The photodynamic and non-photodynamic actions of porphyrins

Abstract

Porphyrias are a family of inherited diseases, each associated with a partial defect in one of the enzymes of the heme biosynthetic pathway. In six of the eight porphyrias described, the main clinical manifestation is skin photosensitivity brought about by the action of light on porphyrins, which are deposited in the upper epidermal layer of the skin. Porphyrins absorb light energy intensively in the UV region, and to a lesser extent in the long visible bands, resulting in transitions to excited electronic states. The excited porphyrin may react directly with biological structures (type I reactions) or with molecular oxygen, generating excited singlet oxygen (type II reactions). Besides this well-known photodynamic action of porphyrins, a novel light-independent effect of porphyrins has been described. Irradiation of enzymes in the presence of porphyrins mainly induces type I reactions, although type II reactions could also occur, further increasing the direct non-photodynamic effect of porphyrins on proteins and macromolecules. Conformational changes of protein structure are induced by porphyrins in the dark or under UV light, resulting in reduced enzyme activity and increased proteolytic susceptibility. The effect of porphyrins depends not only on their physico-chemical properties but also on the specific site on the protein on which they act. Porphyrin action alters the functionality of the enzymes of the heme biosynthetic pathway exacerbating the metabolic deficiencies in porphyrias. Light energy absorption by porphyrins results in the generation of oxygen reactive species, overcoming the protective cellular mechanisms and leading to molecular, cell and tissue damage, thus amplifying the porphyric picture.

Photodynamic Therapy: Current Status and Future Directions

“…They include PS/protein photo-binding and protein cross-linking through the coupling of two tyrosine units. Covalent cross-linking, which is regarded as a secondary reaction between photooxidation products of susceptible amino acid residues and other groups in the protein [62], leads to the formation of molecular aggregates (fig. 3).…”

SDS-PAGE and IR spectroscopy to evaluate modifications in the viral protein profile induced by a cationic porphyrinic photosensitizer

“…The protein damage induced by photosensitization can occur by backbone fragmentation, oxidation of essential amino acid residues and by the formation of cross-links between proteins or between proteins and nucleic acids (Verweu and Steveninck, 1982;Afonso et al, 1999;Shacter, 2000;Macdonald and Dougherty, 2001;Davies, 2003). The reaction of singlet oxygen with electron rich side-chains residues originates new reactive species, which may damage other proteins, lipids or DNA, leading to a series of deleterious events (Davies, 2004).…”

The Response of Human Skin Commensal Bacteria as a Reflection of UV Radiation: UV-B Decreases Porphyrin Production

“…When P. acnes is bombarded with UV radiation, porphyrins absorb the UV and produce free radicals in return [27], [28]. In addition, it has been demonstrated that protein oxidation in bacteria can be as the primary determinant of bacterial reaction to radiation [29], [30].…”