Heme

Heme is a prosthetic group consisting of a porphyrin ring called protoporphyrin IX with an iron ion at its center. The iron is typically in the ferrous (Fe2+) form and can reversibly bind gases such as oxygen in many proteins; in ferric (Fe3+) form it cannot. In most proteins the iron is coordinated by the four nitrogens of the porphyrin and by two axial ligands provided by the surrounding protein, commonly a histidine and a substrate or water molecule. In c-type cytochromes the iron is covalently linked to cysteine residues via thioether bonds.

Heme occurs in a wide range of proteins. Heme b is the most common form and is found in hemoglobin and myoglobin, many cytochromes, and catalases. Heme a and heme c are variants used by specific enzymes, notably cytochrome c oxidase (heme a) and covalently bound cytochromes (heme c).

Biosynthesis takes place in mitochondria and cytosol through eight steps, beginning with δ-aminolevulinic acid and ending with the insertion of iron by ferrochelatase. The pathway is regulated mainly at the first step by ALA synthase (ALAS); ALAS1 operates in most tissues, ALAS2 in erythroid cells. Degradation occurs via heme oxygenase, producing biliverdin, free iron, and carbon monoxide; biliverdin is reduced to bilirubin for excretion.

Functions are diverse: heme is an essential prosthetic group for oxygen transport, electron transfer in the mitochondrial respiratory chain, and catalysis in various enzymes. Free heme is pro-oxidant and toxic, so organisms retain scavenging systems such as hemopexin and haptoglobin. Porphyrias are inherited or acquired disorders of heme synthesis that can cause abdominal pain, photosensitivity, and neurologic symptoms.