| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
American Journal of Clinical Nutrition, Vol 55, 131-138, Copyright © 1992 by The American Society for Clinical Nutrition, Inc
REVIEW ARTICLES |
J Selhub and JW Miller
Vitamin Bioavailability Laboratory, USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111.
A unified, biochemical hypothesis is proposed to explain the pathogenesis of homocysteinemia. This hypothesis is based on the existence of coordinate regulation by S-adenosylmethionine (SAM) of the partitioning of homocysteine between de novo methionine synthesis and catabolism through cystathionine synthesis. This coordination, which serves to modulate the cellular concentration of homocysteine based on the requirements for methionine, is impaired in homocysteinemia. This hypothesis is evaluated in the context of the conditions known to be associated with homocysteinemia, including enzymatic defects and vitamin deficiencies. The novelty of the hypothesis is the assertion that impairment of one homocysteine metabolic pathway must lead to the impairment of the other homocysteine metabolic pathway to cause homocysteinemia. This extends the simplistic view that a block of only one of the pathways is sufficient to cause homocysteinemia.
This article has been cited by other articles:
|
|
 |
|
  M. van den Donk, L. Pellis, J. W. Crott, M. van Engeland, P. Friederich, F. M. Nagengast, J. D. van Bergeijk, S. Y. de Boer, J. B. Mason, F. J. Kok, et al. Folic Acid and Vitamin B-12 Supplementation Does Not Favorably Influence Uracil Incorporation and Promoter Methylation in Rectal Mucosa DNA of Subjects with Previous Colorectal Adenomas J. Nutr., September 1, 2007; 137(9): 2114 - 2120. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. I. Holm, S. Hustad, P. M. Ueland, S. E. Vollset, T. Grotmol, and J. Schneede Modulation of the Homocysteine-Betaine Relationship by Methylenetetrahydrofolate Reductase 677 C->T Genotypes and B-Vitamin Status in a Large-Scale Epidemiological Study J. Clin. Endocrinol. Metab., April 1, 2007; 92(4): 1535 - 1541. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Selhub The Many Facets of Hyperhomocysteinemia: Studies from the Framingham Cohorts J. Nutr., June 1, 2006; 136(6): 1726S - 1730S. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Lajous, E. Lazcano-Ponce, M. Hernandez-Avila, W. Willett, and I. Romieu Folate, vitamin b6, and vitamin B12 intake and the risk of breast cancer among mexican women. Cancer Epidemiol. Biomarkers Prev., March 1, 2006; 15(3): 443 - 448. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Pastore, S. De Angelis, S. Casciani, R. Ruggia, G. Di Giovamberardino, A. Noce, G. Splendiani, C. Cortese, G. Federici, and M. Dessi' Effects of Folic Acid Before and After Vitamin B12 on Plasma Homocysteine Concentrations in Hemodialysis Patients with Known MTHFR Genotypes Clin. Chem., January 1, 2006; 52(1): 145 - 148. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-I. Kim Nutritional Epigenetics: Impact of Folate Deficiency on DNA Methylation and Colon Cancer Susceptibility J. Nutr., November 1, 2005; 135(11): 2703 - 2709. [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]
|
|
|
|
|
|
C. Weikert, K. Hoffmann, J. Dierkes, B.-C. Zyriax, K. Klipstein-Grobusch, M. B. Schulze, R. Jung, E. Windler, and H. Boeing A Homocysteine Metabolism-Related Dietary Pattern and the Risk of Coronary Heart Disease in Two Independent German Study Populations J. Nutr., August 1, 2005; 135(8): 1981 - 1988. [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]
