Heme biosynthesis and the erythroblastic island. The terminal steps of erythroid development occur while erythroblasts are closely associated with a CM via αβ integrins, VCAM1, erythroblast macrophage protein (EMP), and ICAM4. Heme synthesis in this context is fully activated by the basophilic erythroblast (BasoEB) stage of development. CD163 and CD169 are macrophage-specific cell surface markers. Heme synthesis enzymes are in bold green text. CFU-E, colony forming unit–erythroid; CPOX, coproporphyrinogen III oxidase; HMBS, hydroxymethylbilane synthase; HSC, hematopoietic stem cell; OrthoEB, orthochromatic erythroblast; PBGS, porphobilinogen synthase; PolyEB, polychromatic erythroblast; PPOX, protoporphyrinogen oxidase; ProEB, proerythroblasts; RBC, red blood cell; SCoA, succinyl-CoA; UROD, URO decarboxylase; UROS, uroporphyrinogen III synthase.