The degradation of heme by heme oxygenase (HO) releases ferrous iron (Fe2+) as one of the end products[1][2]. Once released, this iron has three main potential outcomes:
1. **Export to plasma**: The iron can be exported out of the cell through iron channels. In the plasma, it binds to transferrin, the iron transport protein[3]. This process requires the iron to be in its Fe2+ state, which is facilitated by the copper-dependent enzyme ceruloplasmin.
2. **Cellular storage**: The iron may be stored within cells as ferritin. Over time, ferritin can become oxidized and degrade to form hemosiderin[3].
3. **Immediate utilization**: The iron can be directly incorporated into proteins that require it, such as cytochrome P450[3].
## Macrophage Processing
Macrophages play a crucial role in iron recycling from heme:
1. They phagocytize senescent or damaged red blood cells.
2. The heme is degraded by heme oxygenase, releasing iron.
3. The released iron can then be exported to plasma via ferroportin, where it binds to transferrin[4].
## Iron Homeostasis
The fate of iron from heme degradation is tightly regulated to maintain iron homeostasis:
- **Hepcidin regulation**: The liver peptide hepcidin controls serum iron levels by causing degradation of ferroportin in iron-absorptive enterocytes and iron-recycling macrophages[4].
- **Intracellular regulation**: Iron regulatory proteins post-transcriptionally control genes involved in iron uptake, recycling, and storage[4].
## Potential Consequences of Excess Iron
While iron is essential, excess free iron from heme degradation can be problematic:
- It may propagate pro-oxidant reactions, potentially leading to cellular damage[5].
- In some contexts, it could trigger ferroptotic cell death[5].
In summary, the iron released from heme degradation is carefully managed by the body's iron homeostasis mechanisms, being either exported, stored, or immediately utilized, depending on the body's needs and the cellular context.
Citations:
[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7766613/
[2] https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2018.00198/full
[3] https://eclinpath.com/chemistry/iron-metabolism/heme-metabolism/
[4] https://haematologica.org/article/view/9512
[5] https://www.mdpi.com/1422-0067/22/11/5509
[6] https://www.sciencedirect.com/science/article/abs/pii/S0003986119302826
[7] https://www.pnas.org/doi/full/10.1073/pnas.96.23.13056
[8] https://www.sciencedirect.com/topics/immunology-and-microbiology/heme