s adenosylhomocysteine

Summary

Summary: 5'-S-(3-Amino-3-carboxypropyl)-5'-thioadenosine. Formed from S-adenosylmethionine after transmethylation reactions.

Top Publications

  1. ncbi Folate status and S-adenosylmethionine/S-adenosylhomocysteine ratio in colorectal adenocarcinoma in humans
    E Alonso-Aperte
    Departamento de Nutricion, Bromatologia y Tecnologia de los Alimentos, Facultad de Farmacia, Universidad San Pablo CEU, Madrid, Spain
    Eur J Clin Nutr 62:295-8. 2008
  2. ncbi Intracellular S-adenosylhomocysteine concentrations predict global DNA hypomethylation in tissues of methyl-deficient cystathionine beta-synthase heterozygous mice
    M A Caudill
    Food, Nutrition and Consumer Sciences Department, California State Polytechnic University, Pomona, CA 91768, USA
    J Nutr 131:2811-8. 2001
  3. ncbi Regulation of p53 activity through lysine methylation
    Sergei Chuikov
    Howard Hughes Medical Institute, Division of Nucleic Acids Enzymology, Department of Biochemistry, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA
    Nature 432:353-60. 2004
  4. ncbi Intracellular S-adenosylhomocysteine increased levels are associated with DNA hypomethylation in HUVEC
    Rita Castro
    Centro de Patogenese Molecular, Faculdade de Farmacia da Universidade de Lisboa, Portugal
    J Mol Med (Berl) 83:831-6. 2005
  5. 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
  6. ncbi DNA cleavage by type III restriction-modification enzyme EcoP15I is independent of spacer distance between two head to head oriented recognition sites
    M Mucke
    Institut fur Virologie, Medizinische Fakultät Charité, der Humboldt Universität zu Berlin, D 10098, Germany
    J Mol Biol 312:687-98. 2001
  7. ncbi A unique RNA Fold in the RumA-RNA-cofactor ternary complex contributes to substrate selectivity and enzymatic function
    Tom T Lee
    Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94143, USA
    Cell 120:599-611. 2005
  8. pmc Characterization of a mimivirus RNA cap guanine-N2 methyltransferase
    Delphine Benarroch
    Sloan Kettering Institute, New York, New York 10065, USA
    RNA 15:666-74. 2009
  9. ncbi Crystal structure of tRNA N2,N2-guanosine dimethyltransferase Trm1 from Pyrococcus horikoshii
    - Ihsanawati
    Systems and Structural Biology Center, Yokohama Institute, RIKEN, 1 7 22 Suehiro, Tsurumi, Yokohama 230 0045, Japan
    J Mol Biol 383:871-84. 2008
  10. pmc Structural basis for the product specificity of histone lysine methyltransferases
    Xing Zhang
    Department of Biochemistry, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA 30322, USA
    Mol Cell 12:177-85. 2003

Detail Information

Publications230 found, 100 shown here

  1. ncbi Folate status and S-adenosylmethionine/S-adenosylhomocysteine ratio in colorectal adenocarcinoma in humans
    E Alonso-Aperte
    Departamento de Nutricion, Bromatologia y Tecnologia de los Alimentos, Facultad de Farmacia, Universidad San Pablo CEU, Madrid, Spain
    Eur J Clin Nutr 62:295-8. 2008
    ....
  2. ncbi Intracellular S-adenosylhomocysteine concentrations predict global DNA hypomethylation in tissues of methyl-deficient cystathionine beta-synthase heterozygous mice
    M A Caudill
    Food, Nutrition and Consumer Sciences Department, California State Polytechnic University, Pomona, CA 91768, USA
    J Nutr 131:2811-8. 2001
    ..These results support the possibility that plasma SAH concentrations may provide a sensitive biomarker for cellular methylation status...
  3. ncbi Regulation of p53 activity through lysine methylation
    Sergei Chuikov
    Howard Hughes Medical Institute, Division of Nucleic Acids Enzymology, Department of Biochemistry, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA
    Nature 432:353-60. 2004
    ..The crystal structure of a ternary complex of Set9 with a p53 peptide and the cofactor product S-adenosyl-l-homocysteine (AdoHcy) provides the molecular basis for recognition of p53 by this lysine methyltransferase...
  4. ncbi Intracellular S-adenosylhomocysteine increased levels are associated with DNA hypomethylation in HUVEC
    Rita Castro
    Centro de Patogenese Molecular, Faculdade de Farmacia da Universidade de Lisboa, Portugal
    J Mol Med (Berl) 83:831-6. 2005
    ..A significant negative correlation was observed between intracellular AdoHcy and genomic DNA methylation status. These findings strongly point to the importance of AdoHcy as a pivotal biomarker of genomic DNA methylation status...
  5. 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
    ....
  6. ncbi DNA cleavage by type III restriction-modification enzyme EcoP15I is independent of spacer distance between two head to head oriented recognition sites
    M Mucke
    Institut fur Virologie, Medizinische Fakultät Charité, der Humboldt Universität zu Berlin, D 10098, Germany
    J Mol Biol 312:687-98. 2001
    ..We assume that the altered patterns are most likely due to a conformational change of the enzyme. Overall, our data further refine the tracking-collision model for type III restriction enzymes...
  7. ncbi A unique RNA Fold in the RumA-RNA-cofactor ternary complex contributes to substrate selectivity and enzymatic function
    Tom T Lee
    Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94143, USA
    Cell 120:599-611. 2005
    ..Active collaboration of RNA in catalysis leads us to conclude that RumA and its substrate RNA may reflect features from the earliest RNA-protein era...
  8. pmc Characterization of a mimivirus RNA cap guanine-N2 methyltransferase
    Delphine Benarroch
    Sloan Kettering Institute, New York, New York 10065, USA
    RNA 15:666-74. 2009
    ..Our results hint that DMG caps can satisfy many of the functions of TMG caps in vivo. We speculate that DMG capping of mimivirus mRNAs might favor viral protein synthesis in the infected host...
  9. ncbi Crystal structure of tRNA N2,N2-guanosine dimethyltransferase Trm1 from Pyrococcus horikoshii
    - Ihsanawati
    Systems and Structural Biology Center, Yokohama Institute, RIKEN, 1 7 22 Suehiro, Tsurumi, Yokohama 230 0045, Japan
    J Mol Biol 383:871-84. 2008
    ..Moreover, the catalytic residues Asp138, Pro139, and Phe140 are in a different motif from that in DNA 6-methyladenosine methyltransferases, suggesting a different methyl transfer mechanism in the Trm1 family...
  10. pmc Structural basis for the product specificity of histone lysine methyltransferases
    Xing Zhang
    Department of Biochemistry, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA 30322, USA
    Mol Cell 12:177-85. 2003
    ....
  11. ncbi Plasma S-adenosylhomocysteine is a more sensitive indicator of cardiovascular disease than plasma homocysteine
    D M Kerins
    Departments of Biochemistry and Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232-0146, USA
    Am J Clin Nutr 74:723-9. 2001
    ..Both plasma total homocysteine and S-adenosylhomocysteine are significantly correlated with plasma creatinine in patients...
  12. ncbi Stable-isotope dilution liquid chromatography-electrospray injection tandem mass spectrometry method for fast, selective measurement of S-adenosylmethionine and S-adenosylhomocysteine in plasma
    Henkjan Gellekink
    Laboratory of Pediatrics and Neurology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    Clin Chem 51:1487-92. 2005
    ..We aimed to develop a rapid and sensitive method to measure AdoHcy and its precursor S-adenosylmethionine (AdoMet)...
