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Research by Aoife Harbison of our Dept of Chemistry investigates why Carbohydrates are seen as public enemy number one in our modern world and why it's time to change this negative perception.  When you hear the words "carbohydrates" or "sugars", what comes to mind? It's probably terms like "unhealthy diets", "diabetes", "obesity", "sugar tax" and "low carb diets ". There is usually nothing positive to say about carbohydrates and this is because carbohydrates are generally seen as public enemy number one in our modern world.

The problem with this negative attitude is that sugars and carbohydrates are umbrella terms used to classify a huge family of molecules that play a massive role in all aspects of life, Learning more about how these molecules fuels our bodies or play a part in how our cells interact and function can help us realise that there is no life without carbohydrates.

The first lesson to learn is that our bodies actually need carbohydrates to function. This is in the form of glucose that we introduce through our diet. Carbohydrates are complex molecules made up of smaller units called monosaccharides. Glucose is a monosaccharide that can be cut-off from larger carbohydrates, such as starch, by enzymes in our digestive system and processed by our livers through a mechanism called glycolysis. This series of reactions produces two molecules of Adenosine Triphosphate (ATP) per unit of glucose. ATP is the energy currency of our cells and, without it, our cells would not be able to function, so we need to supply our bodies with enough glucose for our cells to keep going and ultimately to keep us alive.

So why do carbohydrates have such a bad reputation when it comes to food? Well, it depends on what kind of carbohydrates we are introducing into our bodies. The simpler the construction of carbohydrates, the easier it is to break them down. If we eat a lot of foods containing simple (refined) sugars, these are broken down too quickly in our digestive systems, overloading our livers and triggering our pancreas to produce insulin to convert excess glucose into fat. This is why the food industry is criticised for loading products with high fructose corn syrup, sucrose or other refined sugars that are causing a rise in obesity or other health problems that can controlled by monitoring sugar intake.

On the other hand, plant-based foods containing starch and other complex carbohydrates, which take a longer time for our enzymes to break down, are a healthy source of energy and ensure by construction that less glucose is converted to fat. Starch is a prime example of a hugely branched complex carbohydrate that our bodies can source glucose from.

Knowing more about the chemistry of carbohydrates and their many different roles in biology will make us consider them with much more respect.

The second lesson is that our cells make their own special complex carbohydrates. These carbohydrates, known as glycans, are also built from monosaccharides, linked together either in a linear or branched manner, making them look like microscopic trees. Glycans decorate the surface of many proteins and of our cells, providing them a "sugar coating". These glycans mediate the interactions between the cell and its environment. They also modulate viral, bacterial and toxin infection of cells. They do this through a mechanism that can be seen as a handshake, allowing the cell to recognise other molecules and to activate specific functions.

Like the carbohydrates we eat, glycans differ greatly in the units they are made up from and how these units are linked together. Depending on their structure, glycans can assume different 3D shapes, which affect their behaviour and interactions, thus the cells’ function. Depending on the way the monosaccharides are linked together, carbohydrates can be incredibly flexible and dynamic. This freedom of movement poses a problem as they cannot be observed and characterized experimentally.

In my research, I use High Performance Computing (HPC) to study the 3D shape and the intrinsic flexibility of naturally occurring glycans by molecular simulation techniques. By using computer simulations, we can predict the actual dynamics and the preferred 3D shapes of the glycans at the microsecond (and lower) timescales.

This information is the missing key in understanding their interactions with other glycans and/or proteins and therefore their function. In turn, this helps us to understand their role in human health and disease and can lead to the design of new therapeutics in biopharmaceutical applications, with specifically modified glycans on proteins of interest that will enhance the desired interactions of the therapeutics with their targets.

In a nutshell, sugars are too often considered as the enemy of a healthy lifestyle, while they are an essential source of energy and are also key players in our biology. Knowing more about the chemistry of carbohydrates and their many different roles in biology can change our perception of these beautiful and complex molecules and will make us consider them with much more respect.

This article was originally published on RTE Brainstorm on Wednesday, 9 January 2019