CHAPTER 8: Biological Heme Degradation

Biological heme degradation is a physiologically important process not only for mammals, but also for plants and pathogenic bacteria. Heme catabolism is essential for mammalian iron homeostasis, for light-sensing billin biosynthesis in cyanobacteria and plants, and iron acquisition from host hemin in some pathogenic bacteria. Heme oxygenase, HO, which catalyzes the conversion of hemin to free iron, carbon monoxide, and biliverdin, has been considered as a sole player in biological heme degradation. HO attains this task by three successive monooxygenation reactions through meso-hydroxyheme and verdoheme intermediates, utilizing three oxygen molecules and seven electrons. The HO catalytic mechanism is now mostly understood. Recent discovery of new heme degrading enzymes, IsdG and IsdI, of Staphylococcus aureus and MhuD of Mycobacterium tuberculosis, extends the spectrum of heme degradation. MhuD degrades hemin to free iron and mycobilin where α-meso carbon retains a formyl group through sequential mono- and dioxygenase reactions. The IsdG reaction forms staphylobilin isomers with the release of iron and formaldehyde. This chapter will review the catalytic mechanisms of HO and IsdG-type enzymes.