cystathionine beta synthase

Summary

Gene Symbol: cystathionine beta synthase
Description: cystathionine-beta-synthase
Alias: HIP4, cystathionine beta-synthase, beta-thionase, methylcysteine synthase, serine sulfhydrase
Species: human

Top Publications

  1. ncbi Large-scale population-based metabolic phenotyping of thirteen genetic polymorphisms related to one-carbon metabolism
    Ase Fredriksen
    LOCUS for Homocysteine and Related Vitamins, University of Bergen, Bergen, Norway
    Hum Mutat 28:856-65. 2007
  2. 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
  3. pmc A yeast system for expression of human cystathionine beta-synthase: structural and functional conservation of the human and yeast genes
    W D Kruger
    Department of Psychiatry, University of California at San Francisco 94143
    Proc Natl Acad Sci U S A 91:6614-8. 1994
  4. 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
  5. 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
  6. ncbi Polymorphisms in methionine synthase (A2756G) and cystathionine beta-synthase (844ins68) and susceptibility to carcinomas of the upper gastrointestinal tract
    N Ott
    Department of Pathology, Unfallkrankenhaus Berlin, Warener Strasse 7, 12683 Berlin, Germany
    J Cancer Res Clin Oncol 134:405-10. 2008
  7. 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
  8. pmc The gene for cystathionine beta-synthase (CBS) maps to the subtelomeric region on human chromosome 21q and to proximal mouse chromosome 17
    M Münke
    Department of Human Genetics, Yale University School of Medicine, New Haven, CT 06510
    Am J Hum Genet 42:550-9. 1988
  9. 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
  10. 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

Research Grants

  1. Enzyme therapy for hyperhomocysteinemia
    Yuying Tan; Fiscal Year: 2005
  2. Priyabrata Mukherjee; Fiscal Year: 2016
  3. Homocysteine &Heme: A Role in Thrombosis?
    Jan P Kraus; Fiscal Year: 2012
  4. MENTORED PATIENT ORIENTED RESEARCH CAREER DEVELOPMENT AW
    MARK STEEN; Fiscal Year: 2001
  5. Homocysteine's role in the causation of presbyopia
    CHARLES PRINCE; Fiscal Year: 2002
  6. Johan L Van Hove; Fiscal Year: 2014
  7. INTERACTION OF HOMOCYSTEINE AND LP(A) IN VIVO
    Richard Lawn; Fiscal Year: 2000
  8. NEW AMINO ACID DISORDERS IN CEREBRAL DISEASE
    Vivian Shih; Fiscal Year: 1999
  9. Development of an automated homocysteine assay
    RAYMOND LIEDTKE; Fiscal Year: 2005
  10. INBORN ERRORS--MOLECULAR ANALYSIS IN CULTURED CELLS
    Leon Rosenberg; Fiscal Year: 1990

