The Electrain Series: Iron

Iron is found in the earth and in our bodies. It plays an important role in the human body as hemoglobin; it is also found in the liver, spleen, muscle tissue, and bone marrow as ferritin. [1]  We need around 10–18 milligrams of iron a day. [2]

Iron is involved in ATP production and a deficiency could decrease ATP production.

A surplus of iron is not good. Iron enters the mitochondria through the innermost matrix and is used for heme synthesis.[3] Iron has unpaired electrons and accepts or donates electrons which can let it react readily. 

Iron could also generate ROS or reactive oxygen species which could make it lethal. Humans absorb Fe2+ iron, which is heme iron or ferrous iron. [4

Fe2+ is normally found in hemoglobin and myoglobin. Humans do not absorb Fe3+, which is non-heme iron or ferric iron; this type of iron has to be converted to Fe2+ to be absorbed. [4] This iron is found in plants, grains, and some supplements. 

Fe3+ is found in plants because Fe3O4 is the form of iron found in soil. Ferrous salts (ferrous fumarate, ferrous sulfate, and ferrous gluconate) are the best absorbed iron supplements and other supplements such as ascorbic acid, can aid in absorption. [5] Ascorbic acid binds to iron and forms a molecule that is at a pH that increases the solubility in the duodenum, a part of the large intestine.

FTMT is mitochondrial ferritin, which is a gene that codes for proteins. Mitochondrial ferritin is an iron storage protein in the mitochondria. 

Fe-S synthesis forms iron-sulfur clusters that play an important role in the body. They are involved in respiration, photosynthesis, nitrogen fixation, amino acid, purine metabolism, RNA modification, DNA replication, and repair and regulation of gene expression. []

Fe3+ is insoluble at a neutral pH and only becomes soluble at an acidic pH. Fe2+, on the other hand, has a more acidic pH. Therefore, the body can absorb Fe2+. Fe3+ is better for transportation because it is better able to bind to transferrin which transports iron [6].   

Fe3+ is transported by transferrin(TF) and then binds to a transferrin receptor(TFR). This complex enters into the cell where TF and TFR are recycled. The Fe3+ is then converted to Fe2+ by the Six-Transmembrane Epithelial Antigen of Prostate 3 (STEAP3). [7] STEAP3 is  a malloreductase that converts Fe3+ to Fe2+. This is beneficial because the Fe2+ form is soluble. Then, divalent metal transporter 1(DMT1), a metal transporter, transports Fe2+ out of the endosome. 

An endosome is a vesicle formed by endocytosis. The iron becomes the labile iron pool (LIB). A labile iron pool is a pool of non-protein bound iron that generates oxygen radicals that contribute to oxidative cell damage. 


This iron can then be used for heme synthesis in the mitochondria or be stored in ferritin, a hetero-polymer of ferritin heavy (FTH) and light (FTL) chains, or can be exported from the cell by ferroportin (FPN).  [7

Excess iron consumption can lead to an upset stomach, nausea, diarrhea, and vomiting. Consuming even higher amounts of iron can also lead to organ failure and death. For this reason, supplemental iron should only be taken when a deficiency is identified and addressed by a licensed physician. 

Excessive iron consumption also leads to lower zinc absorption. Some people are born with a condition called hemochromatosishemocirhossis which causes their body to naturally store any iron consumed.

Fe2+ is generally absorbed better by the body, so therefore excess fe2+ will have a stronger effect.

References and Suggested Reading

Carocci, Alessia, et al. “Oxidative stress and neurodegeneration: the involvement of iron.” Biometals 31.5 (2018): 715-735.

Frey, Perry A., and George H. Reed. “The ubiquity of iron.” (2012): 1477-1481.

Lill, Roland, and Sven-A. Freibert. “Mechanisms of mitochondrial iron-sulfur protein biogenesis.” Annual review of biochemistry 89 (2020): 471-499.

Moustarah, Fady, and Shamim S. Mohiuddin. “Dietary iron.” (2019).

Pietrangelo, Antonello. “Hereditary hemochromatosis—a new look at an old disease.” New England Journal of Medicine 350.23 (2004): 2383-2397.

Staneviciene, Inga, et al. “Effect of Selenium on the Iron Homeostasis and Oxidative Damage in Brain and Liver of Mice.” Antioxidants 11.7 (2022): 1216.

Zhao, Zhongwei. “Iron and oxidizing species in oxidative stress and Alzheimer’s disease.” Aging Medicine 2.2 (2019): 82-87.

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