| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Papers In Press, published online ahead of print July 6, 2000
Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, AR 72079
Corresponding Author: jjames{at}nctr.fda.gov
S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH), as the substrate and product of essential cellular methyltransferase reactions, are important metabolic indicators of cellular methylation status. Chronic elevation of SAH, secondary to the homocysteine-mediated reversal of the SAH hydrolase reaction, reduces methylation of DNA, RNA, proteins, and phospholipids. High affinity binding of SAH to the active site of cellular methyltransferases results in product inhibition of the enzyme. Using a sensitive new HPLC method with coulometric electrochemical detection, plasma SAH levels in healthy young women were found to increase linearly with mild elevation in homocysteine levels (r=0.73; p < 0.001); however, SAM levels were not affected. Plasma SAH levels were positively correlated with intracellular lymphocyte SAH levels (r=0.81; p < 0.001) and also with lymphocyte DNA hypomethylation (r=0.74, p < 0.001). Further, the increase in plasma SAH was negatively associated with plasma pyridoxal 5?phosphate levels (p< 0.01). These results suggest that chronic elevation in plasma homocysteine levels, such as those associated with nutritional deficiencies or genetic polymorphisms in the folate pathway, may have an indirect and negative effect on cellular methylation reactions through a concomitant increase in intracellular SAH levels.
J. Biol. Chem, 10.1074/jbc.M002725200
Submitted on March 31, 2000
Revised on May 29, 2000
Accepted on July 5, 2000
Increase in plasma homocysteine associated with parallel increases in plasma S-adenosylhomocyteine and lymphocyte DNA hypomethylation
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  J. C. Figueiredo, A. J. Levine, M. V. Grau, O. Midttun, P. M. Ueland, D. J. Ahnen, E. L. Barry, S. Tsang, D. Munroe, I. Ali, et al. Vitamins B2, B6, and B12 and Risk of New Colorectal Adenomas in a Randomized Trial of Aspirin Use and Folic Acid Supplementation Cancer Epidemiol. Biomarkers Prev., August 1, 2008; 17(8): 2136 - 2145. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. M. J. W. van Driel, R. de Jonge, W. A. Helbing, B. D. van Zelst, J. Ottenkamp, E. A. P. Steegers, and R. P. M. Steegers-Theunissen Maternal Global Methylation Status and Risk of Congenital Heart Diseases Obstet. Gynecol., August 1, 2008; 112(2): 277 - 283. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B.-G. Jeon, G. Coppola, S. D Perrault, G.-J. Rho, D. H Betts, and W A. King S-adenosylhomocysteine treatment of adult female fibroblasts alters X-chromosome inactivation and improves in vitro embryo development after somatic cell nuclear transfer Reproduction, June 1, 2008; 135(6): 815 - 828. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Stopper, A.-T. Treutlein, U. Bahner, N. Schupp, U. Schmid, A. Brink, A. Perna, and A. Heidland Reduction of the genomic damage level in haemodialysis patients by folic acid and vitamin B12 supplementation Nephrol. Dial. Transplant., May 9, 2008; (2008) gfn254v1. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Stenvinkel and T. J. Ekstrom Epigenetics--a helpful tool to better understand processes in clinical nephrology? Nephrol. Dial. Transplant., May 1, 2008; 23(5): 1493 - 1496. [Full Text] [PDF]
|
|
|
|
 |
|
