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Nutrition and health relevant regulation of intestinal sulfur amino acid metabolism

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Abstract

Sulfur amino acids (SAA), particularly methionine and cysteine, are critical for the gut to maintain its functions including the digestion, absorption and metabolism of nutrients, the immune surveillance of the intestinal epithelial layer and regulation of the mucosal response to foreign antigens. However, the metabolism of SAA in the gut, specifically the transmethylation of methionine, will result in a net release of homocysteine, which is shown to be associated with cardiovascular disease and stroke. Furthermore, the extensive catabolism of dietary methionine by the intestine or by luminal microbes may result in a decrease in nutritional efficiency. Therefore, the regulation of SAA metabolism in the gut is not only nutritionally relevant, but also relevant to the overall health and well-being. The superiority of dl-2-hydroxy-4-methylthiobutyrate to dl-methionine in decreasing homocysteine production, alleviating stress responses, and reducing the first-pass intestinal metabolism of dietary methionine may provide a promising implication for nutritional strategies to manipulate SAA metabolism and thus to improve the nutrition and health status of animals and perhaps humans.

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Abbreviations

AA:

Amino acids

BCAA:

Branched-chain amino acids

d-AAOX:

d-Amino acid oxidase

d-HADH:

d-2-Hydroxy acid dehydrogenase

dl-HMTB:

dl-2-Hydroxy-4-methylthiobutyrate

dl-MET:

dl-Methionine

l-HAOX:

l-2-Hydroxy acid oxidase

PDV:

Portal drained viscera

SAA:

Sulfur amino acids

References

  • Baker DH (2009) Advances in protein–amino acid nutrition of poultry. Amino Acids 37:29–41

    Article  PubMed  CAS  Google Scholar 

  • Baracos VE (2004) Animal models of amino acid metabolism: a focus on the intestine. J Nutr 134:1656S–1659S

    PubMed  CAS  Google Scholar 

  • Bauchart-Thevret C, Stoll B, Chacko S, Burrin DG (2009a) Sulfur amino acid deficiency upregulates intestinal methionine cycle activity and suppresses epithelial growth in neonatal pigs. Am J Physiol Endocrinol Metab 296:E1239–E1250

    Article  PubMed  CAS  Google Scholar 

  • Bauchart-Thevret C, Stoll B, Burrin DG (2009b) Intestinal metabolism of sulfur amino acids. Nutr Res Rev 22:175–187

    Article  PubMed  CAS  Google Scholar 

  • Bertolo RFP, Pencharz PB, Ball RO (2005) Role of intestinal first-pass metabolism on whole-body amino acid requirements. In: Burrin DG, Mersmann HJ (eds) Biology of metabolism in growing animals. Elsevier, London, pp 127–156

    Chapter  Google Scholar 

  • Blachier F, Mariotti F, Huneau JF, Tome D (2007) Effects of amino acid-derived luminal metabolites on the colonic epithelium and physiopathological consequences. Amino Acids 33:547–562

    Article  PubMed  CAS  Google Scholar 

  • Bos C, Stoll B, Fouillet H, Gaudichon C, Guan X, Grusak MA, Reeds PJ, Tome D, Burrin DG (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

    PubMed  CAS  Google Scholar 

  • Brachet P, Puigserver A (1992) Regional differences for the d-amino acid oxidase-catalysed oxidation of d-methionine in chicken small intestine. Comp Biochem Physiol B 101:509–511

    Article  PubMed  CAS  Google Scholar 

  • Brosnan JT, Brosnan ME (2006) The sulfur-containing amino acids: an overview. J Nutr 136:1636S–1640S

    PubMed  CAS  Google Scholar 

  • Burrin D, Stoll B, Chang X, Yu H, Reeds P (1999) Total parenteral nutrition does not compromise digestion or absorption of dietary protein in neonatal pigs. FASEB J 13:A1024

    Google Scholar 

  • Campbell KCM, Rybak LP, Meech RP, Hughes L (1996) d-Methionine provides excellent protection from cisplatin ototoxicity in the rat. Hear Res 102:90–98

    Article  PubMed  CAS  Google Scholar 

  • Chen LX, Yin YL, Jobgen WS, Jobgen SC, Knabe DA, Hu WX, Wu G (2007) In vitro oxidation of essential amino acids by intestinal mucosal cells of growing pigs. Livest Sci 109:19–23

