies precede the symptoms of rheumatoid arthritis: a study of serial measurements in blood donors
    Markus M J Nielen
    Jan van Breemen Institute, Amsterdam, The Netherlands
    Arthritis Rheum 50:380-6. 2004
    ..The present study was undertaken to investigate this...
  7. pmc Inhibitors and inactivators of protein arginine deiminase 4: functional and structural characterization
    Yuan Luo
    Department of Chemistry and Biochemistry, University of South Carolina, 631 Sumter Street, Columbia, South Carolina 29208, USA
    Biochemistry 45:11727-36. 2006
    ..coregulator that catalyzes the calcium-dependent conversion of specific arginine residues in proteins to citrulline. Recently, we reported the synthesis and characterization of F-amidine, a potent and bioavailable irreversible ..
  8. ncbi Response of Th17 cells to a citrullinated arthritogenic aggrecan peptide in patients with rheumatoid arthritis
    Alexei von Delwig
    Newcastle University, Newcastle upon Tyne, UK
    Arthritis Rheum 62:143-9. 2010
    ..The aim of this study was to investigate whether T cells specific for citrullinated epitopes from self proteins are present in patients with RA...
  9. pmc Autoantibody systems in rheumatoid arthritis: specificity, sensitivity and diagnostic value
    Martinus A M van Boekel
    Department of Biochemistry, University of Nijmegen, PO Box 9101, 6500 HB Nijmegen, The Netherlands
    Arthritis Res 4:87-93. 2002
    ..We conclude that, at present, the antibody response directed to citrullinated antigens has the most valuable diagnostic and prognostic potential for RA...
  10. ncbi Antibodies to citrullinated alpha-enolase peptide 1 are specific for rheumatoid arthritis and cross-react with bacterial enolase
    Karin Lundberg
    Kennedy Institute of Rheumatology, Imperial College London, London, UK
    Arthritis Rheum 58:3009-19. 2008
    ..To map the antibody response to human citrullinated alpha-enolase, a candidate autoantigen in rheumatoid arthritis (RA), and to examine cross-reactivity with bacterial enolase...
  11. ncbi Almost all about citrulline in mammals
    E Curis
    Laboratoire de Biomathématiques, E A 2498, Faculte de Pharmacie, Universite Rene Descartes, Paris, France
    Amino Acids 29:177-205. 2005
    b>Citrulline (Cit, C6H13N3O3), which is a ubiquitous amino acid in mammals, is strongly related to arginine. Citrulline metabolism in mammals is divided into two fields: free citrulline and citrullinated proteins...
  12. ncbi Increased citrullination of histone H3 in multiple sclerosis brain and animal models of demyelination: a role for tumor necrosis factor-induced peptidylarginine deiminase 4 translocation
    Fabrizio G Mastronardi
    Department of Structural Biology and Biochemistry, The Hospital for Sick Children, Toronto, Ontario, Canada M5G 1X8
    J Neurosci 26:11387-96. 2006
    ..In conclusion, high citrullination of histones consequent to PAD4 nuclear translocation is part of the process that leads to irreversible changes in oligodendrocytes and may contribute to apoptosis of oligodendrocytes in MS...
  13. ncbi Citrulline: from metabolism to therapeutic use
    Senda Bahri
    Laboratoire de Pharmacie Galenique, Faculté de Pharmacie de Monastir, Monastir, Tunisia
    Nutrition 29:479-84. 2013
    b>Citrulline possesses a highly specific metabolism that bypasses splanchnic extraction because it is not used by the intestine or taken up by the liver...
  14. ncbi Pathogenesis of autoimmune diseases: antibodies against transglutaminase, peptidylarginine deiminase and protein-bound citrulline in primary Sjögren's syndrome, multiple sclerosis and Alzheimer's disease
    E Bodil Roth
    Hospital Pharmacy, Malmo University Hospital, Malmo, Sweden
    Scand J Immunol 67:626-31. 2008
    ..The prevalence of anti-PAD, anti-TG2 and ACPA is comparatively restricted. PAD and TG2 do not seem to be involved directly in autoimmune mechanisms in pSS, MS or AD...
  15. pmc T-cell autoreactivity to citrullinated autoantigenic peptides in rheumatoid arthritis patients carrying HLA-DRB1 shared epitope alleles
    Soi Cheng Law
    The University of Queensland Diamantina Institute, Princess Alexandra Hospital, Brisbane, QLD 4102, Australia
    Arthritis Res Ther 14:R118. 2012
    ..To characterise T-cell autoreactivity towards citrullinated self-epitopes, we profiled responses of SE+ healthy controls and RA patients to citrullinated and unmodified epitopes of four autoantigens...
  16. ncbi The periodontium of periodontitis patients contains citrullinated proteins which may play a role in ACPA (anti-citrullinated protein antibody) formation
    Willem Nesse
    Department of Oral and Maxillofacial Surgery, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands
    J Clin Periodontol 39:599-607. 2012
    ..To determine the presence and location (stroma versus epithelium) of citrullinated proteins in periodontitis tissue as compared to non-periodontitis tissue and synovial tissue of RA patients...
  17. ncbi Systemic L-citrulline prevents cerebral vasospasm in haptoglobin 2-2 transgenic mice after subarachnoid hemorrhage
    Gustavo Pradilla
    The Johns Hopkins University School of Medicine, Department of Neurosurgery, Baltimore, Maryland 21287, USA
    Neurosurgery 70:747-56; discussion 756-7. 2012
    ..L-Citrulline increases L-arginine levels, thereby raising NO synthesis...
  18. ncbi Protein carbamylation links inflammation, smoking, uremia and atherogenesis
    Zeneng Wang
    Department of Cell Biology, Cleveland Clinic, Cleveland, Ohio 44195, USA
    Nat Med 13:1176-84. 2007
    ..We propose that protein carbamylation is a mechanism linking inflammation, smoking, uremia and coronary artery disease pathogenesis...
  19. pmc Arginase activities and global arginine bioavailability in wild-type and ApoE-deficient mice: responses to high fat and high cholesterol diets
    Aaron Erdely
    Toxicology and Molecular Biology Branch, National Institute for Occupational Safety and Health, Morgantown, West Virginia, United States of America
    PLoS ONE 5:e15253. 2010
    ..and tissues and on global arginine bioavailability (defined as the ratio of plasma arginine to ornithine + citrulline) in apoE(-/-) and wild-type C57BL/6J mice...
  20. pmc Expression and activity of citrullinating peptidylarginine deiminase enzymes in monocytes and macrophages
    E R Vossenaar
    Department of Biochemistry, University of Nijmegen, Nijmegen, The Netherlands
    Ann Rheum Dis 63:373-81. 2004
    Antibodies directed to proteins containing the non-standard amino acid citrulline, are extremely specific for rheumatoid arthritis (RA). Peptidylcitrulline can be generated by post-translational conversion of arginine residues...
  21. pmc Pharmacokinetic and pharmacodynamic properties of oral L-citrulline and L-arginine: impact on nitric oxide metabolism
    Edzard Schwedhelm
    Institute of Experimental and Clinical Pharmacology and Toxicology, University Medical Centre Hamburg Eppendorf, Germany
    Br J Clin Pharmacol 65:51-9. 2008
    ..In contrast, L-citrulline is readily absorbed and at least in part converted to L-arginine...
  22. ncbi Histone deimination antagonizes arginine methylation
    Graeme L Cuthbert
    Gurdon Institute and Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, United Kingdom
    Cell 118:545-53. 2004
    ..Here we describe a process, deimination, that converts histone arginine to citrulline and antagonizes arginine methylation...