 C. Liu, Q. Wang, H. Guo, M. Xia, Q. Yuan, Y. Hu, H. Zhu, M. Hou, J. Ma, Z. Tang, et al. Plasma S-Adenosylhomocysteine Is a Better Biomarker of Atherosclerosis Than Homocysteine in Apolipoprotein E-Deficient Mice Fed High Dietary Methionine J. Nutr., February 1, 2008; 138(2): 311 - 315. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Devlin, R. Singh, R. E. Wade, S. M. Innis, T. Bottiglieri, and S. R. Lentz Hypermethylation of Fads2 and Altered Hepatic Fatty Acid and Phospholipid Metabolism in Mice with Hyperhomocysteinemia J. Biol. Chem., December 21, 2007; 282(51): 37082 - 37090. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J R. Pilsner, X. Liu, H. Ahsan, V. Ilievski, V. Slavkovich, D. Levy, P. Factor-Litvak, J. H Graziano, and M. V Gamble Genomic methylation of peripheral blood leukocyte DNA: influences of arsenic and folate in Bangladeshi adults Am. J. Clinical Nutrition, October 1, 2007; 86(4): 1179 - 1186. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Carluccio, M. A. Ancora, M. Massaro, M. Carluccio, E. Scoditti, A. Distante, C. Storelli, and R. De Caterina Homocysteine induces VCAM-1 gene expression through NF-{kappa}B and NAD(P)H oxidase activation: protective role of Mediterranean diet polyphenolic antioxidants Am J Physiol Heart Circ Physiol, October 1, 2007; 293(4): H2344 - H2354. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. E Heck, M. V Gamble, Y. Chen, J. H Graziano, V. Slavkovich, F. Parvez, J. A Baron, G. R Howe, and H. Ahsan Consumption of folate-related nutrients and metabolism of arsenic in Bangladesh Am. J. Clinical Nutrition, May 1, 2007; 85(5): 1367 - 1374. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. V Gamble, X. Liu, H. Ahsan, J R. Pilsner, V. Ilievski, V. Slavkovich, F. Parvez, Y. Chen, D. Levy, P. Factor-Litvak, et al. Folate and arsenic metabolism: a double-blind, placebo-controlled folic acid-supplementation trial in Bangladesh. Am. J. Clinical Nutrition, November 1, 2006; 84(5): 1093 - 1101. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M.L. De Bonis, A. Cerase, M.R. Matarazzo, M. Ferraro, M. Strazzullo, R.S. Hansen, P. Chiurazzi, G. Neri, and M. D'Esposito Maintenance of X- and Y-inactivation of the pseudoautosomal (PAR2) gene SPRY3 is independent from DNA methylation and associated to multiple layers of epigenetic modifications Hum. Mol. Genet., April 1, 2006; 15(7): 1123 - 1132. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Beagle, T. L. Yang, J. Hung, E. A. Cogger, D. J. Moriarty, and M. A. Caudill The Glycine N-Methyltransferase (GNMT) 1289 C->T Variant Influences Plasma Total Homocysteine Concentrations in Young Women after Restricting Folate Intake J. Nutr., December 1, 2005; 135(12): 2780 - 2785. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Jang, J. B. Mason, and S.-W. Choi Genetic and Epigenetic Interactions between Folate and Aging in Carcinogenesis J. Nutr., December 1, 2005; 135(12): 2967S - 2971S. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. Lim, M. Schenk, L. E. Kelemen, S. Davis, W. Cozen, P. Hartge, M. H. Ward, and R. Stolzenberg-Solomon Dietary Determinants of One-Carbon Metabolism and the Risk of Non-Hodgkin's Lymphoma: NCI-SEER Case-Control Study, 1998-2000 Am. J. Epidemiol., November 15, 2005; 162(10): 953 - 964. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Fux, D. Kloor, M. Hermes, T. Rock, B. Proksch, A. Grenz, U. Delabar, R. Bucheler, S. Igel, K. Morike, et al. Effect of acute hyperhomocysteinemia on methylation potential of erythrocytes and on DNA methylation of lymphocytes in healthy male volunteers Am J Physiol Renal Physiol, October 1, 2005; 289(4): F786 - F792. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Gellekink, D. van Oppenraaij-Emmerzaal, A. van Rooij, E. A. Struys, M. den Heijer, and H. J. Blom Stable-Isotope Dilution Liquid Chromatography-Electrospray Injection Tandem Mass Spectrometry Method for Fast, Selective Measurement of S-Adenosylmethionine and S-Adenosylhomocysteine in Plasma Clin. Chem., August 1, 2005; 51(8): 1487 - 1492. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Devlin, T. Bottiglieri, F. E. Domann, and S. R. Lentz Tissue-specific Changes in H19 Methylation and Expression in Mice with Hyperhomocysteinemia J. Biol. Chem., July 8, 2005; 280(27): 25506 - 25511. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Esfandiari, J. A. Villanueva, D. H. Wong, S. W. French, and C. H. Halsted Chronic ethanol feeding and folate deficiency activate hepatic endoplasmic reticulum stress pathway in micropigs Am J Physiol Gastrointest Liver Physiol, July 1, 2005; 289(1): G54 - G63. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M Pufulete, R Al-Ghnaniem, A Khushal, P Appleby, N Harris, S Gout, P W Emery, and T A B Sanders Effect of folic acid supplementation on genomic DNA methylation in patients with colorectal adenoma Gut, May 1, 2005; 54(5): 648 - 653. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Stempak, K.-J. Sohn, E.-P. Chiang, B. Shane, and Y.-I. Kim Cell and stage of transformation-specific effects of folate deficiency on methionine cycle intermediates and DNA methylation in an in vitro model Carcinogenesis, May 1, 2005; 26(5): 981 - 990. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Teerlink ADMA metabolism and clearance Vascular Medicine, May 1, 2005; 10(2_suppl): S73 - S81. [Abstract] [PDF]
|
|
|
|
|
|
C. L. Ulrey, L. Liu, L. G. Andrews, and T. O. Tollefsbol The impact of metabolism on DNA methylation Hum. Mol. Genet., April 15, 2005; 14(suppl_1): R139 - R147. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Friso, D. Girelli, E. Trabetti, O. Olivieri, P. Guarini, P. F. Pignatti, R. Corrocher, and S.-W. Choi The MTHFR 1298A>C Polymorphism and Genomic DNA Methylation in Human Lymphocytes Cancer Epidemiol. Biomarkers Prev., April 1, 2005; 14(4): 938 - 943. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. C. Tyagi, W. Rodriguez, A. M. Patel, A. M. Roberts, J. C. Falcone, J. C. Passmore, J. T. Fleming, and I. G. Joshua Hyperhomocysteinemic Diabetic Cardiomyopathy: Oxidative Stress, Remodeling, and Endothelial-Myocyte Uncoupling Journal of Cardiovascular Pharmacology and Therapeutics, January 1, 2005; 10(1): 1 - 10. [Abstract] [PDF]
|
|
|
|
|
|
C. A Hobbs, M. A Cleves, S. Melnyk, W. Zhao, and S J. James Congenital heart defects and abnormal maternal biomarkers of methionine and homocysteine metabolism Am. J. Clinical Nutrition, January 1, 2005; 81(1): 147 - 153. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Zaina, M. W. Lindholm, and G. Lund Nutrition and Aberrant DNA Methylation Patterns in Atherosclerosis: More than Just Hyperhomocysteinemia? J. Nutr., January 1, 2005; 135(1): 5 - 8. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. F. Nijhout, M. C. Reed, P. Budu, and C. M. Ulrich A Mathematical Model of the Folate Cycle: NEW INSIGHTS INTO FOLATE HOMEOSTASIS J. Biol. Chem., December 31, 2004; 279(53): 55008 - 55016. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S J. James, P. Cutler, S. Melnyk, S. Jernigan, L. Janak, D. W Gaylor, and J. A Neubrander Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism Am. J. Clinical Nutrition, December 1, 2004; 80(6): 1611 - 1617. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. M Guerra-Shinohara, O. E Morita, S. Peres, R. A Pagliusi, L. F Sampaio Neto, V. D'Almeida, S. P Irazusta, R. H Allen, and S. P Stabler Low ratio of S-adenosylmethionine to S-adenosylhomocysteine is associated with vitamin deficiency in Brazilian pregnant women and newborns Am. J. Clinical Nutrition, November 1, 2004; 80(5): 1312 - 1321. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Lund, L. Andersson, M. Lauria, M. Lindholm, M. F. Fraga, A. Villar-Garea, E. Ballestar, M. Esteller, and S. Zaina DNA Methylation Polymorphisms Precede Any Histological Sign of Atherosclerosis in Mice Lacking Apolipoprotein E J. Biol. Chem., July 9, 2004; 279(28): 29147 - 29154. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Lange, H. Suryapranata, G. De Luca, C. Borner, J. Dille, K. Kallmayer, M. N. Pasalary, E. Scherer, and J.-H. E. Dambrink Folate Therapy and In-Stent Restenosis after Coronary Stenting N. Engl. J. Med., June 24, 2004; 350(26): 2673 - 2681. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. K. MacLennan, S. J. James, S. Melnyk, A. Piroozi, S. Jernigan, J. L. Hsu, S. M. Janke, T. D. Pham, and R. H. Lane Uteroplacental insufficiency alters DNA methylation, one-carbon metabolism, and histone acetylation in IUGR rats Physiol Genomics, June 17, 2004; 18(1): 43 - 50. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Devlin, E. Arning, T. Bottiglieri, F. M. Faraci, R. Rozen, and S. R. Lentz Effect of Mthfr genotype on diet-induced hyperhomocysteinemia and vascular function in mice Blood, April 1, 2004; 103(7): 2624 - 2629. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. P. Stabler and R. H. Allen Quantification of Serum and Urinary S-Adenosylmethionine and S-Adenosylhomocysteine by Stable-Isotope-Dilution Liquid Chromatography-Mass Spectrometry Clin. Chem., February 1, 2004; 50(2): 365 - 372. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Barak, H. C. Beckenhauer, M. E. Mailliard, K. K. Kharbanda, and D. J. Tuma Betaine Lowers Elevated S-Adenosylhomocysteine Levels in Hepatocytes from Ethanol-Fed Rats J. Nutr., September 1, 2003; 133(9): 2845 - 2848. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. D. Davis and E. O. Uthus Dietary Folate and Selenium Affect Dimethylhydrazine-Induced Aberrant Crypt Formation, Global DNA Methylation and One-Carbon Metabolism in Rats J. Nutr., September 1, 2003; 133(9): 2907 - 2914. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. C. Anguera, J. R. Suh, H. Ghandour, I. M. Nasrallah, J. Selhub, and P. J. Stover Methenyltetrahydrofolate Synthetase Regulates Folate Turnover and Accumulation J. Biol. Chem., August 8, 2003; 278(32): 29856 - 29862. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Castro, I. Rivera, E. A. Struys, E. E.W. Jansen, P. Ravasco, M. E. Camilo, H. J. Blom, C. Jakobs, and I. Tavares de Almeida Increased Homocysteine and S-Adenosylhomocysteine Concentrations and DNA Hypomethylation in Vascular Disease Clin. Chem., August 1, 2003; 49(8): 1292 - 1296. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. P. Riksen, G. A. Rongen, H. J. Blom, F. G.M. Russel, G. H.J. Boers, and P. Smits Potential role for adenosine in the pathogenesis of the vascular complications of hyperhomocysteinemia Cardiovasc Res, August 1, 2003; 59(2): 271 - 276. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Winter-Vann, B. A. Kamen, M. O. Bergo, S. G. Young, S. Melnyk, S. J. James, and P. J. Casey Targeting Ras signaling through inhibition of carboxyl methylation: An unexpected property of methotrexate PNAS, May 27, 2003; 100(11): 6529 - 6534. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-W. Choi, S. Friso, G. G. Dolnikowski, P. J. Bagley, A. N. Edmondson, D. E. Smith, and J. B. Mason Biochemical and Molecular Aberrations in the Rat Colon Due to Folate Depletion Are Age-Specific J. Nutr., April 1, 2003; 133(4): 1206 - 1212. