Fascinating Aspects of Glycobiology—Part 11 (Individual Sugars)

Larry A. Law

There are some 200 sugars in nature, but only eight constitute the glycobiology sugars that build cell receptors on the glycocalyx of cell membranes. Individual sugars form 3-dimensional ring structures. They are linked together with proteins and lipids in branching, tree-like structures. All of the sugars have carbon connected to oxygen and hydrogen. The n-acetyls also have a nitrogen and acetyl group. Xylose is a pentagon of 5 carbons. N-acetyl neuraminic acid (sialic acid) is a nonagon with 9 carbons. All the rest (glucose, mannose, fucose, galactose, n-acetyl glucosamine, and n-acetylgalactosamine) are hexagons with 6 carbons.  

The Hexagons

Glucose: Key source of energy in cells. Metabolized in the mitochondria as fuel to create  adenosine triphosphate (ATP) for this power plant that provides the energy for cellular functions and enzymatic reactions. A very versatile and chemically stable sugar. It is  very abundant in the typical, modern diet.

N-acetyl glucosamine (NAG): A modified version of glucose. It is not metabolized for energy, but is a key activator and mediator of cell signalling. The thyroid gland has a NAG receptor, indicating a key role in the transport of thyroglobulin within that gland. NAG is a building block for damaged cartilage in joints. It inhibits metabolic breakdown. A 2007 study found that NAG suppresses the growth and function of abnormal T-cells responsible for autoimmune attack in multiple sclerosis (MS) and type 1 diabetes. NAG prevented T-cell hyperactivity that results in autoimmune attack on brain myelin and the insulin-producing cells of the pancreas. Preventing this attack protected patients against the development of paralysis in MS as well as elevated glucose levels in diabetes. Dr. Demetriou stated, "This finding shows the potential of using a dietary supplement to help treat autoimmune diseases. Most importantly, we understand how this sugar-based supplement inhibits the cells that attack the body, making metabolic therapy a rational approach to prevent or treat these debilitating diseases." Another study showed improvement in 75% of children with treatment-resistant autoimmune inflammatory bowel disease after a two-year course of NAG. These two studies demonstrate the power of nutritional glycobiology to make a huge difference to the health of those suffering with autoimmune issues. 

Galactose: Galactose, combined with glucose, forms lactose which is the sugar in milk. It is readily available for those whose diet includes dairy, but it is also abundant in celery, sugar beets, cherries, kiwi, beans, peas, and plums. Galactins represent a family of lectins (glycoproteins) that prefer to bind with galactose. They have many interactions with proteins in the cytoplasm and nucleus of the cell. They also play important roles in cancer. They contribute to the conversion of normal cells into tumor cells and tumor metastasis. They can modulate the immune and inflammatory responses. 

N-acetyl galactosamine: Galactose with an n-acetyl group added. It is found in follicle-stimulating hormone (FSH) and luteinizing hormone (LH). It is a constituent of hyaluronic acid, a powerful water-binding agent. Hyaluronic acid is found in the brain, skin, and connective tissue. It acts as a lubricating agent in the synovial fluid of joints and connective tissue. Inside the eye, hyaluronic acid acts as a lubricating agent in the transparent jellylike fluid. 

Fucose: Plays a very important role in cancer. Adding fucose to the body can slow or stop the development of stomach and other cancers. Fucoidans are abundant in seaweed and algae, which helps explain their anti-cancer properties. The sugar fucose induces secretion of tumor necrosis factor, an extremely important cancer-fighting agent. Several fucosylated glyco-biomarkers are linked to colon, liver, lung, and pancreatic cancers. In the gut, bacteria sense the amount of fucose there and use this determination to adjust the proper balance between competing bacteria, thus ensuring optimal gut health. Fucoidans also stimulate adult stem cell production. These are the parent stem cells of the immune system. They are blank cells that can become any type of blood or immune system cell the body needs. With age, production of adult stem cells declines. By adding fucose, this downward trend can be reversed and these new cells can become any cell needed by the body. This represents a significant anti-aging ingredient.

Mannose:  Probably the most important single sugar for the immune system. It is the ingredient in aloe vera which allows that plant to heal burns on skin and stimulate internal activity of macrophages to heal and cure problems faster. But aloe vera has to be harvested and processed properly or the mannose is destroyed within hours—most on the market is not efficacious. Mannose prevents bacterial infections like urinary tract infections (UTIs) by binding to bacteria in the urinary system. Free-floating mannose binds to the glycoproteins (lectins) on the surface of bacteria and thus prevents them from being able to bind/attach to epithelial (surface) cells inside the urethra. Since they can no longer bind to the body, they slough off and are eliminated in the urine, thus eliminating the disorder. In addition, mannose is the gas in the gas tank of macrophages. Macrophages are the immune system cells that destroy bacterial and viral invaders. They also clean out abnormal cells. Macrophages go on alert when mannose is present because the immune system is designed to look for mannose. Mannose is the terminal sugar on bacterial lectins, giving mannose the function of an early warning alert for the immune system. The immune system wakes up from its sleepy, dormant stage and gets busy searching for problems. Because of this wake-up call, the immune system is able to fix the damage faster and more efficiently. Aloe vera, cranberries, blueberries, and peaches are some of the sources of this vital sugar. 

The Pentagon

​Xylose is extracted from wood, in particular, birch wood. Xylose is highly antibacterial and antifungal. It is effective in preventing cancer in the intestinal tract and promotes the growth of friendly bacteria. Xylitol is a sugar alcohol substitute created commercially via hydrogenation coupled with a heavy metal catalyst. Humans should not eat this synthetic version of xylitol. Make sure the extraction process utilizes nature's best version without this cheap chemical processing.  Pure xylitol has powerful benefits for dental health and prevention of tooth decay. While xylitol can be very beneficial to humans, it is highly toxic to dogs, so don't let them ingest it. You can find xylose in guava, pears, many berries, and kelp. 

The Nonagon

​Sialic acid is the most common terminal sugar on human glycoproteins. It plays a key role in brain development, especially at the fetal stage. It is very anti-inflammatory. This sugar is a derivative of mannose, so sources of food abundant in mannose are also important for sialic acid. This sugar has many variations within the human body—it's really a family of sugars. Two variations are shown in the picture below—the human version (Neu5Ac) and the animal (Neu5Gc). Sialic acid is a key component affecting the viscosity (thickness and fluidity) of mucous membranes in respiratory, reproductive, and intestinal tracts. It protects against colonization/infection by bacteria and viruses in the respiratory epithelial cells. In 2008, researchers identified sialic acid as conferring anti-inflammatory activity to a glycoprotein antibody (immunoglobulin G or IgG). This engineered IgG turned out to be 30 times more effective than the standard treatment then in use and was much less expensive.
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​Besides their work with sialic acid and IgG, researchers were investigating glycans in avian flu where sialic acid residues on airway surface tissues served as doorways for viral entry. They stated that "Carbohydrates are the glue that pulls things together, the cell surface matrix in which cells communicate and provide the connections for signal transduction...It's only been within the last decade that we've realized that such structures are critical for all kinds of biological functions. This structure-functional relationship will have a huge impact on our health with respect to immune regulation." Indeed, the flu pandemics and the COVID-19 hysteria all centered on the ability of sialic acid to bind to viral agents. In addition, sialic acid is critical in understanding how red meat causes cancer. If you prefer to see an excellent webinar on red meat/cancer and sialic acid, click here.