  13. ncbi Structure and mechanism of mRNA cap (guanine-N7) methyltransferase
    Carme Fabrega
    Biochemistry Department, Structural Biology Program, Weill Medical College, Cornell University, New York, NY 10021, USA
    Mol Cell 13:77-89. 2004
    ..The enzyme-ligand structures, together with new mutational data, fully account for the biochemical specificity of the cap guanine-N7 methylation reaction, an essential and defining step of eukaryotic mRNA synthesis...
  14. ncbi Two alternative conformations of S-adenosyl-L-homocysteine bound to Escherichia coli DNA adenine methyltransferase and the implication of conformational changes in regulating the catalytic cycle
    Kirsten Liebert
    Biochemistry Laboratory, School of Engineering and Science, Jacobs University Bremen, 28759 Bremen, Germany
    J Biol Chem 282:22848-55. 2007
    ..This suggests that the hexapeptide couples specific DNA binding (Lys(9)), AdoMet binding (Trp(10)), and insertion of the flipped target base into the active site pocket (Lys(14))...
  15. pmc Metabolic derangement of methionine and folate metabolism in mice deficient in methionine synthase reductase
    C Lee Elmore
    Life Sciences Institute, University of Michigan, Ann Arbor, MI, USA
    Mol Genet Metab 91:85-97. 2007
    ..The different metabolite profiles in the various genetic mouse models for hyperhomocyst(e)inemia may be useful in understanding biological effects of elevated homocyst(e)ine...
  16. ncbi The transmethylation cycle in the brain of Alzheimer patients
    Cees Mulder
    Department of Clinical Chemistry, VU University Medical Center, P O Box 7057, 1007 MB Amsterdam, The Netherlands
    Neurosci Lett 386:69-71. 2005
    ..We found no statistical differences between AD patients and controls for 5-MTHF, SAM and SAH levels, and the SAM/SAH-ratio in CSF. These findings argue against a possible change in methylation of the promoter and expression of PS1...
  17. ncbi Reversed-phase high-performance liquid chromatography procedure for the simultaneous determination of S-adenosyl-L-methionine and S-adenosyl-L-homocysteine in mouse liver and the effect of methionine on their concentrations
    W Wang
    Department of Pathology, Medical College of Ohio, Toledo 43614-5806, USA
    J Chromatogr B Biomed Sci Appl 762:59-65. 2001
    ..This indicated that methionine was promptly converted to SAM and then rapidly catabolized into SAH. Thus, the metabolism of methionine to SAM should be considered in the supplementation of methionine to maintain SAM levels in the body...
  18. ncbi Quantification of serum and urinary S-adenosylmethionine and S-adenosylhomocysteine by stable-isotope-dilution liquid chromatography-mass spectrometry
    Sally P Stabler
    Division of Hematology, Department of Medicine, University of Colorado Health Sciences Center, Denver, CO 80262, USA
    Clin Chem 50:365-72. 2004
    ....
  19. ncbi Activation and inhibition of DNA methyltransferases by S-adenosyl-L-homocysteine analogues
    Ritesh Kumar
    Department of Biochemistry, Indian Institute of Science, Banglore 560012, India
    Bioorg Med Chem 16:2276-85. 2008
    ..An understanding of the binding of analogues to DNA methyltransferases will greatly assist the design of novel anti-microbial compounds...
  20. ncbi Simultaneous detection of S-adenosylmethionine and S-adenosylhomocysteine in mouse and rat tissues by capillary electrophoresis
    Eric O Uthus
    USDA ARS Grand Forks Human Nutrition Research Center, Grand Forks, ND 58202, USA
    Electrophoresis 24:1221-6. 2003
    ..The method is linear over ranges of 1-100 microM SAM and 1-250 microM SAH. This method can be used to determine tissue concentrations of SAM and SAH, two metabolites that can provide insight into many biological processes...
  21. ncbi B-vitamin deprivation induces hyperhomocysteinemia and brain S-adenosylhomocysteine, depletes brain S-adenosylmethionine, and enhances PS1 and BACE expression and amyloid-beta deposition in mice
    Andrea Fuso
    Department of Surgery P Valdoni, Sapienza University of Rome, Italy
    Mol Cell Neurosci 37:731-46. 2008
    ..Collectively, these findings are consistent with the hypothesis that abnormal methylation in association with hyperhomocysteinemia may contribute to Alzheimer's disease...
  22. ncbi Maternal global methylation status and risk of congenital heart diseases
    Lydi M J W van Driel
    Departments of Obstetrics and Gynecology, Division of Obstetrics and Prenatal Medicine, Pediatrics, Pediatric Cardiology CAHAL Centre for Congenital Anomalies of the Heart Amsterdam Leiden, The Netherlands
    Obstet Gynecol 112:277-83. 2008
    ..To investigate whether the association between the maternal methylation status as reflected by low S-adenosylmethionine and high S-adenosylhomocysteine, is detrimental for cardiogenesis and congenital heart disease (CHD) in the offspring...
  23. ncbi Biomarkers of nutrient exposure and status in one-carbon (methyl) metabolism
    Joel B Mason
    Tufts University, Boston, MA 02111, USA
    J Nutr 133:941S-947S. 2003
    ..Plasma or tissue concentrations of S-adenosylmethionine and S-adenosylhomocysteine, and genomic DNA methylation are two potential candidates in this regard although much work is yet to be done to define the nature of these relationships...
  24. ncbi A mathematical model of the methionine cycle
    Michael C Reed
    Department of Mathematics, Duke University, Durham, NC 27708, USA
    J Theor Biol 226:33-43. 2004
    ..We conduct computational "experiments" that give understanding of the regulatory behavior of the methionine cycle under normal conditions and the behavior in the presence of genetic variation and dietary deficiencies...
  25. ncbi Homocysteine, S-adenosylmethionine and S-adenosylhomocysteine are associated with retinal microvascular abnormalities: the Hoorn Study
    Manon V Van Hecke
    Department of Ophthalmology, VU University Medical Center, 1007 MB Amsterdam, The Netherlands
    Clin Sci (Lond) 114:479-87. 2008
    ....
  26. ncbi Betaine lowers elevated s-adenosylhomocysteine levels in hepatocytes from ethanol-fed rats
    Anthony J Barak
    VA Alcohol Research Center, Department of Veterans Affairs Medical Center, Omaha, NE 68105, USA
    J Nutr 133:2845-8. 2003
    ....
  27. ncbi Glycine N-methyltransferase-/- mice develop chronic hepatitis and glycogen storage disease in the liver
    Shih Ping Liu
    Division of Preventive Medicine, Institute of Public Health, School of Medicine, Taipei, Taiwan
    Hepatology 46:1413-25. 2007
    ....
  28. pmc Insertional inactivation of the methionine s-methyltransferase gene eliminates the s-methylmethionine cycle and increases the methylation ratio
    Michael G Kocsis
    Horticultural Sciences Department, University of Florida, Gainesville 32611, USA
    Plant Physiol 131:1808-15. 2003
    ..These data indicate that the SMM cycle contributes to regulation of Ado-Met levels rather than preventing depletion of free Met...
  29. ncbi Remethylation and transsulfuration of methionine in cirrhosis: studies with L-[H3-methyl-1-C]methionine
    Stefan Russmann
    Department of Clinical Pharmacology, University of Bern, Switzerland
    Hepatology 36:1190-6. 2002
    ..In contrast, transsulfuration is impaired in patients with alcohol-induced cirrhosis such that an assessment of transsulfuration by a simple breath test may provide a clinically useful estimate of hepatic function...
