Intestinal metabolism of sulfur amino acids

Nutrition Research Reviews

Volumn 22, Issue 2, 2009, Pages 175-187

  Bauchart Thevret, Caroline ^a   Stoll, Barbara ^a   Burrin, Douglas G ^a  

^a CHILDREN S NUTRITION RESEARCH CENTER   (United States)

Author keywords

Cysteine; Glutathione; Methionine; S adenosylmethionine

Indexed keywords

CYSTEINE; GLUTATHIONE; HOMOCYSTEINE; METHIONINE; METHIONINE ADENOSYLTRANSFERASE; S ADENOSYLMETHIONINE; SULFUR AMINO ACID; DIAGNOSTIC AGENT; ISOTOPE;

AMINO ACID METABOLISM; CELL GROWTH; CELL PROLIFERATION; CROHN DISEASE; DIETARY INTAKE; GASTROINTESTINAL DISEASE; HUMAN; INTESTINE EPITHELIUM CELL; INTESTINE FUNCTION; INTESTINE MUCOSA; MAMMAL CELL; METHYLATION; NONHUMAN; NUTRITIONAL DEFICIENCY; OXIDATIVE STRESS; POLYAMINE SYNTHESIS; PROTEIN SYNTHESIS; REVIEW; ULCERATIVE COLITIS; ANIMAL; INTESTINE; METABOLISM;

MAMMALIA; SUIDAE;

AMINO ACIDS, SULFUR; ANIMALS; GASTROINTESTINAL DISEASES; INTESTINAL MUCOSA; INTESTINES; ISOTOPES;

EID: 77950363697     PISSN: 09544224     EISSN: 14752700     Source Type: Journal    
DOI: 10.1017/S0954422409990138     Document Type: Review

References (145)

