Free-radical scavenging by tryptophan and its metabolites through electron transfer based processes

  • Adriana Pérez-González
  • Juan Raúl Alvarez-Idaboy
  • Annia Galano
Original Paper

Abstract

Free-radical scavenging by tryptophan and eight of its metabolites through electron transfer was investigated in aqueous solution at physiological pH, using density functional theory and the Marcus theory. A test set of 30 free radicals was employed. Thermochemical and kinetic data on the corresponding reactions are provided here for the first time. Two different pathways were found to be the most important: sequential proton loss electron transfer (SPLET) and sequential double proton loss electron transfer (SdPLET). Based on kinetic analyses, it is predicted that the tryptophan metabolites kynurenic acid and xanthurenic acid are the best free-radical scavengers among the tested compounds; they were estimated to be at least 24 and 12 times more efficient than Trolox for scavenging OOH. These findings are in line with previous reports suggesting that the antioxidant activity that has been attributed to tryptophan is actually due to its metabolites, and they demonstrate the particular importance of phenolic metabolites to such activity.

Graphical Abstract

Kynurenic acid (KNA) and xanthurenic acid (XNA) are the major contributors to the free-radical scavenging activity of tryptophan

Keywords

Free-radical scavenger Rate constants Single electron transfer 

Supplementary material

894_2015_2758_MOESM1_ESM.pdf (665 kb)
ESM 1(PDF 664 kb)

