Table of Contents
Journal of Amino Acids
Volume 2016, Article ID 8952520, 13 pages
http://dx.doi.org/10.1155/2016/8952520
Review Article

Tryptophan Biochemistry: Structural, Nutritional, Metabolic, and Medical Aspects in Humans

1Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy
2Department of Pharmacy, University of Pisa, 56126 Pisa, Italy
3Interdepartmental Center of “Nutraceutical Research and Food for Health”, University of Pisa, 56124 Pisa, Italy

Received 7 September 2015; Accepted 6 December 2015

Academic Editor: Arthur Conigrave

Copyright © 2016 Lionella Palego et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. W. C. Rose, “II. The sequence of events leading to the establishment of the amino acid needs of man,” American Journal of Public Health and the Nation's Health, vol. 58, no. 11, pp. 2020–2027, 1968. View at Publisher · View at Google Scholar
  2. A. Frazer and J. G. Hensler, “Serotonin involvement in physiological function and behaviour,” in Basic Neurochemistry: Molecular, Cellular and Medical Aspects, G. J. Siegel, B. W. Agranoff, R. W. Albers et al., Eds., Lippincott-Raven, Philadelphia, Pa, USA, 6th edition, 1999. View at Google Scholar
  3. M. Berger, J. A. Gray, and B. L. Roth, “The expanded biology of serotonin,” Annual Review of Medicine, vol. 60, pp. 355–366, 2009. View at Publisher · View at Google Scholar · View at Scopus
  4. J. A. Gingrich and R. Hen, “Dissecting the role of the serotonin system in neuropsychiatric disorders using knockout mice,” Psychopharmacology, vol. 155, no. 1, pp. 1–10, 2001. View at Publisher · View at Google Scholar
  5. P. M. Whitaker-Azmitia, “Serotonin and brain development: role in human developmental diseases,” Brain Research Bulletin, vol. 56, no. 5, pp. 479–485, 2001. View at Publisher · View at Google Scholar · View at Scopus
  6. G. Giannaccini, L. Betti, L. Palego et al., “The expression of platelet serotonin transporter (SERT) in human obesity,” BMC Neuroscience, vol. 14, article 128, 2013. View at Publisher · View at Google Scholar · View at Scopus
  7. J. I. Hudson and H. G. Pope Jr., “The management of treatment-resistant depression in disorders on the interface of psychiatry and medicine,” Psychiatric Clinics, vol. 19, no. 2, pp. 351–369, 1996. View at Google Scholar
  8. G. Oxenkrug and R. Ratner, “N-Acetylserotonin and aging-associated cognitive impairment and depression,” Aging and Disease, vol. 3, no. 4, pp. 330–338, 2012. View at Google Scholar · View at Scopus
  9. H. M. van Praag and C. Lemus, “Monoamine precursors in the treatment of psychiatric disorders,” in Nutrition and the Brain, R. J. Wurtman and J. J. Wurtman, Eds., pp. 89–139, Raven Press, New York, NY, USA, 1986. View at Google Scholar
  10. D. A. Bender, “Biochemistry of tryptophan in health and disease,” Molecular Aspects of Medicine, vol. 6, no. 2, pp. 101–197, 1983. View at Publisher · View at Google Scholar · View at Scopus
  11. J. Normanly, “Approaching cellular and molecular resolution of auxin biosynthesis and metabolism,” Cold Spring Harbor Perspectives in Biology, vol. 2, no. 1, Article ID a001594, 2010. View at Publisher · View at Google Scholar · View at Scopus