1. Stipanuk MH (2004) Sulfur amino acid metabolism: pathways for production and removal of homocysteine and cysteine. Annu Rev Nutr 24, 539-577.
2. Shoveller AK, Stoll B, Ball RO, et al. (2005) Nutritional and functional importance of intestinal sulfur amino acid metabolism. J Nutr 135, 1609-1612.
3. Brosnan JT & Brosnan ME (2006) The sulfur-containing amino acids: an overview. J Nutr 136, 1636S-1640S.
4. Mato JM, Corrales FJ, Lu SC, et al. (2002) S-adenosylmethionine: a control switch that regulates liver function. FASEB J 16, 15-26.
5. Kim YI (2005) Nutritional epigenetics: impact of folate deficiency on DNA methylation and colon cancer susceptibility. J Nutr 135, 2703-2709.
6. Giovannucci E, Rimm EB, Ascherio A, et al. (1995) Alcohol, low-methionine-low-folate diets, and risk of colon cancer in men. J Natl Cancer Inst 87, 265-273.
7. MacCoss MJ, Fukagawa NK & Matthews DE (2001) Measurement of intracellular sulfur amino acid metabolism in humans. Am J Physiol Endocrinol Metab 280, E947-E955.
8. Zhou J & Austin RC (2009) Contributions of hyperhomocysteinemia to atherosclerosis: causal relationship and potential mechanisms. Biofactors 35, 120-129.
9. Schulz RJ (2007) Homocysteine as a biomarker for cognitive dysfunction in the elderly. Curr Opin Clin Nutr Metab Care 10, 718-723.
10. Herrmann M, Peter SJ, Umanskaya N, et al. (2007) The role of hyperhomocysteinemia as well as folate, vitamin B(6) and B(12) deficiencies in osteoporosis: a systematic review. Clin Chem Lab Med 45, 1621-1632.
11. Zlotkin SH & Anderson GH (1982) The development of cystathionase activity during the first year of life. Pediatr Res 16, 65-68.
12. Ball RO, Courtney-Martin G & Pencharz PB (2006) The in vivo sparing of methionine by cysteine in sulfur amino acid requirements in animal models and adult humans. J Nutr 136, 1682S-1693S.
13. Storch KJ, Wagner DA, Burke JF, et al. (1990) [1-13C; methyl-2H3]methionine kinetics in humans: methionine conservation and cystine sparing. Am J Physiol 258, E790-E798.
14. Storch KJ, Wagner DA, Burke JF, et al. (1988) Quantitative study in vivo of methionine cycle in humans using [methyl-2H3]- and [1-13C]methionine. Am J Physiol 255, E322-E331.
15. Matthews DE, Schwarz HP, Yang RD, et al. (1982) Relationship of plasma leucine and a-ketoisocaproate during a L-[1-13C]leucine infusion in man: a method for measuring human intracellular leucine tracer enrichment. Metabolism 31, 1105-1112.
16. Tessari P, Kiwanuka E, Coracina A, et al. (2005) Insulin in methionine and homocysteine kinetics in healthy humans: plasma vs. intracellular models. Am J Physiol Endocrinol Metab 288, E1270-E1276.
17. Tessari P, Coracina A, Kiwanuka E, et al. (2005) Effects of insulin on methionine and homocysteine kinetics in type 2 diabetes with nephropathy. Diabetes 54, 2968-2976.
18. Davis SR, Stacpoole PW, Williamson J, et al. (2004) Tracer-derived total and folate-dependent homocysteine remethylation and synthesis rates in humans indicate that serine is the main one-carbon donor. Am J Physiol Endocrinol Metab 286, E272-E279.
19. Hoffer LJ (2004) Homocysteine remethylation and transsulfuration. Metabolism 53, 1480-1483.
20. Shinohara Y, Hasegawa H, Ogawa K, et al. (2006) Distinct effects of folate and choline deficiency on plasma kinetics of methionine and homocysteine in rats. Metabolism 55, 899-906.
21. Di Buono M, Wykes LJ, Cole DE, et al. (2003) Regulation of sulfur amino acid metabolism in men in response to changes in sulfur amino acid intakes. J Nutr 133, 733-739.
22. Kurpad AV, Regan MM, Varalakshmi S, et al. (2004) Effect of cystine on the methionine requirement of healthy Indian men determined by using the 24-h indicator amino acid balance approach. Am J Clin Nutr 80, 1526-1535.
23. Fukagawa NK (2006) Sparing of methionine requirements: evaluation of human data takes sulfur amino acids beyond protein. J Nutr 136, 1676S-1681S.