|
|
|
|
|
|
H. Ghandour, Z. Chen, J. Selhub, and R. Rozen Mice Deficient in Methylenetetrahydrofolate Reductase Exhibit Tissue-Specific Distribution of Folates J. Nutr., November 1, 2004; 134(11): 2975 - 2978. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. D. Dangour, V. L. Sibson, and A. E. Fletcher Hormones and Supplements: Do They Work?: Micronutrient Supplementation in Later Life: Limited Evidence for Benefit J. Gerontol. A Biol. Sci. Med. Sci., July 1, 2004; 59(7): B659 - B673. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-I. Kim Folate and DNA Methylation: A Mechanistic Link between Folate Deficiency and Colorectal Cancer? Cancer Epidemiol. Biomarkers Prev., April 1, 2004; 13(4): 511 - 519. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. T. Russo, S. Friso, P. F. Jacques, G. Rogers, D. Cucinotta, P. W. F. Wilson, J. M. Ordovas, I. H. Rosenberg, and J. Selhub Age and Gender Affect the Relation between Methylenetetrahydrofolate Reductase C677T Genotype and Fasting Plasma Homocysteine Concentrations in the Framingham Offspring Study Cohort J. Nutr., November 1, 2003; 133(11): 3416 - 3421. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Y. Chan and D. R. Appling Regulation of S-Adenosylmethionine Levels in Saccharomyces cerevisiae J. Biol. Chem., October 31, 2003; 278(44): 43051 - 43059. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. J Powers Riboflavin (vitamin B-2) and health Am. J. Clinical Nutrition, June 1, 2003; 77(6): 1352 - 1360. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. W. Miller, J. Selhub, M. R. Nadeau, C. A. Thomas, R. G. Feldman, and P. A. Wolf Effect of L-dopa on plasma homocysteine in PD patients: Relationship to B-vitamin status Neurology, April 8, 2003; 60(7): 1125 - 1129. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. de Bree, W. M. Verschuren, A.-L. Bjorke-Monsen, N. M. van der Put, S. G Heil, F. J. Trijbels, and H. J Blom Effect of the methylenetetrahydrofolate reductase 677C->T mutation on the relations among folate intake and plasma folate and homocysteine concentrations in a general population sample Am. J. Clinical Nutrition, March 1, 2003; 77(3): 687 - 693. [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]
|
|
|
|
|
|
R. A Heuberger, A. I Fisher, P. F Jacques, R. Klein, B. E. Klein, M. Palta, and J. A Mares-Perlman Relation of blood homocysteine and its nutritional determinants to age-related maculopathy in the third National Health and Nutrition Examination Survey Am. J. Clinical Nutrition, October 1, 2002; 76(4): 897 - 902. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. O. Uthus, K. Yokoi, and C. D. Davis Selenium Deficiency in Fisher-344 Rats Decreases Plasma and Tissue Homocysteine Concentrations and Alters Plasma Homocysteine and Cysteine Redox Status J. Nutr., June 1, 2002; 132(6): 1122 - 1128. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-I. Kim, M. Hayek, J. B. Mason, and S. N. Meydani Severe Folate Deficiency Impairs Natural Killer Cell-Mediated Cytotoxicity in Rats J. Nutr., June 1, 2002; 132(6): 1361 - 1367. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Niyikiza, S. D. Baker, D. E. Seitz, J. M. Walling, K. Nelson, J. J. Rusthoven, S. P. Stabler, P. Paoletti, A. H. Calvert, and R. H. Allen Homocysteine and Methylmalonic Acid: Markers to Predict and Avoid Toxicity from Pemetrexed Therapy Mol. Cancer Ther., May 1, 2002; 1(7): 545 - 552. