cystathionine beta synthase

Summary

Summary: A multifunctional pyridoxal phosphate enzyme. In the second stage of cysteine biosynthesis it catalyzes the reaction of homocysteine with serine to form cystathionine with the elimination of water. Deficiency of this enzyme leads to HYPERHOMOCYSTEINEMIA and HOMOCYSTINURIA. EC 4.2.1.22.

Top Publications

  1. pmc Testing computational prediction of missense mutation phenotypes: functional characterization of 204 mutations of human cystathionine beta synthase
    Qiong Wei
    Program in Molecular and Translational Medicine, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, Pennsylvania 19111, USA
    Proteins 78:2058-74. 2010
  2. ncbi A novel enhancing mechanism for hydrogen sulfide-producing activity of cystathionine beta-synthase
    Ko Eto
    National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4 1 1 Ogawahigashi, Kodaira, Tokyo 187 8551, Japan
    J Biol Chem 277:42680-5. 2002
  3. ncbi Hydrogen sulfide as a neuromodulator
    Hideo Kimura
    National Institute of Neuroscience, Kodaira, Tokyo, Japan
    Mol Neurobiol 26:13-9. 2002
  4. pmc Homocysteine-induced endoplasmic reticulum stress causes dysregulation of the cholesterol and triglyceride biosynthetic pathways
    G H Werstuck
    Department of Pathology and Molecular Medicine, McMaster University and the Hamilton Civic Hospitals Research Centre, Hamilton, Ontario, Canada
    J Clin Invest 107:1263-73. 2001
  5. ncbi Evidence that hydrogen sulfide exerts antinociceptive effects in the gastrointestinal tract by activating KATP channels
    Eleonora Distrutti
    University of Perugia, Clinica di Gastroenterologia, Policlinico Monteluce, Via Enrico Dal Pozzo, 06122 Perugia, Italy
    J Pharmacol Exp Ther 316:325-35. 2006
  6. ncbi Production of the neuromodulator H2S by cystathionine beta-synthase via the condensation of cysteine and homocysteine
    Xulin Chen
    Division of Population Science, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA
    J Biol Chem 279:52082-6. 2004
  7. ncbi Cystathionine beta synthase participates in murine oocyte maturation mediated by homocysteine
    Rong Liang
    Department of Pediatrics, Peoples Hospital, Peking University, 11 South Street, Beijing, China
    Reprod Toxicol 24:89-96. 2007
  8. ncbi Expression of the cystathionine beta synthase (CBS) gene during mouse development and immunolocalization in adult brain
    Karine Robert
    EA3508 Université Paris 7, Denis Diderot, Paris, France
    J Histochem Cytochem 51:363-71. 2003
  9. ncbi Hormonal regulation of cystathionine beta-synthase expression in liver
    Shobhitha Ratnam
    Department of Biochemistry, Memorial University of Newfoundland, St John s, Newfoundland A1B 3X9, Canada
    J Biol Chem 277:42912-8. 2002
  10. pmc S-adenosylmethionine stabilizes cystathionine beta-synthase and modulates redox capacity
    Anna Prudova
    Redox Biology Center and Biochemistry Department, University of Nebraska, Lincoln, NE 68588 0664, USA
    Proc Natl Acad Sci U S A 103:6489-94. 2006

Research Grants

  1. Cystathionine beta synthase (CBS) and angiogenesis
    Priyabrata Mukherjee; Fiscal Year: 2013
  2. Epigenetic regulation of alcoholic steatohepatitis in a mouse model
    CHARLES HOPKINSON HALSTED; Fiscal Year: 2012
  3. Phase 1/2 of Taurine in Cystathionine Beta-Synthase Deficient Homocystinuria
    Johan L Van Hove; Fiscal Year: 2013
  4. Homocysteine &Heme: A Role in Thrombosis?
    Jan P Kraus; Fiscal Year: 2012
  5. HEME PROTEIN STRUCTURE AND DYNAMICS
    Thomas G Spiro; Fiscal Year: 2010
  6. B12 Nutrition in the Aged
    Sally Stabler; Fiscal Year: 2007
  7. Enzyme therapy for hyperhomocysteinemia
    Yuying Tan; Fiscal Year: 2005
  8. MENTORED PATIENT ORIENTED RESEARCH CAREER DEVELOPMENT AW
    MARK STEEN; Fiscal Year: 2001
  9. NEW AMINO ACID DISORDERS IN CEREBRAL DISEASE
    Vivian Shih; Fiscal Year: 1999
  10. INBORN ERRORS--MOLECULAR ANALYSIS IN CULTURED CELLS
    Leon Rosenberg; Fiscal Year: 1990

Detail Information

Publications230 found, 100 shown here

  1. pmc Testing computational prediction of missense mutation phenotypes: functional characterization of 204 mutations of human cystathionine beta synthase
    Qiong Wei
    Program in Molecular and Translational Medicine, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, Pennsylvania 19111, USA
    Proteins 78:2058-74. 2010
    ..these methods further, we have derived a set of random mutations of the enzymatic domains of human cystathionine beta synthase. This enzyme is a dimeric protein that catalyzes the condensation of serine and homocysteine to produce ..
  2. ncbi A novel enhancing mechanism for hydrogen sulfide-producing activity of cystathionine beta-synthase
    Ko Eto
    National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4 1 1 Ogawahigashi, Kodaira, Tokyo 187 8551, Japan
    J Biol Chem 277:42680-5. 2002
    ..The present study demonstrates a novel mechanism for the regulation of CBS activity and provides a possible therapeutic application of SNP for the diseases in which CBS activity is deficient...
  3. ncbi Hydrogen sulfide as a neuromodulator
    Hideo Kimura
    National Institute of Neuroscience, Kodaira, Tokyo, Japan
    Mol Neurobiol 26:13-9. 2002
    ..Recent progress in the study of H2S as a novel neuromodulator/transmitter in the brain is briefly reviewed...
  4. pmc Homocysteine-induced endoplasmic reticulum stress causes dysregulation of the cholesterol and triglyceride biosynthetic pathways
    G H Werstuck
    Department of Pathology and Molecular Medicine, McMaster University and the Hamilton Civic Hospitals Research Centre, Hamilton, Ontario, Canada
    J Clin Invest 107:1263-73. 2001
    ..Furthermore, this mechanism likely explains the development and progression of hepatic steatosis and possibly atherosclerotic lesions observed in hyperhomocysteinemia...
  5. ncbi Evidence that hydrogen sulfide exerts antinociceptive effects in the gastrointestinal tract by activating KATP channels
    Eleonora Distrutti
    University of Perugia, Clinica di Gastroenterologia, Policlinico Monteluce, Via Enrico Dal Pozzo, 06122 Perugia, Italy
    J Pharmacol Exp Ther 316:325-35. 2006
    ..This effect is mediated by K(ATP) channels and NO. H(2)S-releasing drugs might be beneficial in treating painful intestinal disorders...
  6. ncbi Production of the neuromodulator H2S by cystathionine beta-synthase via the condensation of cysteine and homocysteine
    Xulin Chen
    Division of Population Science, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA
    J Biol Chem 279:52082-6. 2004
    ..In addition, these studies provide a biochemical explanation for the previously inexplicable homocysteine-lowering effects of N-acetylcysteine treatments in humans...