References

  1. 1.
    Wang J, Li JZ, Lu AX et al (2014) Anticancer effect of salidroside on A549 lung cancer cells through inhibition of oxidative stress and phospho-p38 expression. Oncol Lett 7:1159–1164Google Scholar
  2. 2.
    Granados-Principal S, El-Azem N, Pamplona R et al (2014) Hydroxytyrosol ameliorates oxidative stress and mitochondrial dysfunction in doxorubicin-induced cardiotoxicity in rats with breast cancer. Biochem Pharmacol 90:25–33CrossRefGoogle Scholar
  3. 3.
    Tekiner-Gulbas B, Westwell AD, Suzen S (2013) Oxidative stress in carcinogenesis: new synthetic compounds with dual effects upon free radicals and cancer. Curr Med Chem 20:4451–4459CrossRefGoogle Scholar
  4. 4.
    Knekt P, Reunanen A, Takkunen H et al (1994) Body iron stores and risk of cancer. Int J Cancer 56:379–382CrossRefGoogle Scholar
  5. 5.
    Al-Aubaidy HA, Jelinek HF (2014) Oxidative stress and triglycerides as predictors of subclinical atherosclerosis in prediabetes. Redox Rep 19:87–91CrossRefGoogle Scholar
  6. 6.
    Şerban C, Drǎgan S (2014) The relationship between inflammatory and oxidative stress biomarkers, atherosclerosis and rheumatic diseases. Curr Pharm Design 20:585–600CrossRefGoogle Scholar
  7. 7.
    Zampetaki A, Dudek K, Mayr M (2013) Oxidative stress in atherosclerosis: the role of microRNAs in arterial remodeling. Free Radic Biol Med 64:69–77CrossRefGoogle Scholar
  8. 8.
    Panasenko OM, Vol’nova TV, Azizova OA et al (1991) Free radical modification of lipoproteins and cholesterol accumulation in cells upon atherosclerosis. Free Radic Biol Med 10:137–148CrossRefGoogle Scholar
  9. 9.
    Rosini M, Simoni E, Milelli A et al (2014) Oxidative stress in Alzheimer’s disease: are we connecting the dots? J Med Chem 57:2821–2831Google Scholar
  10. 10.
    Turunc Bayrakdar E, Uyanikgil Y, Kanit L et al (2014) Nicotinamide treatment reduces the levels of oxidative stress, apoptosis, and PARP-1 activity in Aβ(1–42)-induced rat model of Alzheimer’s disease. Free Radic Res 48:146–158CrossRefGoogle Scholar
  11. 11.
    Fay DS, Fluet A, Johnson CJ et al (1998) In vivo aggregation of β-amyloid peptide variants. J Neurochem 71:1616–1625CrossRefGoogle Scholar
  12. 12.
    Butterfield DA (1997) β-Amyloid-associated free radical oxidative stress and neurotoxicity: implications for Alzheimer’s disease. Chem Res Toxicol 10:495–506Google Scholar
  13. 13.
    Hensley K, Carney JM, Mattson MP et al (1994) A model for β-amyloid aggregation and neurotoxicity based on free radical generation by the peptide: relevance to Alzheimer disease. Proc Natl Acad Sci USA 91:3270–3274Google Scholar
  14. 14.
    Matsuda M, Shimomura I (2014) Roles of adiponectin and oxidative stress in obesity-associated metabolic and cardiovascular diseases. Rev Endocr Metab Disord 15:1–10CrossRefGoogle Scholar
  15. 15.
    Eren E, Ellidag HY, Cekin Y et al (2014) Heart valve disease: the role of calcidiol deficiency, elevated parathyroid hormone levels and oxidative stress in mitral and aortic valve insufficiency. Redox Rep 19:34–39CrossRefGoogle Scholar
  16. 16.
    Stephens NG, Parsons A, Schofield PM et al (1996) Randomised controlled trial of vitamin E in patients with coronary disease: Cambridge Heart Antioxidant Study (CHAOS). Lancet 347:781–786CrossRefGoogle Scholar
  17. 17.
    Street DA, Comstock GW, Salkeld RM et al (1994) Serum antioxidants and myocardial infarction: are low levels of carotenoids and α-tocopherol risk factors for myocardial infarction? Circulation 90:1154–1161Google Scholar
  18. 18.
    Salonen JT, Nyyssönen K, Korpela H et al (1992) High stored iron levels are associated with excess risk of myocardial infarction in Eastern Finnish men. Circulation 86:803–811Google Scholar
  19. 19.
    Ames BN, Cathcart R, Schwiers E et al (1981) Uric acid provides an antioxidant defense in humans against oxidant- and radical-caused aging and cancer: a hypothesis. Proc Natl Acad Sci USA 78:6858–6862Google Scholar
  20. 20.
    Stocker R, Yamamoto Y, McDonagh AF et al (1987) Bilirubin is an antioxidant of possible physiological importance. Science 235:1043–1046CrossRefGoogle Scholar
  21. 21.
    DeLange RJ, Glazer AN (1989) Phycoerythrin fluorescence-based assay for peroxy radicals: a screen for biologically relevant protective agents. Anal Biochem 177:300–306CrossRefGoogle Scholar
  22. 22.
    Richard DM, Dawes MA, Mathias CW et al (2009) L-Tryptophan: basic metabolic functions, behavioral research and therapeutic indications. Int J Tryptophan Res 2:45–60Google Scholar
  23. 23.
    Bravo R, Matito S, Cubero J et al (2013) Tryptophan-enriched cereal intake improves nocturnal sleep, melatonin, serotonin, and total antioxidant capacity levels and mood in elderly humans. Age 35:1277–1285CrossRefGoogle Scholar
  24. 24.
