Figure 1
Heme Biosynthetic Pathway. Initiation of heme biosynthesis begins in the mitochondria with the condensation of succinyl coenzyme A (CoA) and glycine, catalyzed by ALA synthetase (ALA-S), form δ-aminolevulinic acid (ALA). Conserved biosynthetic protoporphyrin IX (PPIX) pathway: ALA is catalyzed by ALA dehydratase (ALA-D) in the cytoplasm to form porphobilinogen (PBG). Four molecules of PBG are combined by PBG deaminase (PBG-D) to form into the cyclic tetrapyrrole hydroxymethylbilane (HMB) and converted to Uroporphyrinogen III (Uro'gen III) by Uroporphyrinogen III synthase (URO-S). Uro'gen III is converted by Uro'gen III decarboxylase (URO-D) to coproorphyrinogen III (Copro'gen III), with the removal of CO2. Subsequent conversion of Copro'gen III to Protoporphyrinogen IX (Proto'gen IX) and finally protoporphyrin IX (PPIX) occurs in the mitochondria. This is catalyzed by the actions of Coproporphyrinogen III Oxidase (CPO) and Protophyrinogen IX Oxidase (PPO) respectively. Finally, ferrous iron (Fe2+) is inserted into the cyclic macrocycle through the action of ferrochelatase (FC) in the mitochondria.