24. Baker DH, Clausing WW, Harmon BG, et al. (1969) Replacement value of cystine for methionine for the young pig. J Anim Sci 29, 581-584.
25. Graber G & Baker DH (1971) Sulfur amino acid nutrition of the growing chick: quantitative aspects concerning the efficacy of dietary methionine, cysteine and cystine. J Anim Sci 33, 1005-1011.
26. Aguilar TS (1982) Studies in vivo on the methioninesparing effect of cysteine in rats. Arch Latinoam Nutr 32, 130-147.
27. Shoveller AK, Brunton JA, House JD, et al. (2003) Dietary cysteine reduces the methionine requirement by an equal proportion in both parenterally and enterally fed piglets. J Nutr 133, 4215-4224.
28. Baker DH (2006) Comparative species utilization and toxicity of sulfur amino acids. J Nutr 136, 1670S-1675S.
29. Hiramatsu T, Fukagawa NK, Marchini JS, et al. (1994) Methionine and cysteine kinetics at different intakes of cystine in healthy adult men. Am J Clin Nutr 60, 525-533.
30. Raguso CA, Ajami AM, Gleason R, et al. (1997) Effect of cystine intake on methionine kinetics and oxidation determined with oral tracers of methionine and cysteine in healthy adults. Am J Clin Nutr 66, 283-292.
31. Fukagawa NK, Yu YM & Young VR (1998) Methionine and cysteine kinetics at different intakes of methionine and cysteine in elderly men and women. Am J Clin Nutr 68, 380-388.
32. Raguso CA, Regan MM & Young VR (2000) Cysteine kinetics and oxidation at different intakes of methionine and cystine in young adults. Am J Clin Nutr 71, 491-499.
33. Di Buono M, Wykes LJ, Ball RO, et al. (2001) Total sulfur amino acid requirement in young men as determined by indicator amino acid oxidation with L-[1-13C]phenylalanine. Am J Clin Nutr 74, 756-760.
34. Kurpad AV, Regan MM, Varalakshmi S, et al. (2003) Daily methionine requirements of healthy Indian men, measured by a 24-h indicator amino acid oxidation and balance technique. Am J Clin Nutr 77, 1198-1205.
35. Di Buono M, Wykes LJ, Ball RO, et al. (2001) Dietary cysteine reduces the methionine requirement in men. Am J Clin Nutr 74, 761-766.
36. Albanese AA, Holt LE Jr, Davis VI, et al. (1948) The sulfur amino acid requirement of the infant. Fed Proc 7, 141.
37. Rose WC & Wixom RL (1955) The amino acid requirements of man. XIII. The sparing effect of cystine on the methionine requirement. J Biol Chem 216, 753-773.
38. Reynolds MS, Steel DL, Jones EM, et al. (1958) Nitrogen balances of women maintained on various levels of methionine and cystine. J Nutr 64, 99-111.
39. Finkelstein JD, Martin JJ & Harris BJ (1988) Methionine metabolism in mammals. The methionine-sparing effect of cystine. J Biol Chem 263, 11750-11754.
40. Humayun MA, Elango R, Ball RO, et al. (2007) Reevaluation of the protein requirement in young men with the indicator amino acid oxidation technique. Am J Clin Nutr 86, 995-1002.
41. Courtney-Martin G, Rafii M, Wykes LJ, et al. (2008) Methionine-adequate cysteine-free diet does not limit erythrocyte glutathione synthesis in young healthy adult men. J Nutr 138, 2172-2178.
42. Mudd SH, Finkelstein JD, Irreverre F, et al. (1965) Transsulfuration in mammals. Microassays and tissue distributions of three enzymes of the pathway. J Biol Chem 240, 4382-4392.
43. Stegink LD & Den Besten L (1972) Synthesis of cysteine from methionine in normal adult subjects: effect of route of alimentation. Science 178, 514-516.
44. Zlotkin SH, Bryan MH & Anderson GH (1981) Cysteine supplementation to cysteine-free intravenous feeding regimens in newborn infants. Am J Clin Nutr 34, 914-923.
45. Shoveller AK, Brunton JA, Pencharz PB, et al. (2003) The methionine requirement is lower in neonatal piglets fed parenterally than in those fed enterally. J Nutr 133, 1390-1397.
46. Stoll B & Burrin DG (2006) Measuring splanchnic amino acid metabolism in vivo using stable isotopic tracers. J Anim Sci 84, Suppl., E60-E72.
47. Stoll B, Henry J, Reeds PJ, et al. (1998) Catabolism dominates the first-pass intestinal metabolism of dietary essential amino acids in milk protein-fed piglets. J Nutr 128, 606-614.