  23. pmc Regulation of nitric oxide production in health and disease
    Yvette C Luiking
    Center for Translational Research in Aging and Longevity, Donald W Reynolds Institute on Aging, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA
    Curr Opin Clin Nutr Metab Care 13:97-104. 2010
    ..The purpose of this review is to highlight recent publications examining nitric oxide production in health and disease and its association with clinical nutrition and alterations in metabolism...
  24. pmc Citrullination is an inflammation-dependent process
    D Makrygiannakis
    Department of Medicine, Rheumatology Unit, CMM, L8 04, Karolinska University Hospital, Solna, S 17176 Stockholm, Sweden
    Ann Rheum Dis 65:1219-22. 2006
    ..To study the presence of citrullinated proteins in inflammatory conditions and in clinically non-affected tissues of controls...
  25. ncbi Effects of maternal L-citrulline supplementation on renal function and blood pressure in offspring exposed to maternal caloric restriction: the impact of nitric oxide pathway
    You Lin Tain
    Department of Pediatrics, Chang Gung Memorial Hospital Kaohsiung Medical Center, Chang Gung University, College of Medicine, Taiwan
    Nitric Oxide 23:34-41. 2010 kidney disease vulnerability in offspring from mothers with caloric restriction diets and whether maternal L-citrulline (L-Cit) supplementation can prevent this...
  26. ncbi Deimination of arginine residues in nucleophosmin/B23 and histones in HL-60 granulocytes
    Teruki Hagiwara
    Graduate School of Integrated Science, Yokohama City University, 22 2, Seto, Kanazawa Ku, Yokohama, 236 0027, Japan
    Biochem Biophys Res Commun 290:979-83. 2002
    Peptidylarginine deiminases (PADs) convert arginine residues in proteins into citrulline residues Ca(2+)-dependently. PAD V was recently found in granulocyte-differentiated HL-60 cells...
  27. ncbi Renal cell carcinoma does not express argininosuccinate synthetase and is highly sensitive to arginine deprivation via arginine deiminase
    Cheol Yong Yoon
    Department of Urology, College of Medicine, Korea University, Seoul 136 705, Korea
    Int J Cancer 120:897-905. 2007
    ..its antitumor activity largely depends on the level of intracellular ASS, which enables tumor cells to recycle citrulline to arginine...
  28. ncbi Anti-cyclic citrullinated peptide antibodies are a collection of anti-citrullinated protein antibodies and contain overlapping and non-overlapping reactivities
    Andreea Ioan-Facsinay
    Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands
    Ann Rheum Dis 70:188-93. 2011
    ..Likewise, it is unknown to what extent antibody responses to different citrullinated antigens are crossreactive...
  29. ncbi Human PAD4 regulates histone arginine methylation levels via demethylimination
    Yanming Wang
    Department of Genetic Medicine, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, USA
    Science 306:279-83. 2004
    ..that human peptidylarginine deiminase 4 (PAD4) regulates histone Arg methylation by converting methyl-Arg to citrulline and releasing methylamine...
  30. ncbi Contribution of myelin autoantigen citrullination to T cell autoaggression in the central nervous system
    Antonio Carrillo-Vico
    Centre for Inflammation Research, Queen s Medical Research Institute, University of Edinburgh, Edinburgh, United Kingdom
    J Immunol 184:2839-46. 2010
    ..A posttranslational modification of particular interest is the deimination of Arg to citrulline, catalyzed by peptidylarginyl deiminase (PAD) enzymes...
  31. pmc Different patterns of associations with anti-citrullinated protein antibody-positive and anti-citrullinated protein antibody-negative rheumatoid arthritis in the extended major histocompatibility complex region
    Bo Ding
    Karolinska Institutet, Stockholm, Sweden
    Arthritis Rheum 60:30-8. 2009
  32. pmc Clinical utility of the anti-CCP assay in patients with rheumatic diseases
    D M Lee
    Department of Medicine, Division of Rheumatology, Immunology and Allergy Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Ann Rheum Dis 62:870-4. 2003
    ..To determine the frequency of antibodies to cyclic citrullinated peptides (CCP) in a group of patients with a diversity of rheumatic diseases...
  33. ncbi Multiple antibody reactivities to citrullinated antigens in sera from patients with rheumatoid arthritis: association with HLA-DRB1 alleles
    O Snir
    Department of Medicine, Rheumatology Unit, Karolinska University Hospital, Karolinska Institute, Solna, Stockholm, Sweden
    Ann Rheum Dis 68:736-43. 2009
    ..Autoantibodies to cyclic citrullinated peptides (anti-CCP) are present in most patients with rheumatoid arthritis (RA), and associate with HLA-DRB1 shared epitope (SE) alleles...
  34. ncbi Localization of peptidylarginine deiminase 4 (PADI4) and citrullinated protein in synovial tissue of rheumatoid arthritis
    X Chang
    Laboratory for Rheumatic Diseases, SNP Research Center, Institute of Physical and Chemical Research RIKEN, 1 7 22 Suehiro, Tsurumi ku, Yokohama, Kanagawa 230 0045, Japan
    Rheumatology (Oxford) 44:40-50. 2005
    Peptidylarginine deiminases (PADIs) convert peptidylarginine into citrulline via post-translational modification. Anti-citrullinated peptide antibodies are highly specific for rheumatoid arthritis (RA)...
  35. ncbi Antibody against mutated citrullinated vimentin: a new sensitive marker in the diagnosis of rheumatoid arthritis
    Ernst Wagner
    Institute for Rheumatology of the Kurstadt Baden RSKA Baden of the NOEGKK and Ludwig Boltzmann Cluster Rheumatology, Balneology and Rehabilitation, Forschungsstelle for Epidemiology of Rheumatic Diseases, 2500 Baden, Austria
    Rheumatol Int 29:1315-21. 2009
    ..In a subgroup of 86 RA patients we found a significant correlation between anti-MCV and disease activity. Anti-MCV appears to be an important marker for the diagnosis of RA, and correlates also with disease activity...
  36. pmc Proteomic analysis of secreted proteins in early rheumatoid arthritis: anti-citrulline autoreactivity is associated with up regulation of proinflammatory cytokines
    Wolfgang Hueber
    Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, and Palo Alto VA Health Care System, MC 154R, 3801 Miranda Avenue, Palo Alto, CA 94304, USA
    Ann Rheum Dis 66:712-9. 2007
    ..To identify peripheral blood autoantibody and cytokine profiles that characterise clinically relevant subgroups of patients with early rheumatoid arthritis using arthritis antigen microarrays and a multiplex cytokine assay...
  37. ncbi Oral L-citrulline supplementation attenuates blood pressure response to cold pressor test in young men
    Arturo Figueroa
    Department of Nutrition, Food and Exercise Sciences, College of Human Sciences, Florida State University, Tallahassee, Florida, USA
    Am J Hypertens 23:12-6. 2010
    Oral L-citrulline is efficiently converted to L-arginine, which has been shown to decrease brachial blood pressure (BP) at rest and during the cold pressor test (CPT)...
  38. pmc Role of L-citrulline transport in nitric oxide synthesis in rat aortic smooth muscle cells activated with LPS and interferon-gamma
    Samantha M Wileman
    Centre for Cardiovascular Biology and Medicine, GKT School of Biomedical Sciences, King s College London, Guy s Campus, London SE1 1UL
    Br J Pharmacol 140:179-85. 2003
    1) l-citrulline, a coproduct of nitric oxide synthase (NOS)-catalysed metabolism of l-arginine to nitric oxide (NO), is an important intermediate of the urea cycle and a precursor for l-arginine biosynthesis in vascular cells...
