Category: biosynthesis
Eight-step pathway from succinyl-CoA + glycine to heme. Mitochondrial / cytosolic shuttle: ALAS (rate-limiting, mitochondrial; hepatic ALAS1 + erythroid ALAS2) → δ-aminolevulinic acid (ALA) → cytosolic steps to coproporphyrinogen III → back into mitochondria for protoporphyrinogen → heme (ferrochelatase). Deficiencies of any step produce the porphyrias — acute intermittent porphyria (PBGD), porphyria cutanea tarda (UROD), variegate porphyria (PPOX), erythropoietic protoporphyria (FECH). Lead inhibits ALA dehydratase + ferrochelatase, producing the basophilic stippling + microcytic anemia of plumbism. Iron deficiency limits heme via ferrochelatase substrate exhaustion.