  30. ncbi Crystal structure of the avilamycin resistance-conferring methyltransferase AviRa from Streptomyces viridochromogenes
    Tanja G Mosbacher
    Institut fur Organische Chemie und Biochemie, Albert Ludwigs Universitat, Albertstr 21, Freiburg im Breisgau, 79104, Germany
    J Mol Biol 329:147-57. 2003
    ..The two additional alpha-helices of AviRa filled a depression in the surface. Since the transferred methyl group of the cofactor is in a pocket beneath the enzyme surface, the targeted guanine base has to flip out for methylation...
  31. ncbi Altered methionine metabolism in long living Ames dwarf mice
    Eric O Uthus
    US Department of Agriculture, ARS, Grand Forks Human Nutrition Research Center, P O Box 9034, Grand Forks, ND 58202, USA
    Exp Gerontol 38:491-8. 2003
    ..Taken together, the data suggest that methionine metabolism may play a role in oxidative defense in the dwarf mouse and should be studied as a potential mechanism of extended lifespan...
  32. ncbi Influence of preconditioning-like hypoxia on the liver of developing methyl-deficient rats
    Sébastien A Blaise
    INSERM U724, Faculte de Medecine, 9 ave de la forêt de Haye, BP 184, F 54500 Vandoeuvre les Nancy, France
    Am J Physiol Endocrinol Metab 293:E1492-502. 2007
    ....
  33. ncbi Anthocyanin administration elevates plasma homocysteine in rats
    Kiyotaka Nakagawa
    Food and Biodynamic Chemistry Laboratory, Graduate School of Life Science and Agriculture, Tohoku University, Sendai 981 8555, Japan
    J Nutr Sci Vitaminol (Tokyo) 48:530-5. 2002
    ..The intake of anthocyanin and its structural homologues may have an effect on the metabolic regulation of sulfur amino acids and possibly increase the risk of vascular disease in humans...
  34. ncbi Homocysteine-mediated PPARalpha,gamma DNA methylation and its potential pathogenic mechanism in monocytes
    Jiang Yideng
    Department of Pathophysiology, Ningxia Medical College, Yinchuan, Ningxia, PR China
    DNA Cell Biol 27:143-50. 2008
    ....
  35. ncbi The effect of dietary folate on genomic and p53-specific DNA methylation in rat colon
    Kyoung Jin Sohn
    Department of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada
    Carcinogenesis 24:81-90. 2003
    ..This implies that neither genomic or p53 hypomethylation within exons 6-7 nor aberrant p53 methylation within the promoter region is likely a mechanism by which folate deficiency enhances colorectal carcinogenesis in the rat...
  36. ncbi Influence of an altered methylation potential on mRNA methylation and gene expression in HepG2 cells
    Marina Hermes
    Department of Pharmacology and Toxicology, Faculty of Medicine, University of Tubingen, D 72074 Tubingen, Germany
    Exp Cell Res 294:325-34. 2004
    ..Our results show that the mRNA levels of the studied genes respond differentially to changes in MP. This implies that genes with a slower transcription rate and mRNAs with a slower turnover are insensitive to short-term changes in MP...
  37. ncbi Homocysteine alterations in experimental cholestasis and its subsequent cirrhosis
    Mohammad R Ebrahimkhani
    Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P O Box 13145 784, Tehran, Iran
    Life Sci 76:2497-512. 2005
    ..NO overproduction may contribute to plasma Hcy elevation and liver SAM depletion after cholestasis...
  38. ncbi Disturbed homocysteine and methionine cycle intermediates S-adenosylhomocysteine and S-adenosylmethionine are related to degree of renal insufficiency in type 2 diabetes
    Wolfgang Herrmann
    Department of Clinical Chemistry, Central Laboratory, Saarland University Hospital, Homburg, Germany
    Clin Chem 51:891-7. 2005
    ....
  39. ncbi Role of S-adenosylhomocysteine hydrolase in adenosine-induced apoptosis in HepG2 cells
    Marina Hermes
    Department of Pharmacology and Toxicology, Faculty of Medicine, University of Tuebingen, Wilhelmstrasse 56, D 72074 Tuebingen, Germany
    Exp Cell Res 313:264-83. 2007
    ..Since several p53-target genes and other apoptosis-related genes were up-regulated by Adox, we conclude that AdoHcy is involved in adenosine-induced apoptosis by altering gene expression...
  40. pmc Metabolic endophenotype and related genotypes are associated with oxidative stress in children with autism
    S Jill James
    Department of Pediatrics, University of Arkansas for Medical Sciences, Arkansas Children s Hospital Research Institute, Little Rock, Arkansas 72202, USA
    Am J Med Genet B Neuropsychiatr Genet 141:947-56. 2006
    ..We propose that an increased vulnerability to oxidative stress (endogenous or environmental) may contribute to the development and clinical manifestations of autism...
  41. ncbi S-adenosylhomocysteine metabolism in different cell lines: effect of hypoxia and cell density
    Marina Hermes
    Department of Pharmacology and Toxicology, Faculty of Medicine, University of Tubingen, Germany
    Cell Physiol Biochem 15:233-44. 2005
    ..Exp Cell Res 294: 325-334, 2004). In the present study, we compared AdoMet/AdoHcy ratio and energy metabolism in HepG2, HEK-293, HeLa, MCF-7 and SK-HEP-1 cell lines under normoxia and hypoxia...
  42. ncbi Maternal polymorphisms 677C-T and 1298A-C of MTHFR, and 66A-G MTRR genes: is there any relationship between polymorphisms of the folate pathway, maternal homocysteine levels, and the risk for having a child with Down syndrome?
    Maria Luisa Martinez-Frias
    ECEMC, Centro de Investigación sobre Anomalías Congénitas, Instituto de Salud Carlos III, Ministerio de Sanidad y Consumo, Madrid, Spain
    Am J Med Genet A 140:987-97. 2006
    ..Three possible mechanisms are considered by evaluating the results in the light of the present knowledge on cytology and molecular biology...
  43. ncbi Suppression of methionine-induced hyperhomocysteinemia by dietary eritadenine in rats
    Atsushi Sekiya
    Forestry and Forest Products Research Institute, Ibaraki, Japan
    Biosci Biotechnol Biochem 70:1987-91. 2006
    ....
  44. ncbi Exogenous glycine partially attenuates homocysteine-induced apoptosis and membrane peroxidation in chick embryos
    Robert R Miller
    Hillsdale College, Biology Department, Hillsdale, MI 49242 1205, USA
    Comp Biochem Physiol C Toxicol Pharmacol 144:25-33. 2006
    ..Exogenous glycine attenuated HoCys-induced reductions in brain SAM/SAH. However, glycine was unable to attenuate HoCys-induced reductions in hepatic SAM/SAH levels...
  45. ncbi Crystal structures of BchU, a methyltransferase involved in bacteriochlorophyll c biosynthesis, and its complex with S-adenosylhomocysteine: implications for reaction mechanism
    Kei Wada
    Department of Biological Sciences, Graduate School of Science, Osaka University, Toyonaka, Osaka 560 0043, Japan
    J Mol Biol 360:839-49. 2006
    ....
  46. ncbi The 5th workshop on the assessment of adequate intake of dietary amino acids: general discussion 1
    John D Fernstrom
    Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh PA, USA
    J Nutr 136:1711S-1715S. 2006
  47. ncbi Encephalitozoon cuniculi mRNA cap (guanine N-7) methyltransferase: methyl acceptor specificity, inhibition BY S-adenosylmethionine analogs, and structure-guided mutational analysis
    Stephane Hausmann
    Molecular Biology and Structural Biology Programs, Sloan Kettering Institute, New York, New York 10021, USA
    J Biol Chem 280:20404-12. 2005
    ..Amino acids Lys-54, Asp-70, Asp-78, and Asp-94, which comprise the AdoMet-binding site, and Phe-141, which contacts the cap guanosine, are essential for cap methyltransferase activity in vitro...
