Production of protoporphyrin and chemical structure. (A) Protoporphyrin is primarily produced within the erythroblast in the bone marrow. Iron enters the cell through the transferrin receptor (TFR) and is converted from the ferric (Fe3+) to the ferrous (Fe2+) form. The formation of heme requires insertion of Fe2+ into protoporphyrin, which is catalyzed by FECH. XLP is caused by gain-of-function variants in ALAS2, and EPP by loss-of-function variants in FECH. (B) Protoporphyrin (depicted in purple) is photoreactive and can cause burning, itching, and pain of the skin. (C) The chemical structure of protoporphyrin (left) and chlorophyl (right) are similar. (D) Plasma protoporphyrin (depicted in purple) enters the liver from plasma and can cause liver damage and protoporphyrin-containing gallstones. PPIX, protoporphyrin IX.
