Skip to main content
SpringerLink
Log in

Mechanism of photooxidation of folic acid sensitized by unconjugated pterins

  • Communication
  • Published:
Photochemical & Photobiological Sciences Aims and scope Submit manuscript

Abstract

Folic acid, or pteroyl-l-glutamic acid (PteGlu), is a precursor of coenzymes involved in the metabolism of nucleotides and amino acids. PteGlu is composed of three moieties: a 6-methylpterin (Mep) residue, a p-aminobenzoic acid (PABA) residue, and a glutamic acid (Glu) residue. Accumulated evidence indicates that photolysis of PteGlu leads to increased risk of several pathologies. Thus, a study of PteGlu photodegradation can have significant ramifications. When an air-equilibrated aqueous solution of PteGlu is exposed to UV-A radiation, the rate of the degradation increases with irradiation time. The mechanism involved in this “auto-photo-catalytic” effect was investigated in aqueous solutions using a variety of tools. Whereas PteGlu is photostable under anaerobic conditions, it is converted into 6-formylpterin (Fop) and p-aminobenzoyl-l-glutamic acid (PABA-Glu) in the presence of oxygen. As the reaction proceeds and enough Fop accumulates in the solution, a photosensitized electron-transfer process starts, where Fop photoinduces the oxidation of PteGlu to Fop, and H2O2 is formed. This process also takes place with other pterins as photosensitizers. The results are discussed with the context of previous mechanisms for processes photosensitized by pterins, and their biological implications are evaluated.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

References

  1. M. Lucock, Folic acid: nutritional biochemistry, molecular biology, and role in disease processes, Mol. Genet. Metab., 2000, 71, 121–138.

    Article  CAS  PubMed  Google Scholar 

  2. L. B. Bailey, J. F. Gregory, Folate metabolism and requirements, J. Nutr., 1999, 129, 779–782.

    Article  CAS  PubMed  Google Scholar 

  3. C. Bower, F. J. Stanley, Dietary folate as a risk factor for neural-tube defects: evidence from a case-control study in Western Australia, Med. J. Aust., 1989, 150, 613–619.

    Article  CAS  PubMed  Google Scholar 

  4. L. E. Mitchell, Epidemiology of neural tube defects, Am. J. Med. Genet. C. Semin Med. Genet., 2005, 135, 88–94.

    Article  Google Scholar 

  5. J. Zittoun, Anemias due to disorder of folate, vitamin B12 and transcobalamin metabolism, Rev. Prat., 1993, 43, 1358–1363.

    CAS  PubMed  Google Scholar 

  6. E. B. Rimm, W. C. Willett, F. B. Hu, L. Sampson, G. A. Colditz, J. E. Manson, C. Hennekens, M. J. Stampfer, Folate and vitamin B6 from diet and supplements in relation to risk of coronary heart disease among women, JAMA, J. Am. Med. Assoc., 1998, 279, 359–364.

    Article  CAS  Google Scholar 

  7. S-W. Choi, J. B. Mason, Folate and carcinogenesis: an integrated scheme, J. Nutr., 2000, 130, 129–132.

    Article  CAS  PubMed  Google Scholar 

  8. E. Reynolds, Vitamin B12, folic acid, and the nervous system, Lancet Neurol., 2006, 5, 949–960.

    Article  CAS  PubMed  Google Scholar 

  9. T. Tamura, M. Frances, Folate and human reproduction, Am. J. Clin. Nutr., 2006, 83, 993–1016.

    Article  CAS  PubMed  Google Scholar 

  10. U. Mathur, S. L. Datta, B. B. Mathur, The effect of aminopterin-induced folic acid deficiency on spermatogenesis, Fertil. Steril., 1977, 28, 1356–1360.

    Article  CAS  PubMed  Google Scholar 

  11. M. J. Cosentino, R. E. Pakyz, J. Fried, Pyrimethamine: an approach to the development of a male contraceptive, Proc. Natl. Acad. Sci. U. S. A., 1990, 87, 1431–1435.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. G. J. Locksmith, P. Duff, Preventing neural tube defects: the importance of periconceptional folic acid supplements, Obstet. Gynecol., 1998, 91, 1027–1034.

    CAS  PubMed  Google Scholar 

  13. M. J. Khoury, J. D. Erickson, L. M. James, Etiologic heterogeneity of neural tube defects: clues from epidemiology, Am. J. Epidemiol., 1982, 115, 538–48.

    Article  CAS  PubMed  Google Scholar 

  14. R. E. Stevenson, W. P. Allen, G. S. Pai, R. Best, L. H. Seaver, J. Dean, S. Thompson, Decline in Prevalence of Neural Tube Defects in a High-Risk Region of the United States, Pediatrics, 2000, 106, 677–683.