  12. Y. Tao, J.-L. Ferrer, K. Ljung et al., “Rapid synthesis of auxin via a new tryptophan-dependent pathway is required for shade avoidance in plants,” Cell, vol. 133, no. 1, pp. 164–176, 2008. View at Publisher · View at Google Scholar · View at Scopus
  13. M. B. Arnao and J. Hernández-Ruiz, “The physiological function of melatonin in plants,” Plant Signaling and Behavior, vol. 1, no. 3, pp. 89–95, 2006. View at Publisher · View at Google Scholar · View at Scopus
  14. L. Lindemann and M. C. Hoener, “A renaissance in trace amines inspired by a novel GPCR family,” Trends in Pharmacological Sciences, vol. 26, no. 5, pp. 274–281, 2005. View at Publisher · View at Google Scholar · View at Scopus
  15. V. Tzin and G. Galili, “New Insights into the shikimate and aromatic amino acids biosynthesis pathways in plants,” Molecular Plant, vol. 3, no. 6, pp. 956–972, 2010. View at Publisher · View at Google Scholar · View at Scopus
  16. M. C. Mackey, M. Santillán, and N. Yildirim, “Modeling operon dynamics: the tryptophan and lactose operons as paradigms,” Comptes Rendus—Biologies, vol. 327, no. 3, pp. 211–224, 2004. View at Publisher · View at Google Scholar · View at Scopus
  17. G. Xie, N. O. Keyhani, C. A. Bonner, and R. A. Jensen, “Ancient origin of the tryptophan operon and the dynamics of evolutionary change,” Microbiology and Molecular Biology Reviews, vol. 67, no. 3, pp. 303–342, 2003. View at Publisher · View at Google Scholar · View at Scopus
  18. Y. Chen, X. Zhang, W. Wu, Z. Chen, H. Gu, and L.-J. Qu, “Overexpression of the wounding-responsive gene AtMYB15 activates the shikimate pathway in Arabidopsis,” Journal of Integrative Plant Biology, vol. 48, no. 9, pp. 1084–1095, 2006. View at Publisher · View at Google Scholar · View at Scopus
  19. S. Ferrari, R. Galletti, C. Denoux, G. de Lorenzo, F. M. Ausubel, and J. Dewdney, “Resistance to Botrytis cinerea induced in Arabidopsis by elicitors is independent of salicylic acid, ethylene, or jasmonate signaling but requires PHYTOALEXIN DEFICIENT3,” Plant Physiology, vol. 144, no. 1, pp. 367–379, 2007. View at Publisher · View at Google Scholar · View at Scopus
  20. A. J. de Jesus and T. W. Allen, “The role of tryptophan side chains in membrane protein anchoring and hydrophobic mismatch,” Biochimica et Biophysica Acta (BBA)—Biomembranes, vol. 1828, no. 2, pp. 864–876, 2013. View at Publisher · View at Google Scholar · View at Scopus
  21. C. M. Santiveri and M. A. Jiménez, “Tryptophan residues: scarce in proteins but strong stabilizers of β-hairpin peptides,” Biopolymers, vol. 94, no. 6, pp. 779–790, 2010. View at Publisher · View at Google Scholar · View at Scopus
  22. P. Grieco, M. Cai, A. V. Mayorov, D. Trivedi, and V. J. Hruby, “Structure-activity studies of new melanocortin peptides containing an aromatic amino acid at the N-terminal position,” Peptides, vol. 27, no. 2, pp. 472–481, 2006. View at Publisher · View at Google Scholar · View at Scopus
  23. B. Mojsoska and H. Jenssen, “Peptides and peptidomimetics for antimicrobial drug design,” Pharmaceuticals, vol. 8, no. 3, pp. 366–415, 2015. View at Publisher · View at Google Scholar
  24. G. Hrazdina and R. A. Jensen, “Spatial organization of enzymes in plant metabolic pathways,” Annual Review of Plant Physiology and Plant Molecular Biology, vol. 43, no. 1, pp. 241–267, 1991. View at Publisher · View at Google Scholar · View at Scopus
