Oxidation of Tyrosine Photoinduced by Pterin in Aqueous Solution

Abstract

Pterins, heterocyclic compounds widespread in biological systems, accumulate in the skin of patients suffering from vitiligo, a chronic depigmentation disorder. Pterins have been previously identified as good photosensitizers under UV-A irradiation. In this work, we have investigated the ability of pterin (Ptr), the parent compound of oxidized pterins, to photosensitize the oxidation of tyrosine (Tyr) in aqueous solutions. Tyr is an important target in the study of the photodynamic effects of UV-A radiation because it is oxidized by singlet oxygen ((1)O2) and plays a key role in polymerization and cross-linking of proteins. Steady UV-A irradiation of solutions containing Ptr and Tyr led to the consumption of Tyr and dissolved O2, whereas the Ptr concentration remained unchanged. Concomitantly, hydrogen peroxide (H2O2) was produced. By combining different analytical techniques, we could establish that the mechanism of the photosensitized process involves an electron transfer from Tyr to the triplet excited state of Ptr. Mass spectrometry, chromatography and fluorescence were used to analyze the photoproducts. In particular, oxygenated and dimeric compounds were identified.

Chemical changes in bovine serum albumin photoinduced by pterin

“…P Å+ leads to the irreversible damage and degradation of the protein (reaction 2), whereas Ptr ÅÀ , under aerobic conditions, transfers one electron to O 2 regenerating Ptr and forming superoxide anion (O 2 ÅÀ ) (reaction 3), which, in turn, is converted into hydrogen peroxide (H 2 O 2 ) by spontaneous disproportionation (reaction 4) [22]. Moreover, it was demonstrated that Ptr is able to photosensitize the oxidation of free Trp and Tyr in aqueous solution [23,24]. In particular, the study of the photosensitization of Tyr revealed that dimers of Tyr, or dityrosine are formed [24].…”

Photosensitization of peptides and proteins by pterin derivatives

“…In general, it is accepted that the photosensitization of proteins occurs mainly through the reactions of 1 O 2 with tryptophan (Trp), tyrosine (Tyr), histidine (His), methionine (Met) and cysteine (Cys) side-chains [7]. Nevertheless, in recent reports, it has been demonstrated that pterins photosensitize peptides [8,9], proteins [10,11] and their components [12][13][14] mainly through a type I mechanism.…”

“…We have focused our attention on the chemical modifications of tyrosine (Tyr) and tryptophan (Trp) residues because these amino acids are particularly susceptible to a variety of oxidizing agents [26]. Moreover, the photosensitization of free Trp and Tyr by Ptr has previously been reported [12,13]. The most relevant results, from a biological point of view, are summarized and discussed in this review.…”

“…More recently, the mechanism involved in the photosensitization of biomolecules by pterins were investigated in a series of studies carried out with free nucleotides [28][29][30] and amino acids [12][13][14]. It was shown that pterins can act as photosensitizers through both type I and type II mechanisms and that the predominant one depends on a combination of many factors, such as quantum yields of Taking into account the studies mentioned in the previous paragraph, a set of competitive mechanisms can be summarized to explain the photooxidation of different biomolecules (S) by pterin derivatives (Pt) (reactions [1][2][3][4][5][6][7][8][9][10][11][12] …”

“…Pterins are photochemically reactive in aqueous solutions, and upon UV-A excitation, they can fluoresce, produce reactive oxygen species (ROS) [23][24][25] and, as mentioned above, photosensitize the oxidation of biomolecules [8][9][10][11][12][13][14].…”