Haemochromatosis: Iron, provider and poisoner

Hello everyone,

Dr Seth and I were discussing a disease known as haemochromatosis on Friday, after the lecture. Essentially, this disease results in iron-overload disorder, a potentially fatal condition. Haemochromatosis can have various causes, but it is generally observed in (human) people with a homozygous cytosine-282-tyrosine mutation in the so-called HFE (High Fe/iron) gene. This results in the body perceiving that it is perpetually deficient in iron, and so iron uptake is continually maximal.

This in itself would not be a major problem if the body had mechanisms to excrete iron: this is not the case, however! In humans, iron cannot be removed from the body except by its use in proteins (etc.). Evolutionarily speaking, this is likely due to the fact that our bodies need to do a lot of work to extract iron from the normal form of iron found in our environment, rust. Most of our iron must thus be reduced before it can be incorporated into the body. Some creatures (e.g. crustaceans) have blue blood because they use copper instead of iron as their oxygen carrier; copper is found in the pure form much more readily than iron, so this is a more efficient metal to use. Thus, in people with iron-overload disorder, iron levels keep building. This can result in death (more on that later).

The body uses iron primarily as an oxygen carrier in haemoglobin but it also has other roles. One of the major side effects of iron presence in the body is the creation of free radicals. Iron in the 2+ ionic form is particularly good at reducing hydrogen peroxide, a by-product of many cellular reactions. The chemical reaction can be summarised as Fe(II) + H2O2 --> Fe(III) + OH- + ·OH. The middle dot next to the second hydroxyl group signifies that this is a free radical group: the hydroxyl group now has a single free electron. Free radical groups are very dangerous to the body because they can interfere with many, many reactions (I will describe some of these in another post); their main problem arises from the fact that they can create other free radicals, exacerbating the issue. This is known as Fenton chemistry or oxidative stress; free radicals can cause DNA damage and cellular dysfunction because they are so reactive and interfere with so many reactions.

So, the problem with excess iron is the extra creation of these free radicals! This is often why anti-oxidants are so famous; they are supposed to stop this from happening in normal life. Fortunately, the body is very good at doing this on its own, except when there is so much iron present that the body cannot cope with it. Thus, most medications for iron-overload disorder (other than flabotomy) rely upon chelating the excess iron: if there is little Fe(II) iron floating around, then the body can cope with it.

Josh H

PS: You may marvel at my title, if you wish. :)