  25. E. R. Radwanski and R. L. Last, “Tryptophan biosynthesis and metabolism: biochemical and molecular genetics,” Plant Cell, vol. 7, no. 7, pp. 921–934, 1995. View at Publisher · View at Google Scholar · View at Scopus
  26. D. M. Richard, M. A. Dawes, C. W. Mathias, A. Acheson, N. Hill-Kapturczak, and D. M. Dougherty, “L-tryptophan: basic metabolic functions, behavioral research and therapeutic indications,” International Journal of Tryptophan Research, vol. 2, no. 1, pp. 45–60, 2009. View at Google Scholar · View at Scopus
  27. World Health Organization, “Protein and amino acid requirements in human nutrition. Report of a joint WHO/FAO/ expert consultation,” WHO Technical Report Series 935, World Health Organization (WHO), Geneva, Switzerland, 2007. View at Google Scholar
  28. D. J. Millward, “The nutritional value of plant-based diets in relation to human amino acid and protein requirements,” Proceedings of the Nutrition Society, vol. 58, no. 2, pp. 249–260, 1999. View at Publisher · View at Google Scholar · View at Scopus
  29. V. R. Young and P. L. Pellett, “Plant proteins in relation to human protein and amino acid nutrition,” American Journal of Clinical Nutrition, vol. 59, no. 5, supplement, pp. 1203S–1212S, 1994. View at Google Scholar · View at Scopus
  30. J. Hegyi, R. A. Schwartz, and V. Hegyi, “Pellagra: dermatitis, dementia, and diarrhea,” International Journal of Dermatology, vol. 43, no. 1, pp. 1–5, 2004. View at Publisher · View at Google Scholar · View at Scopus
  31. P. S. Simmons, J. M. Miles, J. E. Gerich, and M. W. Haymond, “Increased proteolysis. An effect of increases in plasma cortisol within the physiologic range,” The Journal of Clinical Investigation, vol. 73, no. 2, pp. 412–420, 1984. View at Publisher · View at Google Scholar · View at Scopus
  32. L. A. Cynober, “Plasma amino acid levels with a note on membrane transport: characteristics, regulation, and metabolic significance,” Nutrition, vol. 18, no. 9, pp. 761–766, 2002. View at Publisher · View at Google Scholar · View at Scopus
  33. D. Keszthelyi, F. J. Troost, and A. A. M. Masclee, “Understanding the role of tryptophan and serotonin metabolism in gastrointestinal function,” Neurogastroenterology and Motility, vol. 21, no. 12, pp. 1239–1249, 2009. View at Publisher · View at Google Scholar · View at Scopus
  34. R. J. Wurtman and J. D. Fernstrom, “Control of brain monoamine synthesis by diet and plasma amino acids,” The American Journal of Clinical Nutrition, vol. 28, no. 6, pp. 638–647, 1975. View at Google Scholar · View at Scopus
  35. R. J. Wurtman, “Non-nutritional uses of nutrients,” European Journal of Pharmacology, vol. 668, supplement 1, pp. S10–S15, 2011. View at Publisher · View at Google Scholar · View at Scopus
  36. J. D. Fernstrom, “Effects and side effects associated with the non-nutritional use of tryptophan by humans,” Journal of Nutrition, vol. 142, no. 12, pp. 2236S–2244S, 2012. View at Publisher · View at Google Scholar · View at Scopus
