Fascinating Aspects of Glycobiology—Part 15 (False Paradigms)

Larry A. Law

A false paradigm is a belief system that is incorrect. For centuries, people believed the sun went around the Earth. People looked up in the sky and it happened every day without fail. However, it was Copernicus in 1543 and Galileo in the 1600s who finally advanced the idea that what everyone saw each day was an illusion: the Earth actually went around the sun. Mark Twain stated, "It's not what we don't know that prevents us from succeeding; it's what we KNOW that just ain't so." I will discuss 5 false paradigms below. 

1. Sugar is Only Used for Energy Production—False

​Doctors memorize the Krebs Cycle (Citric Acid Cycle) to learn how the body creates adenosine triphosphate (ATP) molecules. ATP provides 95% of the energy necessary to keep the cell machinery operating. Fifty percent of the total volume inside the cell consists of mitochondrial power plants dedicated to producing energy. Glucose is combined with oxygen and burned in a metabolic process that creates the high-energy phosphate molecules. However, the science of glycobiology represents a new paradigm. The eight glycobiology sugars are not fuel sugars. They are structural sugars—monosaccharide building blocks that are constructed in the Golgi apparatus (GA) and endoplasmic reticulum (ER) factories. They are attached to proteins that are created by combining amino acids in the ribosomes (R) and lipids made by combining fatty acids in the ER. 

2. Glucose is the Only Important Sugar—False
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As a result of the first false paradigm, scientists regarded glucose as the only vital sugar for the body. They once believed that all sugar was changed into glucose in the body, and from glucose, any sugar required by the body was manufactured in the liver. The body indeed has a backup system where it can change glucose into fucose or any other needed sugar. But it can take up to 37 enzymatic reactions, and it is extremely energy-intensive. The body does not prefer using the backup system unless it has to. The primary pathway becomes depleted if we are not eating enough whole, plant-based food or if our food is nutritionally deficient. The backup system kicks in to keep us alive. It was French scientists in 1998 who had volunteers ingest mannose and galactose sugar molecules with a radioactive isotope attached so they could track them throughout the body. They discovered that these sugars were never changed into glucose. In fact, they discovered cell receptors in the gut that absorbed these other sugars intact! After digestion, they were transferred to the cells in the body. They rightly concluded that these sugars represented a new classification of nutrition as important as vitamins and minerals. We were designed to eat them in our diet.

Later, other scientists discovered a mannose transport mechanism in the gut. In addition, scientists discovered that bacteria in the gut would cleave fucose from the food we eat and make it available to the bloodstream. Clearly, eating food containing these sugar nutrients is vital for human health, or why would we have these mechanisms to extract them in our digestive system? The gut represents 70% of our immune system. This is really an astounding fact. But it makes sense when you consider that food arrives from outside the body and can contain foreign microbes and germs. The digestive tract is the first line of defense for our bodies to protect the inside of our bodies. Peyer's patches (see picture below) are distributed along the gut and house the soldiers in our defensive army. So, the immune system takes great care and has an entire defensive system lining our gut to identify, resist, and destroy foreign elements. Mannose is a sugar that is like the gas in the gas tank of macrophages. These immune system warrior cells engulf (phagocytize) bacteria, viral components, and any other toxic substance and debris in their effort to protect us from harm invading us from the outside world. Clearly, metabolic processes exist for all of these critical sugar nutrients, so cellular communication and immune system activity can proceed. 
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3. Other Sugars Can't Be Broken Down, So They Are Useless—False
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Early glycobiologists like Dr. Hudson Freeze and Dr. Ronald Schnaar were adamant that, despite what the French scientists had discovered, supplementing these glycobiology sugars was useless. They believed that the beta bonds that held these sugars together were impossible to break. And there were no enzymes in the stomach that were capable of breaking them down into monosaccharides (simple sugars). They even went on ABC's TV show 20/20 in June of 2007 to disparage anyone (including a nutritional company selling a sugar nutrient supplement) that it was all bogus. This got a lot of damaging national attention for nutritional glycobiology.

