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PHEOPHORBIDE a ‐INDUCED PHOTO‐OXIDATION OF CYTOCHROME c : IMPLICATION FOR PHOTODYNAMIC THERAPY
Author(s) -
Chernomorsky S.,
Wong C.,
Poretz R. D.
Publication year - 1992
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1111/j.1751-1097.1992.tb04229.x
Subject(s) - chemistry , heme , cytochrome c , photochemistry , porphyrin , cytochrome c oxidase , hemeprotein , cytochrome p450 reductase , singlet oxygen , photosensitizer , cytochrome , cytochrome c peroxidase , pheophorbide a , coenzyme q – cytochrome c reductase , photodynamic therapy , biochemistry , enzyme , oxygen , mitochondrion , organic chemistry
— Pheophorbide a ‐induced photo‐oxidation, in vitro , of cytochrome c oxidase and cytochrome c results in irreversible modifications to both protein components. Photo‐oxidation of cytochrome c , as exhibited by change in its heme oxidation state, displays exponential kinetics and is detected with a lag period. Both the photo‐induced inactivation of the enzyme, and destruction of the substrate ability of cytochrome c occur as complex multi‐process events. Under similar experimental conditions, the loss of the substrate capability of cytochrome c develops approximately three times faster than inactivation of the enzyme. The slight lag in the photo‐oxidation of cytochrome c is due to pheophorbide a ‐induced superoxide production. However, the relative amount of photo‐oxidant produced is considerably more effective than the cytochrome c reducing capacity of the superoxide. Neither hydroxyl radical nor hydrogen peroxide are involved in the photo‐oxidation of the heme function. The possibilities of heme oxidation by a singlet oxygen mediated pathway or direct electron abstraction involving the heme or apoprotein are not excluded. It is proposed that a multi‐site oxidation of numerous reduced energy cofactors within cells may augment collateral enzyme inactivation in maximizing photosensitizer‐induced cytotoxicity. Accordingly, amphipathic photosensitizers, capable of accessing both lipid and aqueous compartments containing reduced cofactors, may be more effective agents for photodynamic therapy than those which exhibit a high specificity of subcellular localization.