Roles of sulfur-containing amino acids in gastrointestinal physiology and pathophysiology

Métayer S, Seiliez I, Collin A, Duchêne S, Mercier Y, Geraert PA, et al. Mechanisms through which sulfur amino acids control protein metabolism and oxidative status. J Nutr Biochem 2008; 19(4): 207–15.

Shoveller AK, Stoll B, Ball RO, Burrin DG. Nutritional and functional importance of intestinal sulfur amino acid metabolism. J Nutr 2005; 135(7): 1609–12.

Fang ZF, Luo J, Qi ZL, Huang FR, Zhao SJ, Liu MY, et al. Effects of 2-hydroxy-4-methylthiobutyrate on portal plasma flow and net portal appearance of amino acids in piglets. Amino Acids 2009; 36(3): 501–9.

Finkelstein JD. Pathways and regulation of homocysteine metabolism in mammals. Semin Thromb Hemost 2000; 26(3): 219–25.

Bauchart-Thevret C, Stoll B, Chacko S, Burrin DG. Sulfur amino acid deficiency upregulates intestinal methionine cycle activity and suppresses epithelial growth in neonatal pigs. Am J Physiol Endocrinol Metab 2009; 296(6): E1239–50.

Bauchart-Thevret C, Stoll B, Burrin DG. Intestinal metabolism of sulfur amino acids. Nutr Res Rev 2009; 22(2): 175–87.

Finkelstein JD. Methionine metabolism in mammals. J Nutr Biochem 1990; 1(5): 228–37.

Zingg JM, Jones PA. Genetic and epigenetic aspects of DNA methylation on genome expression, evolution, mutation and carcinogenesis. Carcinogenesis 1997; 18(5): 869–82.

Kim YI. Nutritional epigenetics: impact of folate deficiency on DNA methylation and colon cancer susceptibility. J Nutr 2005; 135(11): 2703−9.

Fang Z, Yao K, Zhang X, Zhao S, Sun Z, Tian G, et al. Nutrition and health relevant regulation of intestinal sulfur amino acid metabolism. Amino Acids 2010; 39(3): 633−40. 

Škovierová H, Vidomanová E, Mahmood S, Sopková J, Drgová A, Červeňová T, et al. The Molecular and Cellular Effect of Homocysteine Metabolism Imbalance on Human Health. Int J Mol Sci 2016; 17(10): pii: E1733.

Givvimani S, Munjal C, Narayanan N, Aqil F, Tyagi G, Metreveli N, et al. Hyperhomocysteinemia decreases intestinal motility leading to constipation. Am J Physiol Gastrointest Liver Physiol 2012; 303(3): G281–90.

Cao HX, Gao CM, Takezaki T, Wu JZ, Ding JH, Liu YT, et al. Genetic polymorphisms of methylenetetrahydrofolate reductase and susceptibility to colorectal cancer. Asian Pac J Cancer Prev 2008; 9(2): 203–8.

Munjal C, Givvimani S, Qipshidze N, Tyagi N, Falcone JC, Tyagi SC. Mesenteric vascular remodeling in hyperhomocysteinemia. Mol Cell Biochem 2011; 348(1−2): 99–108.

Stipanuk MH. Sulfur amino acid metabolism: pathways for production and removal of homocysteine and cysteine. Annu Rev Nutr 2004; 24: 539−77.

Jones DP. Redox potential of GSH/GSSG couple: assay and biological significance. Methods Enzymol 2002; 348: 93–112. 

Aw TY. Molecular and cellular responses to oxidative stress and changes in oxidation–reduction imbalance in the intestine. Am J Clin Nutr 1999; 70(4): 557–65.

Deplancke B, Gaskins HR. Redox control of the transsulfuration and glutathione biosynthesis pathways. Curr Opin Clin Nutr Metab Care 2002; 5(1): 85–92.

Jones DP. Extracellular redox state: refining the definition of oxidative stress in aging. Rejuvenation Res 2006; 9(2): 169–81.

Abbasoğlu L, Kalaz EB, Soluk-Tekkeşin M, Olgaç V, Doğru-Abbasoğlu S, Uysal M. Beneficial effects of taurine and carnosine in experimental ischemia/reperfusion injury in testis. Pediatr Surg Int 2012; 28(11): 1125–31.

Haj B, Sukhotnik I, Shaoul R, Pollak Y, Coran AG, Bitterman A, et al. Effect of ozone on intestinal recovery following intestinal ischemia-reperfusion injury in a rat. Pediatr Surg Int 2014; 30(2); 181–8.