Patents

  1. Treatment of elevated plasma homocysteine

Detail Information

Publications213 found, 100 shown here

  1. ncbi Large-scale population-based metabolic phenotyping of thirteen genetic polymorphisms related to one-carbon metabolism
    Ase Fredriksen
    LOCUS for Homocysteine and Related Vitamins, University of Bergen, Bergen, Norway
    Hum Mutat 28:856-65. 2007
    ..2756A>G (tHcy), BHMT c.716G>A (DMG), CBS c.844_845ins68 (tHcy, betaine), CBS c.699C>T (tHcy, betaine, cystathionine) and TCN2 c.776C>G (MMA). No associations were observed for the other polymorphisms investigated...
  2. 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...
  3. pmc A yeast system for expression of human cystathionine beta-synthase: structural and functional conservation of the human and yeast genes
    W D Kruger
    Department of Psychiatry, University of California at San Francisco 94143
    Proc Natl Acad Sci U S A 91:6614-8. 1994
    ..These results demonstrate the evolutionary conservation of CBS and establish the utility of a yeast expression system for studying human CBS...
  4. 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...
  5. 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...
  6. ncbi Polymorphisms in methionine synthase (A2756G) and cystathionine beta-synthase (844ins68) and susceptibility to carcinomas of the upper gastrointestinal tract
    N Ott
    Department of Pathology, Unfallkrankenhaus Berlin, Warener Strasse 7, 12683 Berlin, Germany
    J Cancer Res Clin Oncol 134:405-10. 2008
    ..The purpose of this study is to compare the association of the MTR A2756G polymorphism and CBS insertion polymorphism with susceptibility to carcinomas of the upper gastrointestinal tract...
  7. 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...
  8. pmc The gene for cystathionine beta-synthase (CBS) maps to the subtelomeric region on human chromosome 21q and to proximal mouse chromosome 17
    M Münke
    Department of Human Genetics, Yale University School of Medicine, New Haven, CT 06510
    Am J Hum Genet 42:550-9. 1988
    ..Mice partially trisomic for MMU 16 or MMU 17 should allow gene-specific dissection of the trisomy 21 phenotype...
  9. 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...
  10. 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...
  11. ncbi Transsulfuration depends on heme in addition to pyridoxal 5'-phosphate. Cystathionine beta-synthase is a heme protein
    V Kery
    Department of Pediatrics, University of Colorado School of Medicine, Denver 80262
    J Biol Chem 269:25283-8. 1994
    ..These findings suggest that heme is functionally incorporated into CBS only during protein folding. This report describes the first instance of an enzyme that depends upon both heme and PLP for its function...
  12. 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...
  13. 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...
  14. 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...
  15. ncbi 5,10-Methylenetetrahydrofolate reductase gene variants and congenital anomalies: a HuGE review
    L D Botto
    Birth Defects and Pediatric Genetics Branch, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA 30341, USA
    Am J Epidemiol 151:862-77. 2000
    ..Studies of the C677T allele in relation to oral clefts, Down syndrome, and fetal anticonvulsant syndrome either have yielded conflicting results or have not been yet replicated...
  16. 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...
  17. 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...
  18. 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
    ....
  19. ncbi B-vitamin intake, metabolic genes, and colorectal cancer risk (United States)
    Loic Le Marchand
    Etiology Program, Cancer Research Center of Hawaii, University of Hawaii, Honolulu 96813, USA
    Cancer Causes Control 13:239-48. 2002
    ....
  20. 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...
  21. ncbi Germ-line variants in methyl-group metabolism genes and susceptibility to DNA methylation in normal tissues and human primary tumors
    Maria F Paz
    Cancer Epigenetics Laboratory, Molecular Pathology Program, Spanish National Cancer Research Center CNIO, 28029 Madrid, Spain
    Cancer Res 62:4519-24. 2002
    ..029). The existence of these associations may provide another example of the interplay between genetic and epigenetic factors in the cancer cell...
  22. ncbi Human cystathionine beta-synthase is a heme sensor protein. Evidence that the redox sensor is heme and not the vicinal cysteines in the CXXC motif seen in the crystal structure of the truncated enzyme
    Shinichi Taoka
    Biochemistry Department, University of Nebraska, Lincoln, Nebraska 68588 0664, USA
    Biochemistry 41:10454-61. 2002
    ....
  23. 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...
  24. ncbi [Study of serum Hcy and polymorphisms of Hcy metabolic enzymes in 192 families affected by congenital heart disease]
    Yong Li
    Department of Nutrition, Peking University School of Public Health, Beijing 100083, China
    Beijing Da Xue Xue Bao 37:75-80. 2005
    ..B(12), Hcy levels and CHD...
  25. 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...
  26. ncbi Cystathionine beta-synthase is enriched in the brains of Down's patients
    Akiko Ichinohe
    National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4 1 1 Ogawahigashi, Kodaira, Tokyo 187 8551, Japan
    Biochem Biophys Res Commun 338:1547-50. 2005
    ..The over-expression of CBS may cause the developmental abnormality in cognition in DS children and that may lead to AD in DS adults...
  27. ncbi Solvent-accessible cysteines in human cystathionine beta-synthase: crucial role of cysteine 431 in S-adenosyl-L-methionine binding
    Nina Frank
    Department of Pediatrics, University of Colorado School of Medicine at Fitzsimons, 12800 East 19th Avenue, Mail Stop 8313, P O Box 6511, Aurora, Colorado 80045 0511, USA
    Biochemistry 45:11021-9. 2006
    ....
  28. pmc Neural tube defects and folate pathway genes: family-based association tests of gene-gene and gene-environment interactions
    Abee L Boyles
    Center for Human Genetics, Duke University Medical Center, Durham, North Carolina 27710, USA
    Environ Health Perspect 114:1547-52. 2006