  7. ncbi Cystathionine beta synthase participates in murine oocyte maturation mediated by homocysteine
    Rong Liang
    Department of Pediatrics, Peoples Hospital, Peking University, 11 South Street, Beijing, China
    Reprod Toxicol 24:89-96. 2007
    Our previous study demonstrated that cystathionine beta synthase (CBS) is highly expressed in the cumulus-oocyte complex during ovulation. However, the role of CBS during oocyte maturation remains uncertain...
  8. ncbi Expression of the cystathionine beta synthase (CBS) gene during mouse development and immunolocalization in adult brain
    Karine Robert
    EA3508 Université Paris 7, Denis Diderot, Paris, France
    J Histochem Cytochem 51:363-71. 2003
    Hyperhomocysteinemia, caused by a lack of cystathionine beta synthase (CBS), leads to elevated plasma concentrations of homocysteine. This is a common risk factor for atherosclerosis, stroke, and possibly neurodegenerative diseases...
  9. ncbi Hormonal regulation of cystathionine beta-synthase expression in liver
    Shobhitha Ratnam
    Department of Biochemistry, Memorial University of Newfoundland, St John s, Newfoundland A1B 3X9, Canada
    J Biol Chem 277:42912-8. 2002
    ..These results show that insulin has a direct role in regulating homocysteine metabolism. Altered insulin levels in diseases such as diabetes may influence homocysteine metabolism by regulating the hepatic transsulfuration pathway...
  10. pmc S-adenosylmethionine stabilizes cystathionine beta-synthase and modulates redox capacity
    Anna Prudova
    Redox Biology Center and Biochemistry Department, University of Nebraska, Lincoln, NE 68588 0664, USA
    Proc Natl Acad Sci U S A 103:6489-94. 2006
    ..A mechanistic basis for the coordinate changes in redox and methylation metabolism that are a hallmark of several complex diseases is explained by these observations...
  11. ncbi Cystathionine beta-synthase is essential for female reproductive function
    Mario A Guzman
    Departamento de Bioquimica y Biologia Molecular y Celular, Universidad de Zaragoza, Miguel Servet 177, E 50013 Zaragoza, Spain
    Hum Mol Genet 15:3168-76. 2006
    ..The role of plasma hyperhomocysteinemia in female fertility was examined using cystathionine beta synthase knockout (cbs KO) mice...
  12. pmc Structure of human cystathionine beta-synthase: a unique pyridoxal 5'-phosphate-dependent heme protein
    M Meier
    M E Müller Institute for Structural Biology, Biozentrum, University of Basel, Klingelbergstrasse 70, CH 4056 Basel, Switzerland
    EMBO J 20:3910-6. 2001
    ..This heme binding motif together with a spatially adjacent oxidoreductase active site motif could explain the regulation of its enzyme activity by redox changes...
  13. ncbi Cystathionine beta synthase deficiency promotes oxidative stress, fibrosis, and steatosis in mice liver
    Karine Robert
    EA 3508, Universite Paris 7 Denis Diderot, France
    Gastroenterology 128:1405-15. 2005
    ..To investigate this aspect of hyperhomocysteinemia, we performed a thorough investigation of liver pathology in CBS-deficient mice, a murine model of severe hyperhomocysteinemia...
  14. ncbi Polygenic influence on plasma homocysteine: association of two prevalent mutations, the 844ins68 of cystathionine beta-synthase and A(2756)G of methionine synthase, with lowered plasma homocysteine levels
    M Y Tsai
    Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, MN, USA
    Atherosclerosis 149:131-7. 2000
    ....
  15. ncbi Detection and allele-frequencies of the 833T>C, 844ins68 and a novel mutation in the cystathionine beta-synthase gene
    Pieter H Griffioen
    Department of Clinical Chemistry Erasmus MC, University Medical Center Rotterdam, P O Box 2040, 3000 CA Rotterdam, The Netherlands
    Clin Chim Acta 354:191-4. 2005
    The most common 833T>C/844ins68 in cis double mutation in the cystathionine beta synthase (CBS) gene probably is non-pathogenic because the 68-bp insertion eliminates the 833T>C mutation due to alternative splicing...
  16. pmc Nitrotyrosinylation, remodeling and endothelial-myocyte uncoupling in iNOS, cystathionine beta synthase (CBS) knockouts and iNOS/CBS double knockout mice
    Soumi Kundu
    Department of Physiology and Biophysics, University of Louisville School of Medicine, Louisville, Kentucky 40202, USA
    J Cell Biochem 106:119-26. 2009
    ..generation and matrix remodeling in cardiac dysfunction, left ventricular (LV) tissue was analyzed from cystathionine beta synthase (CBS) heterozygote knockout, iNOS homozygote knockout, CBS-/+/iNOS-/- double knockout, and wild-type (..
  17. ncbi Relationship between polymorphism of cystathionine beta synthase gene and congenital heart disease in Chinese nuclear families
    Xiao Ming Song
    Department of Nutrition and Food Hygiene, School of Public Health, Laboratory of Molecular Toxicology and Developmental Molecular Biology, Peking University, Beijing 100083, China
    Biomed Environ Sci 19:452-6. 2006
    To study the relationship between polymorphism of cystathionine beta synthase (CBS) gene and development of congenital heart disease (CHD).
  18. pmc Impaired heme binding and aggregation of mutant cystathionine beta-synthase subunits in homocystinuria
    M Janosik
    Institute of Inherited Metabolic Disease, Charles University First Faculty of Medicine, Prague, Czech Republic
    Am J Hum Genet 68:1506-13. 2001
    ..These data suggest that abnormal folding, impaired heme binding, and aggregation of mutant CBS polypeptides may be common pathogenic mechanisms in CBS deficiency...
  19. pmc Genetic variation in the cysteine biosynthesis pathway causes sensitivity to pharmacological compounds
    Hyun Seok Kim
    Computational Biology Program, Washington University, St Louis, MO 63108
    Proc Natl Acad Sci U S A 104:19387-91. 2007
    ..These results implicate the cysteine/glutathione biosynthesis pathway as a significant, but not the sole contributor to pharmacological variation in yeast...
  20. ncbi Homocysteine concentrations in adults with trisomy 21: effect of B vitamins and genetic polymorphisms
    Nathalie Fillon-Emery
    Faculte de Medecine, Laboratory of Medical Biochemistry, Vandoeuvre les Nancy, France
    Am J Clin Nutr 80:1551-7. 2004
    ..The effects of supplementation with B vitamins and of common polymorphisms in genes involved in homocysteine metabolism on plasma total homocysteine (tHcy) concentrations in trisomy 21 are unknown...
  21. ncbi Haplotyping of wild type and I278T alleles of the human cystathionine beta-synthase gene based on a cluster of novel SNPs in IVS12
    M Linnebank
    Universitaet Muenster, , Germany
    Hum Mutat 17:350-1. 2001
    ..The novel haplotype system may facilitate future studies on the evolution of the CBS gene and might be suited for genotyping of families affected by homocystinuria...
  22. ncbi Redox regulation and reaction mechanism of human cystathionine-beta-synthase: a PLP-dependent hemesensor protein
    Ruma Banerjee
    Department of Biochemistry, University of Nebraska, Lincoln, NE 68588 0664, USA
    Arch Biochem Biophys 433:144-56. 2005
    ....
  23. ncbi Hyperkeratosis in cystathionine beta synthase-deficient mice: an animal model of hyperhomocysteinemia
    Karine Robert
    EA 3508, University of Paris 7, Denis Diderot, 75251 Paris 05, France
    Anat Rec A Discov Mol Cell Evol Biol 280:1072-6. 2004
    b>Cystathionine beta synthase (CBS) is a crucial regulator of plasma concentrations of homocysteine. Severe hyperhomocysteinemia due to CBS deficiency confers diverse clinical manifestations...
