FIG. 1.

Heme biosynthesis cycle. In mammalian cells, 5-ALA is formed from the condensation of glycine and succinyl coenzyme A (CoA), while most bacteria use glutamate as the substrate. Two molecules of 5-ALA condense to form porphobilinogen, catalyzed by 5-ALA dehydratase. Four molecules of porphobilinogen then condense to form a linear tetrapyrrole, which cyclizes to form 8-carboxyporphyrinogen (uroporphyrinogens I and III). Plants and bacteria can use uroporphyrinogen III as an intermediate in the synthesis of various molecules (e.g., chlorophyll and vitamin B₁₂). Mammals exclusively use PPIX, obtained after numerous enzymatic decarboxylations and desaturations, while different CPs (8-CP, 7-CP, 6-CP, 5-CP, 4-CP) can be found in bacteria.