  48. pmc Structural basis for dual functionality of isoflavonoid O-methyltransferases in the evolution of plant defense responses
    Chang Jun Liu
    Howard Hughes Medical Institute, Jack H Skirball Center for Chemical Biology and Proteomics, Salk Institute for Biological Studies, La Jolla, California, 92037, USA
    Plant Cell 18:3656-69. 2006
    ..The three-dimensional similarity of natural small molecules represents one explanation for how plants may rapidly recruit enzymes for new biosynthetic reactions in response to changing physiological and ecological pressures...
  49. ncbi Relationship between S-adenosylmethionine, S-adenosylhomocysteine, asymmetric dimethylarginine, and endothelial function in healthy human subjects during experimental hyper- and hypohomocysteinemia
    Sagar Doshi
    Cardiovascular Sciences Research Group, Wales Heart Research Institute, University of Wales College of Medicine, Heath Park CF14 4XN Cardiff, UK
    Metabolism 54:351-60. 2005
    ..Our results suggest that endothelial dysfunction due to methionine or homocysteine loading is not associated with an increase in plasma ADMA or a disruption in methylation status...
  50. ncbi Abnormal folate metabolism in foetuses affected by neural tube defects
    Louisa P E Dunlevy
    Neural Development Unit, Institute of Child Health, University College London, UK
    Brain 130:1043-9. 2007
    ..These data suggest that as yet unrecognized genetic variants result in embryonic abnormalities of folate cycling that may be causally related to NTDs...
  51. ncbi Supranormal dietary folic acid supplementation: effects on methionine metabolism in weanling rats
    M Achon
    Departamento de Nutricion, Bromatologia y Tecnologia de los Alimentos, Facultad de Farmacia, Universidad San Pablo CEU, 28668 Boadilla del Monte, Madrid, Spain
    Br J Nutr 98:490-6. 2007
    ..FA supplementation of 40 mg/kg did not lead to hepatic or renal damage. In conclusion, there were no apparent adverse effects on one-carbon metabolism after FA supplementation in the studied conditions...
  52. ncbi Homocysteine clearance and methylation flux rates in health and end-stage renal disease: association with S-adenosylhomocysteine
    Frank Stam
    Department of Internal Medicine, and Institute for Cardiovascular Research, Vrije Universiteit Medical Center, 1081 HV Amsterdam, The Netherlands
    Am J Physiol Renal Physiol 287:F215-23. 2004
    ..Elevated whole blood AdoHcy levels are associated with impaired RM and TM flux rates in these patients, and AdoHcy may be a key regulatory compound in one-carbon flux...
  53. ncbi Modulation of methyl group metabolism by streptozotocin-induced diabetes and all-trans-retinoic acid
    Kristin M Nieman
    Department of Food Science and Human Nutrition, Iowa State University, Ames, Iowa 50011, USA
    J Biol Chem 279:45708-12. 2004
    ....
  54. ncbi Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism
    S Jill James
    Department of Pediatrics, University of Arkansas for Medical Sciences, and the Arkansas Children s Hospital Research Institute, Little Rock, AR 72202, USA
    Am J Clin Nutr 80:1611-7. 2004
    ..Although abnormal metabolism of methionine and homocysteine has been associated with other neurologic diseases, these pathways have not been evaluated in persons with autism...
  55. 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...
  56. ncbi S-adenosylmethionine and its products
    M A Grillo
    Dipartimento di Medicina e Oncologia Sperimentale, Sezione di Biochimica, Universita di Torino, Torino, Italy
    Amino Acids 34:187-93. 2008
    ....
  57. ncbi Increase in S-adenosylhomocysteine content and its effect on the S-adenosylhomocysteine hydrolase activity under transient high plasma homocysteine levels in rats
    Yasuka Isa
    The United Graduate School of Agricultural Science, Gifu University, 1 1 Yanagido, Gifu 501 1193, Japan
    J Nutr Sci Vitaminol (Tokyo) 52:479-82. 2006
    ..Thus, this study showed that hepatic SAH increased without any increase in the SAH-synthetic activity and the expression of SAH hydrolase mRNA under transient high plasma Hcy levels after intravenous infusion of Hcy...
  58. ncbi Crystal structures of CbiL, a methyltransferase involved in anaerobic vitamin B biosynthesis, and CbiL in complex with S-adenosylhomocysteine--implications for the reaction mechanism
    Kei Wada
    Department of Biological Sciences, Graduate School of Science, Osaka University, Toyonaka, Japan
    FEBS J 274:563-73. 2007
    ..Furthermore, the structural model of CbiL binding to its substrate suggests the axial residue coordinated to the central cobalt of cobalt-factor II...
  59. ncbi Differential effects of dietary selenium (se) and folate on methyl metabolism in liver and colon of rats
    Eric O Uthus
    USDA ARS Grand Forks Human Nutrition Research Center, P O Box 9034, Grand Forks, ND 58202 9034, USA
    Biol Trace Elem Res 109:201-14. 2006
    ..This suggests that selenium deficiency appears to be a more important modifier of methyl metabolism than either adequate or supplemental selenium...
  60. ncbi Acute valproate administration impairs methionine metabolism in rats
    Natalia Ubeda
    Sección de Nutrición, Bromatología y Dietética, Facultad de Ciencias Experimentales y de la Salud, Universidad San Pablo CEU, Madrid, Spain
    J Nutr 132:2737-42. 2002
    ..The acute effects of VPA suggest that the alterations in the methionine cycle could be the common mechanism underlying the hepatotoxic, teratogenic and antifolate effects of the drug...
  61. ncbi Catalytic properties and kinetic mechanism of human recombinant Lys-9 histone H3 methyltransferase SUV39H1: participation of the chromodomain in enzymatic catalysis
    Hang Gyeong Chin
    New England Biolabs, 240 County Road, Ipswich, Massachusetts 01938, USA
    Biochemistry 45:3272-84. 2006
    ..Thus, SUV39H1 utilizes both the chromodomain and the SET domain for catalysis...
  62. ncbi Phosphatidylethanolamine N-methyltransferase in human red blood cell membrane preparations. Kinetic mechanism
    R C Reitz
    Department of Biochemistry, School of Medicine, University of Nevada, Reno 89557
    J Biol Chem 264:8097-106. 1989
    ..The product from the utilization of AdoMet, S-adenosylhomocysteine (AdoHcy), was shown to be a competitive inhibitor of its precursor, AdoMet, and a noncompetitive inhibitor of the two phospholipid substrates...
  63. ncbi Increasing levels of dietary homocystine with carotid endarterectomy produced proportionate increases in plasma homocysteine and intimal hyperplasia
    F Southern
    Department of Surgery, Central Arkansas Veterans Healthcare System, Little Rock, AR 72205, USA
    Atherosclerosis 158:129-38. 2001
    ..Thus, increasing levels of plasma homocysteine enhanced and accelerated the smooth muscle cell response after CEA which led to increased intimal hyperplasia and lumenal stenosis...
  64. ncbi Retinoid compounds activate and induce hepatic glycine N-methyltransferase in rats
    M J Rowling
    Department of Food Science and Human Nutrition, Iowa State University, Ames, IA 50011, USA
    J Nutr 131:1914-7. 2001
    ..To our knowledge, this is the first report of a nutritional compound that induces GNMT activity at the transcriptional and/or translational level...
