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Solving the Problem of Iron: Acquisition, Transport, and Control

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Editor’s note: Physicians have a special place among the thinkers who have elaborated the argument for intelligent design. Perhaps that’s because, more than evolutionary biologists, they are familiar with the challenges of maintaining a functioning complex system, the human body. With that in mind, Evolution News & Views is delighted to present this series, “The Designed Body.” For the complete series, see here. Dr. Glicksman practices palliative medicine for a hospice organization.

Without oxygen (O2) we can’t live very long. To get enough O2 to survive, we need the respiratory center in our brain telling our muscles of respiration to breathe air in and out of our lungs. However, because O2 doesn’t dissolve well in blood, we also need to have enough red blood cells to make enough hemoglobin to transport enough O2 to our cells.

the-designed-body4.jpgEvolutionary biologists expect us to believe that blind processes of chance and the laws of nature alone brought about the development of all of the components of the respiratory system and hemoglobin production, including the mechanisms that control them (never mind that without any one component the system would fail, and death would take place).

But that still isn’t enough to explain how our cells get the O2 they need to live and work properly. For it’s the iron (Fe) in the hemoglobin molecule to which O2 actually attaches and enables it to be transported in the blood throughout the body. Therefore, no iron means no hemoglobin, and no hemoglobin means no O2 transport, and no O2 transport means no life. However, having too much iron can be toxic to the body. So the body must be able to not only acquire enough iron to make enough hemoglobin, it must be able to control it as well. Here’s how the body does all that.

We get iron from meat, fish, and poultry, but also from fruits, vegetables, dried beans, nuts, and grains. Iron is mainly taken into the cells that line the upper part of the intestine. But just because iron comes into the intestinal cell doesn’t mean it will automatically pass out of it and into the blood. To enter the blood, the iron must pass out through a protein in the plasma membrane of the intestinal cell called ferroportin. It’s by controlling how much iron leaves the intestinal cells, through ferroportin, that the body controls both its intake of iron and its total iron content.

To take control, the body uses a hormone, made in the liver, called hepcidin. Hepcidin works by locking onto ferroportin and blocks it from letting iron out of the intestinal cell. The liver cell is able to detect its own content of iron and matches this with the amount of hepcidin it releases into the blood.

The more iron stored in the liver, the more hepcidin it releases. More hepcidin results in less iron passing from the intestinal cells, through ferroportin, into the blood and prevents the body from having too much iron. And the less iron stored in the liver, the less hepcidin it releases. Less hepcidin results in more iron passing from the intestinal cells, through ferroportin, into the blood and helps keep the body’s iron level where it should be. The iron that remains in the intestinal cells due to the effect of hepcidin on ferroportin eventually leaves the body when these cells die and slough off within a few days.

However, just like oxygen, iron needs to be transported in the blood by a specialized protein so it can go to where it’s needed. This protein, also made in the liver, is called transferrin. The production of transferrin is inversely related to the amount of iron stored in the liver. The more iron in the liver, the less transferrin is produced, while the less iron in the liver, the more transferrin is produced.

Transferrin carries iron to the bone marrow and other organs and tissues. The cells have specific receptors for transferrin in their plasma membranes. These receptors lock onto transferrin, with its cargo of iron, so they can unload the iron into the cell. The number of transferrin receptors a given cell has is inversely related to how much iron it has stored within it. The less stored iron it has, the more transferrin receptors it has so it can collect more iron. And the more stored iron it has, the less transferrin receptors it has so it will not take in too much iron.

In particular, the developing red blood cells in the bone marrow, which constantly use iron to make hemoglobin, have a high concentration of transferrin receptors. That allows them to pick up most of the iron that is carried to the tissues.

The total absence of iron is incompatible with human life. In developed countries, iron deficiency anemia usually takes place due to chronic blood loss from the gastrointestinal system, or less commonly, from low dietary intake. With worsening iron deficiency anemia the body experiences severe weakness, dizziness, and shortness of breath.

This takes place because, although the lungs may be bringing in adequate amounts of O2, the tissues can’t get enough of it because the blood’s O2 carrying capacity is severely reduced. Iron deficiency anemia can easily be treated with oral supplements of iron and usually the underlying cause can be identified and treated.

On the other hand, if the cells of the body store too much iron, then it is said to be in a state of iron overload. One of the commoner causes for this is condition is hereditary hemochromatosis. Medical scientists have only recently discovered that this type of iron overload is often related to a malfunction of the proteins hepcidin and/or ferroportin, resulting in too much iron being taken into the body through the intestine.

Too much iron in the cell can be toxic and can result in not only malfunction but even cell death. This usually results in multi-organ failure (liver, pancreas, heart) and infertility. The main treatment for this condition is the regular removal of blood by phlebotomy to keep the iron levels down to prevent further organ damage.

Our ancient ancestors, who were trying to win the battle for survival on a daily basis, would have needed the right amount of iron to survive. For they didn’t have the benefit of modern medicine to diagnose and treat conditions like iron deficiency anemia and iron overload.

However, having a properly controlled respiratory system and the ability to produce the right amount of hemoglobin with the right amount of iron to carry enough O2 in the blood still doesn’t fully explain how enough O2 gets to the cells. To understand that, we’ll need to consider the cardiovascular system and what it must do to overcome the laws of nature and thus to function properly.

Image by Alchemist-hp (talk) (www.pse-mendelejew.de) (Own work) [FAL or GFDL 1.2], via Wikimedia Commons.