  24. ncbi Mice lacking cystathionine beta synthase have lung fibrosis and air space enlargement
    Julien Hamelet
    EA 3508, Universite Paris Diderot, Paris 7, Case 7104, 2 place Jussieu, 75251 Paris Cedex 05, Paris, France
    Exp Mol Pathol 83:249-53. 2007
    b>Cystathionine beta synthase (CBS) is a crucial regulator of plasma concentrations of homocysteine. Severe hyperhomocysteinemia due to CBS deficiency confers diverse clinical manifestations, notably pulmonary thrombotic disease...
  25. ncbi Structural insights into pathogenic mutations in heme-dependent cystathionine-beta-synthase
    Mamoru Yamanishi
    Redox Biology Center and Department of Biological Chemistry, University of Nebraska, Lincoln, NE 68588 0664, USA
    J Inorg Biochem 100:1988-95. 2006
    ....
  26. pmc Chemical chaperone rescue of mutant human cystathionine beta-synthase
    Laishram R Singh
    Division of Population Science, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA
    Mol Genet Metab 91:335-42. 2007
    ....
  27. ncbi High prevalence of the I278T mutation of the human cystathionine beta-synthase detected by a novel screening application
    M Linnebank
    Klinik und Poliklinik für Kinderheilkunde, Westfällische Wilhelms Universität Münster, Germany
    Thromb Haemost 85:986-8. 2001
    ..800. Our data indicate that homocystinuria due to cystathionine beta-synthase deficiency is a frequently unrecognized disorder resulting in a high risk of thromboembolic events...
  28. ncbi The folate pool in colorectal cancers is associated with DNA hypermethylation and with a polymorphism in methylenetetrahydrofolate reductase
    Kazuyuki Kawakami
    Department of Surgery, Kanazawa University School of Medicine, Kanazawa, Japan
    Clin Cancer Res 9:5860-5. 2003
    ....
  29. ncbi Hydrogen sulfide is a novel prosecretory neuromodulator in the Guinea-pig and human colon
    Rudolf Schicho
    Department of Human Biology, Technical University Munich, Munich, Germany
    Gastroenterology 131:1542-52. 2006
    ..Hydrogen sulfide (H(2)S) has been suggested as a novel gasomediator. We explored its unknown neuromodulatory role in human and guinea-pig colon...
  30. ncbi Genetic variants of homocysteine metabolizing enzymes and the risk of coronary artery disease
    Bohumila Janosíková
    Institute of Inherited Metabolic Diseases, Charles University 1st Faculty of Medicine, Prague, Czech Republic
    Mol Genet Metab 79:167-75. 2003
    ..In conclusion, the coincidence of clinical and biochemical effects of a common c.844ins68 CBS variant supports the hypothesis that compounds relating to homocysteine metabolism may play role in the development and/or progression of CAD...
  31. ncbi Contrasting behaviors of mutant cystathionine beta-synthase enzymes associated with pyridoxine response
    X Chen
    Division of Population Science, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA
    Hum Mutat 27:474-82. 2006
    ..These mice have extremely elevated plasma homocysteine levels and do not respond significantly to large doses of pyridoxine. Our findings suggest that there may be multiple mechanisms involved in response to pyridoxine...
  32. ncbi Four novel mutations in the cystathionine beta-synthase gene: effect of a second linked mutation on the severity of the homocystinuric phenotype
    R de Franchis
    Department of Pediatrics, University of Colorado School of Medicine, Denver, USA
    Hum Mutat 13:453-7. 1999
    ..In this context, a search for additional mutations in cis may sometimes be necessary to establish a good genotype-phenotype relationship...
  33. ncbi Effects of heme ligand mutations including a pathogenic variant, H65R, on the properties of human cystathionine beta-synthase
    Sunil Ojha
    Department of Biochemistry, University of Nebraska, Lincoln, Nebraska 68588 0664, USA
    Biochemistry 41:4649-54. 2002
    ..Both H65 and C52 variants display low catalytic activity, revealing that changes in the heme binding domain modulate activity, consistent with a regulatory role for this cofactor...
  34. pmc Functional rescue of mutant human cystathionine beta-synthase by manipulation of Hsp26 and Hsp70 levels in Saccharomyces cerevisiae
    Laishram R Singh
    Division of Population Science, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA
    J Biol Chem 284:4238-45. 2009
    ..Based on these results we propose a novel model in which the ratio of Hsp70 and Hsp26 determines whether misfolded proteins will either be refolded or degraded...
  35. pmc Mice deficient in cystathionine beta-synthase: animal models for mild and severe homocyst(e)inemia
    M Watanabe
    Department of Pathology, University of North Carolina, Chapel Hill 27599 7525
    Proc Natl Acad Sci U S A 92:1585-9. 1995
    ..Thus, the heterozygous mutants are promising for studying the in vivo role of elevated levels of homocyst(e)ine in the etiology of cardiovascular diseases...
  36. ncbi Rat cystathionine beta-synthase. Gene organization and alternative splicing
    M Swaroop
    Department of Human Genetics, Yale University School of Medicine, New Haven, Connecticut 06510
    J Biol Chem 267:11455-61. 1992
    ..coli tryptophan synthase beta chain (trpB), 36%; yeast serine deaminase, 33%. Lysine 116 in synthase aligns with the established pyridoxyllysine residue of these enzymes suggesting that it is the pyridoxal 5'-phosphate binding residue...
  37. ncbi Modulation of endogenous production of H2S in rat tissues
    Weimin Zhao
    Department of Physiology, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan S7N 5ES, Canada
    Can J Physiol Pharmacol 81:848-53. 2003
    ..p. injection of PPG. It is concluded that the endogenous production of H2S could be modulated by NO. AOA and PPG have different capacities in regulating the endogenous production of H2S in different types of tissues...
  38. ncbi Screening for mutations by expressing patient cDNA segments in E. coli: homocystinuria due to cystathionine beta-synthase deficiency
    V Kozich
    Department of Pediatrics, University of Colorado School of Medicine, Denver 80262
    Hum Mutat 1:113-23. 1992
    ..This bacterial expression system proved to be a rapid screening method for localizing pathogenic mutations in CBS, allowing us to sequence the affected portions of mutant cDNA within 7-10 days of harvesting cultured fibroblasts...
  39. pmc The molecular basis of homocystinuria due to cystathionine beta-synthase deficiency in Italian families, and report of four novel mutations
    G Sebastio
    Department of Pediatrics, Federico II University, Naples, Italy
    Am J Hum Genet 56:1324-33. 1995
    ..Mutations A114V and I278T are carried by three and by seven independent alleles, respectively. The other four mutations--including G307S and A1224-2C, common among northern European patients--have not been detected...
  40. ncbi Komrower Lecture. Molecular basis of phenotype expression in homocystinuria
    J P Kraus
    Department of Pediatrics, University of Colorado School of Medicine, Denver 80262
    J Inherit Metab Dis 17:383-90. 1994
    ..Using this method we identified the first 14 mutations in homocystinuria. The most common mutation in patients of predominantly 'Celtic' origin is the G919A transition which substitutes serine for glycine 307...
