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Protoporphyrin IX is an endogenous porphyrin and immediate precursor of heme, serving as the substrate for the terminal heme biosynthetic enzyme ferrochelatase. It strongly absorbs visible light (notably 400–600 nm), and upon illumination acts as a photosensitizer that generates singlet oxygen and other reactive oxygen species, leading to oxidative damage of cellular targets such as dermal endothelial cells. Pathologic accumulation of PPIX in erythropoietic protoporphyria and X-linked protoporphyria causes painful cutaneous photosensitivity, and high systemic levels can produce hepatobiliary complications. Clinically, exogenous 5-aminolevulinic acid and its lipophilic derivatives are used to elevate intracellular PPIX in lesions to enable photodynamic therapy; upon light exposure, PPIX-mediated ROS induces cancer cell death, often with apoptotic features. PPIX can also interact with hemoproteins (e.g., hemoglobin, myoglobin) and alter oxygen binding in vitro.
As a photosensitizer, light-excited PPIX transfers energy to molecular oxygen to produce singlet oxygen and other reactive oxygen species, causing oxidative damage (e.g., to endothelial cells) and cytotoxicity used in photodynamic therapy In ALA-based PDT, exogenous ALA bypasses the rate-limiting step to elevate PPIX in tissues; illumination then triggers ROS-mediated apoptosis/necrosis of target cells
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