    Jiang Y, Ng TB, Wang CR et al (2010) First isolation of tryptophan from edible lotus (Nelumbo nucifera Gaertn) rhizomes and demonstration of its antioxidant effects. Int J Food Sci Nutr 61:346–356Google Scholar
  25. 25.
    Bitzer-Quintero OK, Dávalos-Marín AJ, Ortiz GG et al (2010) Antioxidant activity of tryptophan in rats under experimental endotoxic shock. Biomed Pharmacother 64:77–81CrossRefGoogle Scholar
  26. 26.
    Tsopmo A, Diehl-Jones BW, Aluko RE et al (2009) Tryptophan released from mother’s milk has antioxidant properties. Pediatr Res 66:614–618CrossRefGoogle Scholar
  27. 27.
    Watanabe S, Togashi SI, Takahashi N et al (2002) L-Tryptophan as an antioxidant in human placenta extract. J Nutr Sci Vitaminol 48:36–39Google Scholar
  28. 28.
    Moosmann B, Behl C (2000) Cytoprotective antioxidant function of tyrosine and tryptophan residues in transmembrane proteins. Eur J Biochem 267:5687–5692CrossRefGoogle Scholar
  29. 29.
    Domazou AS, Koppenol WH, Gebicki JM (2009) Efficient repair of protein radicals by ascorbate. Free Radic Biol Med 46:1049–1057CrossRefGoogle Scholar
  30. 30.
    Gebicki JM, Nauser T, Domazou A et al (2010) Reduction of protein radicals by GSH and ascorbate: potential biological significance. Amino Acids 39:1131–1137CrossRefGoogle Scholar
  31. 31.
    Perez-Gonzalez A, Muñoz-Rugeles L, Alvarez-Idaboy JR (2014) Tryptophan: antioxidant or target of oxidative stress? A quantum chemistry elucidation. RSC Adv 4:56128–56131CrossRefGoogle Scholar
  32. 32.
    Christen S, Peterhans E, Stocker R (1990) Antioxidant activities of some tryptophan metabolites: possible implication for inflammatory diseases. Proc Natl Acad Sci USA 87:2506–2510Google Scholar
  33. 33.
    Weiss G, Diez-Ruiz A, Murr C et al (2002) Tryptophan metabolites as scavengers of reactive oxygen and chlorine species. Pteridines 13:140–144CrossRefGoogle Scholar
  34. 34.
    Lima VLA, Dias F, Nunes RD et al (2012) The antioxidant role of xanthurenic acid in the Aedes aegypti midgut during digestion of a blood meal. PLoS ONE 7:e38349Google Scholar
  35. 35.
    Zhao Y, Schultz NE, Truhlar DG (2006) Design of density functionals by combining the method of constraint satisfaction with parametrization for thermochemistry, thermochemical kinetics, and noncovalent interactions. J Chem Theory Comput 2:364–382CrossRefGoogle Scholar
  36. 36.
    Marenich AV, Cramer CJ, Truhlar DG (2009) Universal solvation model based on solute electron density and on a continuum model of the solvent defined by the bulk dielectric constant and atomic surface tensions. J Phys Chem B 113:6378–6396CrossRefGoogle Scholar
  37. 37.
    Velez E, Quijano J, Notario R et al (2009) A computational study of stereospecifity in the thermal elimination reaction of menthyl benzoate in the gas phase. J Phys Org Chem 22:971–977CrossRefGoogle Scholar
  38. 38.
    Ando H, Fingerhut BP, Dorfman KE et al (2014) Femtosecond stimulated Raman spectroscopy of the cyclobutane thymine dimer repair mechanism: a computational study. J Am Chem Soc 136:14801–14810CrossRefGoogle Scholar
  39. 39.
    Black G, Simmie JM (2010) Barrier heights for H-atom abstraction by HO2 from η-butanol: a simple yet exacting test for model chemistries? J Comput Chem 31:1236–1248Google Scholar
  40. 40.
    Dargiewicz M, Biczysko M, Improta R et al (2012) Solvent effects on electron-driven proton-transfer processes: adenine–thymine base pairs. Phys Chem Chem Phys 14:8981–8989Google Scholar
  41. 41.
    Furuncuoǧlu T, Uǧur I, Degirmenci I et al (2010) Role of chain transfer agents in free radical polymerization kinetics. Macromolecules 43:1823–1835CrossRefGoogle Scholar
  42. 42.
    Zhao Y, Truhlar DG (2008) How well can new-generation density functionals describe the energetics of bond-dissociation reactions producing radicals? J Phys Chem A 112:1095–1099CrossRefGoogle Scholar
  43. 43.
    Galano A, Alvarez-Idaboy JR (2014) Kinetics of radical-molecule reactions in aqueous solution: a benchmark study of the performance of density functional methods. J Comput Chem 35:2019–2026CrossRefGoogle Scholar
  44. 44.
    Frisch MJ, Trucks GW, Schlegel HB et al (2009) Gaussian 09. Gaussian, Inc., WallingfordGoogle Scholar
  45. 45.
    Galano A, Alvarez-Idaboy JR (2013) A computational methodology for accurate predictions of rate constants in solution: application to the assessment of primary antioxidant activity. J Comput Chem 34:2430–2445CrossRefGoogle Scholar
  46. 46.
    Eyring H (1935) The activated complex in chemical reactions. J Chem Phys 3:63–71CrossRefGoogle Scholar
  47. 47.
    Evans MG, Polanyi M (1935) Some applications of the transition state method to the calculation of reaction velocities, especially in solution. Trans Faraday Soc 31:875–894CrossRefGoogle Scholar
  48. 48.
    Truhlar DG, Garrett BC, Klippenstein SJ (1996) Current status of transition-state theory. J Phys Chem 100:12771–12800CrossRefGoogle Scholar