  41. ncbi Molecular basis of cystathionine beta-synthase deficiency in pyridoxine responsive and nonresponsive homocystinuria
    F L Hu
    Neurology Service, Massachusetts General Hospital, Boston 02129
    Hum Mol Genet 2:1857-60. 1993
    ..This missense mutation was detected in one allele of a pyridoxine nonresponsive patient and in both alleles of a pyridoxine responsive patient. The latter suggests that I278T is probably associated with pyridoxine responsiveness...
  42. ncbi Cystathionine beta-synthase deficiency in Central Europe: discrepancy between biochemical and molecular genetic screening for homocystinuric alleles
    J Sokolova
    Institute of Inherited Metabolic Disorders, 1st Faculty of Medicine, Charles University, Prague, Czech Republic
    Hum Mutat 18:548-9. 2001
    ..In conclusion, homocystinuria in Central Europe may be sufficiently common to consider sensitive newborn screening programs for this disease...
  43. ncbi High homocysteine and thrombosis without connective tissue disorders are associated with a novel class of cystathionine beta-synthase (CBS) mutations
    Kenneth N Maclean
    Department of Pediatrics, University of Colorado School of Medicine, Denver, Colorado, USA
    Hum Mutat 19:641-55. 2002
    ....
  44. ncbi The molecular basis of cystathionine beta-synthase deficiency in Australian patients: genotype-phenotype correlations and response to treatment
    Mette Gaustadnes
    Cardiovascular Genetics Laboratory, Prince of Wales Hospital, Randwick, New South Wales, Australia
    Hum Mutat 20:117-26. 2002
    ..The G307S mutation always resulted in a severe non-responsive phenotype, whereas I278T resulted in a milder B6 responsive phenotype. From our results, we were also able to establish three other mild mutations: P49L, R369C, and V371M...
  45. pmc 3-Deazaadenosine mitigates arterial remodeling and hypertension in hyperhomocysteinemic mice
    Alexander V Ovechkin
    Department of Physiology and Biophysics, Health Sciences Center A 1115, School of Medicine, University of Louisville, KY 40202, USA
    Am J Physiol Lung Cell Mol Physiol 291:L905-11. 2006
    ..The results show that arterial hypertension in HHcy mice is, in part, associated with arterial remodeling and E-M uncoupling in response to MMP activation...
  46. ncbi Hydrogen sulfide is produced in response to neuronal excitation
    Ko Eto
    National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo 187 8551, Japan
    J Neurosci 22:3386-91. 2002
    ..In addition, LTP is altered in CBS knock-out mice. These observations suggest that H2S is produced by CBS in response to neuronal excitation and that it may regulate some aspects of synaptic activity...
  47. ncbi Purification and properties of cystathionine beta-synthase from human liver. Evidence for identical subunits
    J Kraus
    J Biol Chem 253:6523-8. 1978
    ..15 mM and for L-homocysteine of 0.59 mM, and a pI of 5.2 The enzyme is stable over a pH range from 6.5 to 8.0 in phosphate buffers and can be stored in 40% glycerol at -15 degrees C for at least 1 month...
  48. ncbi Structural insights into mutations of cystathionine beta-synthase
    Markus Meier
    M E Müller Institute for Structural Biology, Biozentrum, University of Basel, Klingelbergstrasse 70, CH 4056, Basel, Switzerland
    Biochim Biophys Acta 1647:206-13. 2003
    ..We have recently solved the crystal structure of a truncated form of this enzyme, which enables us to correlate some of these mutations with the structure...
  49. pmc Birth prevalence of homocystinuria in Central Europe: frequency and pathogenicity of mutation c.1105C>T (p.R369C) in the cystathionine beta-synthase gene
    Miroslav Janosik
    Institute of Inherited Metabolic Disorders, Charles University in Prague 1st Faculty of Medicine, Prague, Czech Republic
    J Pediatr 154:431-7. 2009
    ..To estimate the frequency of the cystathionine beta-synthase deficiency caused by c.1105C>T mutation in Central Europe compared to Norway, and to examine the pathogenicity of the corresponding p.R369C mutant enzyme...
  50. ncbi The role of cystathionine beta-synthase in homocysteine metabolism
    Kwang Hwan Jhee
    Department of Applied Chemistry, Kumoh National Institute of Technology, Kyungbuk, Korea
    Antioxid Redox Signal 7:813-22. 2005
    ..This finding suggests it may be possible to develop drugs that interact with the C-terminal domain of CBS to treat elevated homocysteine in humans...
  51. ncbi Hyperhomocysteinemia due to cystathionine beta synthase deficiency induces dysregulation of genes involved in hepatic lipid homeostasis in mice
    Julien Hamelet
    EA 3508, Universite Paris 7 Denis Diderot, Case 7104, 2 place Jussieu, 75251 Paris Cedex 05, France
    J Hepatol 46:151-9. 2007
    b>Cystathionine beta synthase (CBS) deficiency leads to severe hyperhomocysteinemia, which confers diverse clinical manifestations, notably fatty liver...
  52. ncbi Cystathionine beta-synthase: structure, function, regulation, and location of homocystinuria-causing mutations
    Edith Wilson Miles
    NIDDK, National Institutes of Health, Bethesda, Maryland 20892 0830, USA
    J Biol Chem 279:29871-4. 2004
  53. ncbi A 31 bp VNTR in the cystathionine beta-synthase (CBS) gene is associated with reduced CBS activity and elevated post-load homocysteine levels
    K J Lievers
    Department of Pediatrics, University Medical Center Nijmegen, The Netherlands
    Eur J Hum Genet 9:583-9. 2001
    ..The 31 bp VNTR in the CBS gene is associated with post-methionine load hyperhomocysteinaemia that may predispose individuals to an increased risk of cardiovascular diseases...
  54. ncbi Ion specificity and ionic strength dependence of the osmoregulatory ABC transporter OpuA
    N A B Nik Mahmood
    Membrane Enzymology Group, Department of Biochemistry, Groningen Biomolecular Science and Biotechnology Institute and Materials Science Centre, University of Groningen, Nijenborgh 4, 9747 AG Groningen, The Netherlands
    J Biol Chem 281:29830-9. 2006
    ..Our data lend new support for the contention that the CBS module in OpuA constitutes the ionic strength sensor whose activity is modulated by the C-terminal anionic tail...
  55. pmc Mouse models of cystathionine beta-synthase deficiency reveal significant threshold effects of hyperhomocysteinemia
    Sapna Gupta
    Division of Population Science, Fox Chase Cancer Center, 333 Cottman Ave, Philadelphia, PA 19111, USA
    FASEB J 23:883-93. 2009
    ..Our results indicate that there is a clear pathogenic threshold effect for tHcy and bring into question the idea that mild elevations in tHcy are directly pathogenic...
  56. pmc Conversion of methionine to cysteine in Bacillus subtilis and its regulation
    Marie Francoise Hullo
    Unité de Génétique des Génomes Bactériens, 28 rue du Docteur Roux, 75724 Paris Cedex 15, France
    J Bacteriol 189:187-97. 2007
    ..The addition of O-acetyl-serine prevented the formation of this protein-DNA complex...
  57. ncbi Isolated thrombosis due to the cystathionine beta-synthase mutation c.833T>C (1278T)
    M Linnebank
    Klinik und Poliklinik für Kinderheilkunde, Universitaetsklinikum Münster, Germany
    J Inherit Metab Dis 26:509-11. 2003
    ..Thus, not only C-terminal mutations but also the most common mutation in classical homocystinuria, CBS 1278T, can lead to isolated thrombophilic events. These data support the hypothesis that homocystinuria is an underdiagnosed disease...
