The photodynamic and non-photodynamic actions of porphyrins.
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 macro-molecules. 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.
Afonso
S G
SG
Centro de Investigaciones sobre Porfirinas y Porfirias (CIPYP), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Argentina.
Enríquez de Salamanca
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Batlle
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D003624:Darkness; D004798:Enzymes / Q000378:metabolism*; D006418:Heme; D006420:Hemeproteins / Q000528:radiation effects*; D006801:Humans; D008027:Light; D017319:Photosensitizing Agents / Q000378:metabolism*; D011164:Porphyrias / Q000378:metabolism*; D011166:Porphyrins / Q000494:pharmacology* / Q000528:radiation effects*; D011524:Protoporphyrins / Q000494:pharmacology; D017382:Reactive Oxygen Species; D012871:Skin Diseases / Q000139:chemically induced; D014466:Ultraviolet Rays / Q000009:adverse effects; D014578:Uroporphyrins / Q000494:pharmacology
D004798:Enzymes; D006420:Hemeproteins; D017319:Photosensitizing Agents; D011166:Porphyrins; D011524:Protoporphyrins; D017382:Reactive Oxygen Species; D014578:Uroporphyrins; D006418:Heme