The photodynamic and non-photodynamic actions of porphyrins

Porphyrias are a family of inherited diseases, each associated with a parti al defect in one of the enzymes of the heme biosynthetic pathway. In six of the eight porphyrias described, the main clinical manifestation is skin ph otosensitivity brought about by the action of light on porphyrins, which ar e deposited in the upper epidermal layer of the skin. Porphyrins absorb lig ht 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 rea ctions) or with molecular oxygen, generating excited singlet oxygen (type I I reactions). Besides this well-known photodynamic action of porphyrins, a novel light-independent effect of porphyrins has been described. Irradiatio n 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. Conf ormational changes of protein structure are induced by porphyrins in the da rk or under UV light, resulting in reduced enzyme activity and increased pr oteolytic susceptibility. The effect of porphyrins depends not only on thei r 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 i n porphyrias. Light energy absorption by porphyrins results in the generati on of oxygen reactive species, overcoming the protective cellular mechanism s and leading to molecular, cell and tissue damage, thus amplifying the por phyric picture.