48. Shoveller AK, House JD, Brunton JA, et al. (2004) The balance of dietary sulfur amino acids and the route of feeding affect plasma homocysteine concentrations in neonatal piglets. J Nutr 134, 609-612.
49. Riedijk MA, Stoll B, Chacko S, et al. (2007) Methionine transmethylation and transsulfuration in the piglet gastrointestinal tract. Proc Natl Acad Sci U S A 104, 3408-3413.
50. Finkelstein JD (2000) Pathways and regulation of homocysteine metabolism in mammals. Semin Thromb Hemost 26, 219-225.
51. Finkelstein JD (1990) Methionine metabolism in mammals. J Nutr Biochem 1, 228-237.
52. Bauchart-Thevret C, Stoll B, Chacko S, et al. (2009) Sulfur amino acid deficiency upregulates intestinal methionine cycle activity and suppresses epithelial growth in neonatal pigs. Am J Physiol Endocrinol Metab 296, E1239-E1250.
53. Chen LX, Yin YL, Jobgen WJS, et al. (2007) In vitro oxidation of essential amino acids by jejunal mucosal cells of growing pigs. Livest Sci 109, 19-23.
54. Chen L, Li P, Wang J, et al. (2009) Catabolism of nutritionally essential amino acids in developing porcine enterocytes. Amino Acids 37, 143-152.
55. Wilson FA, van den Borne JJ, Calder AG, et al. (2009) Tissue methionine cycle activity and homocysteine metabolism in female rats: impact of dietary methionine and folate plus choline. Am J Physiol Endocrinol Metab 296, E702-E713.
56. Stead LM, Brosnan ME & Brosnan JT (2000) Characterization of homocysteine metabolism in the rat liver. Biochem J 350, 685-692.
57. Mudd SH, Brosnan JT, Brosnan ME, et al. (2007) Methyl balance and transmethylation fluxes in humans. Am J Clin Nutr 85, 19-25.
58. Bos C, Stoll B, Fouillet H, et al. (2003) Intestinal lysine metabolism is driven by the enteral availability of dietary lysine in piglets fed a bolus meal. Am J Physiol Endocrinol Metab 285, E1246-E1257.
59. Stipanuk MH, Ueki I, Dominy JE Jr, et al. (2009) Cysteine dioxygenase: a robust system for regulation of cellular cysteine levels. Amino Acids 37, 55-63.
60. Stipanuk MH & Rotter MA (1984) Metabolism of cysteine, cysteinesulfinate and cysteinesulfonate in rats fed adequate and excess levels of sulfur-containing amino acids. J Nutr 114, 1426-1437.
61. Coloso RM & Stipanuk MH (1989) Metabolism of cyst(e)ine in rat enterocytes. J Nutr 119, 1914-1924.
62. Hirschberger LL, Daval S, Stover PJ, et al. (2001) Murine cysteine dioxygenase gene: structural organization, tissuespecific expression and promoter identification. Gene 277, 153-161.
63. Cottrell J, Stoll B & Burrin DG (2006) Kinetics of splanchnic 13C-cysteine metabolism in infant pigs. FASEB J 20, A9.
64. Malmezat T, Breuille D, Capitan P, et al. (2000) Glutathione turnover is increased during the acute phase of sepsis in rats. J Nutr 130, 1239-1246.
65. Atmaca G (2004) Antioxidant effects of sulfur-containing amino acids. Yonsei Med J 45, 776-788.
66. Huxtable RJ (1992) Physiological actions of taurine. Physiol Rev 72, 101-163.
67. Bouckenooghe T, Remacle C & Reusens B (2006) Is taurine a functional nutrient? Curr Opin Clin Nutr Metab Care 9, 728-733.
68. Schneider SM, Joly F, Gehrardt MF, et al. (2006) Taurine status and response to intravenous taurine supplementation in adults with short-bowel syndrome undergoing long-term parenteral nutrition: a pilot study. Br J Nutr 96, 365-370.
69. Li X, Bazer FW, Gao H, et al. (2009) Amino acids and gaseous signaling. Amino Acids 37, 65-78.
70. Zhao W, Ndisang JF & Wang R (2003) Modulation of endogenous production of H2S in rat tissues. Can J Physiol Pharmacol 81, 848-853.
71. Linden DR, Sha L, Mazzone A, et al. (2008) Production of the gaseous signal molecule hydrogen sulfide in mouse tissues. J Neurochem 106, 1577-1585.
72. Wallace JL (2007) Hydrogen sulfide-releasing anti-inflammatory drugs. Trends Pharmacol Sci 28, 501-505.
