Substrate availability
Iron (II) must be available for ferrochelatase.
Feedback regulation
Heme is a feedback inhibitor of ALA
Subcellular localization
ALA synthase is in the mitochondria, where the substrate, succinyl CoA, is produced. ALA synthase is synthesized in the cytoplasm, and is transported into the mitochondria (like many other mitochondrial proteins). Its transport across the mitochondrial membrane may be regulated.
In erythropoietic cells, heme synthesis is coordinated with globin synthesis. If heme is available, globin synthesis proceeds. If heme is absent:
- a cAMP independent protein kinase is active.
- the kinase phosphorylates and thereby inactivates, the eukaryotic initiation factor, eIF-2. This prevents further globin synthesis
Effects of drugs and steroids
Remember, certain drugs and steroids can increase heme synthesis via increased production of the rate-limiting enzyme, ALA