protoporphyrin

Protoporphyrin is a porphyrin derivative that contains the protoporphyrin IX skeleton when iron has not yet been inserted. It is a natural precursor in the biosynthesis of heme and chlorophyll. The molecule consists of four pyrrole rings linked by methine bridges and bears substituents such as methyl, ethyl, and vinyl groups.

In the heme biosynthetic pathway, protoporphyrin IX is formed after the oxidation of protoporphyrinogen IX. The final step is the insertion of ferrous iron by the enzyme ferrochelatase to yield heme (heme b). In plants and some microorganisms, magnesium can be inserted instead to produce magnesium protoporphyrin IX, a precursor to chlorophyll.

Physically, protoporphyrin IX is a hydrophobic, intensely colored molecule with a strong absorption band around 400 nm (the Soret band) and characteristic fluorescence. It functions as a photosensitizer and can generate reactive oxygen species upon light exposure, a property exploited in biomedical applications.

Clinically and diagnostically, accumulation of protoporphyrin IX—often due to defects in ferrochelatase or related enzymes—causes erythropoietic protoporphyria, which can lead to photosensitivity. In medicine, the administration of precursors such as 5-aminolevulinic acid (ALA) induces cellular PpIX accumulation and is used in photodynamic therapy and for imaging.

Protoporphyrin typically refers to protoporphyrin IX, the non-metallated form, but the term can denote the protoporphyrin skeleton used to form various metalloporphyrins, including heme, chlorophyll, and related cofactors.