Apparently, they were unaware of a scientific study completed in January 2007 (6 months prior to their interview) by the Scripps Center for Integrative Medicine in La Jolla, CA. The study proved that long-chain polysaccharides were broken down and absorbed within the body. While it was true that no enzymes existed in the stomach that could break these beta bonds, they were actually broken down by bacteria in the gastrointestinal (GI) tract. Many bacteria have enzymes called beta-glycosidases that break beta bonds. It wasn't expensive urine as the reputable doctors claimed! Of course, there was no retraction published by ABC, and the doctors never admitted they got it wrong. But their old science wasn't the last word on the new science for anyone who was still listening!

4. We Are A Victim to Our Genes—False 

The Human Genome Project was a scientific effort to map out our genetic code. It took over a decade (1990 to 2003) to complete. Initially, scientists believed they would find about 120,000 genes. They thought it would take that many to create something as complex as the human body. They already knew that the lowly fruit fly had 20,000 genes. Imagine their surprise when they discovered humans had only a mere 20,500 genes. That was less than a Heinz tomato (31,760 genes)! Clearly, something was not computing. Eventually, they realized that something must be modifying the proteins making up the genes. Glycosylation turned out to be the answer. It is the most common posttranslational modification that proteins undergo. As we mentioned before, 70% of all proteins are glycoproteins. The addition of the 8 sugars in various patterns had to be the reason. Like a flag pole made up of protein, the flag made of sugars was giving a distinct message to the body and represented a unique meaning (a particular country). Scientists didn't know anything about these sugars. All of a sudden, there was an urgent scientific push to learn about the science of glycobiology. Eventually, the science of epigenetics evolved, and researchers learned that sugar was what gave meaning to protein. Genetics wasn't the whole story. It wasn't even the most important story. The real story was above the genes and how the trillions of combinations of these 8 sugars could communicate different messages even on the same protein string. This communication system was how the immune system knew where and how to respond to problems within the body. These sugar patterns represented the language of life!

5. Protein is the Language of the Immune System—False

The immune system is a tremendously complex system within the body. There are always defensive immune cells on patrol, looking for problems to report. Defensive white blood cells fight battles against invaders they identify. This defensive army must determine who is a friend and who is a foe. The immune system also coordinates response efforts through a cascading range of alertness. When the battle is won, the immune system winds down the inflammatory response, initiates cell repair, and returns things to normal. The system is always on quiet alert, running war games in preparation for the real thing. Like a general fighting a war, the immune system must be able to communicate with its troops. The old belief was that protein served as the communication signaling molecules at the cell level. But the 20 amino acids that constitute protein do not provide enough different chemically unique combinations to support a vocabulary large enough to account for immune system communication requirements. Amino acids can only link end-to-end like train cars in a linear manner. The 20 train cars linking in a line couldn't be arranged uniquely in enough ways to represent the messages communicated by the immune system.

Scientists had never investigated sugar because there were only 8 utilized biologically on cell receptors. But when they studied them more thoroughly, they discovered that these simple sugars were not that simple after all. They had a level of complexity that blew scientists away. These single sugars in solutions like water (the body is 60% water) formed 3-dimensional ring structures rather than straight lines. One was a pentagon (5 carbons), six were hexagons (6 carbons), and one was a nonagon (9 carbons). They could link at each carbon site on the atom, and they could branch out in bush-like chains containing hundreds and thousands of sugars. These structures had a potential of up to 1 quadrillion possible unique patterns in this sugar-coded alphabet! This is 100,000 billion! And if you counted a billion seconds (one number/second), it would take 31.7 years! This sugar-based communication system is what allows our immune system to communicate the information we know our immune system does on a daily basis. Glycans govern nearly all biological functions in our body.

What happens when sugars are not in their correct place? What does miscommunication look like for the immune system? For a good discussion of how autoimmune or degenerative diseases arise from an over-modulated or under-modulated immune system, see my book (pages 130-132).