Sugar! by marco dydo
“A Rose by any other name would smell as sweet …” (Unless that Rose was made from pure Sugar, then it would probably be sweeter!) Introduction Okay, so lot’s of interest lately about evil, evil Sugar! Far too much misinformation/misdirection from the “diet fad” people and the basic question, “do we need to eat or avoid sugar?” Now, I don’t mean to make “Heavy Weather” out of what should be a mere balmy breeze, but it seems that a definitive summary on the subject has become necessary. Now, with that being said, please keep in mind that with each aspect of this very complicated subject there is a Master’s course of study. That detail is FAR BEYOND the scope of this paper (you’re welcome!). I will attempt to demystify the concept of Sugar (carbohydrate … uh oh, that sounds like a “science word” already sneaking into this paper) and along with some information on the importance of Carbohydrate, I will introduce the concept of Carbohydrate metabolism. (I have created a summary illustration of the interaction of the different metabolic systems … both catabolic
and anabolic … I hope it helps in your understanding). Also, for ease of understanding, this summary will further limit its scope to “normal’ metabolism and omit any consideration to any malabsorption disease, diabetic conditions, Mitochondrial dysfunction, etc. We will have to address those in subsequent, future reports. So, let’s get started!
Carbohydrates **First off … YES we NEED to consume carbohydrate! Not those nasty “added sugars” or “processed sugars” or High Fructose Corn Syrup (HFCS), but naturally occurring, “complex” carbohydrates found in Vegetables and Grains, simple carbohydrates found in Fruits and Roots … and any associated indigestible dietary fiber-carbohydrate used for enhancing digestion and improving digestive motility. Long-term carbohydrate abstention can lead to potentially very dangerous metabolic conditions and irreversible organ, vessel and systemic damage! Taking carbohydrate off of the menu is bad ... and bad for you! But, before considering the metabolic importance and ramifications, the question that requires address is … “What are carbohydrates?” In order to answer that question we will need to venture into the world of “Science” and go directly to a place that I like to call … “Marco’s Chemistry Corner”! In Organic Chemistry we were taught that the humble, modest and meek “Carbohydrate” is a carbonoxygen-hydrogen biomolecule. In Biochemistry, that Carbohydrate definition was expanded to include the polyhydroxy aldehydes, ketones, alcohols and acids. They are called “Saccharides” (Sac-a-rides) and include
sugars, starches and cellulose, which are classified according to their degree of polymerization. They are initially categorized into three principal groups, namely the simple sugars, medium sugars and complex sugars. Before we delve into these groupings there is an important side note concerning inflammation and sugar. There is much misinformation being bandied about on the Internet about dietary carbohydrates and inflammation. Now, the totality of this subject is far from the center of this paper, however allow me a moment to deviate. **Side Note re: Sugar-Inflammation** First off, natural, well-balanced simple and complex carbohydrates, ingested in moderation, will not cause chronic inflammation! It is now understood that the Inflammatory Process and the “Chronic Inflammation” response is the apical connection and initiator among all leading causes of death and possibly all forms of disease. Acute Inflammation is a welcomed reaction to an acute invading stimulus that activates an Immune response that establishes healing. Chronic Inflammation is an adaptive self-perpetuating stimulus and repetitive cycle that increases the Inflammatory Process locally and/or systemically. Physiologic studies have shown how various “over-indulged” processed, dietary components (i.e: processed sugar and foods, hydrogenated oils, Dairy products, animal fat, food additives, GMO’s, toxic build-up, etc.) can modulate key pathways to inflammation including Sympathetic Activity, Oxidative Stress, Transcription Factor Nuclear Factor kappa B (NF-κB) Activation, and Proinflammatory Cytokine Production. However, behavioral studies have further demonstrated that stressful events and depression cause chronic inflammation through these same processes and may be the prime motivator of these disease initiations and progressions. If the equal amalgamation or blending of both diet and behavior in regard to the Inflammatory Process were simply, equally additive, doing so would certainly be significant. However, several far more intriguing interactive observed possibilities are at the core of the overall Inflammatory Process. Stress influences bad food choices and enhances maladaptive metabolic responses to unhealthy meals.