    Article  Google Scholar 

  • Chen L, Li P, Wang J, Li X, Gao H, Yin Y, Hou Y, Wu G (2009) Catabolism of nutritionally essential amino acids in developing porcine enterocytes. Amino Acids 37:143–152

    Article  PubMed  CAS  Google Scholar 

  • Dangin M, Boirie Y, Garcia-Rodenas C, Gachon P, Fauquant J, Callier P, Ballèvre O, Beaufrère B (2001) The digestion rate of protein is an independent regulating factor of postprandial protein retention. Am J Physiol 280:E340–E348

    CAS  Google Scholar 

  • Di Buono M, Wykes LJ, Cole DE, Ball RO, Pencharz PB (2003) Regulation of sulfur amino acid metabolism in men in response to changes in sulfur amino acid intakes. J Nutr 133:733–739

    PubMed  CAS  Google Scholar 

  • Dibner JJ, Buttin P (2002) Use of organic acids as a model to study the impact of gut microflora on nutrition and metabolism. J Appl Poult Res 11:453–463

    CAS  Google Scholar 

  • Dibner JJ, Ivey FJ (1992) Capacity in the liver of the broiler chick for conversion of supplemental methionine activity to l-methionine. Poult Sci 71:1695–1699

    Google Scholar 

  • 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

    PubMed  CAS  Google Scholar 

  • Fang ZF, Luo J, Qi ZL, Huang FR, Zhao SJ, Liu MY, Jiang SW, Peng J (2009) Effects of 2-hydroxy-4-methylthiobutyrate on portal plasma flow and net portal appearance of amino acids in piglets. Amino Acids 36:501–509

    Article  PubMed  CAS  Google Scholar 

  • Fang ZF, Huang FR, Luo J, Wei HK, Ma LB, Jiang SW, Peng J (2010a) Effects of dl-2-hydroxy-4-methylthiobutyrate on the first-pass intestinal metabolism of dietary methionine and its extraintestinal availability. Br J Nutr. doi:10.1017/S0007114509992169

  • Fang ZF, Luo HF, Wei HK, Huang FR, Qi ZL, Jiang SW, Peng J (2010b) Methionine metabolism in piglets fed DL-methionine or its hydroxy analogue was affected by distribution of enzymes oxidizing these sources to keto-methionine. J Agric Food Chem. doi:10.1021/jf903317x

  • Finkelstein JD (2000) Pathways and regulation of homocysteine metabolism in mammals. Semin Thromb Hemost 26:219–225

    Article  PubMed  CAS  Google Scholar 

  • Garlick PT (2006) Toxicity of methionine in humans. J Nutr 136:1722S–1725S

    PubMed  CAS  Google Scholar 

  • Hiramatsu T, Fukagawa NK, Marchini JS, Cortiella J, Yu YM, Chapman TE, Young VR (1994) Methionine and cysteine kinetics at different intakes of cystine in healthy adult men. Am J Clin Nutr 60:525–533

    PubMed  CAS  Google Scholar 

  • Hogeveen M, Blom HJ, Van Amerongen M, Boogmans B, Van Beynum IM, Van De Bor M (2002) Hyperhomocysteinemia as risk factor for ischemic and hemorrhagic stroke in newborn infants. J Pediatr 141:429–431

    Article  PubMed  Google Scholar 

  • Libao-Mercado AJ, Zhu CL, Cant JP, Lapierre H, Thibault JN, Sève B, Fuller MF, de Lange CF (2009) Dietary and endogenous amino acids are the main contributors to microbial protein in the upper gut of normally nourished pigs. J Nutr 139:1088–1094

    Article  PubMed  CAS  Google Scholar 

  • Lobley GE, Wester TJ, Calder AG, Parker DS, Dibner JJ, Vázquez-Añón (2006) Absorption of 2-hydroxy-4-methylthiobutyrate and conversion to methionine in lambs. J Dairy Sci 89:1072–1080

    Article  PubMed  CAS  Google Scholar 

  • Madara JL (1991) Functional morphology of epithelium of the small intestine. In: Shultz SG (ed) Handbook of physiology: the gastrointestinal system. American Physiological Society, Bethesda, MD, pp 83–120

    Google Scholar 

  • Martín-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

    PubMed  Google Scholar 

  • Matsushita K, Takahashi K, Akiba Y (2007) Effects of adequate or marginal excess of dietary methionine hydroxy analogue free acid on growth performance, edible meat yields and inflammatory response in female broiler chickens. Poult Sci 44:265–272