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. B. Mason Biomarkers of Nutrient Exposure and Status in One-Carbon (Methyl) Metabolism J. Nutr., March 1, 2003; 133(3): 941S - 947. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. S. Sood, M. J. Hunt, and S. C. Tyagi Peroxisome proliferator ameliorates endothelial dysfunction in a murine model of hyperhomocysteinemia Am J Physiol Lung Cell Mol Physiol, February 1, 2003; 284(2): L333 - L341. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K.-J. Sohn, J. M. Stempak, S. Reid, S. Shirwadkar, J. B. Mason, and Y.-I. Kim The effect of dietary folate on genomic and p53-specific DNA methylation in rat colon Carcinogenesis, January 1, 2003; 24(1): 81 - 90. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Hunt and S. C. Tyagi Peroxisome proliferators compete and ameliorate Hcy-mediated endocardial endothelial cell activation Am J Physiol Cell Physiol, October 1, 2002; 283(4): C1073 - C1079. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. F. Choumenkovitch, J. Selhub, P. J. Bagley, N. Maeda, M. R. Nadeau, D. E. Smith, and S.-W. Choi 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 J. Nutr., August 1, 2002; 132(8): 2157 - 2160. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. J. James, S. Melnyk, M. Pogribna, I. P. Pogribny, and M. A. Caudill Elevation in S-Adenosylhomocysteine and DNA Hypomethylation: Potential Epigenetic Mechanism for Homocysteine-Related Pathology J. Nutr., August 1, 2002; 132(8): 2361S - 2366. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. H. Halsted, J. A. Villanueva, A. M. Devlin, and C. J. Chandler Metabolic Interactions of Alcohol and Folate J. Nutr., August 1, 2002; 132(8): 2367S - 2372. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-W. Choi and J. B. Mason Folate Status: Effects on Pathways of Colorectal Carcinogenesis J. Nutr., August 1, 2002; 132(8): 2413S - 2418. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. H. Halsted, J. A. Villanueva, A. M. Devlin, O. Niemela, S. Parkkila, T. A. Garrow, L. M. Wallock, M. K. Shigenaga, S. Melnyk, and S. J. James Folate deficiency disturbs hepatic methionine metabolism and promotes liver injury in the ethanol-fed micropig PNAS, July 23, 2002; 99(15): 10072 - 10077. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Friso, S.-W. Choi, D. Girelli, J. B. Mason, G. G. Dolnikowski, P. J. Bagley, O. Olivieri, P. F. Jacques, I. H. Rosenberg, R. Corrocher, et al. A common mutation in the 5,10-methylenetetrahydrofolate reductase gene affects genomic DNA methylation through an interaction with folate status PNAS, April 16, 2002; 99(8): 5606 - 5611. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B Shannon, S Gnanasampanthan, J Beilby, and B Iacopetta A polymorphism in the methylenetetrahydrofolate reductase gene predisposes to colorectal cancers with microsatellite instability Gut, April 1, 2002; 50(4): 520 - 524. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. R Dimitrova, K. DeGroot, A. K Myers, and Y. D Kim Estrogen and homocysteine Cardiovasc Res, February 15, 2002; 53(3): 577 - 588. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M Kerins, M. J Koury, A. Capdevila, S. Rana, and C. Wagner Plasma S-adenosylhomocysteine is a more sensitive indicator of cardiovascular disease than plasma homocysteine Am. J. Clinical Nutrition, December 1, 2001; 74(6): 723 - 729. [Abstract] [Full Text]
|
|
|
|
|
|
M. A. Caudill, J. C. Wang, S. Melnyk, I. P. Pogribny, S. Jernigan, M. D. Collins, J. Santos-Guzman, M. E. Swendseid, E. A. Cogger, and S. J. James Intracellular S-Adenosylhomocysteine Concentrations Pr |
