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Physiological regulation of heme synthesis

Substrate availability

Iron (II) must be available for ferrochelatase.

Feedback regulation

Heme is a feedback inhibitor of ALA synthase.

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 synthase.

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