  37. Y. Kanai, H. Segawa, K.-I. Miyamoto, H. Uchino, E. Takeda, and H. Endou, “Expression cloning and characterization of a transporter for large neutral amino acids activated by the heavy chain of 4F2 antigen (CD98),” The Journal of Biological Chemistry, vol. 273, no. 37, pp. 23629–23632, 1998. View at Publisher · View at Google Scholar · View at Scopus
  38. J. Chillarón, R. Roca, A. Valencia, A. Zorzano, and M. Palacín, “Heteromeric amino acid transporters: biochemistry, genetics, and physiology,” The American Journal of Physiology—Renal Physiology, vol. 281, no. 6, pp. F995–F1018, 2001. View at Google Scholar · View at Scopus
  39. G. Curzon, J. Friedel, and P. J. Knott, “The effect of fatty acids on the binding of tryptophan to plasma protein,” Nature, vol. 242, no. 5394, pp. 198–200, 1973. View at Publisher · View at Google Scholar · View at Scopus
  40. W. M. Pardridge and G. Fierer, “Transport of tryptophan into brain from the circulating, albumin-bound pool in rats and in rabbits,” Journal of Neurochemistry, vol. 54, no. 3, pp. 971–976, 1990. View at Publisher · View at Google Scholar · View at Scopus
  41. J. P. Ruddick, A. K. Evans, D. J. Nutt, S. L. Lightman, G. A. Rook, and C. A. Lowry, “Tryptophan metabolism in the central nervous system: medical implications,” Expert Reviews in Molecular Medicine, vol. 8, no. 20, pp. 1–27, 2006. View at Google Scholar
  42. D. M. Rosenbaum, S. G. F. Rasmussen, and B. K. Kobilka, “The structure and function of G-protein-coupled receptors,” Nature, vol. 459, no. 7245, pp. 356–363, 2009. View at Publisher · View at Google Scholar · View at Scopus
  43. P. Wellendorph and H. Bräuner-Osborne, “Molecular cloning, expression, and sequence analysis of GPRC6A, a novel family C G-protein-coupled receptor,” Gene, vol. 335, no. 1-2, pp. 37–46, 2004. View at Publisher · View at Google Scholar · View at Scopus
  44. A. D. Conigrave, H. C. Mun, and H. C. Lok, “Aromatic L-amino acids activate the calcium-sensing receptor 1–3,” The Journal of Nutrition, vol. 137, pp. 1524S–1527S, 2007. View at Google Scholar
  45. A. D. Conigrave, H.-C. Mun, and S. C. Brennan, “Physiological significance of L-amino acid sensing by extracellular Ca2+-sensing receptors,” Biochemical Society Transactions, vol. 35, no. 5, pp. 1195–1198, 2007. View at Publisher · View at Google Scholar · View at Scopus
  46. S. Nakajima, T. Hira, and H. Hara, “Calcium-sensing receptor mediates dietary peptide-induced CCK secretion in enteroendocrine STC-1 cells,” Molecular Nutrition and Food Research, vol. 56, no. 5, pp. 753–760, 2012. View at Publisher · View at Google Scholar · View at Scopus
  47. A. M. San Gabriel, “Taste receptors in the gastrointestinal system,” Flavour, vol. 4, article 14, 2015. View at Publisher · View at Google Scholar
  48. S. A. Sakowski, T. J. Geddes, D. M. Thomas, E. Levi, J. S. Hatfield, and D. M. Kuhn, “Differential tissue distribution of tryptophan hydroxylase isoforms 1 and 2 as revealed with monospecific antibodies,” Brain Research, vol. 1085, no. 1, pp. 11–18, 2006. View at Publisher · View at Google Scholar · View at Scopus
  49. M. Boldrini, M. Castagna, I. Nardi, A. Giromella, A. Martini, I. Pampaloni I et al., “Serotonin transporter binding density changes seasonally in the human pineal gland,” in Proceedings of the 42nd Annual Meeting of the American College of Neuropsychopharmacology (ACNP '03), San Juan, Puerto Rico, December 2003.