  39. ncbi Organic anion transporter OAT1 is involved in renal handling of citrulline
    Masanori Nakakariya
    Department of Membrane Transport and Pharmacokinetics, Faculty of Pharmaceutical Sciences, Tokyo University ofScience, Tokyo, Japan
    Am J Physiol Renal Physiol 297:F71-9. 2009
    Because citrulline plasma concentration is elevated in kidney failure, citrulline could be a biomarker of renal insufficiency, although the mechanism regulating its disposition in the kidney has not been clarified...
  40. ncbi Anti-citrullinated protein/peptide antibodies (ACPA) in rheumatoid arthritis: specificity and relation with rheumatoid factor
    B Vander Cruyssen
    Department of Rheumatology, Ghent University Hospital, B 9000 Gent, Belgium
    Autoimmun Rev 4:468-74. 2005
    ..Indeed, both antibody systems have a different association with specific RA features like extra-articular manifestations, a different association with the HLA shared epitope and, behave differently following anti-TNF therapy...
  41. ncbi Diagnostic value of anti-cyclic citrullinated Peptide antibody in patients with rheumatoid arthritis
    Xiaofeng Zeng
    Department of Rheumatology, Chinese Academy of Medical Science, Peking Union Medical College Hospital, Beijing, China
    J Rheumatol 30:1451-5. 2003
    ..To explore the diagnostic value of anti-cyclic citrullinated peptide antibody (anti-CCP) detected by ELISA in patients with rheumatoid arthritis (RA)...
  42. ncbi Plasma citrulline: A marker of enterocyte mass in villous atrophy-associated small bowel disease
    Pascal Crenn
    Department of Hepagastroenterology and Nutrion Support, Hopital Lariboisiere, Paris, France
    Gastroenterology 124:1210-9. 2003
    Plasma citrulline, a nonprotein amino acid produced by enterocytes, was suggested as a marker of remnant enterocyte mass in patients with short bowel...
  43. ncbi Antibodies to several citrullinated antigens are enriched in the joints of rheumatoid arthritis patients
    Omri Snir
    Karolinska University Hospital, Karolinska Institutet at Solna, Stockholm, Sweden
    Arthritis Rheum 62:44-52. 2010
    ..Furthermore, we studied their relationships with mutated citrullinated vimentin (MCV), a newly identified RA-specific serum assay, and the classic cyclic citrullinated peptide (CCP) in the synovial fluid of well-defined HLA-DR groups...
  44. pmc Diminished global arginine bioavailability and increased arginine catabolism as metabolic profile of increased cardiovascular risk
    W H Wilson Tang
    Center for Cardiovascular Diagnostics and Prevention, Department of Cell Biology, Lerner Research Institute, Cleveland, OH, USA
    J Am Coll Cardiol 53:2061-7. 2009
    ..We hypothesized that an integrated assessment of arginine with its catabolic products might better predict cardiovascular risks than arginine levels alone...
  45. ncbi Rheumatoid factor and antibodies to cyclic citrullinated Peptide differentiate rheumatoid arthritis from undifferentiated polyarthritis in patients with early arthritis
    Annemarie L M A Jansen
    Jan van Breemen Instituut and the Department of Rheumatology, VU Medical Center, Amsterdam, The Netherlands
    J Rheumatol 29:2074-6. 2002
  46. ncbi Anti-cyclic citrullinated peptide antibodies, IgM and IgA rheumatoid factors in the diagnosis and prognosis of rheumatoid arthritis
    S Bas
    Division of Rheumatology, Department of Internal Medicine, University Hospital, Geneva, Switzerland
    Rheumatology (Oxford) 42:677-80. 2003
  47. ncbi Diagnostic and prognostic usefulness of antibodies to citrullinated peptides
    Vincent Goeb
    Service de Rhumatologie, Institut de recherche biomédicale, CHU Hôpitaux de Rouen, France
    Joint Bone Spine 76:343-9. 2009
    ..The presence of ACPAs predicts poorer functional and structural outcomes, and ACPA titers respond to some of the medications used in RA. Therefore, ACPA titers should be determined at regular intervals throughout follow-up...
  48. ncbi Decreased glutamate, glutamine and citrulline concentrations in plasma and muscle in endotoxemia cannot be reversed by glutamate or glutamine supplementation: a primary intestinal defect?
    Claire Boutry
    INRA, CNRH IdF, UMR914 Nutrition Physiology and Ingestive Behavior, 16 rue Claude Bernard, 75005 Paris, France
    Amino Acids 43:1485-98. 2012
    Endotoxemia affects intestinal physiology. A decrease of circulating citrulline concentration is considered as a reflection of the intestinal function. Citrulline can be produced in enterocytes notably from glutamate and glutamine...
  49. ncbi Generation of a mouse model for citrullinemia by targeted disruption of the argininosuccinate synthetase gene
    G Patejunas
    Institute for Molecular Genetics, Baylor College of Medicine, Houston, Texas 77030
    Somat Cell Mol Genet 20:55-60. 1994
    Argininosuccinate synthetase (ASS) is a urea cycle enzyme that forms argininosuccinate from citrulline and aspartate. Mutations at the ASS locus in man cause the inherited disease, citrullinemia...
  50. ncbi Relative contribution of different l-arginine sources to the substrate supply of endothelial nitric oxide synthase
    Susanne Karbach
    Department of Pharmacology, University Medical Center of the Johannes Gutenberg University Mainz, Germany
    J Mol Cell Cardiol 51:855-61. 2011
    ..hy.926 endothelial cells demonstrated that eNOS can obtain its substrate from the conversion of l-citrulline to l-arginine and from protein breakdown...
  51. pmc Impaired early B cell tolerance in patients with rheumatoid arthritis
    Jonathan Samuels
    Laboratory of Biochemistry and Molecular Immunology, Hospital for Special Surgery, Cornell University, New York, NY 10021, USA
    J Exp Med 201:1659-67. 2005
    ..Thus, RA patients exhibit defective B cell tolerance checkpoints that may favor the development of autoimmunity...
  52. ncbi Citrullination of autoantigens: upstream of TNFα in the pathogenesis of rheumatoid arthritis
    Anne Marie Quirke
    Kennedy Institute of Rheumatology, Imperial College London, London, UK
    FEBS Lett 585:3681-8. 2011
  53. ncbi Association between glutamine extraction and release of citrulline and glycine by the human small intestine
    Tetsuji Fujita
    Department of Surgery, Jikei University School of Medicine, Tokyo, Japan
    Life Sci 80:1846-50. 2007
    ..45%, approximately 3 times higher than 9.41% in the distal colon. Citrulline, proline, alanine, glycine, and arginine were released by the small intestine into the portal circulation...
  54. pmc Citrulline a more suitable substrate than arginine to restore NO production and the microcirculation during endotoxemia
    Karolina A P Wijnands
    Department of Surgery, Maastricht University Medical Center, Maastricht, The Netherlands
    PLoS ONE 7:e37439. 2012
    ..We hypothesized that supplementation of the arginine precursor citrulline rather than arginine would specifically increase eNOS-induced intracellular NO production and thereby improve ..
  55. pmc Prolonged hypoxia augments L-citrulline transport by system A in the newborn piglet pulmonary circulation
    Candice D Fike
    Department of Pediatrics, University School of Medicine, Vanderbilt University Medical Center, 2215 B Garland Ave, Nashville, TN 37232 0656, USA
    Cardiovasc Res 95:375-84. 2012
    ..arterial endothelial cells (PAECs) express the enzymes needed for generation of l-arginine from intracellular l-citrulline but do not express the enzymes needed for de novo l-citrulline synthesis...