  65. ncbi A new caffeine biosynthetic pathway in tea leaves: utilisation of adenosine released from the S-adenosyl-L-methionine cycle
    C Koshiishi
    Department of Biology, Ochanomizu University, Otsuka, Tokyo, Japan
    FEBS Lett 499:50-4. 2001
    ..In contrast, no detectable activity of SAM synthetase was associated with the purified chloroplast fraction. This is a first demonstration that the purine skeleton of caffeine is synthesised from adenosine released from the SAM cycle...
  66. ncbi Blood determinations of S-adenosylmethionine, S-adenosylhomocysteine, and homocysteine: correlations with diet
    L A Poirier
    Division of Molecular Epidemiology, National Center for Toxicological Research, Food and Drug Administration, Jefferson, Arkansas 72079, USA
    Cancer Epidemiol Biomarkers Prev 10:649-55. 2001
    ....
  67. ncbi Mechanisms for auto-inhibition and forced product release in glycine N-methyltransferase: crystal structures of wild-type, mutant R175K and S-adenosylhomocysteine-bound R175K enzymes
    Y Huang
    Department of Molecular Biosciences, University of Kansas, Lawrence, KS 66045 2106, USA
    J Mol Biol 298:149-62. 2000
    ..Consequently GNMT is less active at a low level of AdoMet concentration, and is only weakly inhibited by AdoHcy. These properties of GNMT are particularly suited for regulation of the cellular AdoMet/AdoHcy ratio...
  68. ncbi Wy-14,643-induced hypomethylation of the c-myc gene in mouse liver
    R Ge
    Department of Pathology, Medical College of Ohio, 3055 Arlington Avenue, Toledo, Ohio 43614-5806, USA
    Toxicol Sci 62:28-35. 2001
    ..However, the results indicate that Wy-14,643 does not prevent methylation by decreasing either the availability of SAM or the activity of DNA MTase...
  69. pmc Homocysteine metabolism in children with Down syndrome: in vitro modulation
    M Pogribna
    Division of Biochemical Toxicology, Food and Drug Administration, National Center for Toxicological Research, Jefferson, AR 72079, USA
    Am J Hum Genet 69:88-95. 2001
    ..The decreased availability of homocysteine promotes the well-established "folate trap," creating a functional folate deficiency that may contribute to the metabolic pathology of this complex genetic disorder...
  70. ncbi Alteration in the phosphatidylcholine biosynthesis of rat liver microsomes caused by vitamin B6 deficiency
    Q B She
    United Graduate School of Agricultural Science, Gifu University, Japan
    Biosci Biotechnol Biochem 59:163-7. 1995
    ..Results of this study demonstrate that vitamin B6 deficiency modified methionine metabolism and decreased choline utilization, and thus indirectly affected the biosynthesis of PC in liver microsomes...
  71. ncbi S-Adenosylhomocysteine hydrolase overexpression in HEK-293 cells: effect on intracellular adenosine levels, cell viability, and DNA methylation
    Marina Hermes
    Department of Pharmacology and Toxicology, Faculty of Medicine, University of Tuebingen, Germany
    Cell Physiol Biochem 22:223-36. 2008
    ....
  72. ncbi Hepatic glycine N-methyltransferase is up-regulated by excess dietary methionine in rats
    Matthew J Rowling
    Department of Food Science and Human Nutrition, Iowa State University, Ames, IA 50011, USA
    J Nutr 132:2545-50. 2002
    ..In addition, methionine-induced regulation of GNMT is dose dependent and appears to be tissue specific, the latter suggesting that the role it plays in the kidney and pancreas may in part differ from its hepatic function...
  73. ncbi Tissue levels of S-adenosylhomocysteine in the rat kidney: effects of ischemia and homocysteine
    Doris Kloor
    Department of Pharmacology, Faculty of Medicine, University of Tubingen, Wilhelmstrasse 56, D 72074, Tubingen, Germany
    Biochem Pharmacol 63:809-15. 2002
    ....
  74. ncbi Hyperglycemia-induced membrane lipid peroxidation and elevated homocysteine levels are poorly attenuated by exogenous folate in embryonic chick brains
    Neal W Cole
    Hillsdale College, Biology Department, Dow 213, Hillsdale, MI 49242 1205, USA
    Comp Biochem Physiol B Biochem Mol Biol 150:338-43. 2008
    ..05). These hyperglycemia-induced alterations were poorly attenuated by exogenous folic acid (181.2 micromol/kg egg)...
  75. ncbi The effect of troglitazone on plasma homocysteine, hepatic and red blood cell S-adenosyl methionine, and S-adenosyl homocysteine and enzymes in homocysteine metabolism in Zucker rats
    Vivian Fonseca
    Department of Medicine, Section of Endocrinology, Tulane University School of Medicine, New Orleans LA 70112 2699, USA
    Metabolism 51:783-6. 2002
    ..These data support the hypothesis that insulin may regulate homocysteine metabolism through regulation of hepatic C beta S activity, although activity of other hepatic enzymes not studied here may also contribute to these observations...
  76. pmc Adenosine kinase deficiency is associated with developmental abnormalities and reduced transmethylation
    Barbara A Moffatt
    Department of Biology, University of Waterloo, Waterloo, Ontario, Canada N2L 3G1
    Plant Physiol 128:812-21. 2002
    ..These results indicate that Ado must be steadily removed by ADK to prevent feedback inhibition of SAH hydrolase and maintain SAM utilization and recycling...
  77. pmc Potential for luxS related signalling in marine bacteria and production of autoinducer-2 in the genus Shewanella
    Agnes Bodor
    Helmholtz Center for Infection Research, Group Microbial Communication, Division of Cell Biology, Inhoffenstr, 7, 38124 Braunschweig, Germany
    BMC Microbiol 8:13. 2008
    ....
  78. ncbi Bayesian phylogenetic analysis reveals two-domain topology of S-adenosylhomocysteine hydrolase protein sequences
    Tomasz Stepkowski
    Plant Molecular Biology Laboratory, Institute of Bioorganic Chemistry, Polish Academy of Sciences, 61 704 Poznan, Noskowskiego 12 14, Poland
    Mol Phylogenet Evol 34:15-28. 2005
    ..The majority of cyanobacteria acquired this gene from Archaea, however, in some species the sahH gene was replaced by a copy from the beta- or gamma-Proteobacteria...
  79. ncbi Chemical modification and site-directed mutagenesis of cysteine residues in human placental S-adenosylhomocysteine hydrolase
    C S Yuan
    Department of Biochemistry, The University of Kansas, Lawrence, Kansas 66047, USA
    J Biol Chem 271:28009-16. 1996
    ....
  80. ncbi Butylated hydroxytoluene modulates DNA methylation in rats
    B F Vanyushin
    Division of Molecular Basis of Ontogenesis, A N Belozersky Institute of Physico Chemical Biology, M V Lomonosov Moscow State University, Russia
    Eur J Biochem 256:518-27. 1998
    ..A strong increase in methyl transferase activity in rat liver is accompanied with BHT-induced change in the methyl transferase set observed in this organ...
  81. ncbi Comparative kinetics of cofactor association and dissociation for the human and trypanosomal S-adenosylhomocysteine hydrolases. 1. Basic features of the association and dissociation processes
    Qing Shan Li
    Department of Pharmaceutical Chemistry, The University of Kansas, Lawrence, Kansas 66047, USA
    Biochemistry 46:5798-809. 2007
    ..The rate of loss of activity is equal to the rate of dissociation of the cofactor and thus 80-fold faster at 37 degrees C for Tc-SAHH...
  82. ncbi Copper deficiency myelopathy and subacute combined degeneration of the cord - why is the phenotype so similar?