  50. C. I. Gutiérrez, M. Urbina, F. Obregion, J. Glykys, and L. Lima, “Characterization of tryptophan high affinity transport system in pinealocytes of the rat. Day-night modulation,” Amino Acids, vol. 25, no. 1, pp. 95–105, 2003. View at Publisher · View at Google Scholar · View at Scopus
  51. M. D. Berry, “Mammalian central nervous system trace amines. Pharmacologic amphetamines, physiologic neuromodulators,” Journal of Neurochemistry, vol. 90, no. 2, pp. 257–271, 2004. View at Publisher · View at Google Scholar · View at Scopus
  52. R. Zucchi, G. Chiellini, T. S. Scanlan, and D. K. Grandy, “Trace amine-associated receptors and their ligands,” British Journal of Pharmacology, vol. 149, no. 8, pp. 967–978, 2006. View at Publisher · View at Google Scholar · View at Scopus
  53. L. Lindemann, M. Ebeling, N. A. Kratochwil, J. R. Bunzow, D. K. Grandy, and M. C. Hoener, “Trace amine-associated receptors form structurally and functionally distinct subfamilies of novel G protein-coupled receptors,” Genomics, vol. 85, no. 3, pp. 372–385, 2005. View at Publisher · View at Google Scholar · View at Scopus
  54. O. Kurnasov, L. Jablonski, B. Polanuyer, P. Dorrestein, T. Begley, and A. Osterman, “Aerobic tryptophan degradation pathway in bacteria: novel kynurenine formamidase,” FEMS Microbiology Letters, vol. 227, no. 2, pp. 219–227, 2003. View at Publisher · View at Google Scholar · View at Scopus
  55. Y. Murakami, M. Hoshi, Y. Imamura, Y. Arioka, Y. Yamamoto, and K. Saito, “Remarkable role of indoleamine 2,3-dioxygenase and tryptophan metabolites in infectious diseases: potential role in macrophage-mediated inflammatory diseases,” Mediators of Inflammation, vol. 2013, Article ID 391984, 9 pages, 2013. View at Publisher · View at Google Scholar · View at Scopus
  56. B. M. Campbell, E. Charych, A. W. Lee, and T. Möller, “Kynurenines in CNS disease: regulation by inflammatory cytokines,” Frontiers in Neuroscience, vol. 8, pp. 1–22, 2014. View at Publisher · View at Google Scholar · View at Scopus
  57. A. A.-B. Badawy and M. Evans, “Inhibition of rat liver tryptophan pyrrolase activity and elevation of brain tryptophan concentration by administration of antidepressants,” Biochemical Pharmacology, vol. 30, no. 11, pp. 1211–1216, 1981. View at Publisher · View at Google Scholar · View at Scopus
  58. C. M. Robinson, P. T. Hale, and J. M. Carlin, “The role of IFN-γ and TNF-α-responsive regulatory elements in the synergistic induction of indoleamine dioxygenase,” Journal of Interferon and Cytokine Research, vol. 25, no. 1, pp. 20–30, 2005. View at Publisher · View at Google Scholar · View at Scopus
  59. T. W. Stone, C. M. Forrest, G. M. Mackay, N. Stoy, and L. G. Darlington, “Tryptophan, adenosine, neurodegeneration and neuroprotection,” Metabolic Brain Disease, vol. 22, no. 3-4, pp. 337–352, 2007. View at Publisher · View at Google Scholar · View at Scopus
  60. A. Neumeister, N. Praschak-Rieder, B. Heßelmann et al., “Effects of tryptophan depletion in drug-free depressed patients who responded to total sleep deprivation,” Archives of General Psychiatry, vol. 55, no. 2, pp. 167–172, 1998. View at Publisher · View at Google Scholar · View at Scopus
  61. T. O. C. Kilkens, A. Honig, M. A. van Nieuwenhoven, W. J. Riedel, and R.-J. M. Brummer, “Acute tryptophan depletion affects brain-gut responses in irritable bowel syndrome patients and controls,” Gut, vol. 53, no. 12, pp. 1794–1800, 2004. View at Publisher · View at Google Scholar · View at Scopus
