Protoheme

Protoheme, also known as heme B or iron protoporphyrin IX, is the iron-containing porphyrin prosthetic group that forms the core of many heme proteins. It consists of a protoporphyrin IX macrocycle binding a ferrous iron ion (Fe2+) at its center. In most heme proteins, the iron is axially coordinated by a proximal ligand supplied by the protein (often a histidine residue) and a distal ligand that can be water, hydroxide, or another amino acid depending on the protein and its state.

Biogenesis: In nature, protoheme is produced late in the heme biosynthesis pathway by insertion of Fe2+ into protoporphyrin IX, a reaction catalyzed by ferrochelatase. The precursor molecules are generated via the porphyrin synthesis pathway starting from δ-aminolevulinic acid (ALA).

Functions and occurrence: Protoheme is the prosthetic group in a wide variety of proteins, including hemoglobin and myoglobin for oxygen transport and storage, and many cytochromes involved in electron transfer and catalysis. The exact ligation environment and substitutions on the porphyrin ring can vary among proteins, giving rise to different spectral and redox properties.

Terminology: The term protoheme IX is used to distinguish heme B from other heme types such as heme a and heme c; protoheme IX corresponds to the iron protoporphyrin IX core found in many cytosolic and mitochondrial heme proteins.