    ..Most studies addressed these genes individually, often with different populations providing conflicting results...
  29. 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...
  30. 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
    ....
  31. pmc Purification and characterization of the wild type and truncated human cystathionine beta-synthase enzymes expressed in E. coli
    Nina Frank
    Department of Pediatrics, University of Colorado School of Medicine, UCHSC, RC1 North, Rm 4128, 12800, Mail Stop 8313, P O Box 6511, Aurora, CO 80045 0511, USA
    Arch Biochem Biophys 470:64-72. 2008
    ..The activity of the enzyme was unaffected by the redox status of the heme iron. Finally, we show that CBS is stimulated by S-adenosyl- l-methionine but not its analogs...
  32. 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...
  33. pmc Relative contributions of cystathionine beta-synthase and gamma-cystathionase to H2S biogenesis via alternative trans-sulfuration reactions
    Sangita Singh
    Department of Biological Chemistry, University of Michigan Medical Center, Ann Arbor, Michigan 48109 5606, USA
    J Biol Chem 284:22457-66. 2009
    ....
  34. pmc Novel associations of CPS1, MUT, NOX4, and DPEP1 with plasma homocysteine in a healthy population: a genome-wide evaluation of 13 974 participants in the Women's Genome Health Study
    Guillaume Pare
    Center for Cardiovascular Disease Prevention and the Donald W Reynolds Center for Cardiovascular Research, Brigham and Women s Hospital, Harvard Medical School, 900 Commonwealth Ave East, Boston, MA 02215, USA
    Circ Cardiovasc Genet 2:142-50. 2009
    ..Although genetic variants of MTHFR and CBS are known to influence homocysteine concentration, common genetic determinants of homocysteine remain largely unknown...
  35. pmc Rescue of cystathionine beta-synthase (CBS) mutants with chemical chaperones: purification and characterization of eight CBS mutant enzymes
    Tomas Majtan
    Department of Pediatrics and the Colorado Intellectual and Developmental Disabilities Research Center, School of Medicine, University of Colorado at Denver, Aurora, Colorado 80045, USA
    J Biol Chem 285:15866-73. 2010
    ..This finding could have direct implications for the development of a therapeutical approach to pyridoxine unresponsive homocystinuria...
  36. doi Early-onset ischaemic stroke: analysis of 58 polymorphisms in 17 genes involved in methionine metabolism
    Betti Giusti
    Department of Medical and Surgical Critical Care, University of Florence, Viale Morgagni 85, 50134 Florence, Italy
    Thromb Haemost 104:231-42. 2010
    ..This study identifies significant genetic associations between premature ischaemic stroke and haplotypes in BHMT, CBS, FOLH1, MTR, PON2, TCN2 and TYMS genes involved in methionine metabolism...
  37. pmc Cystathionine beta-synthase mutations: effect of mutation topology on folding and activity
    Viktor Kozich
    First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Institute of Inherited Metabolic Disorders, Prague, Czech Republic
    Hum Mutat 31:809-19. 2010
    ..In summary, our results show that topology of mutations predicts in part the behavior of mutant CBS, and that misfolding may be an important and frequent pathogenic mechanism in CBS deficiency...
  38. pmc Cross-talk between the catalytic core and the regulatory domain in cystathionine β-synthase: study by differential covalent labeling and computational modeling
    Ales Hnizda
    Institute of Inherited Metabolic Disorders, First Medical Faculty, Charles University in Prague and General University Hospital in Prague, Ke Karlovu 2, Prague 2, 128 00 Czech Republic
    Biochemistry 49:10526-34. 2010
    ..Subtle differences at CBS surface indicate that enzyme activity is not regulated by conformational conversions but more likely by different allosteric mechanisms...
  39. pmc Conformational properties of nine purified cystathionine β-synthase mutants
    Ales Hnizda
    Charles University, Prague, Czech Republic
    Biochemistry 51:4755-63. 2012
    ..This study demonstrates that the proteolytic techniques are useful tools for the assessment of the biochemical penalty of missense mutations in CBS...
  40. doi Human cystathionine β-synthase (CBS) contains two classes of binding sites for S-adenosylmethionine (SAM): complex regulation of CBS activity and stability by SAM
    Angel L Pey
    Department of Physical Chemistry, Faculty of Sciences, University of Granada, Granada 18071, Spain
    Biochem J 449:109-21. 2013
    ..Our strategy may be valuable for understanding ligand effects on proteins with a complex architecture and their role in human genetic diseases and for the development of novel pharmacological strategies...
  41. pmc Kinetics of reversible reductive carbonylation of heme in human cystathionine β-synthase
    Sebastián Carballal
    Laboratorio De Enzimologia, Facultad de Ciencias, Facultad de Medicina, Universidad de la Republica, Montevideo, Uruguay
    Biochemistry 52:4553-62. 2013
    ..Reversible reduction of CBS by a physiologically relevant oxidoreductase is consistent with a regulatory role for the heme and could constitute a mechanism for cross talk among the CO, H2S, and superoxide signaling pathways. ..
  42. pmc Tumor-derived hydrogen sulfide, produced by cystathionine-β-synthase, stimulates bioenergetics, cell proliferation, and angiogenesis in colon cancer
    Csaba Szabo
    Department of Anesthesiology, University of Texas Medical Branch, Galveston, TX 77555, USA
    Proc Natl Acad Sci U S A 110:12474-9. 2013
    ..The current findings identify CBS-derived H2S as a tumor growth factor and anticancer drug target. ..
  43. doi Insights into the regulatory domain of cystathionine Beta-synthase: characterization of six variant proteins
    Marisa I S Mendes
    Metabolism and Genetics Group, Research Institute for Medicines, Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal Metabolic Unit, Department of Clinical Chemistry, VU University Medical Centre, Amsterdam, The Netherlands
    Hum Mutat 35:1195-202. 2014
    ....
  44. pmc Structural insight into the molecular mechanism of allosteric activation of human cystathionine β-synthase by S-adenosylmethionine
    June Ereño-Orbea