  62. B. Caballero, N. Finer, and R. J. Wurtman, “Plasma amino acids and insulin levels in obesity: response to carbohydrate intake and tryptophan supplements,” Metabolism, vol. 37, no. 7, pp. 672–676, 1988. View at Publisher · View at Google Scholar · View at Scopus
  63. C. R. Markus, C. Firk, C. Gerhardt, J. Kloek, and G. F. Smolders, “Effect of different tryptophan sources on amino acids availability to the brain and mood in healthy volunteers,” Psychopharmacology, vol. 201, no. 1, pp. 107–114, 2008. View at Publisher · View at Google Scholar · View at Scopus
  64. M. C. W. Kroes, G. A. van Wingen, J. Wittwer, M. H. Mohajeri, J. Kloek, and G. Fernández, “Food can lift mood by affecting mood-regulating neurocircuits via a serotonergic mechanism,” NeuroImage, vol. 84, pp. 825–832, 2014. View at Publisher · View at Google Scholar · View at Scopus
  65. M. Ledochowski, B. Widner, C. Murr, B. Sperner-Unterweger, and D. Fuchs, “Fructose malabsorption is associated with decreased plasma tryptophan,” Scandinavian Journal of Gastroenterology, vol. 36, no. 4, pp. 367–371, 2001. View at Publisher · View at Google Scholar · View at Scopus
  66. G. F. Oxenkrug, “Genetic and hormonal regulation of tryptophan-kynurenine metabolism: implications for vascular cognitive impairment, major depressive disorder, and aging,” Annals of the New York Academy of Sciences, vol. 1122, pp. 35–49, 2007. View at Publisher · View at Google Scholar
  67. R. T. Rubin, “Adrenal cortical activity changes in manic-depressive illness. Influence on intermediary metabolism of tryptophan,” Archives of General Psychiatry, vol. 17, no. 6, pp. 671–679, 1967. View at Publisher · View at Google Scholar · View at Scopus
  68. U. Grohmann, F. Fallarino, and P. Puccetti, “Tolerance, DCs and tryptophan: much ado about IDO,” Trends in Immunology, vol. 24, no. 5, pp. 242–248, 2003. View at Publisher · View at Google Scholar · View at Scopus
  69. A. L. Mellor and D. H. Munn, “IDO expression by dendritic cells: tolerance and tryptophan catabolism,” Nature Reviews Immunology, vol. 4, no. 10, pp. 762–774, 2004. View at Publisher · View at Google Scholar · View at Scopus
  70. A. Heitger, “Regulation of expression and function of IDO in human dendritic cells,” Current Medicinal Chemistry, vol. 18, no. 15, pp. 2222–2233, 2011. View at Publisher · View at Google Scholar · View at Scopus
  71. P. Ligam, U. Manuelpillai, E. M. Wallace, and D. Walker, “Localisation of indoleamine 2,3-dioxygenase and kynurenine hydroxylase in the human placenta and decidua: implications for role of the kynurenine pathway in pregnancy,” Placenta, vol. 26, no. 6, pp. 498–504, 2005. View at Publisher · View at Google Scholar · View at Scopus
  72. A. L. Mellor, J. Sivakumar, P. Chandler et al., “Prevention of T cell-driven complement activation and inflammation by tryptophan catabolism during pregnancy,” Nature Immunology, vol. 2, no. 1, pp. 64–68, 2001. View at Publisher · View at Google Scholar · View at Scopus
  73. H. Soliman, M. Mediavilla-Varela, and S. Antonia, “Indoleamine 2,3-dioxygenase is it an immune suppressor?” Cancer Journal, vol. 16, no. 4, pp. 354–359, 2010. View at Publisher · View at Google Scholar · View at Scopus
  74. A.-M. Myint and Y.-K. Kim, “Network beyond IDO in psychiatric disorders: revisiting neurodegeneration hypothesis,” Progress in Neuro-Psychopharmacology and Biological Psychiatry, vol. 48, pp. 304–313, 2014. View at Publisher · View at Google Scholar · View at Scopus