    Gavin P Winston
    National Hospital for Neurology and Neurosurgery, Queen Square, London, UK
    Med Hypotheses 71:229-36. 2008
    ..If it were confirmed, the hypothesis would not only provide a plausible explanation for the phenotypic similarity between CDM and SCD, but might also open up further therapeutic options such as methionine and betaine supplementation...
  83. ncbi Day-night variations of adenosine and its metabolizing enzymes in the brain cortex of the rat--possible physiological significance for the energetic homeostasis and the sleep-wake cycle
    V Chagoya De Sanchez
    Departamento de Bioenergetica, UNAM, Mexico, D F
    Brain Res 612:115-21. 1993
    ....
  84. ncbi S-adenosylmethionine synthetase is overexpressed in murine neuroblastoma cells resistant to nucleoside analogue inhibitors of S-adenosylhomocysteine hydrolase: a novel mechanism of drug resistance
    R S Dwivedi
    Children s Memorial Institute for Education and Research, Children s Memorial Medical Center, Department of Pediatrics, Northwestern University Medical School, Chicago, Illinois 60614, USA
    Cancer Res 59:1852-6. 1999
    ..This novel mechanism of drug resistance does not appear to require multidrug resistance protein (P-glycoprotein) overexpression...
  85. pmc The nutrigenetics of hyperhomocysteinemia: quantitative proteomics reveals differences in the methionine cycle enzymes of gene-induced versus diet-induced hyperhomocysteinemia
    Patricia M DiBello
    Department of Cell Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA
    Mol Cell Proteomics 9:471-85. 2010
    ..Our results show that hyperhomocysteinemia, whether caused by a genetic mutation or diet, alters the abundance of several liver proteins involved in homocysteine/methionine metabolism, the urea cycle, and antioxidant defense...
  86. ncbi John Montgomery's legacy: carbocyclic adenosine analogues as SAH hydrolase inhibitors with broad-spectrum antiviral activity
    Erik De Clercq
    Rega Institute for Medical Research, Department of Microbiology and Immunology, K U Letven, Minderbroedersstraat 10, B 3000 Leuven, Belgium
    Nucleosides Nucleotides Nucleic Acids 24:1395-415. 2005
    ....
  87. ncbi The vegetarian lifestyle and DNA methylation
    Jurgen Geisel
    Department of Clinical Chemistry, Saarland Medical School, Homburg, Germany
    Clin Chem Lab Med 43:1164-9. 2005
    ..In conclusion, an inhibitory effect of SAH on whole-genome methylation was found, but from our data no interaction between vegetarian lifestyle and DNA methylation could be determined...
  88. ncbi A 9-yr evaluation of carrier erythrocyte encapsulated adenosine deaminase (ADA) therapy in a patient with adult-type ADA deficiency
    Bridget E Bax
    Child Health, Division of Clinical Developmental Sciences, St George s, University of London, London, UK
    Eur J Haematol 79:338-48. 2007
    ..Carrier erythrocyte-ADA therapy in an adult patient with ADA deficiency was shown to be metabolically and clinically effective...
  89. pmc Structural analyses reveal two distinct families of nucleoside phosphorylases
    Matthew J Pugmire
    Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, U S A
    Biochem J 361:1-25. 2002
    ..Several research groups have synthesized a variety of nucleoside phosphorylase inhibitors that are at various stages of preclinical and clinical evaluation...
  90. ncbi Adenosine binding sites at S-adenosylhomocysteine hydrolase are controlled by the NAD+/NADH ratio of the enzyme
    Doris Kloor
    Department of Pharmacology and Toxicology, Faculty of Medicine, University of Tubingen, Wilhelmstrasse 56, D 72074 Tuebingen, Germany
    Biochem Pharmacol 66:2117-23. 2003
    ..In conclusion, our data show that AdoHcy hydrolase has two different Ado binding sites which are dependent upon the enzyme-bound NAD(+)/NADH ratios...
  91. ncbi Effects of site-directed mutagenesis on structure and function of recombinant rat liver S-adenosylhomocysteine hydrolase. Crystal structure of D244E mutant enzyme
    J Komoto
    Department of Molecular Biosciences, University of Kansas, Lawrence, Kansas 66045 210, USA
    J Biol Chem 275:32147-56. 2000
    ..A catalytic mechanism of AdoHcyase has been proposed on the basis of the crystal structures of the wild-type and D244E enzymes...
  92. ncbi Analyzing S-adenosylhomocysteine hydrolase gene sequences in deuterostome genomes
    Jing Nan Zhao
    Department of Marine Biology, Ocean University of China, Qingdao, P R China
    J Biomol Struct Dyn 27:371-80. 2009
    ..Phylogenetic analysis shows that SAHH genes in amphioxus, sea-urchin and sea-squirt form a cluster and locate at the base of neighbor-joining tree, suggesting that they are the archetype of vertebrate SAHH genes...
  93. ncbi S-adenosylhomocysteine hydrolase from the archaeon Pyrococcus furiosus: biochemical characterization and analysis of protein structure by comparative molecular modeling
    Marina Porcelli
    Dipartimento di Biochimica e Biofisica F Cedrangolo, Seconda Universita di Napoli, Naples, Italy
    Proteins 58:815-25. 2005
    ..Interestingly, all these residues are fairly well conserved in hyperthermophilic AdoHcyHDs but not in mesophilic ones, thus suggesting a common adaptation mechanism at high temperatures...
  94. ncbi Treatment of cutaneous T cell lymphoma with 2'-deoxycoformycin (pentostatin)
    A P Dang-Vu
    Division of Dermatology, Duke University Medical Center, Durham, NC 27710
    J Am Acad Dermatol 19:692-8. 1988
    ..Low-dose 2'-deoxycoformycin appears to be safe but may be an insufficiently intensive regimen to treat refractory cutaneous T cell lymphoma. With proper biochemical monitoring, higher doses may be both safe and more effective...
  95. ncbi Enzyme activities of leukemic cells and biochemical changes induced by deoxycoformycin in vitro--lack of correlation with clinical response
    A D Ho
    Department of Internal Medicine V, University of Heidelberg, Federal Republic of Germany
    Leuk Res 13:269-78. 1989
    ..Our results show that neither measurement of these enzymes nor studies of these biochemical sequelae of ADA inhibition in vitro predicts clinical responsiveness to DCF therapy...
  96. ncbi Molecular characterisation of adenosylhomocysteinase from Trichomonas vaginalis
    A S Bagnara
    School of Biochemistry and Molecular Genetics, University of New South Wales, Sydney, Australia
    Mol Biochem Parasitol 81:1-11. 1996
    ..Finally, Southern blots and sequence differences between genomic and cDNA clones indicate that there are multiple copies of the sahh gene in T. vaginalis...
  97. ncbi Adenosine-mediated killing of cultured epithelial cancer cells
    C P Barry
    Division of Hematology and Oncology, Evanston Northwestern Healthcare and Northwestern University Medical School, Illinois 60201, USA
    Cancer Res 60:1887-94. 2000
    ..The enhanced cofactor activity of CF may be attributable to its being a more potent inhibitor of AMP deaminase than is DCF...
  98. ncbi [The role of DNA methylation in the pathogenesis of adult idiopathic thrombocytopenic purpura]
    Jie Tao
    Department of Hematology, The First Hospital of Shanxi Medical University, Taiyuan 030001, China
    Zhonghua Nei Ke Za Zhi 49:208-12. 2010
    ..To explore the role of DNA methylation in pathogenesis of adult idiopathic thrombocytopenic purpura (ITP)...