    Structural Biology Unit, Center for Cooperative Research in Biosciences CIC bioGUNE, Technology Park of Bizkaia, 48160 Derio, Spain and
    Proc Natl Acad Sci U S A 111:E3845-52. 2014
    ..The structure described herein paves the way for the rational design of compounds modulating hCBS activity and thus transsulfuration, redox status, and H2S biogenesis. ..
  45. 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...
  46. pmc Defective cystathionine beta-synthase regulation by S-adenosylmethionine in a partially pyridoxine responsive homocystinuria patient
    L A Kluijtmans
    Department of Pediatrics, University Hospital Nijmegen, Nijmegen, The Netherlands
    J Clin Invest 98:285-9. 1996
    ..Furthermore, it indicates the importance of S-adenosylmethionine regulation of the transsulfuration pathway in homocysteine homeostasis in humans...
  47. 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...
  48. 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).
  49. ncbi Expression of cystathionine beta-synthase is downregulated in hepatocellular carcinoma and associated with poor prognosis
    JongMin Kim
    CbsBioscience, Inc, Daejeon 305 343, Korea
    Oncol Rep 21:1449-54. 2009
    ..0042) after considering tumor stage and tumor size. Thus, the expression level of CBS mRNA could be useful to predict clinical outcome of HCC, especially for patients with low AFP levels...
  50. ncbi Purification and properties of cystathionine beta-synthase from human liver. Evidence for identical subunits
    J Kraus
    J Biol Chem 253:6523-8. 1978
    ..It is possesses serine sulfhydrase as well as cystathionine synthase activity. It has a broad pH optimum from 8.4 to 9...
  51. ncbi Characterization of a cystathionine beta-synthase allele with three mutations in cis in a patient with B6 nonresponsive homocystinuria
    M Marble
    Department of Pediatrics, Johns Hopkins University School, Baltimore, MD 21205
    Hum Mol Genet 3:1883-6. 1994
    ..The apparently simultaneous appearance of more than one mutation in a single exon suggests they may have arisen by a gene conversion event or by nonhomologous recombination...
  52. ncbi Identical genotypes in siblings with different homocystinuric phenotypes: identification of three mutations in cystathionine beta-synthase using an improved bacterial expression system
    R de Franchis
    Department of Pediatrics, University of Colorado School of Medicine, Denver 80262
    Hum Mol Genet 3:1103-8. 1994
    ....
  53. 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
  54. ncbi Characterisation of five missense mutations in the cystathionine beta-synthase gene from three patients with B6-nonresponsive homocystinuria
    P A Dawson
    Department of Medicine, University of Queensland, Princess Alexandra Hospital, Brisbane, Australia
    Eur J Hum Genet 5:15-21. 1997
    ..All of the mutant proteins exhibited decreased catalytic activity in vitro, which confirmed the association between the individual mutation and CBS dysfunction in each patient...
  55. 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...
  56. 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...
  57. 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...
  58. 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...
  59. ncbi Methylenetetrahydrofolate reductase gene mutation and hyperhomocysteinemia as a risk factor for coronary heart disease in the Indian population
    K G Nair
    Breach Candy Hospital, Mumbai
    J Assoc Physicians India 50:9-15. 2002
    ..Our study was aimed at finding the relationship between HCA, folate, vitamins B12 levels, and mutations in the 5,10-methylenetetrahydrofolate reductase (MTHFR) and cystathionine beta-synthase (CBS) genes...
  60. 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)...
  61. ncbi Deletion mutagenesis of human cystathionine beta-synthase. Impact on activity, oligomeric status, and S-adenosylmethionine regulation
    Jana Oliveriusova
    Department of Pediatrics, University of Colorado School of Medicine, Denver 80262, USA
    J Biol Chem 277:48386-94. 2002
    ....
  62. 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...
  63. ncbi The production of transgenic mice expressing human cystathionine beta-synthase to study Down syndrome
    Christine Butler
    The Eleanor Roosevelt Institute at the University of Denver, CO 80206, USA
    Behav Genet 36:429-38. 2006
    ..They can also be used to develop therapies that target abnormalities in 1C-TS metabolism to improve cognition in persons with DS...
  64. doi Polymorphisms in the CBS gene and homocysteine, folate and vitamin B12 levels: association with polymorphisms in the MTHFR and MTRR genes in Brazilian children
    Ana C M Aléssio
    Faculty of Medical Sciences, Hematology Hemotherapy Center, State University of Campinas, Campinas, SP, Brazil
    Am J Med Genet A 146:2598-602. 2008
    ..034). Since B(12) and folate were not different between these groups, a genetic interaction between diverse polymorphisms probably influences Hcy. Our results emphasize the role of genetic interactions in Hcy levels...
  65. pmc Activation of mutant enzyme function in vivo by proteasome inhibitors and treatments that induce Hsp70
    Laishram R Singh
    Cancer Genetics and Signaling Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania, United States of America
    PLoS Genet 6:e1000807. 2010
    ..These findings suggest that proteasome inhibitors and other Hsp70 inducing agents may be useful in the treatment of a variety of genetic diseases caused by missense mutations...
  66. pmc Restoring assembly and activity of cystathionine β-synthase mutants by ligands and chemical chaperones
    Jana Kopecká
    Institute of Inherited Metabolic Disorders, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Praha, Czech Republic
    J Inherit Metab Dis 34:39-48. 2011
    ..This study identified chaperone-responsive mutants that represent 56 of 713 known patient-derived CBS alleles and may serve as a basis for exploring pharmacological approaches aimed at correcting misfolding in homocystinuria...
  67. ncbi Crystallization and preliminary X-ray diffraction analysis of the active core of human recombinant cystathionine beta-synthase: an enzyme involved in vascular disease
    M Janosik