  75. R. Schwarcz, J. P. Bruno, P. J. Muchowski, and H.-Q. Wu, “Kynurenines in the mammalian brain: when physiology meets pathology,” Nature Reviews Neuroscience, vol. 13, no. 7, pp. 465–477, 2012. View at Publisher · View at Google Scholar · View at Scopus
  76. S. J. James, S. Melnyk, S. Jernigan et al., “Metabolic endophenotype and related genotypes are associated with oxidative stress in children with autism,” American Journal of Medical Genetics Part B, vol. 141, no. 8, pp. 947–956, 2006. View at Publisher · View at Google Scholar · View at Scopus
  77. L. Boccuto, C.-F. Chen, A. R. Pittman et al., “Decreased tryptophan metabolism in patients with autism spectrum disorders,” Molecular Autism, vol. 4, no. 1, article 16, 2013. View at Publisher · View at Google Scholar · View at Scopus
  78. S. Nishizawa, C. Benkelfat, S. N. Young et al., “Differences between males and females in rates of serotonin synthesis in human brain,” Proceedings of the National Academy of Sciences of the United States of America, vol. 94, no. 10, pp. 5308–5313, 1997. View at Publisher · View at Google Scholar · View at Scopus
  79. D. Marazziti, A. Rossi, L. Palego et al., “Effect of aging and sex on the [3H]-paroxetine binding to human platelets,” Journal of Affective Disorders, vol. 50, no. 1, pp. 11–15, 1998. View at Publisher · View at Google Scholar · View at Scopus
  80. L. Palego, A. Giromella, M. R. Mazzoni et al., “Gender and age-related variation in adenylyl cyclase activity in the human prefrontal cortex, hippocampus and dorsal raphe nuclei,” Neuroscience Letters, vol. 279, no. 1, pp. 53–56, 2000. View at Publisher · View at Google Scholar · View at Scopus
  81. D. Marazziti, S. Baroni, I. Masala et al., “Impulsivity, gender, and the platelet serotonin transporter in healthy subjects,” Neuropsychiatric Disease and Treatment, vol. 6, no. 1, pp. 9–15, 2010. View at Google Scholar · View at Scopus
  82. C. Hammen, P. A. Brennan, D. Keenan-Miller, N. A. Hazel, and J. M. Najman, “Chronic and acute stress, gender, and serotonin transporter gene-environment interactions predicting depression symptoms in youth,” Journal of Child Psychology and Psychiatry and Allied Disciplines, vol. 51, no. 2, pp. 180–187, 2010. View at Publisher · View at Google Scholar · View at Scopus
  83. N. Goel and T. L. Bale, “Sex differences in the serotonergic influence on the hypothalamic-pituitary-adrenal stress axis,” Endocrinology, vol. 151, no. 4, pp. 1784–1794, 2010. View at Publisher · View at Google Scholar · View at Scopus
  84. W. H. Kaye, “Neurobiology of anorexia and bulimia nervosa,” Physiology and Behavior, vol. 94, no. 1, pp. 121–135, 2008. View at Publisher · View at Google Scholar · View at Scopus
  85. W. H. Kaye, K. A. Gendall, M. H. Fernstrom, J. D. Fernstrom, C. W. McConaha, and T. E. Weltzin, “Effects of acute tryptophan depletion on mood in bulimia nervosa,” Biological Psychiatry, vol. 47, no. 2, pp. 151–157, 2000. View at Publisher · View at Google Scholar · View at Scopus
  86. F. Reimann, G. Tolhurst, and F. M. Gribble, “G-Protein-coupled receptors in intestinal chemosensation,” Cell Metabolism, vol. 15, no. 4, pp. 421–431, 2012. View at Publisher · View at Google Scholar · View at Scopus
  87. D. Narang, S. Tomlinson, A. Holt, D. D. Mousseau, and G. B. Baker, “Trace Amines and their relevance to psychiatry and neurology: a brief overview,” Klinik Psikofarmakoloji Bulteni, vol. 21, no. 1, pp. 73–79, 2011. View at Google Scholar · View at Scopus