Sukhotnik I, Slijper N, Pollak Y, Chemodanov E, Shaoul R, Coran AG, et al. Parenteral omega-3 fatty acids (Omegaven) modulate intestinal recovery after intestinal ischemia-reperfusion in a rat model. J Pediatr Surg 2011; 46(7): 1353–60.

Schaffer SW, Jong CJ, Ito T, Azuma J. Effect of taurine on ischemia-reperfusion injury. Amino Acids 2014; 46(1): 21–30.

Redmond HP, Stapleton PP, Neary P, Bouchier-Hayes D. Immunonutrition: the role of Taurine. Nutrition 1998; 14(7−8): 599–604.

Rodrigues CM, Ma X, Linehan-Stieers C, Fan G, Kren BT. Ursodeoxycholic acid prevents cytochrome c release in apoptosis by inhibiting mitochondrial membrane depolarization and channel formation. Cell Death Differ 1999; 6(9): 842–54.

Garcia RA, Stipanuk MH. The splanchnic organs, liver and kidney have unique roles in the metabolism of sulfur amino acids and their metabolites in rats. J Nutr 1992; 122(8): 1693–701.

Young VR, Borgonha S. Nitrogen and amino acid requirements: the Massachusetts Institute of Technology amino acid requirement pattern. J Nutr 2000; 130(7): 1841S–9S.

Chiang PK, Gordon RK, Tal J, Zeng GC, Doctor BP, Pardhasaradhi K, et al. S-Adenosylmethionine and methylation. FASEB J 1996; 10(4): 471–80.

Spillmann M, Fava M. S-adenosyl-methionine (ademethionine) in psychiatric disorders. CNS Drugs 1996; 6(6): 416–25.

Tang X, Keenan MM, Wu J, Lin CA, Dubois L, Thompson JW, et al. Comprehensive profiling of amino acid response uncovers unique methioninedeprived response dependent on intact creatine biosynthesis. PLoS Genet 2015; 11(4): e1005158.

Vogt W. Oxidation of methionyl residues in proteins: tools, targets, and reversal. Free Radic Biol Med 1995; 18(1): 93–105.

Shoveller AK, Brunton JA, Pencharz PB, Ball RO. The methionine requirement is lower in neonatal piglets fed parenterally than in those fed enterally. J Nutr 2003; 133(5): 1390–7.

Mato JM, Corrales FJ, Lu SC, Avila MA. S-adenosylmethionine: a control switch that regulates liver function. FASEB J 2002; 16(1): 15–26.

Jahoor F, Jackson A, Gazzard B, Philips G, Sharpstone D, Frazer ME, et al. Erythrocyte glutathione deficiency in symptom-free HIV infection is associated with decreased synthesis rate. Am J Physiol Endocrinol Metab 1999; 276(1): E205–11.

Tappaz ML. Taurine biosynthetic enzymes and taurine transporter: molecular identification and regulations. Neurochem Res 2004; 29(1): 83–96.

Zeissig S, Bojarski C, Buergel N, Mankertz J, Zeitz M, Fromm M, et al. Downregulation of epithelial apoptosis and barrier repair in active Crohn's disease by tumour necrosis factor alpha antibody treatment. Gut 2004; 53(9): 1295–302.

Baniyash M. Chronic inflammation, immunosuppression and cancer: new insights and outlook. Semin Cancer Biol 2006; 16(1): 80−8.

Li TW, Yang H, Peng H, Xia M, Mato JM, Lu SC. Effects of S-adenosylmethionine and methylthioadenosine on inflammation-induced colon cancer in mice. Carcinogenesis 2012; 33(2): 427−35.

de Vogel S, Dindore V, van Engeland M, Goldbohm RA, van den Brandt PA, Weijenberg MP. Dietary folate, methionine, riboflavin, and vitamin B-6 and risk of sporadic colorectal cancer. J Nutr 2008; 138(12): 2372−8.

Cavuoto P, Fenech MF. A review of methionine dependency and the role of methionine restriction in cancer growth control and life-span extension. Cancer Treat Rev 2012; 38(6): 726−36.

Sunden SL, Renduchintala MS, Park EI, Miklasz SD, Garrow TA. Betaine–homocysteine methyltransferase expression in porcine and human tissues and chromosomal localization of the human gene. Arch Biochem Biophys 1997; 345(1): 171–4.

Ganguly P, Alam SF. Role of homocysteine in the development of cardiovascular disease. Nutr J 2015; 14: 6.

McCully KS. Homocysteine and vascular disease. Nat Med 1996; 2(4): 386–9.