  99. ncbi LDL cholesterol upregulates synthesis of asymmetrical dimethylarginine in human endothelial cells: involvement of S-adenosylmethionine-dependent methyltransferases
    R H Boger
    Institute of Clinical Pharmacology, Hannover Medical School, Germany
    Circ Res 87:99-105. 2000
    ..These findings suggest a novel mechanism by which ADMA concentration is elevated in hypercholesterolemia, leading to endothelial dysfunction and atherosclerosis...
  100. ncbi Changes in S-adenosylmethionine and GSH homeostasis during endotoxemia in mice
    Kwangsuk Ko
    Department of Medicine, USC Research Center for Liver Diseases, USC UCLA Research Center for Alcoholic Liver and Pancreatic Diseases, Keck School of Medicine USC, Los Angeles, CA 90033, USA
    Lab Invest 88:1121-9. 2008
    ..GSH is markedly depleted largely due to lower expression of GCL. Interestingly, SAMe treatment prevented the fall in GCL and helped to preserve the GSH store and prevent liver injury...
  101. ncbi Stabilization of blood homocysteine in an epidemiological setting
    I Martin
    Laboratorio Bioquímica, Servicio de Analisis Clinicos, Hospital Son Dureta, Andrea Doria, 55 Palma de Mallorca 07014, Spain
    Eur J Cancer Prev 10:473-6. 2001
    ..009). The addition of 3-deazaadenosine may avoid problems in the critical pre-analytical phase in the Hcy measurement. There is no interference with the FPIA assay, nor any dilution effect, and new reference values are not necessary...

Research Grants61

  1. Prospective studies of cancer etiology and prevention in Shanghai and Singapore
    Jian Min Yuan; Fiscal Year: 2013
    ..The findings of the proposed study will have great impact on reducing incidence and mortality of lung and liver cancers in humans. ..
  2. Folate and S-adenosyimethionine in Methyl Group and One-carbon Metabolism
    Conrad Wagner; Fiscal Year: 2012
    ....
  3. EFFECT OF DRUGS OF ABUSE ON NEURONAL REDOX AND METHYLATION STATUS
    Richard C Deth; Fiscal Year: 2012
    ..The results will provide an entirely new way of thinking about how drugs of abuse affect the brain and could lead to improved ways to treatment to treat drug addiction. ..
  4. Epigenetic regulation of alcoholic steatohepatitis in a mouse model
    CHARLES HOPKINSON HALSTED; Fiscal Year: 2012
    ....
  5. Hyperhomocysteinemia, S-adenosylhomocysteine Accumulation, and Epigenetics
    Warren D Kruger; Fiscal Year: 2013
    ..Achieving these aims will lead to understanding the mechanism by which elevated tHcy causes disease and will give us new insight into potential interventions that could delay or eliminate the onset of homocysteine related diseases. ..
  6. Mechanisms of Sensitization to TNF hepatotoxicity in ALD
    Zhenyuan Song; Fiscal Year: 2009
    ..This research will be performed with structured mentoring support and a detailed training program designed to maximize my opportunity to become an independent NIH-funded investigator. ..
  7. Wilson Disease: Regulation of Steatosis by Methionine Metabolism
    Valentina Medici; Fiscal Year: 2013
    ..The study will also provide insights into the role of copper and methionine metabolism in more common diseases, such as non-alcoholic fatty liver disease. ..
  8. Biomarkers of Methionine Metabolism and Risk for Colorectal Adenoma
    Martha J Shrubsole; Fiscal Year: 2010
    ....
  9. Methyltransferease sensors for homogenous HTS assays
    Jeremy S Paige; Fiscal Year: 2012
    ..This project will develop a simple, homogenous fluorescence assay that can be applied to any MT, enabling large-scale HTS for MT inhibitors. ..
  10. HHcy-induced Bax upregulation, Treg apoptosis and vascular disease
    Xiao Feng Yang; Fiscal Year: 2013
    ..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. ..
  11. Borrelia burgdorferi-glycosaminoglycan interactions and Lyme disease pathogenesis
    Nikhat Parveen; Fiscal Year: 2013
    ....
  12. 5Lipoxygenase-mediated vasculopathy in HHcy
    Domenico Pratico; Fiscal Year: 2013
    ..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. ..
  13. DRUG DISCOVERY AGAINST CRYPTOSPORIDIUM PARVUM
    JANET KEITHLY; Fiscal Year: 2003
    ..If the pathway is verified as a parasite-specific target, then a major obstacle in the treatment of this OI in AIDS patients will have been overcome. ..
  14. Hyperhomocysteinemia in Alzheimer's Disease
    Ramon Diaz Arrastia; Fiscal Year: 2003
    ..Each of these specific aims is essential to rationally design a large multicenter trial to determine whether polyvitamin therapy lowers AD risk. ..
  15. NUCLEOSIDES AS ANTI-ORTHOPOXVIRUS AGENTS
    JOHN SECRIST; Fiscal Year: 2003
    ..Dr. Stewart Shuman of the Sloan Kettering Research Institute will be helping us by concentrating on the mechanism of action of the N1-aralkyloxyadenosine analogs. ..
  16. REGULATION OF GABA BIOSYNTHESIS IN THE BRAIN
    Jang Yen Wu; Fiscal Year: 2003
    ..The success of a large scale purification of recombinant human brain GAD65 and GAD67 and the availability of subtype specific antibodies for GAD65 and GAD67, ensure the high feasibility of this proposal. ..
  17. Modulation of DNA methylation status by dietary zinc: role in cancer prevention
    LOUISE FONG; Fiscal Year: 2009
    ..In addition, the results will identify targets for chemoprevention, diagnosis, and treatment of this deadly cancer. ..
  18. STRUCTURAL STUDIES OF METHYL CYCLE ENZYMES
    Fusao Takusagawa; Fiscal Year: 2003
    ..For a long-term objective, we would like to design specific inhibitors of these enzymes in order to develop chemotherapeutic agents using the active site geometries and the catalytic mechanisms of the enzymes gained in this project. ..
  19. Folate, Vitamin D and Calcium in Colorectal Cancer
    Robert Haile; Fiscal Year: 2009
    ..Genotyping will primarily involve SNP-based haplotypes. For both pathways, analyses of gene-gene and gene-environment interactions will be included as appropriate. ..
  20. Accumulation of Isoaspartyl Residue-Bearing Proteins and Alcoholic Liver Disease
    KUSUM KHARBANDA; Fiscal Year: 2009
    ....
  21. STRUCTURAL ANALOGS OF S-ADENOSYLMETHIONINE
    RONALD BORCHARDT; Fiscal Year: 1980
    ..By evaluation of the SAH analogs prepared in our studies as inhibitors of these methyltransferase systems, it is hoped that differences in inhibitory specificity will be detected which can be used to design enzyme specific inhibitors. ..
  22. Fluorescent HTS Assays for Methyltransferases in Neurodegenerative Diseases
    Robert Lowery; Fiscal Year: 2009
    ..The availability of robust, generic fluorescent HTS assay methods and selective chemical probes for MT's should greatly accelerate their validation as drug targets and movement into the pharma drug discovery pipeline. ..
  23. IN VITRO ASSAYS FOR METHIONINE-DEPENDENT CHEMOTHERAPY
    HUIYAN GUO; Fiscal Year: 1993
    ..In Phase II we will compare the assays ability to predict sensitivity to methioninase-based therapy in vivo with the purified methioninase currently produced in our laboratory...
  24. METHIONINE DEPENDENCE, A METABOLIC MARKER IN CANCER
    Robert Hoffman; Fiscal Year: 1992
    ..This experiment will serve as a means to understand the molecular basis of this important aspect of oncogenic transformation...
