Chelatase
Chelatase, also known as ferrochelatase, is an enzyme (EC 4.99.1.1) that catalyzes the final step in heme biosynthesis. This step involves the insertion of ferrous iron (Fe2+) into protoporphyrin IX to form protoheme. Protoheme is a crucial component of several essential proteins, including hemoglobin, myoglobin, and cytochromes.
The enzyme is found in the inner mitochondrial membrane in eukaryotes and in the cell membrane of bacteria. In mammals, ferrochelatase is primarily expressed in erythroid cells in the bone marrow and in hepatocytes in the liver, reflecting the high demand for heme in these tissues.
Deficiency in ferrochelatase activity can lead to erythropoietic protoporphyria (EPP), a genetic disorder characterized by the accumulation of protoporphyrin in erythrocytes, plasma, and tissues. EPP manifests with symptoms such as photosensitivity, resulting in painful skin reactions upon exposure to sunlight.
The activity of chelatase can be influenced by various factors, including the availability of iron and protoporphyrin, as well as the presence of inhibitors such as heavy metals. The enzyme's structure and function are complex, involving several conserved amino acid residues critical for substrate binding and catalysis. Research continues to elucidate the precise mechanism of action of chelatase and its regulation within cells.