  56. pmc Interactions between the NO-citrulline cycle and brain-derived neurotrophic factor in differentiation of neural stem cells
    Claudiana Lameu
    Departamento de Bioquimica, Instituto de Quimica, Universidade de Sao Paulo, 05508 900 Sao Paulo, Brazil
    J Biol Chem 287:29690-701. 2012
    ..Argininosuccinate synthase (AS) is a ubiquitous enzyme in mammals and the key enzyme of the NO-citrulline cycle, because it provides the substrate L-arginine for subsequent NO synthesis by inducible, endothelial, and ..
  57. ncbi Small intestinal alterations in severely obese hyperglycemic subjects
    Froukje J Verdam
    Department of General Surgery, School for Nutrition, Toxicology, and Metabolism Research Institute Maastricht, Maastricht University Medical Center, 6200 MD Maastricht, The Netherlands
    J Clin Endocrinol Metab 96:E379-83. 2011
    ..Type 2 diabetes mellitus (DM2) is associated with small intestinal hyperplasia and hypertrophy in rodents. Moreover, the small intestine is increasingly acknowledged to play a role in the pathophysiology of DM2...
  58. pmc IgG subclass distribution of the rheumatoid arthritis-specific autoantibodies to citrullinated fibrin
    S Chapuy-Regaud
    Laboratory of Epidermis Differentiation and Rheumatoid Autoimmunity, UMR 5165 CNRS Toulouse III University, Toulouse, France
    Clin Exp Immunol 139:542-50. 2005
  59. ncbi Citrulline as a biomarker of intestinal failure due to enterocyte mass reduction
    Pascal Crenn
    Departement de Medecine, Hopital Raymond Poincare, Assistance Publique Hopitaux de Paris, Universite de Versailles Saint Quentin en Yvelines, Garches, France
    Clin Nutr 27:328-39. 2008
    In human, citrulline (plasma concentration about 40 micromol/L) is an amino acid involved in intermediary metabolism and that is not incorporated in proteins. Circulating citrulline is mainly produced by enterocytes of the small bowel...
  60. pmc HLA-DR1001 presents "altered-self" peptides derived from joint-associated proteins by accepting citrulline in three of its binding pockets
    Eddie A James
    Benaroya Research Institute at Virginia Mason, Seattle, Washington, USA
    Arthritis Rheum 62:2909-18. 2010
    ..The present study was undertaken to assess the capacity of DR1001 to accommodate citrulline in its binding pockets and to identify citrullinated T cell epitopes derived from joint-associated proteins.
  61. ncbi Anti-mutated citrullinated vimentin (anti-MCV) and anti-65 kDa heat shock protein (anti-hsp65): new biomarkers in ankylosing spondylitis
    Nóra Bodnár
    Department of Rheumatology, Institute of Medicine, Medical and Health Science Center, University of Debrecen, 98, Nagyerdei street, 4012 Debrecen, Hungary
    Joint Bone Spine 79:63-6. 2012
    ..As new laboratory biomarkers of AS are needed, we investigated the prevalence of anti-mutated citrullinated vimentin (MCV) and anti-hsp65 antibodies in AS...
  62. ncbi Anticitrulline antibodies can be caused by homocitrulline-containing proteins in rabbits
    Sanna Turunen
    University of Oulu, Oulu, Finland
    Arthritis Rheum 62:3345-52. 2010
    To clarify the possible roles of protein-bound homocitrulline in causing an antibody response to citrulline and as a confounding factor in citrulline detection assays.
  63. ncbi Arginine bioavailability ratios are associated with cardiovascular mortality in patients referred to coronary angiography
    Harald Sourij
    Division of Endocrinology and Metabolism, Department of Internal Medicine, Medical University of Graz, Graz, Austria
    Atherosclerosis 218:220-5. 2011
    ..The aim of the current study is to investigate the association of arginine bioavailability ratios with markers of endothelial function and cardiovascular mortality in patients referred to coronary angiography...
  64. ncbi L-Citrulline ameliorates chronic hypoxia-induced pulmonary hypertension in newborn piglets
    Madhumita Ananthakrishnan
    Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, Nashville, TN, USA
    Am J Physiol Lung Cell Mol Physiol 297:L506-11. 2009
    ..NO synthase (eNOS) in the pulmonary vascular endothelium using l-arginine as a substrate and producing l-citrulline as a byproduct...
  65. ncbi Citrullination of central nervous system proteins during the development of experimental autoimmune encephalomyelitis
    Reinout Raijmakers
    Department of Biochemistry, Nijmegen Center for Molecular Life Sciences, Radboud University Nijmegen, NL 6500 HB Nijmegen, The Netherlands
    J Comp Neurol 486:243-53. 2005
    ..This is the first report in which hypercitrullination of CNS proteins in EAE is described and in which proteins other than myelin basic protein are reported to be citrullinated during autoimmune-mediated CNS inflammation...
  66. ncbi Effects of L-citrulline oral supplementation on polymorphonuclear neutrophils oxidative burst and nitric oxide production after exercise
    Antoni Sureda
    Laboratori de Ciencies de l Activitat Fisica, Departament de Biologia Fonamental i Ciencies de la Salut, Universitat de les Illes Balears, Palma de Mallorca, Illes Balears, Spain
    Free Radic Res 43:828-35. 2009
    Seventeen volunteer male professional cyclists were randomly assigned to control or supplemented (6 g L-citrulline-malate) groups and participated in a cycling stage...
  67. ncbi Resistance to the anti-proliferative activity of recombinant arginine deiminase in cell culture correlates with the endogenous enzyme, argininosuccinate synthetase
    Li Jiuan Shen
    Department of Pharmaceutical Sciences, University of Southern California School of Pharmacy, PSC 404B, 1985 Zonal Avenue, Los Angeles, CA 90089 9121, USA
    Cancer Lett 191:165-70. 2003
    ..The activity of argininosuccinate synthetase (AS), the rate-limiting enzyme for converting citrulline to arginine, was also measured...
  68. pmc Restoration of impaired nitric oxide production in MELAS syndrome with citrulline and arginine supplementation
    Ayman W El-Hattab
    Division of Medical Genetics, Department of Child Health, University of Missouri Health Care, Columbia, MO 65212, USA
    Mol Genet Metab 105:607-14. 2012
    ..aimed to assess NO production in subjects with MELAS syndrome and the effect of the NO precursors arginine and citrulline. Using stable isotope infusion techniques, we assessed arginine, citrulline, and NO metabolism in control ..
  69. ncbi L-arginine uptake, the citrulline-NO cycle and arginase II in the rat brain: an in situ hybridization study
    O Braissant
    Central Clinical Chemistry Laboratory, University Hospital, CH 1011, Lausanne, Switzerland
    Brain Res Mol Brain Res 70:231-41. 1999
    ..Arginine can also be recycled from the citrulline produced by NOS activity, through argininosuccinate synthetase (AS) and argininosuccinate lyase (AL) activities, ..
  70. ncbi Functional haplotypes of PADI4, encoding citrullinating enzyme peptidylarginine deiminase 4, are associated with rheumatoid arthritis
    Akari Suzuki
    Laboratory for Rheumatic Diseases, SNP Research Center, The Institute of Physical and Chemical Research RIKEN, 1 7 22, Suehirocho, Tsurumi ku, Yokohama City, Kanagawa 230 0045, Japan
    Nat Genet 34:395-402. 2003
    ..Our results imply that the PADI4 haplotype associated with susceptibility to rheumatoid arthritis increases production of citrullinated peptides acting as autoantigens, resulting in heightened risk of developing the disease...