So, as a negative “feed-back loop”, Stress impacts diet which impacts mood as well as proinflammatory responses to many psycho- envirostressors. This in turn results in more stress and then “the circle is now complete!” Additionally, bad food choices effect the proliferation of the “Bad Bacteria” in the GI tract that send out craving signals for more “bad food” which kills off the good bugs, multiplies the bad bugs which send out even more cravings and this acts as an amplifier to the aforementioned “Feed-Back Loop” … that turns this process up to 11! Additionally, since the Vagus-Cranial Nerve#10 innervates systems involved in the digestion, absorption, and metabolism of nutrients it is of primary concern in the design of these studies. It has been demonstrated that Vagal activation can directly and profoundly influence metabolic responses to stress related bad-food choices, GI tract Flora and Fauna as well as Inflammation. In turn, both depression and stress have welldocumented negative effects on vagal activation, contributing to the negative interplay between the Brain and the Gastrointestinal Tract.
In recent studies it has been determined that the movement of Vagal information is a two way street flowing in both antegrade and retrograde directions. As the Bad Bacteria produce more neurotransmitters and hormones in the GI tract they can travel in a retrograde direction and have a profound effect at higher cortical centers. It seems that there is more truth to the expression “always thinking with your stomach” than we ever thought possible. (That's the 2nd “Star Wars” Quote in this section … for those of you keeping score.) So, a better understanding of how stressors, negative emotions, poor GI tract health and food choices work together to enhance Chronic Inflammation is required. Additionally, a deeper knowledge base of the myriad of Inflammatory related processes will be expanded from continued behavioral and nutritional research. Moreover, the broader biomedical community and average Joes and Julies like you and me will also benefit! Saccharide Groups The Saccharide designations are based on the number of individual sugar molecules contained within any given Saccharide. These Saccharide groups include the Mono- (one) like Glucose, Di- (two) like Sucrose, Oligo- (between 3-10) like Maltodextrin, and Poly- (more than 10) like Starchy sugars comparable to Amylopectin and Amylose and the nonstarch Polysaccharides like Cellulose and Hydrocolloids! The smaller of these groups, the Mono- and Di- Saccharides and commonly called “Sugars” or anything ending in “ose”! They are the sugars that we usually eat like Glucose (the main product of plant Photosynthesis), Fructose, Maltose, Sucrose, etc. The Monosaccharide Ribose, however, is an important “foundational element” in the genetic molecule RNA and Deoxyribose (another Sugar), is a basic structural element in DNA. You know, the tread like chain of four nucleotides that carry the genetic instructions to create the very “stuff” that is responsible for the extraordinarily distinctive characteristics, physical attributes and fundamental qualities that make you … well … YOU! And all of that built on a sugar-phosphate backbone! Once again, sugar to the rescue! Additionally, Monosaccharide’s also play important roles in blood clotting, immunology and reproduction to name just a few. Disaccharides are two sugars that are bonded together to form saccharides like Sucrose (Cane Sugar) and Lactose (Milk Sugar). Now Sucrose, the most abundant disaccharide, is comprised of one molecule of D-Glucose and one of D-Fructose. (Note: As we saw in a previous article, these “D-“ and “L-“ prefixes are in reference to the orientation of the asymmetric carbon furthest from
the carbonyl group and not the “d-“ or “l-“ prefix which indicates the direction that the sugar rotates. So don’t get confused!) Oligosaccharides (Oh-lee-go-sac-a-rides) are polymers that contain a small number of monosaccharides. They are configured as Glycoproteins or Glycolipids and are involved in a number of metabolic processes like antigenicity, solubility, adhesion, protease resistance, etc. Every cell is coated with either Glycoproteins or Glycolipids, which determines cell type (like blood typing for instance). One important Oligosaccharide process is found in the role of Mother-to-Child HIV-1 Transmission. When newborns are fed a diet of breast-milk and formula, this combination increases the risk of postnatal mother-to-child HIV-1 transmission. When Infants are exclusively breastfed only, they do not contract the virus from the infected mother. This is due to the specific Glycans that are present in human breast milk that inhibit HIV-1 transfer by competing with the HIV-1 surface glycoprotein for binding. Human breastmilk contains many complex Oligosaccharides that carry multiple Antigen Oligosaccharide Glycans.
