Porphyrins are organic compounds. Many porphyrins are involved in oxygen transportation. Porphyrin ring biosynthesis begins in the mitochondria and involves glycine and succinyl-CoA condensation by δ-aminolevulinic acid synthase (ALAS) to produce δ-aminolevulinic acid (ALA), also known as 5-aminolevulinic acid. ALA is then transported to the cytosol where it becomes dimerized by ALA dehydratase (also known as porphobilinogen synthase) to produce porphobilinogen. The pathway continues with the condensation of 4 molecules of porphobilinogen catalyzed by porphobilinogen deaminase (PBG deaminase, also called hydroxymethylbilane synthase or uroporphyrinogen I synthase) to produce hydroxymethylbilane. Hydroxymethylbilane may then be converted to uroporphyrinogen III, a heme intermediate, or it may be non-enzymatically cyclized to uroporphyrinogen I. In the cytosol, uroporphyrinogen I and III substituents become decarboxylated to become coproporphyrinogens. Coproporphyrinogen III is an important intermediate in the synthesis of heme. In the inner mitochondria, coproporphyrinogen III undergoes decarboxylation of 2 propionate residues producing protoporphyrinogen IX. Protoporphyrinogen IX oxidase converts protoporphyrinogen IX to protoporphyrin IX. The final reaction of heme synthesis is ferrochelatase catalyzing the insertion of iron into the ring, producing heme b. Heme is broken down when heme oxygenase opens the heme ring. This oxidation produces linear tetrapyrrole biliverdin, ferric iron (Fe3+), and carbon monoxide (CO). Biliverdin reductase then produces bilirubin.

Porphyrin Metabolism References