A close and slippery escort: is our mucus involved in the body’s metabolism?

The scientists of the institute discovered a surprising involvement of the intestinal mucus in the absorption process of copper – a metal that, like iron and zinc, is necessary for our bodies, but can be dangerous.

The mucus that covers the inner walls of some of our organs is not just a viscous layer lacking properties, but a smart substance that knows how to protect and nourish the tissues. Lung mucus, for example, filters out harmful microorganisms while allowing the passage of essential gases for breathing. In the intestine, another type of mucus covers large areas, blocking the path of unwanted substances while allowing the smooth passage of nutrients and fluids. Recently, scientists at the Weizmann Institute of Science discovered that the mucus in the intestine is responsible for another important and unexpected action: it helps in the safe absorption of copper – a metal that is necessary for the normal functioning of the body, but can be toxic.

This discovery was revealed when a research team in the laboratory of Prof. Deborah Fass from the Department of Structural and Chemical Biology was engaged in deciphering the structure of the main component in mucus – the protein mucin. The deciphering challenge was particularly difficult due to the large size of the mucin molecules – one of the largest in the human body – which combine together to form even larger two-and-a-half structures, which give mucus its varied and slippery abilities. In the process of deciphering the structure, the researchers were surprised to discover a cluster of amino acids, which looks like a metal binding site – a possible clue to the unknown involvement of mucus in the body’s metabolism. The researchers exposed the mucin protein to a variety of metals, and the conclusion was not long in coming: it is a binding site for copper.

The mucin protein (in purple) lining a mouse intestine, under microscope magnification

The importance of copper – found in seafood, fish, nuts and dark chocolate – is less known to the public than other metals, such as iron and zinc, but this metal is also essential for the proper functioning of our body. In combination with various enzymes, copper allows cells to produce energy, contributes to the formation of connective tissues, paves the way for the growth of new blood vessels, and has many other functions. But copper can also harm the body. The same property that allows copper ions to easily transfer electrons that are necessary for biochemical reactions, also carries a danger: the transfer of electrons to oxygen molecules and the creation of free radicals that are harmful to cells.

“The body’s task is to manage to transfer the desired amount of copper from the food we eat to the places in the body where it is needed – without allowing the copper ions to wreak havoc along the way,” says Prof. Fass. Could it be that the mucus helps the body in this task?

Nava Reznik, a research student in Prof. Fass’s lab, led the experiments designed to test the hypothesis. Using X-ray crystallography, Resnik discovered that the mucus protein in the intestine actually has not one binding site for copper, but two: one is for copper ions with a double positive charge – Cu2+ – the configuration of copper obtained from the food we eat, while the other is for copper ions with a single positive charge – Cu+ – the configuration that enters the cells of the body.

A healthy cell layer (left) began to disintegrate following exposure to copper (middle) but remained intact when the exposure was accompanied by the addition of the protein mucin (right)
A healthy cell layer (left) began to disintegrate following exposure to copper (middle) but remained intact when the exposure was accompanied by the addition of the protein mucin (right)

The researchers hypothesized that the mucin protein found in the intestinal mucosa binds the copper ions coming from the food and helps to convert them into the configuration necessary for the body, copper with a single positive charge, that is, by absorbing one electron. It also keeps the converted ions with it and thus prevents them from releasing the electron they just received in the wrong place. “Mucin prevents copper from running freely in the body and damaging the tissues,” Reznik says.

In experiments aimed at confirming this hypothesis, the team showed that the protein does inhibit the damage that could have been caused to the cells as a result of exposure to copper, while at the same time allowing the cells that need it to absorb it safely. Although the experiments were carried out in laboratory equipment, the researchers believe that the processes discovered faithfully reflect what is happening inside the body.

Like a responsible adult accompanying a new driver, the mucin protein in the intestine accompanies the disaster-prone copper ions as soon as they enter the body and ensures that they behave properly on their way to the places where they are needed – and it is probably not only the body tissues, but also the bacterial population in the intestine that also needs copper in order to survive . “It has been known for many decades that inside the cells copper is closely accompanied by proteins, but until now no one thought to ask what happens to this metal when it first enters the body,” says Prof. Fass.

Foods rich in antioxidants, such as green tea or berries, are the last word in the field of nutrition, and it appears that our mucus is coming towards us on this front as well. By binding the copper ions, the researchers believe, the mucus actually prevents a harmful flow cycle of electrons from the antioxidants to the copper ions and from there to the oxygen molecules and the creation of free radicals that damage the tissues.

Our mucus does not always receive the appreciation and research attention it deserves, but the new findings pave the way for further studies of the properties of mucus and its involvement in various medical conditions characterized by serious and life-threatening metal deficiencies. For example, Prof. Fass and Resnick recently participated in a scientific conference on the role of copper in human metabolism. Among the participants were also a child suffering from a severe disability due to a lack of copper and a scientist studying the molecular mechanisms involved in his condition. “The conference made it clear to us how tangible metabolic problems related to copper can be, not only as an issue in human physiology but actually as a health condition,” says Prof. Fass. “When we better understand how the copper crosses the mucus layer and is absorbed into the cells, we may be able to develop better ways to direct copper to the tissues that need it and help patients.”

The structure of the binding site for copper ions (in red) in the mucin molecule
The structure of the binding site for copper ions (in red) in the mucin molecule

Also participating in the study were Gabriel Shavit, Dr. Tal Ilani and Noa Anna Nairner from the Department of Structural and Chemical Biology; Dr. Simon Pishilevich and Dr. David Gochman from the Department of Molecular Genetics; Dr. Yael Friedman Sirkis from the Department of Life Science Research Infrastructures; Dr. Anastasia D. Gallo and Prof. Kathryn G. Frantz from Duke University in North Carolina, USA; Prof. Kelly N. Chacon from Reed College in Oregon, USA and Dr. Kathryn V. Rosh from Reed College and Oregon Health and Science University , USA.

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