    Article  CAS  Google Scholar 

  • McCollum MQ, Vázquez-Añón M, Dibner JJ, Webb KE Jr (2000) Absorption of 2-hydroxy-4-(methylthio)butanoic acid by isolated sheep ruminal and omasal epithelia. J Anim Sci 78:1078–1083

    PubMed  CAS  Google Scholar 

  • Printen KJ, Brummel MC, Ei Soon Cho MS, Stegink LD (1979) Utilization of d-methionine during total parenteral nutrition in postsurgical patients. Am J Clin Nutr 32:1200–1205

    PubMed  CAS  Google Scholar 

  • Raguso CA, Ajami AM, Gleason R, Young VR (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

    PubMed  CAS  Google Scholar 

  • Richards JD, Atwell CA, Vázquez-Añón M, Dibner JJ (2005) Comparative in vitro and in vivo absorption of 2-hydroxy-4(methylthio) butanoic acid and methionine in the broiler chicken. Poult Sci 84:1397–1405

    PubMed  CAS  Google Scholar 

  • Riedijk MA, van Goudoever JB (2007) Splanchnic metabolism of ingested amino acids in neonates. Curr Opin Clin Nutr Metab Care 10:58–62

    Article  PubMed  CAS  Google Scholar 

  • Riedijk MA, Stoll B, Chacko S, Schierbeek H, Sunehag AL, van Goudoever JB, Burrin DG (2007) Methionine transmethylation and transsulfuration in the piglet gastrointestinal tract. Proc Natl Acad Sci USA 104:3408–3413

    Article  PubMed  CAS  Google Scholar 

  • Saunderson CL (1985) Comparative metabolism of l-methionine, dl-methionine and dl-2-hydroxy-4-methylthiobutanoic acid by broiler chicks. Br J Nutr 54:621–633

    Article  PubMed  CAS  Google Scholar 

  • Selhub J (1999) Homocysteine metabolism. Annu Rev Nutr 19:217–246

    Article  PubMed  CAS  Google Scholar 

  • Shoveller AK, Brunton JA, Pencharz PB, Ball RO (2003a) The methionine requirement is lower in neonatal piglets fed parenterally than in those fed enterally. J Nutr 133:1390–1397

    PubMed  CAS  Google Scholar 

  • Shoveller AK, Brunton JA, House JD, Pencharz PB, Ball RO (2003b) Dietary cysteine reduces the methionine requirement by an equal proportion in both parenterally and enterally fed piglets. J Nutr 133:4215–4224

    PubMed  CAS  Google Scholar 

  • Shoveller AK, House JD, Brunton JA, Pencharz PB, Ball RO (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

    PubMed  CAS  Google Scholar 

  • Shoveller AK, Stoll B, Ball RO, Burrin DG (2005) Nutritional and functional importance of intestinal sulfur amino acid metabolism. J Nutr 135:1609–1612

    PubMed  CAS  Google Scholar 

  • Stegink LD, Besten LD (1972) Synthesis of cysteine from methionine in normal adult subjects: effect of route of alimentation. Science 178:514–516

    Article  PubMed  CAS  Google Scholar 

  • Stipanuk MH (2004) Sulfur amino acid metabolism: pathways for production and removal of homocysteine and cysteine. Annu Rev Nutr 24:539–577

    Article  PubMed  CAS  Google Scholar 

  • Stoll B, Burrin DG (2006) Measuring splanchnic amino acid metabolism in vivo using stable isotope tracers. J Anim Sci 84:E60–E72

    PubMed  Google Scholar 

  • Stoll B, Henry J, Reeds PJ, Yu H, Jahoor F, Burrin DG (1998) Catabolism dominates the first-pass intestinal metabolism of dietary essential amino acids in milk protein-fed piglets. J Nutr 128:606–614

    PubMed  CAS  Google Scholar 

  • Van Beynum IM, Smeitink JA, den Heijer M, te Poele Pothoff MT, Blom HJ (1999) Hyperhomocysteinemia: a risk factor for ischemic stroke in children. Circulation 99:2070–2072

    PubMed  Google Scholar 

  • van der Schoor SR, van Goudoever JB, Stoll B, Henry JF, Rosenberger JR, Burrin DG, Reeds PJ (2001) The pattern of intestinal substrate oxidation is altered by protein restriction in pigs. Gastroenterology 121:1167–1175