    Department of Pediatrics, University of Colorado School of Medicine, Denver, CO 80262, USA
    Acta Crystallogr D Biol Crystallogr 57:289-91. 2001
    ..The truncated CBS yielded crystals diffracting to 2.6 A which belong to space group P3(1) or P3(2). This is the first comprehensive structural investigation of a PLP and heme-containing enzyme...
  68. ncbi Gene polymorphisms of homocysteine metabolism-related enzymes in Chinese patients with occlusive coronary artery or cerebral vascular diseases
    G Zhang
    Laboratory of Molecular Hematology, Division of Hematology, The Second Affiliated Hospital, Hunan Medical University, Changsha, Hunan 410011, China
    Thromb Res 104:187-95. 2001
    ..However, CBS 844ins68 may be a protective factor against vascular thromboembolic disease. The prevalence of CBS 844ins68 and MS A2756G in Chinese population is obviously lower than in Western Caucasian population...
  69. pmc Investigation of CBS, MTR, RFC-1 and TC polymorphisms as maternal risk factors for Down syndrome
    N Fintelman-Rodrigues
    Departamento de Genetica, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil
    Dis Markers 26:155-61. 2009
    ..Our results suggest that maternal folate-related polymorphisms studied here have no influence on trisomy 21 susceptibility in subjects of Brazilian population...
  70. doi The 844ins68 polymorphism of the cystathionine beta-synthase gene is associated with schizophrenia
    Vera Golimbet
    Mental Health Research Center, Russian Academy of Medical Sciences, Moscow, Russia
    Psychiatry Res 170:168-71. 2009
    ..In conclusion, our study revealed a possible relation of the CBS 844ins68 polymorphism to schizophrenia...
  71. ncbi The human cystathionine beta-synthase (CBS) gene: complete sequence, alternative splicing, and polymorphisms
    J P Kraus
    Department of Pediatrics, University of Colorado School of Medicine, Denver, Colorado 80262, USA
    Genomics 52:312-24. 1998
    ..Additionally, we report on a number of DNA sequence repeats that are polymorphic in North American and European Caucasians...
  72. ncbi CBS 844ins68, MTHFR TT677 and EPCR 4031ins23 genotypes in patients with deep-vein thrombosis
    Ralf Grossmann
    Institute of Clinical Biochemistry and Pathobiochemistry, University of Wuerzburg, Josef Schneider Str 2, 97080, Wurzburg, Germany
    Thromb Res 107:13-5. 2002
    ..A putative protective effect of CBS 844ins68 should be further investigated...
  73. ncbi Gene-gene interaction between the cystathionine beta-synthase 31 base pair variable number of tandem repeats and the methylenetetrahydrofolate reductase 677C > T polymorphism on homocysteine levels and risk for neural tube defects
    Lydia A Afman
    University Medical Center Nijmegen, Department of Pediatrics, Laboratory of Pediatrics and Neurology, PO Box 9101, 6500 HB Nijmegen, Netherlands
    Mol Genet Metab 78:211-5. 2003
    ..Recently, our group showed that a 31 bp VNTR in the CBS gene was associated with decreased CBS activity and increased tHcy levels after methionine loading in a CVD population...
  74. ncbi Sulfur amino acid metabolism in Schizosaccharomyces pombe: occurrence of two O-acetylhomoserine sulfhydrylases and the lack of the reverse transsulfuration pathway
    J Brzywczy
    Institute of Biochemistry and Biophysics, Warszawa, Poland
    FEMS Microbiol Lett 121:171-4. 1994
    ..Consequently no repression of sulfate assimilation is observed when methionine is added to the growth medium...
  75. ncbi B vitamins and homocysteine in cardiovascular disease and aging
    D E Wilcken
    Department of Cardiovascular Medicine, University of New South Wales, Prince Henry Hospital, Sydney
    Ann N Y Acad Sci 854:361-70. 1998
    ..Pyridoxine, vitamin B6, is a cofactor for cystathionine beta synthase, which mediates the transformation of homocysteine to cystathionine, the initial step in the ..
  76. ncbi Yeast cystathionine beta-synthase is a pyridoxal phosphate enzyme but, unlike the human enzyme, is not a heme protein
    K H Jhee
    Laboratory of Biochemistry and Genetics, NIDDK, National Institutes of Health, Bethesda, Maryland 20892 0830, USA
    J Biol Chem 275:11541-4. 2000
    ..The results are consistent with the absence of heme in the closely related enzymes O-acetylserine sulfhydrylase, threonine deaminase, and tryptophan synthase...
  77. pmc A novel transgenic mouse model of CBS-deficient homocystinuria does not incur hepatic steatosis or fibrosis and exhibits a hypercoagulative phenotype that is ameliorated by betaine treatment
    Kenneth N Maclean
    Departments of Pediatrics and Medicine, University of Colorado School of Medicine, Aurora, CO 80045, USA
    Mol Genet Metab 101:153-62. 2010
    ..Our findings indicate that this mouse model will be a valuable tool in the study of pathogenesis in classical homocystinuria and the rational design of novel treatments...
  78. 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...
  79. 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...
  80. pmc Diversity of cystathionine beta-synthase haplotypes bearing the most common homocystinuria mutation c.833T>C: a possible role for gene conversion
    Petr Vyletal
    Center for Applied Genomics, Institute of Inherited Metabolic Disorders, Charles University 1st Faculty of Medicine, Prague, Czech Republic
    Hum Mutat 28:255-64. 2007
    ..833C; -] chromosomes may have originated by recurrent gene conversion employing the common nonpathogenic c.[833C; 844_845ins68] chromosomes as templates...
  81. ncbi Cystathionine beta-synthase, a key enzyme for homocysteine metabolism, is preferentially expressed in the radial glia/astrocyte lineage of developing mouse CNS
    Yasushi Enokido
    Department of Molecular Geneticsy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan
    FASEB J 19:1854-6. 2005
    ....
  82. doi Investigation of residues Lys112, Glu136, His138, Gly247, Tyr248, and Asp249 in the active site of yeast cystathionine beta-synthase
    Pratik H Lodha
    Department of Biology, Carleton University, Ottawa, ON, Canada
    Biochem Cell Biol 87:531-40. 2009
    ....
  83. 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...
  84. ncbi A deficiency of cysteine impairs fibrillin-1 deposition: implications for the pathogenesis of cystathionine beta-synthase deficiency
