Question

Normally when iron is in excess, hepcidin A. increases the formation of ferritin. B. inactivates ferroportin. C. prevents the reduction of \(\mathrm{Fe}^{+3}\) to \(\mathrm{Fe}^{+2}\). D. transports the iron across the cell membrane. E. catalyzes the oxidation of \(\mathrm{Fe}^{+2}\) to \(\mathrm{Fe}^{+3}\).

Short answer

A. Increases the formation of ferritin B. Inactivates ferroportin C. Prevents the reduction of Fe3+ to Fe2+ D. Transports iron across the cell membrane E. Catalyzes the oxidation of Fe2+ to Fe3+ Answer: B. Inactivates ferroportin

Step-by-step solution

Background knowledge on hepcidin and iron metabolism

Hepcidin is a peptide hormone that plays a crucial role in iron homeostasis. When iron is in excess, hepcidin acts to reduce iron absorption and release from enterocytes and macrophages by binding to the iron transport protein ferroportin. This binding leads to the internalization and degradation of ferroportin, ultimately reducing iron transport across the cell membrane.

Analyzing the choices

We will analyze each choice one-by-one. A. Hepcidin does not directly increase the formation of ferritin. Ferritin is an iron storage protein that stores iron in a soluble and non-toxic form, but its formation is independent of hepcidin. B. As discussed earlier, hepcidin does inactivate ferroportin by binding to it. This results in reduced iron transport across the cell membrane. C. Hepcidin does not directly prevent the reduction of \(\mathrm{Fe}^{3+}\) to \(\mathrm{Fe}^{2+}\). This is a separate process that occurs during iron absorption. D. Hepcidin does not transport iron across the cell membrane. Instead, it regulates iron transport indirectly by affecting ferroportin. E. Hepcidin does not catalyze the oxidation of \(\mathrm{Fe}^{2+}\) to \(\mathrm{Fe}^{3+}\). This process is unrelated to the regulatory function of hepcidin in iron metabolism.

Conclusion

Based on the analysis of the choices, the correct answer is option B: inactivates ferroportin. When iron is in excess, hepcidin reduces iron absorption and release by binding to and inactivating ferroportin, preventing iron transport across the cell membrane.

Key concepts

Iron Homeostasis

Iron homeostasis refers to the body's intricate management system for maintaining optimal levels of iron within the body. It's a critical balance; too little iron can lead to anemia, while too much can cause organ damage. The liver produces hepcidin, a central regulatory hormone, which plays a pivotal role in this equilibrium.

When iron levels are high, hepcidin levels increase, which in turn leads to a decrease in iron absorption in the intestines. Hepcidin achieves this by regulating the main iron transporter, ferroportin. When iron is scarce, hepcidin production is suppressed, allowing for increased iron absorption. The storage protein ferritin helps sequester excess iron, thereby preventing its toxic accumulation in cells.

Ferroportin Regulation

Ferroportin, a cellular protein, is the only known iron transporter that moves iron into the bloodstream from cells. Its activity is tightly controlled by hepcidin. In the presence of excess iron, hepcidin binds to ferroportin, which leads to the internalization and degradation of the transporter, effectively putting a stop to further iron release into the circulation.

Response to Iron Overload

When an overload of iron is detected, the upsurge in hepcidin ensures that ferroportin is inactivated, preventing further exacerbation of the high iron levels. This demonstrates how the body maintains iron balance, and prevents the detrimental effects associated with too much free iron.

Iron Transport Protein

Ferroportin is not just an iron transport protein; it's essential for controlling iron flow from certain cells into the bloodstream. These cells include enterocytes in the gut, where iron is absorbed from our diet, and macrophages that recycle iron from old red blood cells. It's critical for maintaining systemic iron balance.

The regulation of ferroportin by hepcidin prevents iron from flooding the bloodstream during conditions of iron excess. Understanding how ferroportin functions elaborate on the precise mechanisms the body employs to safeguard against iron-related disorders, such as hemochromatosis, wherein iron accumulates to toxic levels in the body.