  49. 49.
    Marcus RA (1993) Electron transfer reactions in chemistry. Theory and experiment. Rev Modern Phys 65:599–610CrossRefGoogle Scholar
  50. 50.
    Marcus RA (1997) Electron transfer reactions in chemistry: theory and experiment. J Electroanal Chem 438:251–259Google Scholar
  51. 51.
    Marcus RA (1997) Electron transfer reactions in chemistry. Theory and experiment. Pure Appl Chem 69:13–29CrossRefGoogle Scholar
  52. 52.
    Collins FC, Kimball GE (1949) Diffusion-controlled reaction rates. J Colloid Sci 4:425–437CrossRefGoogle Scholar
  53. 53.
    Smoluchowski M (1917) Mathematical theory of the kinetics of the coagulation of colloidal solutions. Z Phys Chem 92:129–168Google Scholar
  54. 54.
    Einstein A (1905) On the movement of small particles suspended in a stationary liquid demanded by the molecular-kinetic theory of heat. Ann der Phys (Leipzig) 17:559–560Google Scholar
  55. 55.
    George SG (1903) Mathematical and physical papers, vol 3. Cambridge University Press, CambridgeGoogle Scholar
  56. 56.
    Ho J, Coote ML (2009) A universal approach for continuum solvent pK a calculations: are we there yet? Theory Chem Acc 125:3–21Google Scholar
  57. 57.
    Shields GC, Seybold PG (2013) Nitrogen acids (Chapter 6). In: Computational approaches for the prediction of pK a values. QSAR in environmental and health sciences. CRC, Boca Raton, pp 57–72Google Scholar
  58. 58.
    Kelen M, Sanli N (2009) Determination of pK a values of some auxins in methanol–water mixtures by reversed phase liquid chromatography and potentiometric methods. J Braz Chem Soc 20:133–140Google Scholar
  59. 59.
    Liao X, Zhu J, Rubab M et al (2010) An analytical method for the measurement of acid metabolites of tryptophan-NAD pathway and related acids in urine. J Chromatogr B 878:1003–1006Google Scholar
  60. 60.
    Kelly CP, Cramer CJ, Truhlar DG (2006) Adding explicit solvent molecules to continuum solvent calculations for the calculation of aqueous acid dissociation constants. J Phys Chem A 110:2493–2499CrossRefGoogle Scholar
  61. 61.
    Cramer CJ, Truhlar DG (2008) A universal approach to solvation modeling. Acc Chem Res 41:760–768CrossRefGoogle Scholar
  62. 62.
    Pérez-González A, Galano A (2012) On the outstanding antioxidant capacity of edaravone derivatives through single electron transfer reactions. J Phys Chem B 116:1180–1188CrossRefGoogle Scholar
  63. 63.
    Litwinienko G, Ingold KU (2003) Abnormal solvent effects on hydrogen atom abstractions. 1. The reactions of phenols with 2,2-diphenyl-1-picrylhydrazyl (dpph•) in alcohols. J Org Chem 68:3433–3438Google Scholar
  64. 64.
    Litwinienko G, Ingold KU (2004) Abnormal solvent effects on hydrogen atom abstraction. 2. Resolution of the curcumin antioxidant controversy. The role of sequential proton loss electron transfer. J Org Chem 69:5888–5896CrossRefGoogle Scholar
  65. 65.
    Litwinienko G, Ingold KU (2005) Abnormal solvent effects on hydrogen atom abstraction. 3. Novel kinetics in sequential proton loss electron transfer chemistry. J Org Chem 70:8982–8990CrossRefGoogle Scholar
  66. 66.
    Litwinienko G, Ingold KU (2007) Solvent effects on the rates and mechanisms of reaction of phenols with free radicals. Acc Chem Res 40:222–230CrossRefGoogle Scholar
  67. 67.
    Marino T, Galano A, Russo N (2014) Radical scavenging ability of gallic acid toward OH and OOH radicals. Reaction mechanism and rate constants from the density functional theory. J Phys Chem B 118:10380–10389CrossRefGoogle Scholar
  68. 68.
    Pérez-González A, Galano A, Alvarez-Idaboy JR (2014) Dihydroxybenzoic acids as free radical scavengers: mechanisms, kinetics, and trends in activity. New J Chem 38:2639–2652CrossRefGoogle Scholar
  69. 69.
    Alberto ME, Russo N, Grand A et al (2013) A physicochemical examination of the free radical scavenging activity of trolox: mechanism, kinetics and influence of the environment. Phys Chem Chem Phys 15:4642–4650CrossRefGoogle Scholar
  70. 70.
    Ulstrup J, Jortner J (1975) The effect of intramolecular quantum modes on free energy relationships for electron transfer reactions. J Chem Phys 63:4358–4368CrossRefGoogle Scholar
  71. 71.
    Marcus RA, Sutin N (1985) Electron transfers in chemistry and biology. BBA Rev Bioenergetics 811:265–322Google Scholar
  72. 72.
    Marcus RA (1993) Electron transfer reactions in chemistry: theory and experiment (Nobel lecture). Angew Chem Int Ed Engl 32:1111–1121CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Adriana Pérez-González
    • 1
  • Juan Raúl Alvarez-Idaboy
    • 1
  • Annia Galano
    • 2
  1. 1.Departamento de Física y Química Teórica, Facultad de QuímicaUniversidad Nacional Autónoma de MéxicoMéxicoMexico
  2. 2.Departamento de QuímicaUniversidad Autónoma Metropolitana-IztapalapaMéxicoMexico

Personalised recommendations