What Is Hepcidin?
Hepcidin, a protein-based hormone, works to balance and modulate the blood’s iron proportion. The liver cells, or the hepatocytes, manufacture and yield hepcidin, and hence, the liver is designated to be the source of the hepcidin hormone. The liver cells formulate hepcidin in its non-functional state, pre-pro-hepcidin, encompassing 84 amino acid units. Pre-pro-hepcidin gets transfigured into functionally active hepcidin, which is catalyzed and effectuated by certain enzymes. The bioactive hepcidin structurally entails 25 amino acids in it. Hepcidin holds the critical responsibility of iron homeostasis, and therefore, the hepcidin proportions in the blood and its secretions are governed by the fluctuations in the iron proportions. In addition, it could also impart innate immunity and comprehend defense against certain diseases.
How Does Hepcidin Aid in Achieving Iron Homeostasis?
Several food sources house notable amounts of iron in them, so upon intake, the iron from the food gets into the body. Once absorbed, these iron molecules get stockpiled within the body, and there is no bodily process to clear off the excess iron that is absorbed from the ingested food. The spleen, bone marrow, and liver are the organs where iron gets stockpiled. When the iron proportions in the blood tapers, the iron stores are being utilized to reinstate the healthy iron level. Similarly, when the iron proportions surpass the healthy limits, the iron uptake will be repressed to delimit the further ingress of iron atoms into the circulation. All these processes are being governed and modulated by hepcidin. The hepcidin proportions and its discharge have direct implications on the blood’s iron proportions. Apart from the iron level, hepcidin discharge is governed and directed by erythropoiesis (red blood cell generation process), hypoxia (condition instigated by depleted oxygen delivery), and inflammation (presentation invoked by immune cells in the event of an infection or injury).
When the iron proportion in the blood upscales, the hepatocytes let out and unleash more hepcidin. Thus, liberated hepcidin holds back further iron uptake from the small intestine, which delimits the further ingress of iron from dietary inputs. This inhibition is channeled through the hepcidin’s association with ferroportin (an iron exporter that fetches and conveys iron atoms from the cellular reservoir to the blood). Hepcidin clings onto the ferroportin molecules and instigates disfigurements and total defacing of the ferroportin molecules. As the conveyance of iron molecules from the cellular compartment (inside of the cell) into the extracellular area is channeled by ferroportin, impeding the ferroportin shuts off iron ingress into the bloodstream from both the reservoirs and dietary inputs. Thus, the iron from the small intestine could not be uptaken and channeled into the bloodstream owing to the ferroportin’s structural mutilation, which was inflicted by the hepcidin. Similarly, the iron atoms stockpiled in discrete organs were also restrained from ingressing into the bloodstream as their channeling from the reservoir cells into the blood is also assisted and mastered by the ferroportin. Thus, the ingress of iron, neither from the reservoir nor from the dietary input, is permitted without ferroportin.
When the blood’s iron proportion palliates, the hepatocytes are signaled to mitigate the hepcidin liberation. Therefore, more of the ferroportin molecules become functional, facilitating and expediting iron uptake through the small intestines. Similarly, iron atoms from the storage reservoir are also set free into the blood, piloted by the ferroportin exporter molecule. Both these initiatives bring up the blood’s iron proportion up till it attains the healthy range.
Routinely, following a 120-day lifespan, the red blood cells (RBC) expire, and in their dying phase, the macrophage (a form of white blood cell) captures and takes custody of the iron atoms that are enwrapped in the moribund red blood cell. The captured iron atoms are again reserved within the macrophages, and the hepcidin governs their liberation.
What Are the Diseases Associated With Hepcidin Imbalance?
Imbalance or impairment with regard to the hepcidin functions and proportions could bring forth certain medical conditions.
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Hereditary Hemochromatosis: Hereditary hemochromatosis is instigated by alterations or aberrations in the HFE (hemostatic iron regulator) gene. The faulty HFE gene downturns the hepcidin production, which in turn upscales the active ferroportin availability, and so does the iron uptake for dietary inputs and its liberation from the storage reservoirs. Therefore, the plasma iron proportion surpasses the healthy range, causing iron overload.
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Anemia of Chronic Disease: Hepcidin also exerts authoritative participation in prompting anemia of chronic disease. Hepcidin proportions are vulnerable to inflammations. So inflammatory conditions upregulate the hepcidin liberation. Therefore more of the ferroportin molecules get shut off, eventually palliating the iron uptake and its mobilization. The iron atoms that are accessible in the bloodstream tapers down, projecting anemia. Cancers, kidney disease, and infections could bring forth anemia of chronic disease.
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Iron Deficiency Anemia: When hepcidin proportions are upscaled, the iron proportions in the blood turn down, giving rise to iron deficiency anemia. In iron deficiency anemia, the red cell proportions in the bloodstream collapse.
What Are the Variables That Guide and Modulate the Hepcidin Level?
Certain bodily variables could regulate and master the hepcidin proportions in the blood.
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Fluctuations in the Blood’s Iron Proportions: Hepcidin is directly governed by blood’s iron proportions. Both inflation and deflation of the blood’s iron proportion instigate modulations in the hepcidin liberation.
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Downturned Oxygen Level in the Tissue: When the cellular oxygen level depletes (hypoxia), the body needs more hemoglobin and iron to channel more oxygen so as to offset oxygen deprivation. Thus, hypoxia signals the body to shut off hepcidin liberation, augmenting the availability of plasma iron.
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Erythropoiesis (Red Blood Cell Generation): During erythropoiesis, the exigency for iron upscales. In order to comply with the body’s need, hepcidin liberation will be turned down.
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Inflammation: Inflammation signals the body to gear up for hepcidin liberation.
Conclusion:
Hepcidin is the key integrant in iron homeostasis, which assists in up-regulating and down-regulating iron proportions in accordance with plasma iron levels. It could also govern certain disease development and progression owing to its ascendancy in iron homeostasis. Furthermore, certain diseases could also bring forth derangements in the hepcidin level. Hepcidin masters the iron proportion and acts as a check on iron overloading, where the iron proportions exhibit unhealthy inflation. Thorough apprehension of the intricacies inflicted by hepcidin derangements is, therefore, essential for instituting prompt management strategies.
