Ferritin

 

Selective Transport and Storage of Ferritin

Ferritin plays a crucial role in the selective transport and storage of iron, which is vital for maintaining iron homeostasis and preventing toxicity in biological systems. Its ability to store iron safely and release it in a controlled manner is key to numerous physiological processes.

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Selective Transport of Iron by Ferritin:

 

Uptake of Iron (Selective Absorption):

 

1. Ferritin specifically binds ferrous iron (Fe²⁺), which is the bioavailable and transportable form of iron.

2. Iron enters ferritin through hydrophilic channels in its 24-subunit shell. These channels guide Fe²⁺ to the ferroxidase centers of the H-chains.

1. 

Ferroxidase Reaction:

 

1. At the ferroxidase center, Fe²⁺ is rapidly oxidized to Fe³⁺ using oxygen (O2O_2) or hydrogen peroxide (H2O2H_2O_2): 4Fe2++O2+6H2O→4Fe(OH)3+4H+4\text{Fe}^{2+} + O_2 + 6H_2O \rightarrow 4\text{Fe(OH)}_3 + 4H^+

2. This oxidation step prevents Fe²⁺ from participating in harmful reactions (e.g., the Fenton reaction).

 

Specificity of Transport:

 

1. Ferritin ensures selective transport by targeting only Fe²⁺, ignoring other ions such as Mg²⁺ or Ca²⁺.

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Storage of Iron in Ferritin:

1. 

Iron Mineralization:

 

1. After oxidation, Fe³⁺ ions are deposited as a hydrated ferric oxide-phosphate complex within the hollow core of ferritin: Fe(OH)3→Fe2O3⋅xH2O\text{Fe(OH)}_3 \rightarrow \text{Fe}_2\text{O}_3 \cdot xH_2O

2. The storage capacity of ferritin is remarkably high, holding up to 4500 iron atoms per ferritin molecule.

 

Role of L-Chains:

 

1. L-chains in ferritin facilitate the nucleation and stable mineralization of the iron core, promoting efficient storage.

 

Stabilization:

 

1. Phosphate ions (PO43−\text{PO}_4^{3-}) and water molecules help stabilize the ferric oxide core, ensuring long-term iron storage in a non-toxic form.

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Controlled Iron Release:

 

Reduction and Export:

 

1. For release, Fe³⁺ in the ferritin core is reduced back to Fe²⁺ by cellular reductants (e.g., NADH or ascorbic acid).

2. The Fe²⁺ exits through the same hydrophilic channels used for iron uptake.

 

Regulation by Cellular Needs:

 

1. Iron release is tightly regulated by iron demand, controlled by iron-regulatory proteins (IRPs) and signals like low cellular iron levels or hypoxia.

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Selectivity in Iron Transport and Storage:

 

Avoidance of Toxicity:

 

1. By sequestering iron as Fe³⁺ and preventing Fe²⁺ from participating in harmful reactions, ferritin minimizes oxidative stress caused by the Fenton reaction.

 

Iron-Responsive Elements (IREs):

 

1. The synthesis of ferritin is regulated at the mRNA level by iron-responsive elements (IREs):

1. High iron levels: Ferritin synthesis increases to store excess iron.

2. Low iron levels: Ferritin synthesis decreases to prioritize iron use.

 

Tissue-Specific Distribution:

 

1. Ferritin is distributed across tissues based on iron storage needs:

1. Liver and Spleen: Major iron storage organs.

2. Bone Marrow: Supplies iron for hemoglobin synthesis.

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Ferritin ensures selective transport and storage of iron through specialized pathways that prioritize safety, efficiency, and bioavailability. Its hydrophilic channels, ferroxidase activity, and tightly regulated release mechanisms make it indispensable for maintaining iron balance and protecting cells from iron-mediated toxicity.