  88. M. Nakamura, S. Ueno, A. Sano, and H. Tanabe, “Polymorphisms of the human homologue of the Drosophila white gene are associated with mood and panic disorders,” Molecular Psychiatry, vol. 4, no. 2, pp. 155–162, 1999. View at Publisher · View at Google Scholar · View at Scopus
  89. A. Rotondo, C. Mazzanti, L. Dell'Osso et al., “Catechol O-methyltransferase, serotonin transporter, and tryptophan hydroxylase gene polymorphisms in bipolar disorder patients with and without comorbid panic disorder,” American Journal of Psychiatry, vol. 159, no. 1, pp. 23–29, 2002. View at Publisher · View at Google Scholar · View at Scopus
  90. E. Suviolahti, L. J. Oksanen, M. Öhman et al., “The SLC6A14 gene shows evidence of association with obesity,” The Journal of Clinical Investigation, vol. 112, no. 11, pp. 1762–1772, 2003. View at Publisher · View at Google Scholar · View at Scopus
  91. G. F. Oxenkrug, “Tryptophan metabolism as a new target for the treatment of schizophrenia,” US Psychiatry Review, pp. 38–39, 2007, (Touch Briefings). View at Google Scholar
  92. D. Marazziti, S. Baroni, M. Picchetti, A. Piccinni, S. Silvestri, and L. Dell'Osso, “New developments on the serotonin hypothesis of depression: shunt of tryptophan,” Rivista di Psichiatria, vol. 48, no. 1, pp. 23–34, 2013. View at Google Scholar · View at Scopus
  93. A. Frydman-Marom, M. Rechter, I. Shefler, Y. Bram, D. E. Shalev, and E. Gazit, “Cognitive-performance recovery of Alzheimer's disease model mice by modulation of early soluble amyloidal assemblies,” Angewandte Chemie—International Edition, vol. 48, no. 11, pp. 1981–1986, 2009. View at Publisher · View at Google Scholar · View at Scopus
  94. S. A. Funke and D. Willbold, “Peptides for therapy and diagnosis of Alzheimer's disease,” Current Pharmaceutical Design, vol. 18, no. 6, pp. 755–767, 2012. View at Publisher · View at Google Scholar · View at Scopus
  95. T. W. Stone, N. Stoy, and L. G. Darlington, “An expanding range of targets for kynurenine metabolites of tryptophan,” Trends in Pharmacological Sciences, vol. 34, no. 2, pp. 136–143, 2013. View at Publisher · View at Google Scholar · View at Scopus
  96. D.-Y. Hou, A. J. Muller, M. D. Sharma et al., “Inhibition of indoleamine 2,3-dioxygenase in dendritic cells by stereoisomers of 1-methyl-tryptophan correlates with antitumor responses,” Cancer Research, vol. 67, no. 2, pp. 792–801, 2007. View at Publisher · View at Google Scholar · View at Scopus
  97. C. Granchi, S. Roy, C. Giacomelli et al., “Discovery of N-hydroxyindole-based inhibitors of human lactate dehydrogenase isoform A (LDH-A) as starvation agents against cancer cells,” Journal of Medicinal Chemistry, vol. 54, no. 6, pp. 1599–1612, 2011. View at Publisher · View at Google Scholar · View at Scopus
  98. L. Palego, L. Betti, and G. Giannaccini, “Sulfur metabolism and sulfur-containing amino acids derivatives—part II: autism spectrum disorders, schizophrenia and fibromyalgia,” Biochemical Pharmacology, vol. 4, article 159, 2015. View at Google Scholar
  99. G. A. Evans, “Designer science and the ‘omic’ revolution,” Nature Biotechnology, vol. 18, article 127, 2000. View at Publisher · View at Google Scholar · View at Scopus
  100. L. Atzori, R. Antonucci, L. Barberini, J. L. Griffin, and V. Fanos, “Metabolomics: a new tool for the neonatologist,” Journal of Maternal-Fetal and Neonatal Medicine, vol. 22, no. 3, pp. 50–53, 2009. View at Publisher · View at Google Scholar · View at Scopus