Ferrochelatase

Ferrochelatase is a metal-insertion enzyme that catalyzes the final step of heme biosynthesis: the insertion of ferrous iron (Fe2+) into protoporphyrin IX to form heme b. The reaction can be summarized as protoporphyrin IX plus Fe2+ yielding heme b and two protons. It is classified as EC 4.99.1.1 and is essential for heme production in aerobic and anaerobic organisms.

The enzyme is found across domains of life, including bacteria, archaea, and eukaryotes. In animals, plants, and fungi, ferrochelatase resides in the mitochondria and is encoded by the FECH gene; in many bacteria it is encoded by hemH. In mammals and some fungi, the enzyme is associated with the inner mitochondrial membrane and often functions as a homodimer. Some ferrochelatases harbor a [2Fe-2S] cluster that can participate in regulation and catalysis, while others do not. The presence of the iron-sulfur cluster can influence enzyme stability and activity in response to cellular redox conditions.

Clinical and physiological relevance is linked to ferrochelatase activity. Deficiency or dysfunction can lead to disorders such as erythropoietic protoporphyria, characterized by accumulation of protoporphyrin IX and photosensitivity. Ferrochelatase activity is also influenced by cellular iron status and mitochondrial health, reflecting its role as the terminal enzyme in the heme biosynthetic pathway.