Oxidation of biomolecules photosensitized by pterins and lumazines: mechanisms and biomedical implications

M. PAULA DENOFRIO; MARIANA VIGNONI; M. LAURA DÁNTOLA; ESTHER OLIVEROS; CAROLINA LORENTE; ANDRÉS H. THOMAS

La Serena

Congreso; X Encuentro Latinoamericano de Fotoquímica y Fotobiología (X ELAFOT),; 2010

X Encuentro Latinoamericano de Fotoquímica y Fotobiología (X ELAFOT)

Pterins and lumazines, heterocyclic compounds present in biological systems, play various roles ranging from pigments to enzymatic cofactors for numerous redox and one-carbon transfer reactions. Under UV-A excitation, these biomolecules generate reactive oxygen species, such as singlet oxygen, and are able to photoinduce DNA damage.1 Moreover, their photodynamic activity has been demonstrated in HeLa cells.2 Studies carried out with purine nucleotides2,3 or EDTA4 as substrates and pterins or lumazines as sensitizers revealed a general experimental behavior. When an air-equilibrated solution containing a given substrate and a given sensitizer is exposed to UV-A irradiation, the concentrations of the substrate and O2 decrease, production of H2O2 is observed and the concentration of the sensitizer remains constant. The photosensitized process is favored by superoxide dismutase, but inhibited in O2-equilibrated solutions or by the presence of iodide. The mechanism proposed consists in a type I photooxidation that involves an initial electron transfer from the nucleotide to the triplet excited state of the sensitizer. In the following step, the resulting radical anion reduces dissolved O2 to form the superoxide anion and regenerate the sensitizer. Finally a group of processes, that include the reactions of substrate radical cation and its deprotonated form with O2 and H2O, leads to the oxidation of the substrate. Folic acid (PteGlu) and 7,8-dihydrobiopterin (H2Bip) undergo photooxidation in air-equilibrated aqueous solution upon UV-A exposure to yield 6-formylpterin and biopterin (Bip), respectively. Photodegradation of PteGlu is involved in depletion of serum folate levels caused by sunlight exposure, whereas photooxidation of H2Bip is a potential source of Bip, a compound toxic for melanocytes, in the skin of patients suffering vitiligo. In both cases, the rate of the reactant degradation increases with irradiation time. Analysis of this “auto-photo-catalytic” effect on the basis of the general mechanism described in the previous paragraph revealed5 that the reactions consist in photosensitized processes in which the photoproduct acts as a sensitizer of its own production. Again, the first step involves an electron transfer from the substrate (reactant) to the triplet excited state of the sensitizer (product. References 1 C. Lorente, A. H. Thomas, Acc. Chem. Res., 2006, 39, 395. 2 M. P. Denofrio et al., Photochem. Photobiol. Sci., 2009, 8, 1539. 3 G. Petroselli et al., J. Am. Chem. Soc., 2008, 130, 3001. 4 M. L. Dántola et al., Free Radic. Biol. Med., 2010, DOI: 10.1016/j.freeradbiomed.2010.06.011 5 M. Vignoni et al., Org. Biomol. Chem., 2010, 8, 800.