  25. Modeling Folate, One-Carbon Metabolism & DNA Methylation
    Cornelia Ulrich; Fiscal Year: 2007
    ..We plan to make the model generally available to the research community, and anticipate that it will become a useful tool that can be used as an adjunct to experimental investigations and as an aid to study design. ..
  26. Fused Pyrimidine (IsoA) Nucleosides:Design and Synthesis
    KATHERINE RADTKE; Fiscal Year: 2006
    ..We believe this inhibition will result in meaningful biological activity, as well as to induce cell differentiation. ..
  27. Purchase of an X-Ray Generator for Macromolecular Crystallography
    STEVEN BRUNER; Fiscal Year: 2007
    ..We have in place a new detector and cryogenic apparatus, and the acquisition of a new generator will provide us with a modern and efficient macromolecular diffractometer. [unreadable] [unreadable] [unreadable]..
  28. FASEB CONFERENCE--SAM AND METHYLATION
    PETER CHIANG; Fiscal Year: 1993
    ..This meeting is the only conference on this topic since 1985, and should stimulate collaborative research effort and point to therapeutic directions for future research on methylation and S-adenosylmethionine...
  29. Metabolic Biomarkers of Autism: Predictive Potential and Genetic Susceptibility
    SANDRA JILL JAMES; Fiscal Year: 2010
    ....
  30. 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. ..
  31. FOLATE, HOMOCYSTEINE AND METHYL GROUP METABOLISM
    Conrad Wagner; Fiscal Year: 2003
    ..Specific Aim 2 is to determine the factors responsible for dissociation of tetrameric GNMT and determine to which region of DNA the dissociated GNMT is bound. ..
  32. Studies of Human Folate Hydrolase
    Charles Halsted; Fiscal Year: 2005
    ..abstract_text> ..
  33. SAMe and Folate Deficiency in Alcoholic Mircropigs
    Charles Halsted; Fiscal Year: 2006
    ..While furthering understanding of interactions of methionine metabolites on pathways of liver injury, the project may establish novel approaches to the prevention and treatment of ALD. [unreadable] [unreadable] [unreadable]..
  34. B12 Nutrition in the Aged
    Sally Stabler; Fiscal Year: 2007
    ..abstract_text> ..
  35. EFFECTS OF SAM IN PATIENTS WITH ALCOHOLIC LIVER DISEASE
    Charles Halsted; Fiscal Year: 2007
    ..By confirming the relationship of abnormal methionine metabolism to clinical, biochemical, and pathologic disease severity, the study will establish a metabolic basis for determining the efficacy of SAM intervention in ALD. ..
  36. CYCLIC AMP/ADENOSINE PATHWAY
    Edwin Jackson; Fiscal Year: 2002
    ..abstract_text> ..
  37. Homeostatic Regulation of Folate Metabolism
    Patrick J Stover; Fiscal Year: 2010
    ..5. regulation of cSHMT by folate/choline preserves dTMP pools at the expense of AdoMet synthesis. The long-term goals of this project are: 1. to define homeostatic mechanisms used bv cells to regulate folate metabolism. ..
  38. Sulfur Amino Acid Metabolism in NAFLD
    Satish C Kalhan; Fiscal Year: 2010
    ..The proposed studies are aimed at examining the metabolic mechanisms involved in the progression of this disease, so that specific targeted intervention strategies related to the stage of the disease can be identified and evaluated. ..
  39. Mechanisms of S-adenosylmethionine in NASH
    Craig McClain; Fiscal Year: 2009
    ..Determine by proteomic analysis of serum and liver biopsies the proteins (esp. oxidative stress, oxidized and mitochondrial proteins) that may play a role in the diagnosis or etiology of NASH, and which may be modified by SAMe therapy ..
  40. S-adenosylhomocysteine and S-adenosylmethionine in Alcoholic Liver Disease
    Craig J McClain; Fiscal Year: 2010
    ..These studies utilize state-of-the-art models/techniques in a translational approach to develop an enhanced understanding of mechanisms involved in ALD and potential new therapy for ALD. ..
  41. Mechanism and Inhibition of S-Ribosylhomocysteinase
    Dehua Pei; Fiscal Year: 2009
    ..The mechanism-based inhibitors will also serve as mechanistic probes for studying the LuxS mechanism. Finally, Specific Aim 5 is to purify and identify additional receptor(s) for AI-2. ..
  42. IMP Dehydrogenase and the Hydra of Cancer Chemotherapy
    GEORGE MARKHAM; Fiscal Year: 2008
    ..These results will reveal the inner working of an essential enzyme and whether there is promise for enhancing clinical efficacy through combinations of known drugs or the discovery of novel subdomain ligands. ..
  43. Glutamine Metabolism in the Human Newborn
    Satish Kalhan; Fiscal Year: 2007
    ..RESEARCH GRANT TABLE OF CONTENTS Page Numbers Face Page .............................................................................................................................................. 1 Description, ..
  44. DbpA/B proteins of Borrelia burgdorferi & Lyme arthritis
    Nikhat Parveen; Fiscal Year: 2005
    ..This study will characterize the role of two spirochete lipoprotein adhesins in Lyme arthritis in the murine model. ..
  45. Peptide Deformylase: Mechanism and Inhibitor Design
    Dehua Pei; Fiscal Year: 2005
    ..These enzymes are thought to be responsible for inactivating the chemotactic peptides released by commensal bacteria and preventing inflammatory responses in mammals. ..
  46. FASEB Summer Conference: Folate, B12 and 1C Metabolism
    PATRICK STOVER; Fiscal Year: 2004
    ..Similarly, the poster sessions also highlight the activities and needs of the younger participants. ..
  47. 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. ..
  48. A.S.P.E.N. Research Workshop on Functional Foods
    Craig McClain; Fiscal Year: 2002
    ..abstract_text> ..
  49. REGULATION OF FOLATE CATABOLISM
    PATRICK STOVER; Fiscal Year: 2007
    ..2). to determine the risk that folate catabolism contributes to folate-associated pathologies. (3). to establish relationships between catecholamines and folate metabolism. ..
  50. Planning Grant for Louisville Clinical and Translational Science Award
    Craig McClain; Fiscal Year: 2006
    ..Expand and integrate a clinical and translational research resources and outreach network. [unreadable] [unreadable] [unreadable]..
  51. Molecular Models of Adenosine Signaling and Asthma
    Michael Blackburn; Fiscal Year: 2008
    ..These studies will lead to a better understanding of adenosine's impact on the severity of chronic lung diseases such as asthma and COPD, which will help guide the development of novel therapies for their treatment. ..
  52. 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. ..
  53. ENZYMATIC MECHANISMS OF SULFUR NUCLEOSIDE METABOLISM
    GEORGE MARKHAM; Fiscal Year: 2008
    ..These studies will unmask why nature conserves use of a pyruvoyl cofactor for this metabolic function instead of adopting the common pyridoxal cofactor. ..
  54. 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]..
  55. Role of PP2A in tauopathies
    Estelle Sontag; Fiscal Year: 2006
    ....
  56. 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. ..
  57. Ethanol Effects on Antigen Presentation in Liver Cells
    Natalia Osna; Fiscal Year: 2006
    ..unreadable] [unreadable]..
  58. Folate-Genome Interactions in Colorectal Cancer
    PATRICK STOVER; Fiscal Year: 2007
    ..The long-term goal of this project is: (1). to determine the mechanism whereby alterations in folate metabolism influence cancer risk. ..
  59. ADENOSINE SIGNALING AND LUNG INFLAMMATION
    Michael Blackburn; Fiscal Year: 2001
    ..4. Evaluate acute and long-term changes of airway function in ADA deficient mice as well as ADA deficient mice exposed to environmental challenges. ..