Other important Oligosaccharides are the Fructo-oligosaccharides (FOS), which consist of short chains of Fructose molecules and are found in many vegetables. They are considered a soluble dietary fiber. Another, Galacto-oligosaccharides (GOS), which also occur naturally, consist of short chains of Galactose molecules. These “Prebiotic” compounds cannot be digested in the human small intestine, and instead pass through to the large intestine, where they are metabolized by the healthy, “Probiotic” Bifidobacteria, which are beneficial to overall Gastrointestinal Tract health! Finally, let’s consider the massive Polysaccharide! They are an important class of Biologic Polymers. In all living organisms the Polysaccharide function is either structural or storage related. In plants, Starch is a polymer of Glucose, which is used as a storage polysaccharide. Amylopectin is an example of such a storagevessel polysaccharide. Cellulose and Chitin are examples of structural “plant” polysaccharides. In humans, on the other hand, the “structurally-similar” Glucose polymer is more densely branched to form Glycogen (a very important component of the Glucose Cycle). Glycogen's unique physical properties allow it to be easily stored and then metabolized into “energy units” very quickly when required. This suits the active lives of movers and shakers quite nicely. So, by now it must be clear that Saccharides are involved in several very important processes within the systematic metabolism of Carbon Based life forms … like you and me! **So, when the Misinformed make statements like, “ALL Sugars are exactly the same” … Now you absolutely know that they are wrong … just dead wrong! Nutrition So, Utilizing the aforementioned information … now we can surmise, from a nutritional standpoint that consuming Carbohydrates … is vital! As we shall see, Glucose is the “least common denominator” in the foodto-energy equation … and the most important cellular carbohydrate! Although, through several different processes, the body is capable of Turning Glucose into Fat (Lipogenesis), Fat into Glucose (Fatty Acid Spiral), Protein into Glucose (Urea Cycle) … So, as it’s main energy source, it’s important that the body is capable to reduce everything into Glucose which, is the universal and easily accessible source of metabolic “Energy”! However, all of these Glucogenic processes are NOT created equal and do not yield the same quantity of “energy units” or ATP’s (Adenosine Triphosphate). As we have seen, not all carbohydrates can be utilized as an energy source. Most organisms typically cannot metabolize all types of carbohydrate to yield energy. Some carbohydrates are merely structural and indigestible; while others provide the micro flora and fauna present within the gastrointestinal tract a source of accessible, digestible energy. These saccharides are called “Prebiotics”. Where many Polysaccharides (Starches) are common sources of plant energy storage that can easily be broken down into Glucose, we cannot metabolize the necessary Prebiotic Dietary Fiber of cellulose or other similar polysaccharides that represent an otherwise important dietary element for humans enhancing digestion, among other benefits.
Now from a physiologic basis, it is common and proper to refer to carbohydrates as either simple or complex. Although the exact distinction between these groups can sometimes be ambiguous, within the standard term usage, it is conventional to classify carbohydrates into two chemical classes. The first class is designated as “Simple” if they are sugars in the Monosaccharide and Disaccharide groups and “Complex” if they are either within the Oligosaccharide or Polysaccharide groups. The tragically misinformed continue a long-held, yet confused and ambiguous practice, of putting "fruits, roots, vegetables and whole-grains" in the complex carbohydrate column, despite the fact that these may contain Mono- and Disaccharides as well as Oligo- and Polysaccharides. Many self-proclaimed holistic nutritionists further use the term complex carbohydrate to refer to any sort of digestible saccharide present in a whole food, where fiber, vitamins and minerals are also found. Once again, they are wrong! In any case, with all of that being said, the simple sugar / complex sugar chemical distinction has little value for determining the physiologic nutritional quality of carbohydrates. It’s unrealistic to compare the Nutritional Superiority of the total metabolic benefit received from eating a bowl of fresh, organic fruits, roots and vegetables that are filled with a multitude of bioavailable phytonutrients … opposed to processed, condensed carbohydrates, which provide energy but, no other nutrients whatsoever. **So, what’s a person supposed to do … or eat … in regard to sugar? Like all things in life, “moderation is regulated by wisdom”! However, “to many, total abstinence is easier than perfect moderation”! Ingesting too much water can be fatal and so it goes for sugar. When considering the all-important question, “which carbohydrates make to most sense to consume?” … There are several concepts that require careful consideration. Already we have uncovered much summary information on the nature of carbohydrates but the next step is considerable in regard to the voluminous amount of available information and that’s not even mentioning the vast regions of untold information as yet uncovered! Since the initial query of this paper addressed the question of, “which sugars should be ingested”, let’s turn our attention to the Mono- and Disaccharides. Keep in mind that several of the complex sugars are metabolized into their simpler components while others are utilized by the gastrointestinal flora and fauna and others still are utilized as dietary fiber and are all vitally important. It has been determined by successive studies on these complex saccharides that inadequate intake can lead to significant increases in mortality. Fruits, Roots, Veggies and Grains Naturally occurring sugars are mostly found in Fruits, Roots, Veggies and Whole Grains. Although the quantitation of multiple saccharides differs greatly between food sources, there seems to be agreement that, of all the simple sugars, it’s Fructose that is physiologically preferable over ingesting Sucrose and/or Glucose.
