Iron, Copper, and Zinc Homeostasis: Physiology, Physiopathology, and Nanomediated Applications

Abstract

Understanding of how the human organism functions has preoccupied researchers in medicine for a very long time. While most of the mechanisms are well understood and detailed thoroughly, medicine has yet much to discover. Iron (Fe), Copper (Cu), and Zinc (Zn) are elements on which organisms, ranging from simple bacteria all the way to complex ones such as mammals, rely on these divalent ions. Compounded by the continuously evolving biotechnologies, these ions are still relevant today. This review article aims at recapping the mechanisms involved in Fe, Cu, and Zn homeostasis. By applying the knowledge and expanding on future research areas, this article aims to shine new light of existing illness. Thanks to the expanding field of nanotechnology, genetic disorders such as hemochromatosis and thalassemia can be managed today. Nanoparticles (NPs) improve delivery of ions and confer targeting capabilities, with the potential for use in treatment and diagnosis. Iron deficiency, cancer, and sepsis are persisting major issues. While targeted delivery using Fe NPs can be used as food fortifiers, chemotherapeutic agents against cancer cells and microbes have been developed using both Fe and Cu NPs. A fast and accurate means of diagnosis is a major impacting factor on outcome of patients, especially when critically ill. Good quality imaging and bed side diagnostic tools are possible using NPs, which may positively impact outcome.

Keywords: copper physiology; hepcidin; inflammation; iron deficiency; iron overload; iron physiology; nanoparticles; nutritional immunity; sepsis; zinc physiology.

Figure 1

The roles of Fe, Cu, and Zn in human organs (left, in blue) and bacteria (right, in red).

Figure 2

Regulation of iron efflux from enterocytes and macrophages by hepcidin. Reproduced with permission after Pantopoulos K. et al., 2008 [16].

Figure 3

Regulation of hepcidin transcription. (A) Hepcidin regulation by the extracellular iron. (B) Hepcidin regulation by inflammation. Reproduced with permission after Ruchala et al., 2014 [25].

Figure 4

Absorption of ions by enterocyte. (A) Cu absorption during normal homeostasis and in iron deficiency; main pathway during iron deficiency marked with ^★; (B) Zn absorption during normal homeostasis.

Figure 5

Medical uses of Iron nanoparticles: (a) normal Iron homeostasis; (b) pathologies resulting from abnormal Iron homeostasis; (c) properties of nanoparticles. DMT1—divalent metal transporter 1; FPT—ferroportin; Fe—iron; Hep—hepcidin; BMP—bone morphogenic protein; IL-6—interleukin 6; HH—hemochromatosis; Tha—Thalassemia; IA—inflammatory anemia.