  71. ncbi L-citrulline reduces time to exhaustion and insulin response to a graded exercise test
    Robert C Hickner
    Human Performance Laboratory, East Carolina University, Greenville, NC 27858, USA
    Med Sci Sports Exerc 38:660-6. 2006
    ..Furthermore, L-citrulline supplementation increases plasma L-arginine concentration to a level higher than that achieved by oral L-..
  72. ncbi Involvement of peptidylarginine deiminase-mediated post-translational citrullination in pathogenesis of sporadic Creutzfeldt-Jakob disease
    Byungki Jang
    Ilsong Institute of Life Science, Hallym University, Anyang, Republic of Korea
    Acta Neuropathol 119:199-210. 2010
    ..processes play key roles in protein functions and structural stability through the conversion of arginine to citrulline in the presence of excessive calcium concentrations...
  73. ncbi Citrulline and arginine utility in treating nitric oxide deficiency in mitochondrial disorders
    Ayman W El-Hattab
    Medical Genetics Section, Department of Pediatrics, The Children s Hospital at King Fahad Medical City and King Saud bin Abdulaziz University for Health Science, Riyadh, Kingdom of Saudi Arabia
    Mol Genet Metab 107:247-52. 2012
    ..shunting into reactive nitrogen species formation, and decreased availability of the NO precursors arginine and citrulline. Arginine and citrulline supplementation can result in increased NO production and hence potentially have ..
  74. ncbi Synovial fluid is a site of citrullination of autoantigens in inflammatory arthritis
    Andrew Kinloch
    Imperial College London, London, UK
    Arthritis Rheum 58:2287-95. 2008
    ..To examine synovial fluid as a site for generating citrullinated antigens, including the candidate autoantigen citrullinated alpha-enolase, in rheumatoid arthritis (RA)...
  75. ncbi A new model for an etiology of rheumatoid arthritis: smoking may trigger HLA-DR (shared epitope)-restricted immune reactions to autoantigens modified by citrullination
    Lars Klareskog
    Rheumatology Unit, Department of Medicine, Karolinska Institutet Karolinska University Hospital, 171 76 Stockholm, Sweden
    Arthritis Rheum 54:38-46. 2006
    To investigate whether smoking and HLA-DR shared epitope (SE) genes may interact in triggering immune reactions to citrulline-modified proteins.
  76. pmc Intravenous administration of L-citrulline to pregnant ewes is more effective than L-arginine for increasing arginine availability in the fetus
    Arantzatzu Lassala
    Department of Animal Science, Texas A and M University, College Station, TX 77843, USA
    J Nutr 139:660-5. 2009
    ..Therefore, we used an ovine model to test the hypothesis that infusion of L-citrulline into the maternal circulation increases L-arginine availability to the fetus...
  77. ncbi Nutrient intake in lysinuric protein intolerance
    L M Tanner
    Department of Pediatrics, University of Turku, Kiinamyllynkatu 4 8, 20520, Turku, Finland
    J Inherit Metab Dis 30:716-21. 2007
    ..Oral supplementation with citrulline, which is absorbed normally and metabolized to arginine and ornithine, improves protein tolerance to some extent,..
  78. ncbi Effect of arginine, ornithine and citrulline supplementation upon performance and metabolism of trained rats
    M O Meneguello
    Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Brazil
    Cell Biochem Funct 21:85-91. 2003
    ..In the present study we evaluated the effect of arginine, citrulline and ornithine supplementation, intermediates of the urea cycle, on the performance of sedentary and swimming-..
  79. ncbi Is there a correlation between circulating levels of citrulline and intestinal dysfunction in the critically ill?
    S Oaleed Noordally
    Centre Hospitalier de Jolimont, Jolimont, Belgium
    Nutr Clin Pract 27:527-32. 2012
    The aim of this study was to assess the correlation between plasma citrulline and Sequential Organ Failure Assessment (SOFA) score, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, survival, inflammation (C-reactive ..
  80. ncbi The effect of L-arginine and citrulline on endothelial function in patients in heart failure with preserved ejection fraction
    Arturo Orea-Tejeda
    Heart Failure Clinic, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico
    Cardiol J 17:464-70. 2010
    To evaluate the effect of the amino acids L-arginine and citrulline on endothelial function in patients in stable diastolic and right heart failure using photoplethysmography.
  81. ncbi Therapeutic use of citrulline in cardiovascular disease
    Maritza J Romero
    Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta GA, USA
    Cardiovasc Drug Rev 24:275-90. 2006
    L-citrulline is the natural precursor of L-arginine, substrate for nitric oxide synthase (NOS) in the production of NO...
  82. ncbi Peptidyl argininedeiminase 2 CpG island in multiple sclerosis white matter is hypomethylated
    Fabrizio G Mastronardi
    Molecular Structure and Function, The Hospital for Sick Children, Toronto, Ontario, Canada
    J Neurosci Res 85:2006-16. 2007
  83. ncbi Serum citrulline is a potential marker for rejection of intestinal allografts
    G Gondolesi
    The Recanati Miller Transplantation Institute, The Mount Sinai Medical Center, New York, NY 10029, USA
    Transplant Proc 34:918-20. 2002
  84. ncbi Specific modification of peptide-bound citrulline residues
    Anders Holm
    Institute of Immunology, University of Oslo, NO 0027 Oslo, Norway
    Anal Biochem 352:68-76. 2006
    Immune reactions to citrulline-containing proteins appear to be central in the immunopathogenesis of rheumatoid arthritis...
  85. pmc The role of citrullinated proteins suggests a novel mechanism in the pathogenesis of multiple sclerosis
    Mario A Moscarello
    Department of Structural Biology and Biochemistry, Hospital for Sick Children, 555 University Avenue, M5G 1X8, Toronto, ON, Canada
    Neurochem Res 32:251-6. 2007
    ..The conversion of arginine to citrulline in brain is carried out by an enzyme peptidyl arginine deiminase (PAD) 2...
  86. pmc Oral citrulline as arginine precursor may be beneficial in sickle cell disease: early phase two results
    W H Waugh
    Department of Physiology and Medicine, Brody School of Medicine, East Carolina University, Greenville, North Carolina 27858, USA
    J Natl Med Assoc 93:363-71. 2001
    ..L-Citrulline as precursor amino acid was given orally twice daily in daily doses of approximately 0...
  87. ncbi Autoantibodies to cyclic citrullinated peptides predict progression to rheumatoid arthritis in patients with undifferentiated arthritis: a prospective cohort study
    F A Van Gaalen
    Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands
    Arthritis Rheum 50:709-15. 2004
  88. ncbi Smoking increases peptidylarginine deiminase 2 enzyme expression in human lungs and increases citrullination in BAL cells
    D Makrygiannakis
    Department of Medicine, Division of Rheumatology, Karolinska University Hospital, Solna, Karolinska Institutet, Stockholm, Sweden
    Ann Rheum Dis 67:1488-92. 2008
    ..Identification of citrullinated proteins in bronchoalveolar lavage (BAL) cells from smokers has led to the suggestion that citrullination induced by smoking might be the first step in the pathogenic chain of RA...
  89. pmc Citrullination of CXCL8 increases this chemokine's ability to mobilize neutrophils into the blood circulation
    Tamara Loos
    Laboratory of Molecular Immunology, Rega Institute, K U Leuven, Minderbroedersstraat 10, 3000 Leuven, Belgium
    Haematologica 94:1346-53. 2009
    ..Recently, we discovered a new natural post-translational modification of CXCL8, i.e. the deimination of arginine into citrulline by peptidylarginine deiminases.