73. Teague B, Asiedu S & Moore PK (2002) The smooth muscle relaxant effect of hydrogen sulphide in vitro: evidence for a physiological role to control intestinal contractility. Br J Pharmacol 137, 139-145.
74. Gallego D, Clave P, Donovan J, et al. (2008) The gaseous mediator, hydrogen sulphide, inhibits in vitro motor patterns in the human, rat and mouse colon and jejunum. Neurogastroenterol Motil 20, 1306-1316.
75. Schicho R, Krueger D, Zeller F, et al. (2006) Hydrogen sulfide is a novel prosecretory neuromodulator in the guinea-pig and human colon. Gastroenterology 131, 1542-1552.
76. Distrutti E, Sediari L, Mencarelli A, et al. (2006) Evidence that hydrogen sulfide exerts antinociceptive effects in the gastrointestinal tract by activating KATP channels. J Pharmacol Exp Ther 316, 325-335.
77. Distrutti E, Mencarelli A, Santucci L, et al. (2008) The methionine connection: homocysteine and hydrogen sulfide exert opposite effects on hepatic microcirculation in rats. Hepatology 47, 659-667.
78. Lobley GE, Connell A & Revell D (1996) The importance of transmethylation reactions to methionine metabolism in sheep: effects of supplementation with creatine and choline. Br J Nutr 75, 47-56.
79. Lobley GE, Shen X, Le G, et al. (2003) Oxidation of essential amino acids by the ovine gastrointestinal tract. Br J Nutr 89, 617-630.
80. Lobley GE, Wester TJ, Calder AG, et al. (2006) Absorption of 2-hydroxy-4-methylthiobutyrate and conversion to methionine in lambs. J Dairy Sci 89, 1072-1080.
81. Lobley GE, Wester TJ, Holtrop G, et al. (2006) Absorption and digestive tract metabolism of 2-hydroxy-4-methylthiobutanoic acid in lambs. J Dairy Sci 89, 3508-3521.
82. Dibner JJ & Knight CD (1984) Conversion of 2-hydroxy- 4-(methylthio)butanoic acid to L-methionine in the chick: a stereospecific pathway. J Nutr 114, 1716-1723.
83. Rangel-Lugo M & Austic RE (1998) Transamination of 2-oxo-4-[methylthio]butanoic acid in chicken tissues. Poult Sci 77, 98-104.
84. Ferjancic-Biagini A, Dupuis L, De Caro J, et al. (1995) In vitro oxidative decarboxylation of L-2-hydroxy- 4-methylthiobutanoic acid by L-2-hydroxy acid oxidase A from chicken liver. Biochimie 77, 249-255.
85. Langer BW Jr (1965) The biochemical conversion of 2-hydroxy-4- methylthiobutyric acid into methionine by the rat in vitro. Biochem J 95, 683-687.
86. Robinson JC, Keay L, Molinari R, et al. (1962) L-a- Hydroxy acid oxidases of hog renal cortex. J Biol Chem 237, 2001-2010.
87. McCollum MQ, Vazquez-Anon M, Dibner JJ, et al. (2000) Absorption of 2-hydroxy-4-(methylthio)butanoic acid by isolated sheep ruminal and omasal epithelia. J Anim Sci 78, 1078-1083.
88. Martin-Venegas R, Soriano-Garcia JF, Vinardell MP, et al. (2006) Oligomers are not the limiting factor in the absorption of DL-2-hydroxy-4- (methylthio)butanoic acid in the chicken small intestine. Poult Sci 85, 56-63.
89. Martin-Venegas R, Geraert PA & Ferrer R (2006) Conversion of the methionine hydroxy analogue DL-2- hydroxy-(4-methylthio) butanoic acid to sulfur-containing amino acids in the chicken small intestine. Poult Sci 85, 1932-1938.
90. Dilger RN, Kobler C, Weckbecker C, et al. (2007) 2-Keto- 4-(methylthio)butyric acid (keto analog of methionine) is a safe and efficacious precursor of L-methionine in chicks. J Nutr 137, 1868-1873.
91. Stipanuk MH (2007) The keto acid of methionine is a safe and efficacious substitute for dietary L-methionine: the answer from chick bioassays. J Nutr 137, 1844-1845.
92. Feiten SF, Draibe SA, Watanabe R, et al. (2005) Short-term effects of a very-low-protein diet supplemented with ketoacids in nondialyzed chronic kidney disease patients. Eur J Clin Nutr 59, 129-136.
93. Johnson LR (1988) Regulation of gastrointestinal mucosal growth. Physiol Rev 68, 456-502.
94. Burrin DG, Stoll B, Jiang R, et al. (2000) GLP-2 stimulates intestinal growth in premature TPN-fed pigs by suppressing proteolysis and apoptosis. Am J Physiol Gastrointest Liver Physiol 279, G1249-G1256.