  58. ncbi Human cystathionine beta-synthase cDNA: sequence, alternative splicing and expression in cultured cells
    J P Kraus
    Department of Pediatrics, University of Colorado School of Medicine, Denver 80262
    Hum Mol Genet 2:1633-8. 1993
    ..Lastly, we demonstrate that expression of the human enzyme in CHO cells yields enzymatically active protein of the expected size with a half-life of approximately 14 hrs...
  59. ncbi Kinetic characterization of recombinant human cystathionine beta-synthase purified from E. coli
    Muluken S Belew
    Department of Biology, Institute of Biochemistry, Carleton University, 1125 Colonel By Drive, Ottawa, Ontario K1S5B6, Canada
    Protein Expr Purif 64:139-45. 2009
    ....
  60. pmc Expression of mutant human cystathionine beta-synthase rescues neonatal lethality but not homocystinuria in a mouse model
    Liqun Wang
    Division of Population Science, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA
    Hum Mol Genet 14:2201-8. 2005
    ..These transgenic animals should be useful in the study of homocysteine related human disease...
  61. ncbi Cystathionine beta synthase as a risk factor for Alzheimer disease
    Katrin Beyer
    Department of Pathology, Hospital Universitari Germans Trias i Pujol, Autonomous University of Barcelona, Spain
    Curr Alzheimer Res 1:127-33. 2004
    ....
  62. ncbi DNA methylation status is not impaired in treated cystathionine beta-synthase (CBS) deficient patients
    Sandra G Heil
    Laboratory of Pediatrics and Neurology, Radboud University Nijmegen Medical Centre, 6500 HB Nijmegen, The Netherlands
    Mol Genet Metab 91:55-60. 2007
    ..In this study we aimed to investigate whether DNA methylation is disturbed in patients with hyperhomocysteinemia due to CBS-deficiency...
  63. pmc Cloning and screening with nanogram amounts of immunopurified mRNAs: cDNA cloning and chromosomal mapping of cystathionine beta-synthase and the beta subunit of propionyl-CoA carboxylase
    J P Kraus
    Proc Natl Acad Sci U S A 83:2047-51. 1986
    ..In situ hybridization of this cDNA to q22 of human chromosome 21 confirmed two previous tentative assignments of the synthase locus to this chromosome...
  64. ncbi Screening for serum total homocysteine in newborn children
    Helga Refsum
    Department of Pharmacology, University of Oxford, UK
    Clin Chem 50:1769-84. 2004
    ..Newborn screening for total homocysteine (tHcy) in blood may identify babies with vitamin B12 (B12) deficiency or homocystinuria, but data on the causes of increased tHcy in screening samples are sparse...
  65. ncbi 844ins68 in the cystathionine beta-synthase gene in Israel and review of its distribution in the world
    Avshalom Zoossmann-Diskin
    Department of Haematology and Genetic Pathology, School of Medicine, Flinders University, Adelaide, Australia
    Anthropol Anz 62:147-55. 2004
    ..Its use as a reliable anthropogenetic marker discriminating between the major human groups may also be problematic until more populations are sampled...
  66. ncbi Birth prevalence of homocystinuria
    Helga Refsum
    Department of Pharmacology, University of Oxford, United Kingdom
    J Pediatr 144:830-2. 2004
    ..Our results suggest that homocystinuria is more common than previously reported. Newborn screening for homocystinuria through mutation detection should be further considered...
  67. ncbi Modulation of cystathionine beta-synthase level regulates total serum homocysteine in mice
    Liqun Wang
    Division of Population Science, Fox Chase Cancer Center, Philadelphia, PA 19111, USA
    Circ Res 94:1318-24. 2004
    ..In addition, the creation of an inducible mouse system to modulate plasma homocysteine will also be useful in the study of homocysteine-related vascular disease...
  68. ncbi Mapping peptides correlated with transmission of intrasteric inhibition and allosteric activation in human cystathionine beta-synthase
    Suvajit Sen
    Biochemistry Department, University of Nebraska, Lincoln, Nebraska 68588 0664, USA
    Biochemistry 44:14210-6. 2005
    ..Our hydrogen exchange data identify surfaces that are potentially involved in the juxtaposition of the regulatory and catalytic domains and form the basis of a docked structural model for the full-length enzyme...
  69. ncbi Functional assays testing pathogenicity of 14 cystathionine-beta synthase mutations
    Roser Urreizti
    Departament de Genetica, Universitat de Barcelona, Barcelona, Spain
    Hum Mutat 27:211. 2006
    ..M173V, p.A226T, and p.G548Q, this structure grade was dramatically reduced and was completely absent in the rest of the mutations...
  70. pmc Functional and structural conservation of CBS domains from CLC chloride channels
    Raúl Estévez
    Zentrum für Molekulare Neurobiologie Hamburg ZMNH, Hamburg University, Falkenried 94, D 20246 Hamburg, Germany
    J Physiol 557:363-78. 2004
    ..Thus, we propose that the structure of CBS domains from CLC channels is highly conserved and that they play a functional role in the common gate...
  71. ncbi Cystathionine beta-synthase deficiency in Georgia (USA): correlation of clinical and biochemical phenotype with genotype
    W D Kruger
    Division of Population Science, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA
    Hum Mutat 22:434-41. 2003
    ..We conclude that these two mutations occurred after ethnic socialization and that the CBS genotype is predictive of phenotype...
  72. ncbi Molecular defect in a patient with pyridoxine-responsive homocystinuria
    V Kozich
    Department of Pediatrics, University of Colorado School of Medicine, Denver 80262
    Hum Mol Genet 2:815-6. 1993
  73. ncbi A yeast assay for functional detection of mutations in the human cystathionine beta-synthase gene
    W D Kruger
    Department of Genetics, Stanford University, School of Medicine, CA 94305, USA
    Hum Mol Genet 4:1155-61. 1995
    ..Our results also demonstrate that the yeast CBS assay can detect a large percentage of individuals heterozygous for mutations in CBS. This system should be useful in determining the relationship between CBS mutations and human disease...
  74. ncbi Cystathionine beta-synthase mutations in homocystinuria
    J P Kraus
    Department of Pediatrics, University of Colorado School of Medicine, Denver 80262, USA
    Hum Mutat 13:362-75. 1999
    ..Mutations due to deaminations of methylcytosines represent 53% of all point substitutions in the coding region of the CBS gene...
  75. ncbi Functional modeling of vitamin responsiveness in yeast: a common pyridoxine-responsive cystathionine beta-synthase mutation in homocystinuria
    C E Kim
    Division of Population Science, Fox Chase Cancer Center, Philadelphia, PA 19111, USA
    Hum Mol Genet 6:2213-21. 1997
    ..These studies show that the G797A mutation is an important cause of pyridoxine-responsive CBS deficiency and demonstrate the utility of yeast functional assays in the analysis of human mutations...
  76. pmc A pathogenic linked mutation in the catalytic core of human cystathionine beta-synthase disrupts allosteric regulation and allows kinetic characterization of a full-length dimer
    Suvajit Sen
    Redox Biology Center and the Biochemistry Department, University of Nebraska, Lincoln, Nebraska 68588 0664, USA
    Biochemistry 46:4110-6. 2007
    ..Furthermore, analysis of individual single mutations has permitted, for the first time, partial kinetic characterization of a full-length dimeric form of human cystathionine beta-synthase...