    Article  CAS  PubMed  Google Scholar 

  15. F. J. Van Rootselaar, The epidemiology of neural tube defects: a mathematical model, Med. Hypotheses, 1993, 41, 78–82.

    Article  PubMed  Google Scholar 

  16. N. G. Jablonski, Ultraviolet light-induced neural tube defects in amphibian larvae and their implications for the evolution of melanized pigmentation and declines in amphibian populations, J. Herpetol., 1998, 32, 455–457.

    Article  Google Scholar 

  17. P. Lapunzina, Ultraviolet light-related neural tube defects?, Am. J. Med. Genet., 1996, 67, 106.

    Article  CAS  PubMed  Google Scholar 

  18. O. H. Lowry, O. A. Bessey, E. J. Crawford, Photolytic and enzymatic transformations of pteroylglutamic acid, J. Biol. Chem., 1949, 180, 389–398.

    Article  CAS  PubMed  Google Scholar 

  19. R. F. Branda, J. W. Eaton, Skin color and nutrient photolysis: an evolutionary hypothesis, Science, 1978, 201, 625–626.

    Article  CAS  PubMed  Google Scholar 

  20. M. Der-Petrossian, M. Födinger, R. Knobler, H. Hönigsmann, F. Trautinger, Photodegradation of folic acid during extracorporeal photopheresis, Br. J. Dermatol., 2007, 156, 117–121.

    Article  CAS  PubMed  Google Scholar 

  21. T. Fukuwatari, M. Fujita, K. Shibata, Effects of UVA irradiation on the concentration of folate in human blood, Biosci., Biotechnol., Biochem., 2009, 73, 322–327.

    Article  CAS  Google Scholar 

  22. N. G. Jablonski, G. Chaplin, The evolution of human skin coloration, J. Hum. Evol., 2000, 39, 57–106.

    Article  CAS  PubMed  Google Scholar 

  23. N. G. Jablonski, G. Chaplin, Skin deep, Sci. Am., 2002, 287, 74–81.

    Article  PubMed  Google Scholar 

  24. M. J. Akhtar, M. A. Khan, I. Ahmad, Photodegradation of folic acid in aqueous solution, J. Pharm. Biomed. Anal., 1999, 19, 269–275.

    Article  CAS  PubMed  Google Scholar 

  25. M. J. Akhtar, M. A. Khan, I. Ahmad, Identification of photoproducts of folic acid and its degradation pathways in aqueous solution, J. Pharm. Biomed. Anal., 2003, 31, 579–588.

    Article  CAS  Google Scholar 

  26. A. H. Thomas, G. Suárez, F. M. Cabrerizo, R. Martino, A. L. Capparelli, Study of the photolysis of folic acid and 6-formylpterin in acid aqueous solutions, J. Photochem. Photobiol., A, 2000, 135, 147–154.

    Article  CAS  Google Scholar 

  27. A. H. Thomas, G. Suárez, F. M. Cabrerizo, F. S. García Einschlag, R. Martino, C. Baiocchi, E. Pramauro, A. L. Capparelli, Photochemical behavior of folic acid in alkaline aqueous solutions and evolution of its photoproducts, Helv. Chim. Acta, 2002, 85, 2300–2315.

    Article  CAS  Google Scholar 

  28. M. K. Off, A. E. Steindal, A. C. Porojnicu, A. Juzeniene, A. Vorobey, A. Johnsson, J. Moan, Ultraviolet photodegradation of folic acid, J. Photochem. Photobiol., B, 2005, 80, 47–55.

    Article  CAS  Google Scholar 

  29. F. M. Cabrerizo, G. Petroselli, C. Lorente, A. L. Capparelli, A. H. Thomas, A. M. Braun, E. Oliveros, Substituent effects on the photophysical properties of pterin derivatives in acidic and alkaline aqueous solutions, Photochem. Photobiol., 2005, 81, 1234–1240.

    Article  CAS  PubMed  Google Scholar 

  30. A. H. Thomas, C. Lorente, A. L. Capparelli, M. R. Pokhrel, A. M. Braun, E. Oliveros, Fluorescence of pterin, 6-formylpterin, 6-carboxypterin and folic acid in aqueous solutions: pH effects, Photochem. Photobiol. Sci., 2002, 1, 421–426.

    Article  CAS  PubMed  Google Scholar 

  31. A. H. Thomas, C. Lorente, A. L. Capparelli, C. G. Martínez, A. M. Braun, E. Oliveros, Singlet oxygen (1Δg) production by pterin derivatives in aqueous solutions, Photochem. Photobiol. Sci., 2003, 2, 245–250.

    Article  CAS  PubMed  Google Scholar 

  32. K. Hirakawa, H. Suzuki, S. Oikawa, S. Kawanishi, Sequencespecific DNA damage induced by ultraviolet A-irradiated folic acid via its photolysis product, Arch. Biochem. Biophys., 2003, 410, 261–268.