    A K Majors
    Department of Human Genetics, MCP Hahnemann School of Medicine, Pittsburgh, Pennsylvania 15212, USA
    Mol Genet Metab 70:252-60. 2000
    ....
  85. pmc Cystathionine beta-synthase null homocystinuric mice fail to exhibit altered hemostasis or lowering of plasma homocysteine in response to betaine treatment
    Kenneth N Maclean
    Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO 80045, United States
    Mol Genet Metab 101:163-71. 2010
    ....
  86. pmc Vascular presentation of cystathionine beta-synthase deficiency in adulthood
    Martin Magner
    Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University in Prague, Praha, Czech Republic
    J Inherit Metab Dis 34:33-7. 2011
    ..833T>C (p.I278T) is often present...
  87. doi Triacylglycerol/phospholipid molecular species profiling of fatty livers and regenerated non-fatty livers in cystathionine beta-synthase-deficient mice, an animal model for homocysteinemia/homocystinuria
    Kazutaka Ikeda
    Department of Metabolome, Graduate School of Medicine, The University of Tokyo, Tokyo, 113 0033, Japan
    Anal Bioanal Chem 400:1853-63. 2011
    ..Our results suggest that cellular signaling mediated by altered phospholipid contents might be involved in pathogenesis of fatty liver in Cbs(-/-)...
  88. ncbi Genetic determinants of hyperhomocysteinaemia: the roles of cystathionine beta-synthase and 5,10-methylenetetrahydrofolate reductase
    H J Blom
    Department of Paediatrics, University Hospital Nijmegen, The Netherlands
    Eur J Pediatr 159:S208-12. 2000
    ..The elevated Hcy levels due to these mutations can be normalised by administration of folate, but whether folate reduces the risk of cardiovascular disease remains to be established...
  89. 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...
  90. ncbi Biosynthesis of sulfur-containing amino acids in Streptomyces venezuelae ISP5230: roles for cystathionine beta-synthase and transsulfuration
    Z Chang
    Department of Biology, Dalhousie University, Halifax, Nova Scotia, Canada B3H 4J1
    Microbiology 148:2135-47. 2002
    ..Based on assay results, the cys-28 mutation in Str. venezuelae VS263 does not inactivate the cysteine synthase gene but impairs expression in cultures grown in minimal medium...
  91. ncbi Carotid and femoral artery wall thickness and stiffness in patients at risk for cardiovascular disease, with special emphasis on hyperhomocysteinemia
    T J Smilde
    Department of Medicine, Division of General Internal Medicine, University Hospital Nijmegen, The Netherlands
    Arterioscler Thromb Vasc Biol 18:1958-63. 1998
    ..02) and in CC in the CFA (R2=0.04). In this study, no relationship was found between homocysteine level and the thickness of the arterial wall, with only a marginal influence on stiffness...
  92. pmc The endogenous production of hydrogen sulphide in intrauterine tissues
    Pushpa Patel
    Dept of Medical and Social Care Education, School of Medicine, University of Leicester, Leicester, UK
    Reprod Biol Endocrinol 7:10. 2009
    ..The aim of the present study was to investigate the endogenous production of hydrogen sulphide in rat and human intrauterine tissues in vitro...
  93. doi Taurine-deficient diet up-regulated cystathionine beta-synthase monoallele in hemizygous cystathionine beta-synthase knockout mice
    Wei Hsun Chao
    Department of Early Childhood Educare, WuFeng Institute of Technology, Ming Hsiung, Chia Yi, Taiwan, ROC
    Nutr Res 29:794-801. 2009
    ..We conclude that the remaining CBS monoallele is up-regulated in mice when fed a taurine-deficient diet to produce additional CBS mRNA...
  94. doi Astrocytes produce the antiinflammatory and neuroprotective agent hydrogen sulfide
    MoonHee Lee
    Kinsmen Laboratory of Neurological Research, University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC, Canada
    Neurobiol Aging 30:1523-34. 2009
    ..H(2)S releasing drugs may have therapeutic potential in neurodegenerative disorders of aging such as Alzheimer disease and Parkinson disease...
  95. ncbi In the cystathionine beta-synthase knockout mouse, elevations in total plasma homocysteine increase tissue S-adenosylhomocysteine, but responses of S-adenosylmethionine and DNA methylation are tissue specific
    Silvina F Choumenkovitch
    Vitamin Metabolism Laboratory, Jean Mayer U S Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111, USA
    J Nutr 132:2157-60. 2002
    ....
  96. ncbi Stopped-flow kinetic analysis of the reaction catalyzed by the full-length yeast cystathionine beta-synthase
    Shinichi Taoka
    Biochemistry Department, University of Nebraska, Lincoln, Nebraska 68588 0664, USA
    J Biol Chem 277:22421-5. 2002
    ..H., Niks, D., McPhie, P., Dunn, M. F., and Miles, E. W. (2001) Biochemistry 40, 10873-10880)...
  97. doi Hydrogen sulphide synthesis in the rat and mouse gastrointestinal tract
    Gary R Martin
    Inflammation Research Network, Department of Medicine, University of Calgary, Calgary, Alberta, Canada T2N 4N1
    Dig Liver Dis 42:103-9. 2010
    ..Little is known about H2S synthesis in the gastrointestinal tract. The aim of this study was to characterize H2S synthesis throughout the gastrointestinal tract...
  98. ncbi Relation between plasma homocysteine concentration, the 844ins68 variant of the cystathionine beta-synthase gene, and pyridoxal-5'-phosphate concentration
    M Y Tsai
    Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, Minnesota 55455 0392, USA
    Mol Genet Metab 67:352-6. 1999
    ....
  99. 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 (..
  100. ncbi Characterization of transsulfuration and cysteine biosynthetic pathways in the protozoan hemoflagellate, Trypanosoma cruzi. Isolation and molecular characterization of cystathionine beta-synthase and serine acetyltransferase from Trypanosoma
    T Nozaki
    Department of Parasitology, National Institute of Infectious Diseases, 1 23 1 Toyama, Shinjuku ku, Tokyo 162 8640, Japan
    J Biol Chem 276:6516-23. 2001
    ..Together, these studies demonstrate the T. cruzi is a unique protist in possessing both transsulfuration and sulfur assimilatory pathways...
  101. 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...