warnings about HFCS are added into the conversation. However, this isn’t an over-processed form of Fructose like that found in commercial syrups and sweeteners (i.e. HFCS). No, again we are considering NATURALLY OCCURRING Fructose that you most likely picked from a tree, pulled from the ground or ate from the vine!
Now, that previous statement may sound a bit counterintuitive, especially when all of the
Fructose exists in foods either as a free Fructose monosaccharide or as a combined Sucrose
- Fructose/Glucose disaccharide unit. When consumed, free Fructose digestion is determined by a number of dependent variables including which other nutrients are consumed with the carbohydrate, how the food is prepared, cooked, raw, etc. The vast
individual differences in cellular metabolism, and the actual chemistry of the saccharide also need to be considered. Like I’ve been saying, the depth and detail of this subject is voluminous.
It is important to remember that, at this point, the body makes an ultimate “decision” in regard to, “what is the ultimate destination of any given saccharide”. It will either be utilized immediately as an energy source, and in this case it is metabolized into Glucose and then processed into ATP or Adenosine Triphosphate. If not, then it will be metabolized into glycogen as an “instant” form of easily available sugar/energy or it will be processed into a “deeper storage”, a form of fat called Triglyceride. **So “why” is consuming Fructose preferable to Glucose and Sucrose anyway? Well Sucrose is enzymatically catalyzed in the membrane lining of the small intestine to yield one unit of Glucose and one unit of Fructose. Glucose and free Fructose are both absorbed directly by the intestine and into the Hepatic Portal Vein System. The transport of Glucose is Insulin dependent whereas Fructose, whose mechanism of absorption in the small intestine is not completely understood (some amalgam of transporter protein, active transport and passive gradient transport or “some kind of magic”) is, however, known to be Insulin “independent”. But once through the intestinal wall
… perhaps magically … they are whisked away to the Liver! Now, it is here where those journeys diverge. Glucose can be transported “as-is” into the systemic body to be immediately absorbed and metabolized by the individual cells. This is responsible for the sickening “Sugar Spike” that people often refer to after eating their weight in chocolate cake. A minute on the lips and forever on your hips happens via the cardio-vascular transport super-highway when Insulin is like the Tesla Sports car … Zero to Sixty in 1.4 seconds … now that’s fast!
When Fructose arrives at the Liver, it is here where a veritable metabolic “down-shift” occurs in the processing of this saccharide. With Glucose, it is released into the body like the allies invading Normandy. Fructose, on the other hand, goes through a multi-step transformation of sorts that is confined to the interior of the Liver. This “Fructose metabolism” process is commonly referred to as Fructolysis! This is a multi-enzymatic and isomerization pathway that converts Fructose into a number of intermediate metabolites that can be utilized in a multitude of processes like the Gluconeogenic pathway, Fatty Acid synthesis and Triglyceride synthesis to mention a few. It can also be converted into Glucose. But it is this “transformation” that is time and space dependent. The Liver can only do “so much” at any given point in time so the resultant metabolites are released into the systemic circulation much more “gradually” as compared to Glucose! This avoids that “Sugar Spike” and diminishes the need for a Tesla to something more like a Gondola in Venice! … ‘O sole mio! So, to break this down into an easily-digestible-smidgen, the ingestion of the simple carbohydrate, Fructose raises blood glucose slowly, while some complex carbohydrates (starches), especially if processed, raise blood sugar rapidly. So, taken in moderation, Fructose has considerably lower Postprandial Blood Sugar levels (after meal blood sugar levels). However, it should be indicated that “over-consumption” of Fructose and processed Fructose (HFCS) will develop metabolic complications such as dyslipidemia, which is an abnormal amount of lipids like triglycerides, cholesterol and/or fat phospholipids, in the blood. Insulin