  90. ncbi Acute intestinal failure in critically ill patients: is plasma citrulline the right marker?
    Gaël Piton
    Intensive Care Unit, Besancon University Hospital, Besancon, France
    Intensive Care Med 37:911-7. 2011
    ..However, a validated definition of acute intestinal failure is lacking, in absence of a marker to measure it. Consequently, small bowel dysfunction is not clearly integrated into the overall approach used to treat ICU patients...
  91. ncbi Dietary fish and fish oil and the risk of rheumatoid arthritis
    Magdalena Rosell
    Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
    Epidemiology 20:896-901. 2009
    ..Whether the intake of oily fish and fish oil might also protect against the development of rheumatoid arthritis is not known...
  92. ncbi Fine specificity of the anti-citrullinated protein antibody response is influenced by the shared epitope alleles
    K N Verpoort
    Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands
    Arthritis Rheum 56:3949-52. 2007
    ..ACPA levels are higher in SE-positive patients with RA than in SE-negative patients with RA. The aim of the present study was to determine whether SE influences not only the magnitude but also the specificity of the ACPA response...
  93. ncbi Anti-citrulline antibodies in the diagnosis and prognosis of rheumatoid arthritis: evolving concepts
    Amalia Raptopoulou
    Department of Internal Medicine and Division of Rheumatology, Clinical Immunology and Allergy, University of Crete, Heraklion, Greece
    Crit Rev Clin Lab Sci 44:339-63. 2007
    b>Citrulline is a non-standard amino acid that can be incorporated into proteins only by post-translational modification of arginine by peptidylarginine deiminase (PAD) enzymes during a variety of biologic processes, including inflammation...
  94. ncbi Integrity and stability of the citrulline-arginine pathway in normal and tumour cell lines
    Denys N Wheatley
    BioMedES, Hilton Campus, Hilton Place, Aberdeen AB24 4FA, UK
    Cancer Lett 227:141-52. 2005
    ..g. melanomas and hepatocellular carcinomas (HCC) that have poor citrulline converting ability, it is possible that the deprivation can be applied to many other types of cancer...
  95. ncbi Clinical and pathophysiological significance of the autoimmune response to citrullinated proteins in rheumatoid arthritis
    Mireille Sebbag
    Faculte de Medecine, Purpan IFR30, Unité Différenciation Épidermique et Auto immunité Rhumatoïde, UMR 5165 CNRS Toulouse III Université, CNRS Inserm Université Paul Sabatier CHU de Toulouse, Place du Docteur Baylac, 31059 Toulouse, France
    Joint Bone Spine 71:493-502. 2004
    ..Numerous questions about the pathophysiological significance of the autoimmune response to deiminated proteins in RA remain to be answered to confirm this model...
  96. ncbi Association of rheumatoid arthritis treatment response and disease duration with declines in serum levels of IgM rheumatoid factor and anti-cyclic citrullinated peptide antibody
    T R Mikuls
    Department of Medicine, University of Nebraska Medical Center, Omaha, Nebraska 68198, USA
    Arthritis Rheum 50:3776-82. 2004
    ..To examine the association of treatment response and disease duration with changes in rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibody levels among patients with rheumatoid arthritis (RA)...
  97. ncbi Inducible nitric oxide synthase gene expression and enzyme activity correlate with disease activity in murine experimental autoimmune encephalomyelitis
    A H Cross
    Department of Neurology and Neurosurgery, Washington University School of Medicine, St Louis, MO 63110, USA
    J Neuroimmunol 71:145-53. 1996
    ..Functional iNOS activity, as assessed by assay of calcium-independent citrulline production, was also significantly increased in spinal cords from mice with acute EAE in comparison to normal ..
  98. ncbi Nitric oxide precursors and congenital heart surgery: a randomized controlled trial of oral citrulline
    Heidi A B Smith
    Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tenn, USA
    J Thorac Cardiovasc Surg 132:58-65. 2006
    The study sought to determine whether citrulline supplementation, a precursor to nitric oxide synthesis, is safe and efficacious in increasing plasma citrulline concentrations and decreasing the risk of postoperative pulmonary hypertension...
  99. pmc Prevalence and clinical significance of anti-cyclic citrullinated peptide antibodies in juvenile idiopathic arthritis
    T Avcin
    Department of Paediatrics, University of Ljubljana, Slovenia, Italy
    Ann Rheum Dis 61:608-11. 2002
    ..Antibodies against cyclic citrullinated peptide (anti-CCP) are considered to be specific for rheumatoid arthritis (RA)...
  100. ncbi Myelin localization of peptidylarginine deiminases 2 and 4: comparison of PAD2 and PAD4 activities
    Dorothy D Wood
    Molecular Structure and Function, The Hospital for Sick Children, Toronto, ON, Canada
    Lab Invest 88:354-64. 2008
    ..The presence of citrulline in myelin proteins in particular myelin basic protein (MBP) causes an important change in myelin structure, ..
  101. ncbi Methylation of arginine residues interferes with citrullination by peptidylarginine deiminases in vitro
    Reinout Raijmakers
    Department of Biomolecular Chemistry, Nijmegen Center for Molecular Life Sciences, Institute for Molecules and Materials, Radboud University Nijmegen, Nijmegen, The Netherlands
    J Mol Biol 367:1118-29. 2007
    Peptidylarginine deiminase (PAD) enzymes catalyze the conversion of arginine residues in proteins to citrulline residues...

Research Grants63

  1. Regulation of the Endothelial Citrulline-Nitric Oxide Cycle
    Duane C Eichler; Fiscal Year: 2010
    ..has provided a unique perspective of endothelial health, showing that argininosuccinate synthase (AS) of the citrulline-nitric oxide cycle must be functional to sustain nitric oxide (NO) production and to maintain cell viability...
  2. Iron-mediated vascular disease in sickle cell disease.
    John C Wood; Fiscal Year: 2010
    ..dehydrogenase), inflammation (high-sensitivity CRP), dysfunction of NO metabolism (arginine, ornithine &citrulline, vitamin C, tetrahydrobiopterin, dihydrobiopterin,) and night time hypoxia (overnight pulse oximetry)...
  3. Citrulline to Prevent or Mitigate Acute Lung Injury in Severe Sepsis
    Todd W Rice; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): The purpose of this application is to investigate the role of citrulline in preventing or mitigatin acute lung injury (ALI) in patients with severe sepsis...
  4. TSQ Vantage Bundle with Acquity UltraPerformance LC
    Nicolaas E Deutz; Fiscal Year: 2010
    ..Notably, the NIH-funded projects all rely on one or both of two core methodologies: utilization of (i) L-citrulline and related arginine pathway substrates as metrics of intestinal health and activity;and (ii) stable (heavy) ..
    Itzhak Nissim; Fiscal Year: 2009
    ..3) Does AGM or AICAR increase the relative contribution of glutamine-N and/or blood ammonia for mitochondrial citrulline synthesis, perhaps secondary to an AGM-mediated elevation of cAMP? Experiments will be performed using a rat ..
  6. Post Translational Modifications in Tolerance and Autoimmunity
    Mark J Mamula; Fiscal Year: 2012
    ..With relevance to our work, autoantibodies to other protein modifications, notably citrulline proteins, have become diagnostic for autoimmune syndromes such as rheumatoid arthritis...
    Natalia Nieto; Fiscal Year: 2012
    ..ASS is an enzyme from the L-citrulline/NO cycle which could have a rate-limiting role for high-output NO synthesis via NOS2...