  77. ncbi Mutational analysis of the cystathionine beta-synthase gene: a splicing mutation, two missense mutations and an insertion in patients with homocystinuria. Mutations in brief no. 120. Online
    R B Gordon
    Department of Medicine, University of Queensland, Princess Alexandra Hospital, Brisbane 4102, Australia
    Hum Mutat 11:332. 1998
    ..Expression of recombinant CBS protein, containing the C165Y mutation, had no detectable catalytic activity. Each mutation was confirmed in genomic DNA...
  78. ncbi Regulation of human cystathionine beta-synthase by S-adenosyl-L-methionine: evidence for two catalytically active conformations involving an autoinhibitory domain in the C-terminal region
    M Janosik
    Department of Pediatrics, University of Colorado School of Medicine, Denver, Colorado 80262, USA
    Biochemistry 40:10625-33. 2001
    ....
  79. pmc Cystathionine beta-synthase p.S466L mutation causes hyperhomocysteinemia in mice
    Sapna Gupta
    Division of Population Science, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA
    Hum Mutat 29:1048-54. 2008
    ..Our results show that p.S466L causes homocystinuria by affecting both the steady state level of CBS protein and by reducing the efficiency of the enzyme in vivo...
  80. ncbi Mutations in the genes regulating methylene tetrahydrofolate reductase (MTHFR C-->T677) and cystathione beta-synthase (CBS G-->A919, CBS T-->c833) are not associated with myocardial infarction in African Americans
    A Dilley
    Hematologic Diseases Branch, National Center for Infectious Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road, Mailstop E 64, Atlanta, GA 30333, USA
    Thromb Res 103:109-15. 2001
    ..No mutations for G-->A919 (CBS) were detected in the cases or controls. The racial differences of the CBS T-->C833 polymorphism suggest that further investigation into the other areas of the CBS gene is needed...
  81. ncbi Correction of disease-causing CBS mutations in yeast
    X Shan
    Division of Population Sciences, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA
    Nat Genet 19:91-3. 1998
    ..These findings suggest a new drug target to treat homocystinuria and homocysteine-related vascular disease...
  82. pmc Biochemical and structural characterization of a novel family of cystathionine beta-synthase domain proteins fused to a Zn ribbon-like domain
    Michael Proudfoot
    Banting and Best Department of Medical Research, University of Toronto, 112 College Street, Room 72, Toronto, ON, Canada
    J Mol Biol 375:301-15. 2008
    ..We suggest that, in vivo, some Zn ribbon domains might also bind iron and therefore possess an electron carrier activity, adding another physiological role to this large family of important proteins...
  83. ncbi Disposition of homocysteine in subjects heterozygous for homocystinuria due to cystathionine beta-synthase deficiency: relationship between genotype and phenotype
    A B Guttormsen
    LOCUS for Homocysteine and Related Vitamins, University of Bergen, Armauer Hansens Hus, Bergen, Norway
    Am J Med Genet 100:204-13. 2001
    ..Abnormal tHcy response after methionine loading was the most sensitive test. Our data suggest that the urinary tHcy excretion rate is a simple, non-invasive approach for studying mild disturbances in Hcy metabolism...
  84. ncbi Mutations in the regulatory domain of cystathionine beta synthase can functionally suppress patient-derived mutations in cis
    X Shan
    Division of Population Science, Fox Chase Cancer Center, Philadelphia, PA 19111, USA
    Hum Mol Genet 10:635-43. 2001
    ..Our results indicate that subtle changes to the C-terminus of CBS can restore activity to mutant proteins and provide a rationale for screening for compounds that can activate mutant CBS alleles...
  85. ncbi Influence of 699C-->T and 1080C-->T polymorphisms of the cystathionine beta-synthase gene on plasma homocysteine levels
    O Aras
    Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, USA
    Clin Genet 58:455-9. 2000
    ..01 for 1080T/T genotype compared to 1080C/C genotype). We speculate that the 699C-->T and 1080C-->T polymorphisms may be in linkage disequilibrium with regulatory elements that upregulate CBS gene transcription...
  86. ncbi The frequency of 844ins68 mutation in the cystathionine beta-synthase gene is not increased in patients with venous thrombosis
    R Franco
    Department of Clinical Medicine, Brazil
    Haematologica 83:1006-8. 1998
    ..In the present study we investigated this mutation as a candidate risk factor for venous thrombosis...
  87. ncbi Cystathionine beta-synthase is coordinately regulated with proliferation through a redox-sensitive mechanism in cultured human cells and Saccharomyces cerevisiae
    Kenneth N Maclean
    Department of Pediatrics, University of Colorado School of Medicine, Denver, Colorado 80262, USA
    J Cell Physiol 192:81-92. 2002
    ..Our data indicates that screening compounds for the ability to affect transsulfuration in cultured cell models must take proliferation status into account to avoid masking regulatory interactions that may be of significance in vivo...
  88. pmc Purification, crystallization and preliminary X-ray diffraction analysis of a cystathionine beta-synthase domain-containing protein, CDCP2, from Arabidopsis thaliana
    Byung Cheon Jeong
    School of Life Sciences and Biotechnology, Korea University, Anam Dong, Seoungbuk gu, Seoul 136 701, Republic of Korea
    Acta Crystallogr Sect F Struct Biol Cryst Commun 64:825-7. 2008
    ..360, c = 82.596 A, alpha = beta = 90, gamma = 120 degrees . The asymmetric unit contains one CDCP2 molecule and the solvent content is approximately 41%...
  89. ncbi Homocysteine response to methionine challenge in four obligate heterozygotes for homocystinuria and relationship with cystathionine beta-synthase mutations
    M P Sperandeo
    Department of Pediatrics, Federico II University, Naples, Italy
    J Inherit Metab Dis 19:351-6. 1996
    ..These observations could explain the conflicting results reported for vascular pathologies in parents of homocystinuric patients and direct the search for genetic mutations in these vascular pathologies...
  90. ncbi Human cystathionine beta-synthase is a target for sumoylation
    Omer Kabil
    Redox Biology Center, Biochemistry Department, University of Nebraska, Lincoln, Nebraska 68588 0664, USA
    Biochemistry 45:13528-36. 2006
    ..The discovery that CBS is a target of sumoylation adds another layer to the complex regulation of this enzyme and reveals a previously unknown residence for this protein, i.e., in the nucleus...
  91. pmc High prevalence of a mutation in the cystathionine beta-synthase gene
    M Y Tsai
    Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, USA
    Am J Hum Genet 59:1262-7. 1996
    ..Although the mutation does not seem to affect the activity of the CBS enzyme, the prevalence is somewhat increased in patients with premature coronary-artery disease, although the difference is not statistically significant...
  92. ncbi Regulation of 3' splice site selection in the 844ins68 polymorphism of the cystathionine Beta -synthase gene
    Maurizio Romano
    International Centre for Genetic Engineering and Biotechnology, Padriciano 99, Trieste I 34012, Italy
    J Biol Chem 277:43821-9. 2002
    ..Our results therefore suggest the possibility that the insertion was an evolutionary event that allowed the rescue of the wild-type sequence, so preserving protein function...
  93. ncbi Alleviation of intrasteric inhibition by the pathogenic activation domain mutation, D444N, in human cystathionine beta-synthase
    Ruby Evande
    Biochemistry Department, University of Nebraska, Lincoln, NE 68588 0664, USA
    Biochemistry 41:11832-7. 2002
    ..e., wild-type enzyme as isolated), "activated" (wild-type enzyme + AdoMet or the D444N mutant as isolated), and superactivated (D444N mutant + AdoMet or wild-type enzyme lacking the C-terminal regulatory domain)...