    Article  PubMed  Google Scholar 

  • Van Goudoever JB, Stoll B, Henry JF, Burrin DG, Reeds PJ (2000) Adaptive regulation of intestinal lysine metabolism. Proc Natl Acad Sci USA 97:11620–11625

    Article  PubMed  Google Scholar 

  • van Goudoever JB, van der Schoor SR, Stoll B, Burrin DG, Wattimena D, Schierbeek H, Schaart MW, Riedijk MA, van der Lugt J (2006) Intestinal amino acid metabolism in neonates. Nestle Nutr Workshop Ser Pediatr Program 58:95–102, discussion 102–108

    Google Scholar 

  • van Goudoever JB, Corpeleijn W, Riedijk M, Schaart M, Renes I, van der Schoor S (2008) The impact of enteral insulin-like growth factor 1 and nutrition on gut permeability and amino acid utilization. J Nutr 138:1829S–1833S

    PubMed  Google Scholar 

  • Van Klinken BJ, Einerhand AW, Buller HA, Dekker J (1998) Strategic biochemical analysis of mucins. Anal Biochem 265:103–116

    Article  PubMed  Google Scholar 

  • Velez-Carrasco W, Merkel M, Twiss CO, Smith JD (2008) Dietary methionine effects on plasma homocysteine and HDL metabolism in mice. J Nutr Biochem 19:362–370

    Article  PubMed  CAS  Google Scholar 

  • Walter A, Gutknecht J (1984) Monocarboxylic acid permeation through lipid bilayer membranes. J Membr Biol 77:255–264

    Article  PubMed  CAS  Google Scholar 

  • Wang WW, Qiao SY, Li DF (2009) Amino acids and gut function. Amino Acids 37:105–110

    Article  PubMed  CAS  Google Scholar 

  • Wilson RH, Leibholz J (1981) Digestion in the pig between 7 and 35 d of age. 2. The digestion of dry matter and the pH of digesta in pigs given milk and soya-bean proteins. Br J Nutr 45:321–336

    Article  PubMed  CAS  Google Scholar 

  • Windmueller HG (1982) Glutamine utilization by the small intestine. Adv Enzymol 53:201–237

    PubMed  CAS  Google Scholar 

  • Wu G (1998) Intestinal mucosa amino acid metabolism. J Nutr 128:1249–1252

    PubMed  CAS  Google Scholar 

  • Wu G (2009) Amino acids: metabolism, functions, and nutrition. Amino Acids 37:1–17

    Article  PubMed  CAS  Google Scholar 

  • Wu G, Knabe DA, Flynn NE (2005) Amino acid metabolism in the small intestine: biochemical bases and nutritional significance. In: Burrin DG, Mersmann HJ (eds) Biology of metabolism in growing animals. Elsevier, London, pp 107–126

    Chapter  Google Scholar 

  • Xie M, Hou SS, Huang W, Fan HP (2007) Effect of excess methionine and methionine hydroxy analogue on growth performance and plasma homocysteine of growing Pekin ducks. Poult Sci 86:1995–1999

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by the National Natural Science Foundation of China (30901042), the Program for Changjiang Scholars and Innovative Research Team in the University (IRTO555), and the Key Project of Sichuan Provincial Education Department (00924100). The authors thank graduate students, technicians, and colleagues for their important contributions to the work described in this article.

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Authors and Affiliations

  1. Key Laboratory for Animal Disease Resistance Nutrition of the Ministry of Education of China, Animal Nutrition Institute, Sichuan Agricultural University, Ya’an, 625014, People’s Republic of China

    Zhengfeng Fang, Gang Tian, Bing Yu, Yan Lin, Biquan Zhu, Gang Jia, Keying Zhang, Daiwen Chen & De Wu

  2. Institute of Subtropical Agriculture, The Chinese Academy of Sciences, Changsha, 410128, People’s Republic of China

    Kang Yao & Zhihong Sun

  3. College of Life Science and Technology, Sichuan Agricultural University, Ya’an, 625014, People’s Republic of China

    Xiaoling Zhang

  4. Department of Feed Science, Wuhan Polytechnic University, Wuhan, 430023, People’s Republic of China

    Shengjun Zhao

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  1. Zhengfeng Fang
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  2. Kang Yao
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Correspondence to De Wu.

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Fang, Z., Yao, K., Zhang, X. et al. Nutrition and health relevant regulation of intestinal sulfur amino acid metabolism. Amino Acids 39, 633–640 (2010). https://doi.org/10.1007/s00726-010-0502-x

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