  8. Bacterial peptidylarginine deiminase, a link between gums and joint disease
    JAN S POTEMPA; Fiscal Year: 2013
    ..gingivalis peptidylarginine deiminase (PPAD), which has the ability to convert arginine residues in proteins to citrulline. Protein citrullination alters protein structure and function, hence, PPA may be involved in dysregulation of ..
  9. Arginine, Nitric Oxide, and Severe Malaria
    JOE BRICE WEINBERG; Fiscal Year: 2012
    ..Arginine can be converted to citrulline and NO by NOS, and to ornithine and urea by arginase...
  10. A protein array platform for anti-citrulline antibodies in Rheumatoid Arthritis
    Ji Qiu; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Anti-citrulline antibodies are specific and predictive of rheumatoid arthritis (RA). Seropositivity against citrulline is clinically assayed using cyclic citrullinated peptide (CCP) ELISA...
  11. Pathogenesis of Ketosis Prone Diabetes
    Ashok Balasubramanyam; Fiscal Year: 2010
    ..and markedly higher concentrations of glutamine / glutamate, together with higher ornithine, lower citrulline and arginine, and depressed levels of amino acids that enter the TCA cycle via anaplerosis...
  12. Dissection of the ACPA response in African-Americans with Rheumatoid Arthritis
    S Louis Bridges; Fiscal Year: 2013
    ..Post- translational modification of arginine residues to citrulline residues is catalyzed by enzymes called peptidyl argininyl deiminases (e.g...
  13. Mechanisms and Regulation of Inducible Nitric Oxide Synthase
    JOSEPH EDWARD SABAT; Fiscal Year: 2010
    Inducible Nitric Oxide Synthase (iNOS) converts L-arginine to L-citrulline and NO using two molecules of oxygen and a tetrahydrobiopterin cofactor...
  14. Family History, Genes, Environment and G X E Interaction in Predicting RA Risk
    Elizabeth W Karlson; Fiscal Year: 2013
    ..As CCP antibodies occur years before RA onset, I hypothesize that this interaction induces anti-citrulline immunity, a critical step in RA pathogenesis...
  15. Improving Prematurity-related Respiratory Outcomes at Vanderbilt (IMPROV)
    JUDY LYNN ASCHNER; Fiscal Year: 2013
    ..Our hypothesis invokes an immature hepatic and gut synthetic capacity to make citrulline and GSH, functional genetic variations in the UC-NO and GSH pathways, nutritional deficiencies and the ..
  16. Mechanism of Resistance to Arginine Deiminase Therapy in Advance Melanoma
    Macus T Kuo; Fiscal Year: 2013 not express argininosuccinate synthetase (AS), the rate-limiting enzyme for the biosynthesis of arginine from citrulline. Thus, melanoma cells require arginine from extracellular sources for survival...
  17. Immune Recognition of Citrullinated Cartilage PG Aggrecan in Autoimmune Arthritis
    Katalin Mikecz; Fiscal Year: 2013
    ..While citrullination (enzymatic conversion of arginine residues to citrulline) is a post-translational protein modification that may occur in healthy individuals, the majority of patients ..
  18. Structural/Functional Modularity in Nitric Oxide Synthase
    Linda J Roman; Fiscal Year: 2012
    ..L-Arginine is the natural substrate for NOS isoforms, producing L-citrulline and NO, which serves as a gaseous messenger in the processes of neurotransmission, cytotoxicity or ..
  19. TAS::75 0849::TAS
    Wenlin Deng; Fiscal Year: 2011
    ..Intestinal barrier integrity will be evaluated by measuring plasma citrulline and serum endotxoin levels...
  20. Enzyme Delivery With Supercharged Proteins to Address Citrullinemia
    John Zuris; Fiscal Year: 2013
    ..AS1 catalyzes the ATP- dependent conversion of citrulline and aspartate to argininosuccinic acid...
  21. Dynamic Regulation of Methyl-arginine and Citrulline in Breast Cancer Cells
    CHARLES DAVID ALLIS; Fiscal Year: 2013
    ..In this proposal, we seek to unravel the dynamic regulation of histone and non-histone methyl-arginine and citrulline, both at genomic and mechanistic levels...
  22. Selective Inhibition of Neuronal Nitric Oxide Synthase
    Richard B Silverman; Fiscal Year: 2013
    ..studies will be undertaken to elucidate the mechanism for how NOS catalyzes the oxidation of L-arginine to citrulline and NO using alternative substrates...
  23. Structural and biochemical characterization of redox reactions within nitric oxid
    SARAH C HOKANSON; Fiscal Year: 2012
    ..Nitric oxide synthase (NOS) proteins are heme-based monooxygenase enzymes that convert L-arginine to L-citrulline and nitric oxide (NO) by a two-step electron transfer process...
  24. Shining Light on the Mechanism and Regulation of Nitric Oxide Synthases
    BRIAN CHRISTOPHER SMITH; Fiscal Year: 2012
    ..NOS enzymes catalyze the oxidation of arginine to NO and citrulline using oxygen and NADPH as cosubstrates in a two-step reaction with N[G]-hydroxyarginine, NHA, as an intermediate...
  25. Nitric oxide deficiency in chronic renal disease
    Chris Baylis; Fiscal Year: 2013
    ..In Aim 2 we will determine how renal and total (whole body) uptake of citrulline and synthesis of L-Arg differs in CKD vs normal kidneys...
    Craig E Lunte; Fiscal Year: 2010
    ..Second, the NOS and arginase products citrulline and ornithine will be determined using CE-LIF after derivatization by naphthalene-2,3-dicarboxaldehyde/cyanide (..
  27. Investigations into the Glutamine-Citruline-Arginine Pathway in Sepsis
    Christina C Kao; Fiscal Year: 2012
    ..These amino acids are linked by an inter-organ pathway involving intestinal conversion of glutamine to citrulline followed by renal uptake of citrulline and conversion to arginine...
  28. Optimal Amino Acid Nutrition in Sepsis
    Robert R Wolfe; Fiscal Year: 2012
    ..5% citrulline. Specific Aim 3: To test the hypothesis that ingestion of mixtures of amino acids based on EAAs (either with or ..
  29. RBC-derived microparticles function in cerebral malaria
    Irene Gramaglia; Fiscal Year: 2013
    ..that administration of compounds that restore NO bioavailability (nitric oxide [NO] donor, NO gas, arginine and citrulline) protect all recipients fom experimental CM (ECM);NO gas and arginine are currently undergoing clinical trials ..
  30. PAD2: An Arginine Deiminase that Regulates Arthritis
    Kerri A Mowen; Fiscal Year: 2013
    ..The citrulline posttranslational modification is forme by the conversion of peptidylarginine residues into the citrulline amino ..
  31. Chronic progressive hypoxia-induced pulmonary hypertension in newborns
    Candice D Fike; Fiscal Year: 2013
    ..Our experimental design will test the hypothesis that treatment with oral L-citrulline, a precursor for L-arginine and NO, increases pulmonary vascular NO production and ameliorates the progressive ..
  32. COPD Metabolome, Smoking Oxidants and Aberrant Ciliated Cell Function
    Ronald G Crystal; Fiscal Year: 2013
    ..Preliminary metabolic data led to our first clues - COPD smokers have decreased serum citrulline levels, consistent with a deficiency in lung nitric oxide synthase (NOS) activity, and thus lung nitric oxide (..
  33. Cytokine Gene Regulation by Modification of Arginine Residues
    Kerri A Mowen; Fiscal Year: 2010
    ..The five PAD enzymes convert arginine residues within proteins into the atypical amino acid citrulline. PAD4 is expressed mainly in lymphocytes...