Ueland PM, Refsum H. Plasma homocysteine, a risk factor for vascular disease: Plasma levels in health, disease, and drug therapy. J Lab Clin Med 1989; 114(5): 473–501.

Jardine MJ, Kang A, Zoungas S, Navaneethan SD, Ninomiya T, Nigwekar SU, et al. The effect of folic acid based homocysteine lowering on cardiovascular events in people with kidney disease: Systematic review and meta-analysis. BMJ 2012; 344: e3533.

Suliman ME, Lindholm B, Bárány P, Qureshi AR, Stenvinkel P. Homocysteine-lowering is not a primary target for cardiovascular disease prevention in chronic kidney disease patients. Semin Dial 2007; 20(6): 523−9.

Jamison RL, Hartigan P, Kaufman JS, Goldfarb DS, Warren SR, Guarino PD, et al. Veterans Affairs Site Investigators Effect of homocysteine lowering on mortality and vascular disease in advanced chronic kidney disease and end-stage renal disease: A randomized controlled trial. JAMA 2007; 298(10): 1163–70.

Chao MC, Hu SL, Hsu HS, Davidson LE, Lin CH, Li CI, et al. Serum homocysteine level is positively associated with chronic kidney disease in a Taiwan Chinese population. J Nephrol 2014; 27(3): 299–305.

Chico A, Pérez A, Córdoba A, Arcelús R,Carreras G, de Leiva A, et al. Plasma homocysteine is related to albumin excretion rate in patients with diabetes mellitus: A new link between diabetic nephropathy and cardiovascular disease? Diabetologia 1998; 41(6): 684–93.

Stojanović M, Šćepanović Lj, Mitrović D, Šćepanović V, Stojanović T, Stojković M, et al. Rat duodenal motility in vitro: procinetic effects of D,L-homocysteine thiolactone and modulation of nitric oxide mediated inhibition. Arch Biol Sci 2013; 65(4): 1323−30.

Stojanović M, Šćepanović L, Hrnčić D, Rašić-Marković A, Djuric D, Stanojlović O. Multidisciplinary approach to nitric oxide signaling: Focus on the gastrointestinal and the central nervous system. Vojnosanit Pregl 2015; 72(7): 619−24.

Hierholzer C, Kalff JC, Billiar TR, Bauer AJ, Tweardy DJ, Harbrecht BG. Induced nitric oxide promotes intestinal inflammation following hemorrhagic shock. Am J Physiol Gastrointest Liver Physiol 2004; 286(2): G225–33.

Garg P, Vijay-Kumar M, Wang L, Gewirtz AT, Merlin D, Sitaraman SV. Matrix metalloproteinase-9-mediated tissue injury overrides the protective effect of matrix metalloproteinase-2 during colitis. Am J Physiol Gastrointest Liver Physiol 2009; 296(2): G175–84.

Stojanović M, Šćepanović Lj, Bosnić O, Mitrović D, Jozanov-Stankov O, Šćepanović V, et al. Effects of the acute administration of D,L-homocysteine thiolactone on antioxidative status of rat intestine and liver. Acta Vet Beograd 2016; 66(1): 26−36.

Stojanović M, Šćepanović Lj, Mitrović D, Šćepanović V, Šćepanović R, Đuric M, et al. Different pathways involved in stimulatory effects of homocysteine on rat duodenal smooth muscle. Acta Vet Beograd 2017; 67(2): 254−70.

Warnecke PM, Bestor TH. Cytosine methylation and human cancer. Curr Opin Oncol 2000; 12(1): 68–73.

Kato I, Dnistrian AM, Schwartz M, Toniolo P, Koenig K, Shore RE, et al. Serum folate, homocysteine and colorectal cancer risk in women: A nested case-control study. Br J Cancer 1999; 79(11−12): 1917–22.

Fruchart JC, Nierman MC, Stroes ES, Kastelein JJ, Duriez P. New risk factors for atherosclerosis and patient risk assessment. Circulation 2004; 109(23 Suppl. 1): III15–9.

Danese S, Sgambato A, Papa A, Scaldaferri F, Pola R, Sans M, et al. Homocysteine triggers mucosal microvascular activation in inflammatory bowel disease. Am J Gastroenterol 2005; 100(4): 886–95.

Oussalah A, Gueant JL, Peyrin-Biroulet L. Meta-analysis: hyperhomocysteinaemia in inflammatory bowel diseases. Aliment Pharmacol Ther 2011; 34(10): 1173–84.

