Eight enzymes are involved in heme biosynthesis, four each in the mitochondria and the cytosol. The process starts in the mitochondria with the condensation of succinyl CoA (from the TCA cycle) and glycine to form 5-aminolevulinate (ALA). The next four steps take place in the cytosol. Two molecules of ALA are condensed to form the monopyrrole porphobilinogen (PBG). The next two steps convert four molecules of PBG into the cyclic tetrapyrrole uroporphyringen III, which is then decarboxylated into coproporphyrinogen III. The last three steps occur in the mitochondria and involve modifications to the tetrapyrrole side chains and finally, insertion of iron. In addition to these synthetic steps, a spontaneous cytosolic reaction allows the formation of uroporphyringen I which is then enzymatically decarboxylated to coproporphyrinogen I, which cannot be metabolized further.

Two heme biosynthetic processes can be distinguished in vivo: one confined to immature erythroid cells that provides the large amount of heme needed for hemoglobin, and a ubiquitous one that provides the variable amounts of heme needed for cytochrome P450 enzymes (Riddle et al. 1989). The two processes differ most significantly at their first step, the condensation of succinyl CoA and glycine catalyzed by delta-aminolevulinate synthase, and its regulation.