  94. ncbi Enzymatic hydrogen sulfide production in marine invertebrate tissues
    David Julian
    Romberg Tiburon Center for Environmental Studies, San Francisco State University, San Francisco, CA, USA
    Comp Biochem Physiol A Mol Integr Physiol 133:105-15. 2002
    ..marina was doubled by the addition of a second thiol substrate (2.5 mmol l(-1) 2-mercaptoethanol), suggesting the presence of an 'activated serine sulfhydrase pathway', which had previously been demonstrated only in some microfauna...
  95. ncbi Polymorphisms of genes controlling homocysteine levels and IQ score following the treatment for childhood ALL
    Maja Krajinovic
    Hopital Sainte Justine, Service d hématologie oncologie, Centre de Recherche, 3175 Cote Sainte Catherine, Montreal, Quebec H3T 1C5, Canada
    Pharmacogenomics 6:293-302. 2005
    ..Several enzymes are essential to maintain the homocysteine levels. Their different functional forms, associated with common genetic polymorphisms, may modulate homocysteine levels and thereby influence MTX-associated neurotoxicity...
  96. ncbi Molecular analysis of homocystinuria in Brazilian patients
    Marianna P R Porto
    Department of Pediatrics, Universidade Federal de São Paulo UNIFESP EPM Brazil
    Clin Chim Acta 362:71-8. 2005
    ..Cystathionine beta-synthase (CBS) deficiency is the most common cause of homocystinuria. However, no data are available concerning the molecular basis of this disease in Brazilian populations...
  97. ncbi Prevalence and mechanisms of hyperhomocysteinemia in chronic alcoholics
    Carmen Blasco
    Liver Unit, Institut de Malalties Digestives i Metaboliques, Hospital Clinic, Institut d Investigacions Biomediques August Pi i Sunyer, University of Barcelona, Barcelona, Spain
    Alcohol Clin Exp Res 29:1044-8. 2005
    ..The aim of the study was to investigate the prevalence of hyperhomocysteinemia in chronic alcoholics and the influence of alcohol consumption, vitamin deficiencies and liver damage on the plasma levels of Hcy...
  98. ncbi Mice deficient in cystathionine beta synthase display altered homocysteine remethylation pathway
    Jean Marc Alberto
    INSERM U724, Faculte de Medecine, Vandoeuvre les Nancy, France
    Mol Genet Metab 91:396-8. 2007
    b>Cystathionine beta synthase (CBS) deficiency is a metabolic disorder that is biochemically characterized by severe hyperhomocysteinemia...
  99. ncbi [Disruption of amino acid metabolism in astrocyte and neurological disorders--possible implication of abnormal glia-neuron network in homocystineuria]
    Yasushi Enokido
    Department of Neuropathology, Medical Research Institute, Tokyo Medical and Dental University, 1 5 45 Yushima, Bunkyo ku, Tokyo 113 8519, Japan
    Brain Nerve 59:731-7. 2007
    ....
  100. ncbi Mutations in methylenetetrahydrofolate reductase or cystathionine beta-synthase gene, or a high-methionine diet, increase homocysteine thiolactone levels in humans and mice
    Grazyna Chwatko
    Department of Microbiology and Molecular Genetics, UMDNJ New Jersey Medical School, International Center for Public Health, 225 Warren St, Newark, NJ 07101 1709, USA
    FASEB J 21:1707-13. 2007
    ..7-fold and 25-fold increases in plasma and urinary Hcy-thiolactone levels, respectively. Thus, we conclude that hyperhomocysteinemia leads to significant increases in the atherogenic metabolite Hcy-thiolactone in humans and mice...
  101. ncbi Are heterocygotes for classical homocystinuria at risk of vitamin B12 and folic acid deficiency?
    Mahmoud F Elsaid
    Department of Pediatrics Neurology Unit, Hamad General Hospital, Hamad Medical Corporation, Qatar, and Department of Evidence for Population Health Unit, School of Epidemiology and Health Sciences, The University of Manchester, UK
    Mol Genet Metab 92:100-3. 2007
    ..Comparative cross-sectional study to assess homocysteine and vitamin status in carriers of CBS gene mutations...

Research Grants44

  1. Cystathionine beta synthase (CBS) and angiogenesis
    Priyabrata Mukherjee; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Cystathionine beta synthase (CBS) deficiency has been implicated in the pathogenesis of many cardiovascular and neurovascular diseases such atherosclerosis, thrombosis, stroke and many more...
  2. Epigenetic regulation of alcoholic steatohepatitis in a mouse model
    CHARLES HOPKINSON HALSTED; Fiscal Year: 2012
    ..The study will use the cystathionine beta synthase (CbS) deficient mouse model of aberrant methionine metabolism in which wildtype (+/+) and heterozygous (..
  3. Phase 1/2 of Taurine in Cystathionine Beta-Synthase Deficient Homocystinuria
    Johan L Van Hove; Fiscal Year: 2013
    ..Completion of these proposed studies will both increase our knowledge of pathogenesis in CBSDH and deliver candidate markers for a future phase 2b study. ..
  4. Homocysteine &Heme: A Role in Thrombosis?
    Jan P Kraus; Fiscal Year: 2012
    ..abstract_text> ..
  5. HEME PROTEIN STRUCTURE AND DYNAMICS
    Thomas G Spiro; Fiscal Year: 2010
    ..The signal transducers CooA and the H-NOX family of proteins, as well as the heme-regulated enzyme cystathionine beta synthase, have been selected for detailed characterization and dynamical studies of protein conformational ..
  6. B12 Nutrition in the Aged
    Sally Stabler; Fiscal Year: 2007
    ..abstract_text> ..
  7. Enzyme therapy for hyperhomocysteinemia
    Yuying Tan; Fiscal Year: 2005
    ..Phase II results will lead to an IND for MEGC-PEG-rMETase for end stage renal disease patients and other patients with intractable hyperhomocysteinemia and high cardiovascular disease mortality. ..
  8. MENTORED PATIENT ORIENTED RESEARCH CAREER DEVELOPMENT AW
    MARK STEEN; Fiscal Year: 2001
    ..Third, the CAP will begin the direct study of MS by developing biochemical discriminants for MS carriers in a rare large family with MS deficiency, and will result in the initiation of direct investigation of the enzyme. ..
  9. NEW AMINO ACID DISORDERS IN CEREBRAL DISEASE
    Vivian Shih; Fiscal Year: 1999
    ..The goals of this work are to understand the relationship between the biochemical, molecular, pathophysiologic and clinical aspects in these disorders so that effective therapies can be developed. ..
  10. INBORN ERRORS--MOLECULAR ANALYSIS IN CULTURED CELLS
    Leon Rosenberg; Fiscal Year: 1990
    ..These studies should provide new information on both the role of individual mutations in the pathogenesis of these inborn errors and on normal mechanisms of metabolism and homeostasis in man...
  11. Homocysteine's role in the causation of presbyopia
    CHARLES PRINCE; Fiscal Year: 2002
    ..Estimates of regression coefficients and tests of significance will be based on t-test and F-test statistics. ..
  12. Pharmacogenetics of Methotrexate Therapy in Arthritis
    ALEXANDER WHITEHEAD; Fiscal Year: 2006
    ..It has the potential to facilitate individualized treatment protocols that are less empirical and therefore more effective, and to reduce the incidence of cardiovascular co-morbidity. ..