Guerin A, Pannier B, London G. Atherosclerosis versus arterial stiffness in advanced renal failure. Adv Cardiol 2007; 44: 187–98.

Koutroubakis IE. Therapy insight: vascular complications in patients with inflammatory bowel disease. Nat Clin Pract Gastroenterol Hepatol 2005; 2(6): 266–72.

Mahmud N, Molloy A, McPartlin J, Corbally R, Whitehead AS, Scott JM, et al. Increased prevalence of methylenetetrahydrofolate reductase C677T variant in patients with inflammatory bowel disease, and its clinical implications. Gut 1999; 45(3): 389–94.

Williams HR, Willsmore JD, Cox IJ, Walker DG, Cobbold JF, Taylor-Robinson SD, et al. Serum metabolic profiling in inflammatory bowel disease. Dig Dis Sci 2012; 57(8): 2157–65.

Bjerrum JT, Nielsen OH, Hao F, Tang H, Nicholson JK, Wang Y, et al. Metabonomics in ulcerative colitis: diagnostics, biomarker identification, and insight into the pathophysiology. J Proteome Res 2010; 9(2): 954–62.

Cresenzi CL, Lee JI, Stipanuk MH. Cysteine is the metabolic signal responsible for dietary regulation of hepatic cysteine dioxygenase and glutamate cysteine ligase in intact rats. J Nutr 2003; 133(9): 2697‒702.

Micovic Z, Stamenkovic A, Nikolic T, Stojanovic M, Scepanovic Lj, Hadzibegovic A, et al. The effects of subchronic methionine overload administered alone or simultaneously with L-cysteine or N-acetyl-L-cysteine on body weight, homocysteine levels and biochemical parameters in the blood of male wistar rats. Ser J Exp Clin Res 2016; 17(3): 215‒23.

Go YM, Jones DP. Cysteine/cystine redox signaling in cardiovascular disease. Free Radic Biol Med 2011; 50(4): 495‒509.

Jones DP, Go YM, Anderson CL, Ziegler TR, Kinkade JM Jr, Kirlin WG. Cysteine/cystine couple is a newly recognized node in the circuitry for biologic redox signaling and control. FASEB J 2004; 18(11): 1246‒8.

Kumar P, Maurya PK. L-cysteine efflux in erythrocytes as a function of human age: correlation with reduced glutathione and total anti-oxidant potential. Rejuvenation Res 2013; 16(3): 179‒84.

Yin J, Ren W, Yang G, Duan J, Huang X, Fang R, et al. L-Cysteine metabolism and its nutritional implications. Mol Nutr Food Res 2016; 60(1): 134‒46.

Jones DP, Park Y, Gletsu-Miller N, Liang Y, Yu T, Accardi CJ, et al. Dietary sulfur amino acid effects on fasting plasma cysteine/cystine redox potential in humans. Nutrition 2011; 27(2): 199‒205.

Jonas CR, Ziegler TR, Gu LH, Jones DP. Extracellular thiol/disulfide redox state affects proliferation rate in a human colon carcinoma (Caco2) cell line. Free Radic Biol Med 2002; 33(11): 1499–506.

Noda T, Iwakiri R, Fujimoto K, Aw TY. Induction of mild intracellular redox imbalance inhibits proliferation of CaCo-2 cells. FASEB J 2001; 15(12): 2131–9.

Wijtten PJ, van der Meulen JV, Verstegen MW. Intestinal barrier function and absorption in pigs after weaning: a review. Br J Nutr 2011; 105(7): 967–81.

Blikslager AT, Moeser AJ, Gookin JL, Jones SL, Odle J. Restoration of barrier function in injured intestinal mucosa. Physiol Rev 2007; 87(2): 545–64. 

Oz HS, Chen TS, Nagasawa H. Comparative efficacies of 2 cysteine prodrugs and a glutathione delivery agent in a colitis model. Transl Res 2007; 150(2): 122–9. 

Oz HS, Chen TS, McClain CJ, de Villiers WJ. Antioxidants as novel therapy in a murine model of colitis. J Nutr Biochem 2005; 16(5): 297–304.

Liu Y, Chen F, Odle J, Lin X, Jacobi SK, Zhu H, et al. Fish oil enhances intestinal integrity and inhibits TLR4 and NOD2 signaling pathways in weaned pigs after LPS challenge. J Nutr 2012; 142(11): 2017–24. 

Kim CJ, Kovacs-Nolan J, Yang C, Archbold T, Fan MZ, Mine Y. L-cysteine supplementation attenuates local inflammation and restores gut homeostasis in a porcine model of colitis. Biochem Biophys Acta 2009; 1790(10): 1161–9.