95. Burrin DG, Stoll B, Jiang R, et al. (2000) Minimal enteral nutrient requirements for intestinal growth in neonatal piglets: how much is enough? Am J Clin Nutr 71, 1603-1610.
96. Pias EK & Aw TY (2002) Apoptosis in mitotic competent undifferentiated cells is induced by cellular redox imbalance independent of reactive oxygen species production. FASEB J 16, 781-790.
97. Noda T, Iwakiri R, Fujimoto K, et al. (2001) Induction of mild intracellular redox imbalance inhibits proliferation of CaCo-2 cells. FASEB J 15, 2131-2139.
98. Jonas CR, Ziegler TR, Gu LH, et al. (2002) Extracellular thiol/disulfide redox state affects proliferation rate in a human colon carcinoma (Caco2) cell line. Free Radic Biol Med 33, 1499-1506.
99. Aw TY (2003) Cellular redox: a modulator of intestinal epithelial cell proliferation. News Physiol Sci 18, 201-204.
100. Jones DP (2002) Redox potential of GSH/GSSG couple: assay and biological significance. Methods Enzymol 348, 93-112.
101. Aw TY (1999) Molecular and cellular responses to oxidative stress and changes in oxidation-reduction imbalance in the intestine. Am J Clin Nutr 70, 557-565.
102. Martensson J, Jain A & Meister A (1990) Glutathione is required for intestinal function. Proc Natl Acad Sci U S A 87, 1715-1719.
103. Tian J, Washizawa N, Gu LH, et al. (2007) Local glutathione redox status does not regulate ileal mucosal growth after massive small bowel resection in rats. J Nutr 137, 320-325.
104. Noda T, Iwakiri R, Fujimoto K, et al. (2002) Exogenous cysteine and cystine promote cell proliferation in CaCo-2 cells. Cell Prolif 35, 117-129.
105. Anderson CL, Iyer SS, Ziegler TR, et al. (2007) Control of extracellular cysteine/cystine redox state by HT-29 cells is independent of cellular glutathione. Am J Physiol Regul Integr Comp Physiol 293, R1069-R1075.
106. Martinez-Lopez N, Varela-Rey M, Ariz U, et al. (2008) S-adenosylmethionine and proliferation: new pathways, new targets. Biochem Soc Trans 36, 848-852.
107. Kotb M, Mudd SH, Mato JM, et al. (1997) Consensus nomenclature for the mammalian methionine adenosyltransferase genes and gene products. Trends Genet 13, 51-52.
108. Halim AB, LeGros L, Geller A, et al. (1999) Expression and functional interaction of the catalytic and regulatory subunits of human methionine adenosyltransferase in mammalian cells. J Biol Chem 274, 29720-29725.
109. Lu SC & Mato JM (2005) Role of methionine adenosyltransferase and S-adenosylmethionine in alcohol-associated liver cancer. Alcohol 35, 227-234.
110. Ito K, Ikeda S, Kojima N, et al. (2000) Correlation between the expression of methionine adenosyltransferase and the stages of human colorectal carcinoma. Surg Today 30, 706-710.
111. Chen H, Xia M, Lin M, et al. (2007) Role of methionine adenosyltransferase 2A and S-adenosylmethionine in mitogen-induced growth of human colon cancer cells. Gastroenterology 133, 207-218.
112. Chiang PK, Gordon RK, Tal J, et al. (1996) S-adenosylmethionine and methylation. FASEB J 10, 471-480.
113. Brosnan JT, da Silva R & Brosnan ME (2007) Amino acids and the regulation of methyl balance in humans. Curr Opin Clin Nutr Metab Care 10, 52-57.
114. Reik W & Dean W (2001) DNA methylation and mammalian epigenetics. Electrophoresis 22, 2838-2843.
115. Patra SK, Patra A, Rizzi F, et al. (2008) Demethylation of (cytosine-5-C-methyl) DNA and regulation of transcription in the epigenetic pathways of cancer development. Cancer Metastasis Rev 27, 315-334.
116. Moinard C, Cynober L & de Bandt JP (2005) Polyamines: metabolism and implications in human diseases. Clin Nutr 24, 184-197.
117. Bettuzzi S, Davalli P, Astancolle S, et al. (1999) Coordinate changes of polyamine metabolism regulatory proteins during the cell cycle of normal human dermal fibroblasts. FEBS Lett 446, 18-22.
118. McCormack SA & Johnson LR (1991) Role of polyamines in gastrointestinal mucosal growth. Am J Physiol 260, G795-G806.
119. Wang JY (2007) Polyamines and mRNA stability in regulation of intestinal mucosal growth. Amino Acids 33, 241-252.