Research Grants64

  1. 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. ..
  2. Priyabrata Mukherjee; Fiscal Year: 2016
    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...
  3. Homocysteine &Heme: A Role in Thrombosis?
    Jan P Kraus; Fiscal Year: 2012
    ..abstract_text> ..
  4. 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. ..
  5. 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. ..
  6. Johan L Van Hove; Fiscal Year: 2014
    ..Completion of these proposed studies will both increase our knowledge of pathogenesis in CBSDH and deliver candidate markers for a future phase 2b study. ..
  7. INTERACTION OF HOMOCYSTEINE AND LP(A) IN VIVO
    Richard Lawn; Fiscal Year: 2000
    ..End of Abstract) ..
  8. 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. ..
  9. 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. ..
  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. 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...
  12. PHYSIOLOGICAL FUNCTION OF ENDOGENOUS HYDROGEN SULFIDE
    David Schubert; Fiscal Year: 1999
    ....
  13. 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 (..
  14. Sylvia B Smith; Fiscal Year: 2016
    ....
  15. 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 ..
  16. B12 Nutrition in the Aged
    Sally Stabler; Fiscal Year: 2007
    ..abstract_text> ..
  17. 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. ..
  18. GENETIC BIOCHEMICAL DISORDERS IN MENTAL RETARDATION
    Stephen Goodman; Fiscal Year: 2004
    ..abstract_text> ..
  19. 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 ..
  20. Cystathionine B Synthase and ARA C Therapy for Leukemia
    JEFFREY TAUB; Fiscal Year: 2005
    ..abstract_text> ..
  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. 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) ..
  23. Utpal Sen; Fiscal Year: 2015
    ..abstract_text> ..
  24. Microvascular Dysfunction in Hyperhomocysteinemia
    Shawn E Bearden; Fiscal Year: 2012
    ....
  25. Mechanism of Vascular Remodeling in Hyperhomocysteinemia
    Suresh C Tyagi; Fiscal Year: 2010
    ..This study will provide new insights into the mechanism of arterial remodeling and will have therapeutic ramifications for vessel wall disease. ..
  26. Paras Kumar Mishra; Fiscal Year: 2016
    ..These studies will elucidate the mechanism of homocysteine-mediated attenuation of [unreadable]2-AR in diabetes and cardio-protective role of [unreadable]2-AR agonist, exercise and H2S in diabetic complications. ..
  27. Implications of Endothelial-Myocyte Uncoupling in Cardiac Arrhythmia
    Suresh C Tyagi; Fiscal Year: 2010
    ..These studies will delineate the mechanism of Hcy-dependent endothelial-myocyte uncoupling in cardiac arrhythmia and failure, and will have therapeutic ramifications for sudden cardiac death. ..
  28. Hong Wang; Fiscal Year: 2014
    ..Aim 3 will study the effects of homocysteine-lowering on preventing MC trans-endothelium migration into the vessel wall and on reducing spontaneous atherosclerotic lesion formation. ..
  29. Cardioprotective Actions of Hydrogen Sulfide
    DAVID JOSEPH LEFER; Fiscal Year: 2013
    ..Information gained from these studies will help with the development of novel therapies for the treatment of patients suffering from acute myocardial infarction. ..
  30. Albert van Der Vliet; Fiscal Year: 2016
    ....
  31. Hong Wang; Fiscal Year: 2016
    ..If the key steps in Hcy-induced dyslipidemia and atherosclerosis can be identified, new genetic or pharmacological therapeutic targets can be utilized for treatment. ..
  32. Xiao Feng Yang; Fiscal Year: 2016
    ..Success of this project is significant, which may lead to the development of new therapeutic approaches to inhibit HHcy-induced Treg apoptosis and enhance Treg suppression of HHcy-induced vascular inflammation. ..
  33. Charles W Leffler; Fiscal Year: 2016
    ..The gasotransmitter, H2S, will certainly prove to be one of these major mechanisms of which greater understanding is urgently needed. ..
  34. Suresh C Tyagi; Fiscal Year: 2016
    ..The results of the proposed research should uncover the molecular mechanisms regulating Hcy-Fg-Ab-collagen complex formation and lead to effective strategies for the treatment of cerebrovascular complications during diseases such as AD. ..
  35. Solomon H Snyder; Fiscal Year: 2016
    ..Akt/mTOR signaling is critical for brain function so that our elucidation of its regulation by inositol pyrophosphates may have therapeutic relevance. ..
  36. Domenico Pratico; Fiscal Year: 2016
    ..In the third one, we will establish the role of HHcy, and 5-LO upregulation in the development of the pathological vascular phenotype of the Tg-hCBS Cbs-/- mice. ..
  37. EXPRESSION OF CYSTATHIONINE SYNTHASE AND HUMAN DISEASE
    JAN KRAUS; Fiscal Year: 1993
    ..The results of this work will complement our studies of normal and mutant CBS genes and will elucidate the significance of their products in human disease...
