Sources and Intestinal Barrier
The body obtains iron through two pathways: externally via the diet (exogenous pathway) and through the breakdown of senescent erythrocytes (endogenous recycling). For dietary iron to be absorbed, an acidic gastric environment and the presence of reducing agents are required. The primary reducing agent is vitamin C, which converts ferric iron into ferrous iron (Fe2+). It is in this form that the trace element crosses the enterocytes (intestinal mucosal cells).
Inside the enterocytes, the "mucosal block" mechanism operates. Its purpose is to prevent excess iron from entering the bloodstream:
- If the body's requirement is low, the cells actively synthesize the protein apoferritin. It binds iron ions, turning into ferritin (Fe3+). This iron remains in the mucosa and is eliminated in the feces during normal epithelial desquamation.
- If there is a deficiency, apoferritin synthesis is inhibited, and ions pass freely through the enterocyte into the bloodstream.
Transport and Cellular Receptor-Mediated Uptake
Leaving the intestine through the basolateral membrane, the Fe2+ ion enters the plasma, where it is re-oxidized to Fe3+. This is mediated by the copper-containing enzyme ferroxidase (also known as ceruloplasmin). During the reaction, copper is reduced (Cu2+ → Cu+), and the prepared iron binds to the transport glycoprotein apotransferrin. This forms the transferrin-Fe3+ complex, which is distributed throughout the body.
Delivery of iron to target tissues occurs via specific transferrin receptors:
- The complex binds to the receptor on the cell surface.
- Endocytosis forms a vesicle (endosome).
- Inside the cell, iron is released (again as Fe2+) and utilized for metabolic needs.
Upregulation of membrane receptors depends directly on intracellular stores. When iron is scarce, transcription of the receptor gene is enhanced, and the cell takes up more transferrin from the blood.
Distribution, Storage, and Excretion
Iron delivered to tissues is consumed in the synthesis of hemoproteins (e.g., hemoglobin in bone marrow or myoglobin in muscles) and iron-sulfur proteins. Excess iron is stored in the liver, spleen, and bone marrow.
The primary storage protein is ferritin. However, if too much iron enters and ferritin capacity is exceeded, it transforms into hemosiderin. This is a poorly soluble complex capable of storing up to 37% of its structure as iron.
Normally, massive losses of the trace element are minimal. The body loses iron via feces (including bile and desquamated epithelium), sweat, urine, as well as during menstruation, bleeding, pregnancy, and lactation. At the same time, a significant portion of iron is constantly in circulation: macrophages of the reticuloendothelial system engulf destroyed erythrocytes, release iron from hemoglobin, and return it to the blood.