The largest cellular receptor in the body, which binds to vitamin B12, has now been identified. "What we're looking at is evolution at a structural level. A receptor with a toadstool structure that stems from way back and the common ancestors of insects and humans,” said researcher Christian Brix Folsted Andersen, Ph.D., an Associate Professor at the Department of Biomedicine at Aarhus University in Denmark. The work has been reported in Nature Communications.
We need vitamin B12 for a variety of important functions including making red blood cells and controlling DNA. Most adults need around 2.4 micrograms a day, and the vitamin is not produced in our bodies, so we have to ingest it in foods like beef, eggs or fish or use supplements. While some people may benefit from supplementation, others cannot absorb it even when large amounts are taken. That makes B12 deficiency fairly common, which can lead to anemia, problems in the nervous system, and other health issues.
The receptor for B12 is a strange and ancient molecule that seems to have been created when two proteins combined. Researchers still don’t know why biology has been kept like this. Dorothy Hodgkin won the Nobel Prize for elucidating the structure of B12 in the 1960s; now we know its receptor is over than one thousand times larger. It’s helped the researchers understand why absorption of the vitamin can go wrong in so many people.
"With the help of x-ray crystallography, we've succeeded in determining how the receptor is able to organize itself in a previously unknown way in human biology. With this new knowledge we're finally able to explain why thousands of people around the world with specific genetic changes are unable to absorb the vitamin," Andersen said from where he's currently working at the University of Washington.
"But in my mind, the most interesting aspect is that with the help of advanced electron microscopy, which I'm learning about in detail here in Seattle, we have been able to see how the receptor as a whole looks and thus also see how the receptor absorbs the B12 vitamin in the intestines and various other substances in the kidneys. It's fantastic to have the opportunity to see this as the first person ever," he added.
Andersen noted that in the context of evolution, the receptor is unusual; it’s not like anything else that’s been discovered before. "At the same time, by comparing genes we can see that the receptor has the same structure as we find in insects and that it must have been evolved very early in evolution - many millions of years ago and thus long before the origin of mammals," he said.
Christian Brix Folsted Andersen has been at collaborating with Søren K. Moestrup on studies of B12 transport for a long time. In 2010, their efforts led to insight into how the receptor identifies B12 in the small intestine.
"The research we're carrying out today is a continuation of decades of research into the vitamin B12. Indeed, twenty-five years ago we had no idea about what was going on the shadowy recesses of the intestines. Now the lights have been turned on, and we can see how it all works in a way that none of us could have imagined," said Søren K. Moestrup.
"Apart from obviously being very satisfying from a scientific viewpoint, it also opens completely new perspectives for medical treatment. For example, we now have in-depth knowledge about a receptor that could evidently be used to transport drugs into the kidneys and intestines," he added.
Learn more about vitamin B12 absorption in the body from the video.
Sources: AAAS/Eurekalert! via Aarhus University, Harvard Health Publishing, Nature Communications