    Article  CAS  PubMed  Google Scholar 

  33. Q.-H. Song, K. C. Hwang, Direct observation for photophysical and photochemical processes of folic acid in DMSO solution, J. Photochem. Photobiol., A, 2007, 185, 51–56.

    Article  CAS  Google Scholar 

  34. C. B. Martin, D. Walker, M. Soniat, Density functional theory study of possible mechanisms of folic acid photodecomposition, J. Photochem. Photobiol., A, 2009, 208, 1–6.

    Article  CAS  Google Scholar 

  35. S. E. Braslavsky, Glossary of terms used in photochemistry 3rd edition (IUPAC Recommendations 2006), Pure Appl. Chem., 2007, 79, 293–465.

    Article  CAS  Google Scholar 

  36. A. M. Braun, M. T. Maurette and E. Oliveros, Photochemical Technology, translated by D. Ollis and N. Serpone, Wiley, Chichester, 1991, ch. 2, pp. 85–88.

  37. H. J. Kuhn, S. E. Braslavsky, R. Schmidt, Chemical actinometry (IUPAC technical report), Pure Appl. Chem., 2004, 76, 2105–2146.

    Article  CAS  Google Scholar 

  38. C. C. Allain, L. S. Poon, C. S. G. Chan, W. Richmond, P. C. Fu, Enzymatic determination of total serum cholesterol, Clin. Chem., 1974, 20, 470–475.

    Article  CAS  PubMed  Google Scholar 

  39. H. M. Flegg, An investigation of the determination of serum cholesterol by an enzymatic method, Ann. Clin. Biochem., 1973, 10, 79–84.

    Article  CAS  Google Scholar 

  40. T. Keszthelyi, D. Weldon, T. N. Andersen, T. D. Poulsen, K. V. Mikkelsen, P. R. Ogilby, Radiative transitions of singlet oxygen: New tools, new techniques and new interpretations, Photochem. Photobiol., 1999, 70, 531–539.

    Article  CAS  Google Scholar 

  41. C. Lorente, A. H. Thomas, Photophysics and Photochemistry of Pterins in Aqueous Solution, Acc. Chem. Res., 2006, 39, 395–402.

    Article  CAS  PubMed  Google Scholar 

  42. G. Petroselli, J. M. Bartsch, A. H. Thomas, Photoinduced Generation of H2O2 and O2˙− by 6-formylpterin in Aqueous Solutions, Pteridines, 2006, 17, 82–89.

    Article  CAS  Google Scholar 

  43. B. H. J. Bielski, D. E. Cabelli, R. L. Arudi, A. B. Ross, Reactivity of HO2/O2- radicals in aqueous solution, J. Phys. Chem. Ref. Data., 1985, 14, 1041–1100.

    Article  CAS  Google Scholar 

  44. I. Fridovich, Superoxide radicals, superoxide dismutases, and the aerobic lifestyle, Photochem. Photobiol., 1978, 28, 733–741.

    Article  CAS  PubMed  Google Scholar 

  45. K. V. Neverov, E. A. Mironov, T. A. Lyudnikova, A. A. Krasnovsky, M. S. Kritsky, Phosphorescence analysis of the triplet state of pterins in connection with their photoreceptor function in biochemical systems, Biokhimiya (Moscow), 1996, 61, 1149–1155.

    Google Scholar 

  46. R. T. Parker, R. S. Freelander, E. M. Schulman, R. B. Dunlap, Room-temperature phosphorescence of selected Pteridines, Anal. Chem., 1979, 51, 1921–1926.

    Article  CAS  Google Scholar 

  47. M. S. Kritsky, T. A. Lyudnikova, E. A. Mironov, I. V. Moskaleva J. Photochem. Photobiol., B, 1997, 39, 43–48.

    Article  CAS  Google Scholar 

  48. M. Vignoni, F. M. Cabrerizo, C. Lorente, C. Claparols, E. Oliveros, A. H. Thomas, Photochemistry of dihydrobiopterin in aqueous solution, Org. Biomol. Chem., 2010, 8, 800–810.

    Article  CAS  PubMed  Google Scholar 

  49. M. L. Dántola, M. Vignoni, C. González, C. Lorente, P. Vicendo, E. Oliveros, A. H. Thomas, Electron transfer processes induced by the triplet state of pterins in aqueous solutions, Free Radical Biol. Med., 2010, 49, 1014–1022.

    Article  CAS  Google Scholar 

  50. M. Kristiansen, R. D. Scurlock, K.-K. Iu, P. R. Ogilby, Charge-transfer state and singlet oxygen (1Δg O2) production in photoexcited organic molecule-molecular oxygen complexes, J. Phys. Chem., 1991, 95, 5190–5197.