  13. The assessment of hydrogen sulfide in vascular biology
    David Kraus; Fiscal Year: 2006
    ..Activity of cystathionine beta synthase (CBS) increases under oxidative stress to catalyze both H2S production and homocysteine (Hcy) breakdown...
  14. GENETIC BIOCHEMICAL DISORDERS IN MENTAL RETARDATION
    Stephen Goodman; Fiscal Year: 2004
    ..abstract_text> ..
  15. Mechanism of A5P Isomerase
    RONALD WESLEY WOODARD; Fiscal Year: 2010
    ..The ultimate goal of these studies is to better understand the role of LPS, a critical macromolecule essential to both the survival and virulence of Gram-(-) microorganisms ..
  16. PHYSIOLOGICAL FUNCTION OF ENDOGENOUS HYDROGEN SULFIDE
    David Schubert; Fiscal Year: 1999
    ....
  17. HOMOCYSTEINE AND ENDOTHELIAL CELL DYSFUNCTION
    KATHERINE HAJJAR; Fiscal Year: 2000
    ..Finally, they plan to define the pathway by which homocysteine induces transcriptional up-regulation of a family of translational regulatory proteins, elongation factor-1alpha, Beta and 0. (End of Abstract) ..
  18. INTERACTION OF HOMOCYSTEINE AND LP(A) IN VIVO
    Richard Lawn; Fiscal Year: 2000
    ..End of Abstract) ..
  19. Cystathionine B Synthase and ARA C Therapy for Leukemia
    JEFFREY TAUB; Fiscal Year: 2005
    ..abstract_text> ..
  20. Development of an automated homocysteine assay
    RAYMOND LIEDTKE; Fiscal Year: 2005
    ..Production of reagents and calibrators will be scaled-up along with quality control processes in anticipation of commercialization. ..
  21. RISK OF VASCULAR DISEASE IN CBS HETEROZYGOTES
    Warren Kruger; Fiscal Year: 2000
    ..One cause of hyperhomocyst(e)inemia is mutation in the cystathionine beta synthase gene (CBS)...
  22. MINORITY PREDOCTORAL FELLOWSHIP PROGRAM
    MICHAEL SANTIAGO CINTRON; Fiscal Year: 2007
    ..proteins including the NO receptor, soluble guanylyl cyclase, the CO receptor, CooA and heme-regulated cystathionine beta synthase. In addition to studying the function of these proteins, the Burstyn laboratory is also designing ..
  23. REGULATION OF FOLATE METABOLISM
    ROWENA MATTHEWS; Fiscal Year: 2008
    ..We predict that phosphorylation will play an important role in modulating the flux of one-carbon units. ..
  24. PHASE I/II STUDY OF SIMVASTATIN (ZOCOR) THERAPY IN SICKLE CELL DISEASE
    Carolyn Hoppe; Fiscal Year: 2008
    ..unreadable] [unreadable] 2. To assess the safety and tolerability of oral simvastatin in patients with SCD. [unreadable] [unreadable] [unreadable]..
  25. GENE-NUTRIENT INTERACTIONS IN REDOX HOMEOSTASIS
    Ruma Banerjee; Fiscal Year: 2002
    ....
  26. GENETIC MODULATION OF CBS TO LOWER PLASMA HOMOCYSTEINE
    Warren Kruger; Fiscal Year: 2009
    ..Cystathionine beta-synthase (CBS) is a key enzyme in the metabolism of homocysteine. In this proposal we will develop new strategies and reagents to activate CBS thereby reducing plasma homocysteine levels. ..
  27. Gordon Research Sponsored Conference on Cobalamins
    Ruma Banerjee; Fiscal Year: 2003
    ....
  28. Incident cancer studies in a unique arsenic-exposed area of Chile
    Craig M Steinmaus; Fiscal Year: 2010
    ..Information on early-life exposure, MMA3, diet, and the future genetic and proteomic studies we will plan as part of this project could add further insight into the important co-factors and mechanisms of environmental carcinogenesis. ..
  29. FASEB Summer Conference: Folate, B12 and 1C Metabolism
    JAMES FINKELSTEIN; Fiscal Year: 2002
    ..The format encourages discussions between the presenters and the fellows, residents and junior investigators in attendance. Similarly, the poster sessions also highlight the activities and the needs of the younger participants. ..
  30. Role of PP2A in tauopathies
    Estelle Sontag; Fiscal Year: 2006
    ....
  31. Attentional Dysfunction in Fragile X Syndrome
    Kenneth Maclean; Fiscal Year: 2007
    ..Individual md combination tests of these drugs will determine the relative roles of each of these systems, and lead to [unreadable]-,-combination treatments for this Important problem In FXS. ..
  32. 14th International Congress on Flavins and Flavoproteins
    ROWENA MATTHEWS; Fiscal Year: 2002
    ..Tea will be served at each poster session. Presentations were selected by an International Organizing Committee with an eye to a diverse representation of speakers at the meeting. ..
  33. EFFECT OF AGE AND GLYCEMIA ON TRANSCRIPTION FACTORS
    NAOMI FUKAGAWA; Fiscal Year: 2004
    ..abstract_text> ..
  34. Folate Polymorphisms, Dietary Folate and Prostate Cancer
    Victoria Stevens; Fiscal Year: 2005
    ..The results of this study are expected to indicate the importance of folate for prostate cancer and whether changing folate consumption can modify the risk associated with genetic variants in the pathway for folate metabolism. ..
  35. Effect of Hepatotoxins & Adomet on Liver Gene Expression
    Warren Kruger; Fiscal Year: 2003
    ..This work may also be useful in the identification of biological pathways affected in chronic liver disease that are not affected by AdoMet supplementation, which may represent other correctable targets in chronic liver disease. ..
  36. NO DAMAGE TO FOLATE CYCLE IN THE CENTRAL NERVOUS SYSTEM
    Kenneth Hensley; Fiscal Year: 2005
    ..abstract_text> ..
  37. MORPHOLOGY AND FUNCTION OF BRAIN VESSELS
    GARY BAUMBACH; Fiscal Year: 2006
    ..These studies should provide important new insight into the mechanisms of vascular remodeling. [unreadable] [unreadable] [unreadable]..
  38. Regulation of Renal Oxygenation and Blood Pressure
    Pin Lan Li; Fiscal Year: 2006
    ..abstract_text> ..
  39. The Unfolding of Marfan Syndrome
    ALANA MAJORS; Fiscal Year: 2006
    ..We will also examine the extracellular matrix at the ultrastructural level and will assess the role of ER stress in MFS. [unreadable] [unreadable]..
  40. COX-2 and PPARgamma: Targets for BRCA Prevention
    Warren Kruger; Fiscal Year: 2007
    ....
  41. Nutritional Regulation of y-Glutamylcysteine Synthetase
    MARTHA STIPANUK; Fiscal Year: 2007
    ..Capacity for GSH synthesis, availability of the precursor amino acid cysteine, and steady-state GSH levels all contribute to the body's ability to defend itself against oxidative or chemical stressors. ..
  42. Age-related changes in glutathione synthesis
    NAOMI FUKAGAWA; Fiscal Year: 2007
    ..unreadable] [unreadable]..
  43. Role of PP2A in tauopathies
    Estelle Sontag; Fiscal Year: 2007
    ..If our model is validated, dietary folate supplementation and PPMT may be novel therapeutic targets for strategies aimed at slowing down the disease process in AD, and possibly other neurodegenerative dementias. [unreadable] [unreadable]..