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. L. Sedjo, P. Inserra, M. Abrahamsen, R. B. Harris, D. J. Roe, S. Baldwin, and A. R. Giuliano Human Papillomavirus Persistence and Nutrients Involved in the Methylation Pathway among a Cohort of Young Women Cancer Epidemiol. Biomarkers Prev., April 1, 2002; 11(4): 353 - 359. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. J. Weinstein, G. Gridley, L. C. Harty, S. R. Diehl, L. M. Brown, D. M. Winn, E. Bravo-Otero, and R. B. Hayes Folate Intake, Serum Homocysteine and Methylenetetrahydrofolate Reductase (MTHFR) C677T Genotype Are Not Associated with Oral Cancer Risk in Puerto Rico J. Nutr., April 1, 2002; 132(4): 762 - 767. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. S. Fuchs, W. C. Willett, G. A. Colditz, D. J. Hunter, M. J. Stampfer, F. E. Speizer, and E. L. Giovannucci The Influence of Folate and Multivitamin Use on the Familial Risk of Colon Cancer in Women Cancer Epidemiol. Biomarkers Prev., March 1, 2002; 11(3): 227 - 234. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. G. Bostom, P. F. Jacques, G. Liaugaudas, G. Rogers, I. H. Rosenberg, and J. Selhub Total Homocysteine Lowering Treatment Among Coronary Artery Disease Patients in the Era of Folic Acid-Fortified Cereal Grain Flour Arterioscler. Thromb. Vasc. Biol., March 1, 2002; 22(3): 488 - 491. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. M. Ulrich, Y. Yasui, R. Storb, M. M. Schubert, J. L. Wagner, J. Bigler, K. S. Ariail, C. L. Keener, S. Li, H. Liu, et al. Pharmacogenetics of methotrexate: toxicity among marrow transplantation patients varies with the methylenetetrahydrofolate reductase C677T polymorphism Blood, July 1, 2001; 98(1): 231 - 234. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-I. Kim, K. Fawaz, T. Knox, Y.-M. Lee, R. Norton, E. Libby, and J. B. Mason Colonic Mucosal Concentrations of Folate Are Accurately Predicted by Blood Measurements of Folate Status among Individuals Ingesting Physiologic Quantities of Folate Cancer Epidemiol. Biomarkers Prev., June 1, 2001; 10(6): 715 - 719. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. TSUKAMOTO and S. C. LU Current concepts in the pathogenesis of alcoholic liver injury FASEB J, June 1, 2001; 15(8): 1335 - 1349. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. C McKinley, H. McNulty, J. McPartlin, J. Strain, K. Pentieva, M. Ward, D. G Weir, and J. M Scott Low-dose vitamin B-6 effectively lowers fasting plasma homocysteine in healthy elderly persons who are folate and riboflavin replete Am. J. Clinical Nutrition, April 1, 2001; 73(4): 759 - 764. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Sesmilo, B. M. K. Biller, J. Llevadot, D. Hayden, G. Hanson, N. Rifai, and A. Klibanski Effects of Growth Hormone (GH) Administration on Homocyst(e)ine Levels in Men with GH Deficiency: A Randomized Controlled Trial J. Clin. Endocrinol. Metab., April 1, 2001; 86(4): 1518 - 1524. [Abstract] [Full Text]
|
|
|
|
 |
|
 N. M.J. van der Put, H. W.M. van Straaten, F. J.M. Trijbels, and H. J. Blom Folate, Homocysteine and Neural Tube Defects: An Overview Experimental Biology and Medicine, April 1, 2001; 226(4): 243 - 270. [Abstract] [Full Text]
|
|
|
|
 |
|