    WILLIAM O BRIEN; Fiscal Year: 2002
    ..NOS2 assays will measure the Ca+-independent conversion of L-anginine to L-citrulline. RT-PCR will be used to estimate changes in steady state NOS messages from all three NOS isoforms...
  35. Severe falciparum malaria: mechanisms of hypoargininemia
    Bert Lopansri; Fiscal Year: 2006
    ..This will be accomplished by infusing non-radioactive tracers of arginine, citrulline, ornithine and leucine and measuring the metabolic byproducts of these tracers...
  36. Dosimetry of Lipid-Derived Amino Acid Adducts by LC/MS
    Ian Blair; Fiscal Year: 2006
    ..covalent modification of free plasma arginine would prevent deiminase-mediated conversion to citrulline and nitric oxide...
    Michael Joyner; Fiscal Year: 2004
    ..will determine if nitric oxide production (across a limb vascular bed) as assessed by conversion of arginine to citrulline is blunted during either pharmacologic stimulation of the vascular endothelium or during exercise in patients ..
    Marshall Summar; Fiscal Year: 2001
    ..or decreases in urea cycle intermediates (arginine and citrulline)...
    WILLIAM CHANCE; Fiscal Year: 1990
    ..effects of a glutamine synthetase inhibitor on cancer anorexia; (6) assessing whether infusion of arginine and citrulline will aid in host detoxificiation of ammonia and reduce the anorexia; (7) exploring dietary changes that reduce ..
    THOMAS LOEHR; Fiscal Year: 1999
    ..Nitric oxide synthase (NOS) also generates a diatomic gas molecule by catalyzing the conversion of L-arginine to citrulline, and the product NO is a major regulator in the nervous, immune, and cardiovascular systems...
    Louis Ignarro; Fiscal Year: 2001
    ..We have found that N/G-hydroxy-L- arginine (NOHA), an intermediate in the oxidation of arginine to NO + citrulline, is synthesized and released from cells in culture...
  42. Metabolism of Endothelial Dysfunction in Renal Disease
    Leticia Castillo; Fiscal Year: 2006
    ..isotope tracers L4guanidino 15N2] arginine, L-2H3-methyl]methionine and L- I) 3C]methionine;L-' 3Cureido]citrulline and L-' 3C]cysteine. (l...
    Owen Griffith; Fiscal Year: 2004
    ..Nitric oxide (NO) is produced during the oxidation of L-arginine to L-citrulline by NO synthase (NOS), and plays a critical role in mediating cellular function in diverse physiologic settings...
    MASSAKO KADEKARO KUTYNA; Fiscal Year: 2002
    ..The specific aims are to determine: 1a) whether the activities of NOS (i.e. citrulline) and guanylyl cyclase (i.e...
  45. Structure/Mechanism of an FMN- and FAD-containing Enzyme
    Jung Ja Kim; Fiscal Year: 2005
    ..NOS (iNOS) and endothelial NOS (eNOS) catalyze the NADPH-dependent formation of nitric oxide (NO) and L-citrulline from L-arginine and molecular oxygen...
    Brendan Lee; Fiscal Year: 2000
    ..Plasma, metabolites, ammonia, and citrulline can be easily quantitated to monitor the efficacy of therapeutic intervention, and both murine and bovine models ..
    Joshua Bederson; Fiscal Year: 2001
    ..These will include: a) the activity of nitric oxide synthase (NOS) measured by a modified citrulline assay, b) the extracellular concentrations of catecholamines and glutamate measured by cerebral microdialysis ..
    SUSANNA DODGSON; Fiscal Year: 1991
    ..for citrullinogenesis plus the sulfonamide carbonic anhydrase inhibitor acetazolamide results in decreased citrulline production...
    William Baumgartner; Fiscal Year: 2000
    ..amino acid neurotransmitters glutamate and glycine precede a 12-fold rise in the conversion of arginine to citrulline by nitric oxide synthase (NOS) during the postoperative reperfusion period...
    Ethan Lerner; Fiscal Year: 2002
    ..using RT-PCR and measurement of NO using the Griess reaction and the conversion of radioactive L-arginine to citrulline. The effects of selected cytokines in the regulation of NOS will be examined...
  51. Arginine Deprivation: A targeted therapy for Melanoma
    Lynn Feun; Fiscal Year: 2006
    ..exposure of melanoma cells to arginine deiminase (ADI), an enzyme that catalyzes the hydrolysis of arginine to citrulline, results in apoptotic cell death...
    HAMMED OLANREWAJU; Fiscal Year: 2001
    ..of adenosine agonists and antagonists; NOS activity using [14C]-arginine through the conversion of L-arginine to citrulline and NADPH diaphorase histochemistry; and reverse transcription/PCR (RT-PCR), Northern and Western Blotting for ..
  53. Regulation of Mitochondrial Nitric-oxide Synthase
    Cecilia Giulivi; Fiscal Year: 2003 the oxidation of oxymyoglobin, electron spin resonance spectroscopy with the spin trapping technique, and L-citrulline production...
  54. Mechanisms of Adaptation in Human Short Bowel Syndrome
    Thomas Ziegler; Fiscal Year: 2005
    ..also show markedly increased IgA and IgG antibody titers to bacterial flagellin in SBS and suggest that plasma citrulline may be a useful biomarker of functional enterocyte mass...
    RAMAMURTHY SHANKAR; Fiscal Year: 2005
    ..NO) which is formed when the enzyme nitric oxide synthase (NOS) catalyzes the conversion of L-arginine to L-citrulline. Both the direct tissue effect, as well as the vascular effect of insulin is blunted in subjects with insulin ..
  56. Vulnerability of the Fetal Brain to Hypoxic-Ischemia
    Jorge Figueroa; Fiscal Year: 2006
    ..effects of chronic hypoxia on Type I NOS expression by measuring enzymatic activity and protein mass using the citrulline assay and western blotting in distinct subcellular compartments of selected brain regions...
  57. Chemotherapy Toxicity: Reduction via Urea Cycle Support
    Brian Christman; Fiscal Year: 2004
    ..determine the optimal agent for supporting urea cycle function in vivo, and conduct a Phase II trial of citrulline augmentation in patients undergoing BMT...
  58. Neuronal NOS, Nitroarenes, and Neurotoxicity
    Richard Miller; Fiscal Year: 2009
    ..we hypothesize that in the presence of nitroarenes, nNOS is converted from a purely nitric oxide (NO*) and L-citrulline synthase to a peroxynitrite (ONOO-) and L-citrulline synthase...
    David Badesch; Fiscal Year: 2004
    ..The specific aims are to determine whether: 1. NO activity (NOx, citrulline) is increased in patients with various forms of PH (PPH and SPH). 2...
    Alfred Ajami; Fiscal Year: 1999
    ..The method traces the conversion of an arginine analog into the corresponding analog of citrulline, a process that is mediated by nitric oxide synthase...
    RAYMOND QUOCK; Fiscal Year: 1999
    ..mice; (2) compare NOS function in C57BL/6 and DBA/2 mice by measuring conversion of [14C]L-arginine to [14C]L-citrulline in brain regions and spinal cords of naive and N20-exposed C57BL/6 and DBA/2 mice; (3) compare the role of NO in ..
    SANDRA ROERIG; Fiscal Year: 2001
    ..Total NOS activity is spinal cord homogenates will also be determined by measuring conversion of arginine to citrulline. These results will be compared to those obtained with spinal injection of missense ODN or vehicle...
  63. PI3-kinase and mTOR in NO production by macrophages
    STEVE WEINSTEIN; Fiscal Year: 2002
    ..blotting and by an in vitro activity assay measuring the rate of conversion of radiolabeled L-arginine to L-citrulline (and NO), respectively...