Rushworth GF, Megson IL. Existing and potential therapeutic uses for N-acetylcysteine: the need for conversion to intracellular glutathione for antioxidant benefits. Pharmacol Ther 2014; 141(2): 150‒

Atalay F, Odabasoglu F, Halici M, Cadirci E, Aydin O, Halici Z, et al. N-Acetyl Cysteine Has Both Gastro-Protective and Anti-Inflammatory Effects in Experimental Rat Models: Its Gastro-Protective Effect Is Related to Its In Vivo and In Vitro Antioxidant Properties. J Cell Biochem 2016; 117(2): 308‒

Huxtable RJ. Physiological actions of taurine. Physiol Rev 1992; 72(1): 101‒

Oudit GY, Trivieri MG, Khaper N, Husain T, Wilson GJ, Liu P, et al. Taurine supplementation reduces oxidative stress and improves cardiovascular function in an iron-overload murine model. Circulation 2004; 109(15): 1877‒

Schaffer S, Azuma J, Takahashi K, Mozaffari M. Why is taurine cytoprotective? Adv Exp Med Biol 2003; 526: 307–21.

Sukhotnik I, Aranovich I, Ben Shahar Y, Bitterman N, Pollak Y, Berkowitz D, et al. Effect of taurine on intestinal recovery following intestinal ischemia-reperfusion injury in a rat. Pediatr Surg Int 2016; 32(2): 161‒

Balkan J, Kanbağli O, Hatipoğlu A, Kücük M, Cevikbaş U, Aykaç-Toker G, et al. Improving effect of dietary taurine supplementation on the oxidative stress and lipid levels in the plasma, liver and aorta of rabbits fed on a high-cholesterol diet. Biosci Biotechnol Biochem 2002; 66(8): 1755‒

Hansen SH. The role of taurine in diabetes and the development of diabetic complications. Diabetes Metab Res Rev 2001; 17(5): 330–46.

Franconi F, Di Leo MA, Bennardini F, Ghirlanda G. Is taurine beneficial in reducing risk factors for diabetes mellitus? Neurochem Res 2004; 29(1): 143–50.

Doğru-Abbasoğlu S, Kanbağli O, Balkan J, Cevikbaş U, Aykaç-Toker G, Uysal M. The protective effect of taurine against thioacetamide hepatotoxicity of rats. Hum Exp Toxicol 2001; 20(1): 23–7.

Cetiner M, Sener G, Sehirli AO, Ekşioğlu-Demiralp E, Ercan F, Sirvanci S, et al. Taurine protects against methotrexate-induced toxicity and inhibits leucocyte death. Toxicol Appl Pharmacol 2005; 209(1): 39–50.

Oriyanhan W, Yamazaki K, Miwa S, Takaba K, Ikeda T, Komeda M. Taurine prevents myocardial ischemia/reperfusion-induced oxidative stress and apoptosis in prolonged hypothermic rat heart preservation. Heart Vessels 2005; 20(6): 278–85.

Casey RG, Gang C, Joyce M, Bouchier-Heyes DJ. Taurine attenuates acute hyperglycaemia-induced endothelial cell apoptosis, leucocyte–endothelial cell interactions and cardiac dysfunction. J Vasc Res 2007; 44(1): 31–9.

Giriş M, Depboylu B, Doğru-Abbasoğlu S, Erbil Y, Olgaç V, Aliş H, et al. Effect of taurine on oxidative stress and apoptosis-related protein expression in trinitrobenzenesulphonic acid-induced colitis. Clin Exp Immunol 2008; 152(1): 102‒10.

Joo K, Lee Y, Choi D, Han J, Hong S, Kim YM, et al. An anti-inflammatory mechanism of taurine conjugated 5-aminosalicylic acid against experimental colitis: taurine chloramine potentiates inhibitory effect of 5-aminosalicylic acid on IL-1beta-mediated NFkappaB activation. Eur J Pharmacol 2009; 618(1‒3): 91‒7.

Zhao Z, Satsu H, Fujisawa M, Hori M, Ishimoto Y, Totsuka M, et al. Attenuation by dietary taurine of dextran sulfate sodium-induced colitis in mice and of THP-1-induced damage to intestinal Caco-2 cell monolayers. Amino Acids 2008; 35(1): 217‒24.

Zhang X, Tu S, Wang Y, Xu B, Wan F. Mechanism of taurine-induced apoptosis in human colon cancer cells. Acta Biochim Biophys Sin (Shanghai) 2014; 46(4): 261‒72.