Ferritin is a protein that binds iron and stores it in a safe form intracellularly. Transferrin is a protein that carries iron through the blood. So ferritin stores iron, transferrin transports it.
TRANSferrin TRANSports iron
I came across a really excellent article that breaks down the proteomics side of this. Although proteomics confuses me slightly, I really liked how they handled this comparison. Most of the rest of this post comes from several fantastic articles on Medscape, LabTestsOnline, and Wikipedia.
We have approximately 3.7g of iron stored in our bodies, all of it supplied by our diet. 2.5g of that is in hemoglobin, 1g of it is stored inside our cells and the remaining 0.02g is split up among molecules like myoglobin, and components of the electron transport chain.
Having free iron floating around in the body is a dangerous thing. In the ferrous state (+2), iron participates in the Fenton reaction which produces reactive oxygen species and free radicals. Ingesting iron can cause corrosion of the GI tract, bleeding, and diarrhea. In the bloodstream it can be taken up into cells and wreak havoc with oxidative phosphorylation processes and mitochondrial function.
To that end, the body has a protein called ferritin which serves to store iron intracellularly in the ferric (+3) state and prevent it from misbehaving until it’s required. Ferritin is basically a giant hollow ball with a few pores that allow iron to get inside. It is made of 24 identical subunits and about 4500 irons can fit inside. Ferritin is found in virtually all cells of the body, but is concentrated in cells of the “mononuclear phagocyte system” which are things like macrophages and monocytes concentrated in the liver (Kupffer cells), spleen and bone. When iron is needed, the ferritin is broken down in the cytosol and the iron is released.
Ferritin is mainly intracellular, but there are small amounts found in the blood. Blood levels generally reflect total body iron stores so measurement of blood ferritin is a useful way to approximate iron levels. Low ferritin can indicate iron deficiency anemia, it is also found in hypothyroidism, celiac disease, and pure vegetarianism. High ferritin can signal iron overload, but it can also be found in women taking oral contraceptive pills. Importantly, ferritin is also an acute phase reactant and levels can be increased in response to anoxia, cancer, infection (response to endotoxin), inflammation, etc. A measurement of CRP (C reactive protein, elevated during inflammation) can differentiate ferritin elevation as a marker of iron overload vs. an acute phase response. The normal reference range is 22 – 561 pmol/L (10 – 250 ng/mL).
Transferrin is the protein that carries iron in the bloodstream. It can securely bind 2 irons and it circulates until it encounters a cell with a transferrin receptor. It binds to the receptor, gets swallowed up by the cell, has the iron removed, and then gets spat back out into the bloodstream again. Transferrin is mainly produced in the liver and serves mostly to transfer iron from the duodenum, where it is absorbed, to cells that require it.
The normal amount of iron present in serum (bound to transferrin) is 11 – 32 µmol/L (60 – 178 µg/dL). Normal transferrin levels are 1.88 – 3.41 g/L (188 – 341 mg/dL). In iron deficient states there is an increase in transferrin levels. The rise in transferrin levels and the fact that there is an iron deficiency means that the total percentage of transferrin that is actually bound to iron decreases. So in these disease states there is a decreased “transferrin saturation”. Another way to say this, is that there is an increase in the “iron binding capacity” i.e. transferrin sitting around waiting for iron to show up. A transferrin saturation of <20% is indicative of iron deficiency, a transferrin saturation of >50% indicates iron overload.
Now here’s a little wrinkle in the story. There are multiple things that are measured when trying to determine someone’s iron status. Obviously we can just measure iron in the blood or iron in the bone marrow. We can also measure ferritin. But, instead of measuring transferrin, what you see a lot of is “total iron binding capacity”, “unsaturated iron binding capacity” and “transferrin saturation” as part of a workup. So why bother with these? The issue is cost. It turns out it’s cheaper to measure iron binding capacities and infer what that means about transferrin levels, rather than measuring transferrin directly. Basically, you take blood, add a known amount of iron to it and see how much iron is absorbed by the blood until it’s completely saturated. If you have to add a lot, it must mean there was a lot of unbound transferrin inside and/or the transferrin saturation was low. If you didn’t have to add much, there was very little transferrin inside and/or the transferrin was saturated already. This test just described is the “unsaturated iron binding capacity” or UIBC. Combined with a serum iron measurement (which is just iron bound to transferrin in blood) you get the “total iron binding capacity” or TIBC. TIBC can be used as a rough estimate of transferrin levels. The transferrin saturation can be calculated from these values.
UIBC = measured with radioactive iron or spectrophotometric tests
TIBC = UIBC + serum iron (normal range 45 – 82 µmol/L or 251 – 460 µg/dL)
Transferrin saturation = (serum iron X 100)/TIBC
More details can be found here.
In iron deficiency, the first things to be affected are ferritin levels, marrow iron levels, and iron binding capacity (transferrin levels). Next you see changes in serum iron, transferrin saturation, and hemoglobin.
Probably the most helpful thing I came across is a table from the LabTestsOnline page here. It goes through various combinations of test results and describes what they might indicate i.e. iron deficiency anemia, anemia of chronic disease, hemochromatosis, etc.
One final thing … although it’s not the topic of today’s discussion, it bears mentioning that iron can also be stored as hemosiderin. This is usually formed when a macrophage, or similar cell, tries to digest ferritin by sucking it into a lysosome. The ferritin is partially denatured and the iron is not readily bioavailable. This occurs in high iron states like iron overload due to multiple blood transfusions or hemochromatosis. It also occurs where there is a large local supply of iron due to internal hemorrhage or hemolysis. The condition of having too much hemosiderin is called hemosiderosis and it is problematic because the hemosiderin often deposits in tissues (or is removed very slowly) causing fibrosis. Hemosiderin deposition can be seen in the brain after a hemorrhage, in the lungs in patients with Goodpasture syndrome, in the pancreas leading to diabetes, or in the heart causing cardiomyopathy.
Here is that excellent proteomics article again
The LabTestsOnline table
And a great summary article on Medscape