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The first, rate-limiting step is catalyzed by δ-aminolevulinic acid synthase (ALAS), which requires pyridoxal phosphate and is inhibited by heme. ALAS1 is chiefly associated with hepatic regulation by heme, whereas erythroid ALAS2 responds to iron and erythropoietin. As intermediates move through cytosolic reactions and return to mitochondria, specific enzyme blocks lead to precursor accumulation and distinct porphyrias. Lead inhibits both δ-ALA dehydratase and ferrochelatase, linking impaired heme production with microcytic anemia and basophilic stippling. The pathway also connects mitochondrial metabolism, through succinyl-CoA, with heme formation.