Essentials of Glycobiology—Part 2 (Sugar Alphabet)

Larry A. Law

Sugars (scientists call these sugars/carbohydrates glycans) are attached to proteins (amino acids) or lipids (fatty acids) in trillions of different patterns. While there are hundreds of sugars in nature, only 8 simple sugars (monosaccharides) are used by cells in the biological process called glycosylation. These glycans are glucose, galactose, mannose, fucose (not fructose), xylose, n-acetyl glucosamine, n-acetyl galactosamine, and n-acetyl nueraminic acid (sialic acid for short). They are arranged in various geometric shapes and these patterns represent distinct letters in a sugar-coded alphabet. The alphabet constitutes the communication system for our cells. Our immune system relies upon it to communicate and function correctly.  

Flagpoles

When sugars are attached to proteins (or lipids), I often describe these sugar antennas as 'flag poles.' The pole part is made up of protein and the flag part is made up of glycans (sugars). There are thousands of ways the amino acid components of proteins can be arranged to make different 'poles.' That sounds like a lot, but it cannot account for the billions of ways our genes (genetics) express themselves to create and operate a human being. In 2003, scientists were able to complete their decades-long counting exercise to determine the number of unique genes humans had. Turns out, we have only 20,500 genes—they were expecting over a hundred thousand. It seemed embarassing because a Heinz tomato had 31,760 genes and we are a lot more complicated than a tomato! Something was not adding up! 

Sugar—the Forgotten and Anonymous Nutrient

They finally realized that sugar nutrients were responsible—no one had ever paid much attention to them, thinking they were just for energy (not nutrition). It turned out that just like at the United Nations, you could use the same flag pole, but run up a different flag and it would represent a completely different country (see picture above). The glycans (sugars) were making all the difference on how the body read, responded, and acted towards the protein (which was actually a glycoprotein). Even more bizarre, the protein (flag pole) can be made to fold over on itself by adding certain sugars. Protein folding is a vital tool enabling linear proteins to assume three-dimensional shapes and act as enzymes within the body to facilitate millions of metabolic processes. Misfolded proteins can accumulate and cause serious harm. They account for several neurodegenerative diseases like Parkinsons and Alzheimer's.

Cellular Communication

If the glycans (sugars) are placed properly, then communication takes place properly (proper structure = proper function). If the sugars are missing or not placed properly, then communication breaks down and the immune system begins to act erratically. These glycans can be arranged in a lot of different patterns. The coding capacity of this sugar code is estimated between 100 trillion and 1 quadrillion unique instances. 1 billion seconds represents 31.7 years. 1 quadrillion is a million billions. The complexity of this language is unmatched by anything in the known universe. This is the language of life—it facilitates cellular communication and immune system function.