120. Ansorena E, Garcia-Trevijano ER, Martinez-Chantar ML, et al. (2002) S-adenosylmethionine and methylthioadenosine are antiapoptotic in cultured rat hepatocytes but proapoptotic in human hepatoma cells. Hepatology 35, 274-280.
121. Clarke SG (2006) Inhibition of mammalian protein methyltransferases by 50-methylthioadenosine (MTA): a mechanism of action of dietary SAMe? In The Enzymes, vol.24, pp. 467-493 [SG Clarke and F Tamanoi, editors]. New York: Elsevier/Academic Press.
122. Grillo MA & Colombatto S (2008) S-adenosylmethionine and its products. Amino Acids 34, 187-193.
123. Li TW, Zhang Q, Oh P, et al. (2009) S-adenosylmethionine and methylthioadenosine inhibit cellular FLICE inhibitory protein expression and induce apoptosis in colon cancer cells. Mol Pharmacol 76, 192-200.
124. Seiler N & Raul F (2005) Polyamines and apoptosis. J Cell Mol Med 9, 623-642.
125. Sanderson P, Stone E, Kim YI, et al. (2007) Folate and colorectal cancer risk. Br J Nutr 98, 1299-1304.
126. Kim YI (2003) Role of folate in colon cancer development and progression. J Nutr 133, 3731S-3739S.
127. Ulrich CM (2007) Folate and cancer prevention: a closer look at a complex picture. Am J Clin Nutr 86, 271-273.
128. Smith AD, Kim YI & Refsum H (2008) Is folic acid good for everyone? Am J Clin Nutr 87, 517-533.
129. Kim YI (2008) Folic acid supplementation and cancer risk: point. Cancer Epidemiol Biomarkers Prev 17, 2220-2225.
130. Giovannucci E (2002) Epidemiologic studies of folate and colorectal neoplasia: a review. J Nutr 132, 2350S-2355S.
131. Jones PA & Baylin SB (2002) The fundamental role of epigenetic events in cancer. Nat Rev Genet 3, 415-428.
132. Duthie SJ, Narayanan S, Sharp L, et al. (2004) Folate, DNA stability and colo-rectal neoplasia. Proc Nutr Soc 63, 571-578.
133. Kim DH (2007) The interactive effect of methyl-group diet and polymorphism of methylenetetrahydrofolate reductase on the risk of colorectal cancer. Mutat Res 622, 14-18.
134. Frosst P, Blom HJ, Milos R, et al. (1995) A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet 10, 111-113.
135. Hubner RA & Houlston RS (2007) MTHFR C677T and colorectal cancer risk: a meta-analysis of 25 populations. Int J Cancer 120, 1027-1035.
136. Chen J, Giovannucci E, Kelsey K, et al. (1996) A methylenetetrahydrofolate reductase polymorphism and the risk of colorectal cancer. Cancer Res 56, 4862-4864.
137. Ma J, Stampfer MJ, Giovannucci E, et al. (1997) Methylenetetrahydrofolate reductase polymorphism, dietary interactions, and risk of colorectal cancer. Cancer Res 57, 1098-1102.
138. Avila MA, Garcia-Trevijano ER, Lu SC, et al. (2004) Methylthioadenosine. Int J Biochem Cell Biol 36, 2125-2130.
139. Morgenstern I, Raijmakers MT, Peters WH, et al. (2003) Homocysteine, cysteine, and glutathione in human colonic mucosa: elevated levels of homocysteine in patients with inflammatory bowel disease. Dig Dis Sci 48, 2083-2090.
140. Danese S, Sgambato A, Papa A, et al. (2005) Homocysteine triggers mucosal microvascular activation in inflammatory bowel disease. Am J Gastroenterol 100, 886-895.
141. Papatheodorou L & Weiss N (2007) Vascular oxidant stress and inflammation in hyperhomocysteinemia. Antioxid Redox Signal 9, 1941-1958.
142. Zhang C, Cai Y, Adachi MT, et al. (2001) Homocysteine induces programmed cell death in human vascular endothelial cells through activation of the unfolded protein response. J Biol Chem 276, 35867-35874.
143. Papa A, Scaldaferri F, Danese S, et al. (2008) Vascular involvement in inflammatory bowel disease: pathogenesis and clinical aspects. Dig Dis 26, 149-155.
144. Deban L, Correale C, Vetrano S, et al. (2008) Multiple pathogenic roles of microvasculature in inflammatory bowel disease: a Jack of all trades. Am J Pathol 172, 1457-1466.
145. Lu SC & Mato JM (2008) S-adenosylmethionine in cell growth, apoptosis and liver cancer. J Gastroenterol Hepatol 23, Suppl. 1, S73-S77.