 T. J. Hartman, K. Woodson, R. Stolzenberg-Solomon, J. Virtamo, J. Selhub, M. J. Barrett, and D. Albanes Association of the B-Vitamins Pyridoxal 5'-Phosphate (B6), B12, and Folate with Lung Cancer Risk in Older Men Am. J. Epidemiol., April 1, 2001; 153(7): 688 - 693. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Suliman, J. C. D. Filho, P. Barany, B. Anderstam, B. Lindholm, and J. Bergstrom Effects of methionine loading on plasma and erythrocyte sulphur amino acids and sulph-hydryls before and after co-factor supplementation in haemodialysis patients Nephrol. Dial. Transplant., January 1, 2001; 16(1): 102 - 110. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. K. Le Leu, G. P. Young, and G. H. McIntosh Folate deficiency reduces the development of colorectal cancer in rats Carcinogenesis, December 1, 2000; 21(12): 2261 - 2265. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Diaz-Arrastia Homocysteine and Neurologic Disease Arch Neurol, October 1, 2000; 57(10): 1422 - 1427. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. L. Stern, J. B. Mason, J. Selhub, and S.-W. Choi Genomic DNA Hypomethylation, a Characteristic of Most Cancers, Is Present in Peripheral Leukocytes of Individuals Who Are Homozygous for the C677T Polymorphism in the Methylenetetrahydrofolate Reductase Gene Cancer Epidemiol. Biomarkers Prev., August 1, 2000; 9(8): 849 - 853. [Abstract] [Full Text]
|
|
|
|
|
|
A. J. Levine, K. D. Siegmund, C. M. Ervin, A. Diep, E. R. Lee, H. D. Frankl, and R. W. Haile The Methylenetetrahydrofolate Reductase 677C{->}T Polymorphism and Distal Colorectal Adenoma Risk Cancer Epidemiol. Biomarkers Prev., July 1, 2000; 9(7): 657 - 663. [Abstract] [Full Text]
|
|
|
|
 |
|
 J. Song, K.-J. Sohn, A. Medline, C. Ash, S. Gallinger, and Y.-I. Kim Chemopreventive Effects of Dietary Folate on Intestinal Polyps in Apc+/- Msh2-/- Mice Cancer Res., June 1, 2000; 60(12): 3191 - 3199. [Abstract] [Full Text]
|
|
|
|
 |
|
 H. KIMURA, F. GEJYO, S. SUZUKI, and R. MIYAZAKI The C677T Methylenetetrahydrofolate Reductase Gene Mutation in Hemodialysis Patients J. Am. Soc. Nephrol., May 1, 2000; 11(5): 885 - 893. [Abstract] [Full Text]
|
|
|
|
|
|
M. Martinez, G. J. Cuskelly, J. Williamson, J. P. Toth, and J. F. Gregory III Vitamin B-6 Deficiency in Rats Reduces Hepatic Serine Hydroxymethyltransferase and Cystathionine {beta}-Synthase Activities and Rates of In Vivo Protein Turnover, Homocysteine Remethylation and Transsulfuration J. Nutr., May 1, 2000; 130(5): 1115 - 1123. [Abstract] [Full Text]
|
|
|
|
|
|
C. M. Ulrich, E. Kampman, J. Bigler, S. M. Schwartz, C. Chen, R. Bostick, L. Fosdick, S. A. A. Beresford, Y. Yasui, and J. D. Potter Lack of Association between the C677T MTHFR Polymorphism and Colorectal Hyperplastic Polyps Cancer Epidemiol. Biomarkers Prev., April 1, 2000; 9(4): 427 - 433. [Abstract] [Full Text]
|
|
|
|
|
|
J. Selhub, L. C Bagley, J. Miller, and I. H Rosenberg B vitamins, homocysteine, and neurocognitive function in the elderly1 Am. J. Clinical Nutrition, February 1, 2000; 71(2): 614s - 620s. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Fonseca, S. C. Guba, and L. M. Fink Hyperhomocysteinemia and the Endocrine System: Implications for Atherosclerosis and Thrombosis Endocr. Rev., October 1, 1999; 20(5): 738 - 759. [Abstract] [Full Text]
|
|
|
|
|
|
E. B. Stamm and R. D. Reynolds Plasma Total Homocyst(e)ine May Not Be the Most Appropriate Index for Cardiovascular Disease Risk J. Nutr., October 1, 1999; 129(10): 1927 - 1930. [Full Text]
|
|
|
|
 |
|
 J. D. Kark, J. Selhub, B. Adler, J. Gofin, J. H. Abramson, G. Friedman, and I. H. Rosenberg Nonfasting Plasma Total Homocysteine Level and Mortality in Middle-Aged and Elderly Men and Women in Jerusalem Ann Intern Med, September 7, 1999; 131(5): 321 - 330. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. Ulrich, E. Kampman, J. Bigler, S. M. Schwartz, C. Chen, R. Bostick, L. Fosdick, S. A. A. Beresford, Y. Yasui, and J. D. Potter Colorectal Adenomas and the C677T MTHFR Polymorphism: Evidence for Gene-Environment Interaction? Cancer Epidemiol. Biomarkers Prev., August 1, 1999; 8(8): 659 - 668. [Abstract] [Full Text]