    Article  CAS  Google Scholar 

  51. F. M. Cabrerizo, M. L. Dántola, G. Petroselli, A. L. Capparelli, A. H. Thomas, A. M. Braun, C. Lorente, E. Oliveros, Reactivity of Conjugated and Unconjugated Pterins with Singlet Oxygen (O21Δg)): Physical Quenching and Chemical Reaction, Photochem. Photobiol., 2007, 83, 526–534.

    Article  CAS  PubMed  Google Scholar 

  52. F. M. Cabrerizo, C. Lorente, M. Vignoni, R. Cabrerizo, A. H. Thomas, A. L. Capparelli, Photochemical behaviour of 6-methylpterin in aqueous solutions: Generation of reactive oxygen species, Photochem. Photobiol., 2005, 81, 793–801.

    Article  CAS  PubMed  Google Scholar 

  53. F. Wilkinson, H. P. Helman, A. B. Ross, Rate Constants for the Decay and Reactions of the Lowest Electronically Excited Singlet State of Molecular Oxygen in Solution. An Expanded and Revised Compilation, J. Phys. Chem. Ref. Data, 1995, 24, 663–677.

    Article  CAS  Google Scholar 

  54. K. Ito, S. Kawanishi, Oxidation of 2′-deoxyguanosine 5′-monophosphate photoinduced by pterin: type I versus type II mechanism, Biochemistry, 1997, 36, 1774–1781.

    Article  CAS  PubMed  Google Scholar 

  55. G. Petroselli, M. L. Dántola, F. M. Cabrerizo, A. L. Capparelli, C. Lorente, E. Oliveros, A. H. Thomas, Photosensitization of 2′-deoxyadenosine-5′-monophosphate by pterin, J. Am. Chem. Soc., 2008, 130, 3001–3011.

    Article  CAS  PubMed  Google Scholar 

  56. G. Petroselli, R. Erra-Balsells, F. M. Cabrerizo, C. Lorente, A. L. Capparelli, A. M. Braun, E. Oliveros, A. H. Thomas, Photosensitization of 2′-deoxyadenosine-5′-monophosphate by pterin, Org. Biomol. Chem., 2007, 5, 2792–2799.

    Article  CAS  PubMed  Google Scholar 

  57. M. J. Akhtar, M. A. Khan, I. Ahmad, Effect of riboflavin on the photolysis of folic acid in aqueous solution, J. Pharm. Biomed. Anal., 2000, 23, 1039–1044.

    Article  CAS  PubMed  Google Scholar 

  58. J.-L. Ravanat, T. Douki, J. Cadet, Direct and indirect effects of UV radiation on DNA and its components, J. Photochem. Photobiol., B, 2001, 63, 88–102.

    Article  CAS  Google Scholar 

  59. T. Douki, J. Cadet, Modification of DNA bases by photosensitized one-electron oxidation, Int. J. Radiat. Biol., 1999, 75, 571–581.

    Article  CAS  PubMed  Google Scholar 

  60. S. A. Brazill, P. Singhal, W. G. Kuhr, Detection of Native Amino Acids and Peptides Utilizing Sinusoidal Voltammetry, Anal. Chem., 2000, 72, 5542–5548.

    Article  CAS  PubMed  Google Scholar 

  61. C. Chahidi, M. Aubailly, A. Momzikoff, M. Bazin, R. Santus, Photophysical and photosensitizing properties of 2-amino-4-pteridinone: A natural pigment, Photochem. Photobiol., 1981, 33, 641–649.

    Article  CAS  Google Scholar 

  62. J. W. Ledbetter, W. Pfleiderer, J. H. Freisheim, Photosensitized reduction of L-biopterin in the active ternary complex of dihydrofolate reductase, Photochem. Photobiol., 1995, 62, 71–81.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. INIFTA, Departamento de Química, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, CCT La Plata-CONICET. C.C. 16, Suc. 4, (1900), La Plata, Argentina

    M. Laura Dántola, M. Paula Denofrio, Beatriz Zurbano, Carlos S. Gimenez, Carolina Lorente & Andrés H. Thomas

  2. Center for Oxygen Microscopy and Imaging, Department of Chemistry, University of Aarhus, DK-8000, Århus, Denmark

    Peter R. Ogilby

Authors
  1. M. Laura Dántola
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. Paula Denofrio
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Beatriz Zurbano
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Carlos S. Gimenez
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Peter R. Ogilby
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Carolina Lorente
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Andrés H. Thomas
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Andrés H. Thomas.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dántola, M.L., Denofrio, M.P., Zurbano, B. et al. Mechanism of photooxidation of folic acid sensitized by unconjugated pterins. Photochem Photobiol Sci 9, 1604–1612 (2010). https://doi.org/10.1039/c0pp00210k

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1039/c0pp00210k

Search

Navigation