Background
Iron is the highest content of iron in the body and it is used for survival, growth and differentiation of cells, tissues and organs. Instabilities in iron homeostasis are strongly associated with diseases in other systems such as the nervous, cardiovascular, hematological and immune systems. Many illnesses, from infection to cancer, seem linked to iron homeostasis. As a transition metal, iron possesses unique biological properties characterized by significant changes in its Fe2+/Fe3+ redox potential. This ability to donate and accept electrons makes it advantageous for essential biological processes. Therefore, from unicellular bacteria to multicellular organisms like humans, iron is one of the most critical elements for sustaining life. It is indispensable in various life processes such as cellular respiration, growth, and death, and it contributes to host defense and cell signaling.
Ferritin is an iron-storing protein, so it is also the most used metric for calculating iron reserves. It is composed of 24 protein units that synthesise into a highly structured, spherical nano-shell having an outer diameter of 12 nm and an inner diameter of 8 nm. Its core can accommodate up to 4,500 trivalent iron atoms. Iron is stored in the form of hydroxide and phosphate complexes, which allows it to be safely stored without causing toxic effects to the cell. In eukaryotes, ferritin typically consists of heavy ferritin chain (HFn, 21 kDa) and light ferritin chain (LFn, 19 kDa) subunits. HFn contains a ferroxidase catalytic center responsible for oxidizing Fe2+, while LFn is involved in the nucleation of oxidized iron. During oxidative stress, HFn and LFn work together to convert Fe2+ into harmless Fe3+, thereby protecting cells from the damage caused by Fe2+.
Figure 1. Structures of human H-ferritin and L-ferritin
(Source: Plays M, et al. 2021)
A normal fecundity of ferritin testing is common in the healthy but, given that women, men and children differ in gender, age and physical state, the definition of iron deficiency from ferritin has been changed in recent years. Some researchers recommend transferrin saturation as an adjunct to functional iron deficiency in the context of inflammation and chronic disease. Additionally, during inflammatory processes, ferritin can increase as an acute-phase protein, independent of iron status. Beyond inflammation and infection, other factors such as heavy alcohol consumption, liver disease or damage, kidney failure, muscle cell breakdown, metabolic syndrome, acute myocardial infarction, and various malignancies can also lead to elevated ferritin levels.
References
- 1. Plays M, et al. Chemistry and biology of ferritin. Metallomics. 2021 May 12;13(5):mfab021.
- 2. He D, et al. Ferritin family proteins and their use in bionanotechnology. N Biotechnol. 2015 Dec 25;32(6):651-7.