|
|
|
|
 |
|
 P. Ambrosi, P. H. Rolland, H. Bodard, A. Barlatier, P. Charpiot, G. Guisgand, A. Friggi, O. Ghiringhelli, G. Habib, G. Bouvenot, et al. Effects of folate supplementation in hyperhomocysteinemic pigs J. Am. Coll. Cardiol., July 1, 1999; 34(1): 274 - 279. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. L. Slattery, J. D. Potter, W. Samowitz, D. Schaffer, and M. Leppert Methylenetetrahydrofolate Reductase, Diet, and Risk of Colon Cancer Cancer Epidemiol. Biomarkers Prev., June 1, 1999; 8(6): 513 - 518. [Abstract] [Full Text]
|
|
|
|
 |
|
 S. N. Doshi, J. Goodfellow, M. J. Lewis, and I. F.W. McDowell Homocysteine and endothelial function Cardiovasc Res, June 1, 1999; 42(3): 578 - 582. [Full Text] [PDF]
|
|
|
|
|
|
J. Lambert, M. van den Berg, M. Steyn, J. A. Rauwerda, A. J.M. Donker, and C. D.A. Stehouwer Familial hyperhomocysteinaemia and endothelium-dependent vasodilatation and arterial distensibility of large arteries Cardiovasc Res, June 1, 1999; 42(3): 743 - 751. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. G. BOSTOM and B. F. CULLETON Hyperhomocysteinemia in Chronic Renal Disease J. Am. Soc. Nephrol., April 1, 1999; 10(4): 891 - 900. [Full Text]
|
|
|
|
|
|
L. B. Bailey and J. F. Gregory III Folate Metabolism and Requirements J. Nutr., April 1, 1999; 129(4): 779 - 782. [Abstract] [Full Text]
|
|
|
|
|
|
K. Wu, K. J. Helzlsouer, G. W. Comstock, S. C. Hoffman, M. R. Nadeau, and J. Selhub A Prospective Study on Folate, B12, and Pyridoxal 5'-Phosphate (B6) and Breast Cancer Cancer Epidemiol. Biomarkers Prev., March 1, 1999; 8(3): 209 - 217. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. Jacob, D. J. Jenden, M. A. Allman-Farinelli, and M. E. Swendseid Folate Nutriture Alters Choline Status of Women and Men Fed Low Choline Diets J. Nutr., March 1, 1999; 129(3): 712 - 717. [Abstract] [Full Text]
|
|
|
|
|
|
A. D Mackey and M. F. Picciano Maternal folate status during extended lactation and the effect of supplemental folic acid Am. J. Clinical Nutrition, February 1, 1999; 69(2): 285 - 292. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Cattaneo, R. Lombardi, A. Lecchi, M. L. Zighetti;, D. Girelli, O. Olivieri, C. Russo, and R. Corrocher Is the Oral Methionine Loading Test Insensitive to the Remethylation Pathway of Homocysteine? Blood, February 1, 1999; 93(3): 1118 - 1120. [Full Text] [PDF]
|
|
|
|
 |
|
 P. J. Bagley and J. Selhub A common mutation in the methylenetetrahydrofolate reductase gene is associated with an accumulation of formylated tetrahydrofolates in red blood cells PNAS, October 27, 1998; 95(22): 13217 - 13220. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. W. Siri, P. Verhoef, and F. J. Kok Vitamins B6, B12, and Folate: Association with Plasma Total Homocysteine and Risk of Coronary Atherosclerosis J. Am. Coll. Nutr., October 1, 1998; 17(5): 435 - 441. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Verhoef, E. B. Rimm, D. J. Hunter, J. Chen, W. C. Willett, K. Kelsey, and M. J. Stampfer A common mutation in the methylenetetrahydrofolate reductase gene and risk of coronary heart disease: results among U.S. men J. Am. Coll. Cardiol., August 1, 1998; 32(2): 353 - 359. [Abstract] [Full Text] [PDF]
|
|