  38. 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. ..
  39. CBS GENE IN HOMOCYSTINURIA AND ARTERIOSCLEROSIS
    JAN KRAUS; Fiscal Year: 2000
    ..Finally the applicant proposes to study how the mutations in regulatory portions of the CBS gene may have caused the low CBS expression leading to abnormal homocysteine metabolism. ..
  40. Integrated signaling of eicosanoids in HSC formation and regeneration
    Trista E North; Fiscal Year: 2013
    ..These results are expected to reveal deeper insight into interactive roles of inflammatory mediators in marrow regeneration and have relevance for combinatorial targeting to direct clinical outcome in transfusion biology. ..
  41. LEE R KROOS; Fiscal Year: 2014
    ..In addition to expanding knowledge of RasP, the approach could be used to identify substrates of other MIPs, overcoming a critical barrier to progress in the field. ..
  42. Mechanisms of dietary restriction in Drosophila
    Scott Pletcher; Fiscal Year: 2009
    ..abstract_text> ..
  43. Miroslav Dundr; Fiscal Year: 2015
    ..abstract_text> ..
  44. Nuclear bodies and ribonucleoprotein biogenesis
    Michael D Hebert; Fiscal Year: 2012
    ..Certain diseases, such as cancer and some neurodegenerative disorders, may alter Cajal body and Gem activity. ..
  45. Maintenance of Stem Cell Fates in Drosophila
    Edwin L Ferguson; Fiscal Year: 2010
    ..This knowledge could be very useful in attempts to use stem cells to heal injury or cure disease. ..
  46. Effects of Cannabinoids on Pain-Stimulated and Pain-Depressed Behavior in Rats
    Andrew J Kwilasz; Fiscal Year: 2013
    ..The primary goal of this project is to assess antinociceptive effects of CBs using a model that may be more predictive of analgesia in humans. ..
  47. RUMA V BANERJEE; Fiscal Year: 2016
    ....
  48. GABA Deficits and Vulnerability to Cannabinoid-Induced Psychosis
    DEEPAK CYRIL D apos SOUZA; Fiscal Year: 2010
    ....
  49. Bruce L Miller; Fiscal Year: 2016
    ..abstract_text> ..
  50. Health related quality of life: Elders in long-term care
    Mary D Naylor; Fiscal Year: 2010
    ..The findings from this study will enable policy makers and providers, as well as recipients of long term care services, to evaluate and make informed choices related to long-term care. ..
  51. Phase 2B Trial of Memantine for the Treatment of Amyotrophic Lateral Sclerosis
    TODD DYLAN LEVINE; Fiscal Year: 2013
    ..ln particular the investigators will measure the ratio of phosphorylated heavy neurofilament to complement 3 (pNFH/C3) to see if this ratio is predictive of disease progression and if the levels change during therapy with memantine. ..
  52. Hong Wang; Fiscal Year: 2015
    ..It is believed that completion of the specific aims of this proposal may provide important insights into the role of Hcy in CVD, and identify the underline mechanism. ..
  53. DeltaVision OMX 3-D Structured Illumination Microscope
    Michael R Paddy; Fiscal Year: 2010
    ..This scheme includes an annual commitment of $25,000 towards the service contract from the MCB Chair. ..
  54. The Functional Neurobiology of Cannabinoids in Brain
    EDWARD FRENCH; Fiscal Year: 2006
    ..abstract_text> ..
  55. The Functional Neurobiology of Cannabinoids in Brain
    EDWARD FRENCH; Fiscal Year: 2001
    ..abstract_text> ..
  56. Forensic Web Adventures to Teach about Prescription Drug Abuse
    LESLIE M MILLER; Fiscal Year: 2013
    ..Much of the content will be devoted to topics in neuroscience and the effects of prescription drugs on other human body systems. ..
  57. PATRICIA HODAPP REGGIO; Fiscal Year: 2016
    ..Results of the studies proposed here have the potential for the development of therapeutic agents for the treatment of inflammation and metabolic syndrome. ..
  58. Sibling Donor Cord Blood Banking and Transplantation
    Bertram Lubin; Fiscal Year: 2004
    ..abstract_text> ..
  59. Mechanisms of Activity-Dependent Synaptic Plasticity
    AZEEZ AILERU; Fiscal Year: 2005
    ....
  60. PERINATAL HYPEROXIA AND ADULT ARTERIAL CHEMORECEPTION
    Gerald Bisgard; Fiscal Year: 2004
    ....
  61. PERIPHERAL AND CENTRAL VENTILATORY CONTROL
    Gerald Bisgard; Fiscal Year: 2000
    ..The studies will also add to our understanding of the control of respiration in normal individuals exposed to hypoxia, e.g., ascent to high altitude. ..
  62. WORKING MEMORY IN HUMAN BRAIN DAMAGE
    MARK D ESPOSITO; Fiscal Year: 1999
    ..These studies will improve our knowledge of working memory and provide a rational basis for diagnostic and therapeutic intervention in patients with working memory impairments. ..
  63. Methylation and Oxidation in Breast Cancer Epidemiology
    Jo Freudenheim; Fiscal Year: 2005
    ....
  64. Genetic Profiles for Perioperative Applications
    ROBERT KWIATKOWSKI; Fiscal Year: 2001
    ..abstract_text> ..

Patents1

  1. Treatment of elevated plasma homocysteine
    Patent Number: EP1396537-A1; Date:2004-03-10