resistance, and increased visceral adiposity (ex: Beer Belly) is also a potential danger. So … moderation, with all things … moderation! Sugar Metabolism and Enzyme Catalyzed Oxidation Okay, so where does this leave us. Well, it’s probably best to summarize our summary! Carbohydrate, or more specifically Saccharide metabolism signifies the multitude of various Biochemical, Physiological and Digestive processes that are responsible for the Anabolism, Catabolism, Metabolism and the Transformation of the various Saccharides within all sentient entities. That almost sounds like poetry! As we learned, the Carbohydrate Glucose is by far the most important physiologic Monosaccharide as the primary source of metabolic energy. After all of the ingested simple and complex carbohydrates are broken down, the “least common denominator” remaining … is Glucose. It plays an essential and indispensable role in a wide variety of metabolic pathways, with the most vital being used as a fuel in aerobic cellular respiration. Oxidation of one molecule of Glucose through the combined processes of Glycolysis, Pyruvate Oxidation, The Krebs Cycle and The Electron Transport Chain produces a total net yield of approximately 38 ATP. Even though the process of Gluconeogenesis, that synthesizes Glucose from specific amino acids, the glycerol backbone found in triglycerides and fatty acids, “that” Glucose can be used to produce ATP. However, that ATP quantity-yield pales in comparison due to the ATP metabolic “cost”. Aerobic Oxidation (the Krebs Cycle etal) is by far the most efficient metabolic energy production method within the human body. Three parts of the ATP Molecule (Adenosine triphosphate)
Last Words Included in this paper is a chart that depicts a summary of Glucose metabolism. I had every intention of spending a good portion of this report addressing this chart. As I started writing a summary about carbohydrates it became clear that the Krebs Cycle would have to wait. There is too much information about sugar that needs to be
addressed before we can discuss its Oxidation and Cellular Energy Production. And with that, there is much detail that is far beyond the scope of this paper. Hopefully this summary has drawn a straight line through the tumultuously tangled labyrinth … that is Carbohydrates.
So finally, is it clear that avoidance of both simple and complex carbohydrate is done in the face of peril? DNA, RNA, Proteins, Lipids and Carbohydrates are the major macromolecules that are essential for life. If you are not yet convinced that carbohydrate abstinence is unhealthy, then may I suggest that you go back and re-read this paper … and this time … open your eyes! As always … Don’t forget to breathe … and maybe eat a carrot or an apple … or perhaps a nice fruit, root and veggie salad! (Your cells are counting on you).
Glycogen Metabolism Glucose-1-Phosphate Glycogen
by Marco Dydo
1 Molecule of Glucose -Glucose Catabolism2ATP
(LIVER & RENAL CORTEX) 2 NADH
GLUCONEOGENESIS 2 Lactate
Coenzyme A NADH NAD+
NADH 2ADP Lac
Energetic Net 2- ATP, 2-NADH
Acetyl CoA (Krebs)
Protein Catabolism The Matrix Fat Catabolism Protein Catabolism Fat Catabolism
Total Energetic Yield Glycolysis, Pyruvate Oxidation, Krebs Cycle ATP 4-ATP 4 30 10-NADH (1-NADP = 3-ATP) 2-FADH2 (1-FADH2 = 2-ATP) 4 ATP Total Yield 38
KREBS CYCLE & The Electron Transport Chain
((2) Citric Acid)
(2) Isocitric Acid
Energetic Net 2-NADH
CO2 UREA Cycle
Tissue Protein NH 3
Cell Membrane Lysosomes
NADH 2ADP CC ADP NAD+
FATTY ACID SPIRAL
Protein Metabolism Protein Amino Acids
Fats & Lipids
BIC ERO A N A CORI CYCLE
Fat Metabolism The Cell
Liver& Renal Cortex
Microvilli Centrioles RER
Energetic Net 2- ATP, 6-NADH, 2-FADH2
(2) Ketoglutaric Acid
(2) Fumarate FAD
CO2 NADH NADH NAD+
Enzyme Catalyzed Oxidation (2) Succinyl CoA ADP
by marco dydo “A Rose by any other name would smell as sweet ...” (Unless that Rose was made from pure Sugar, then it would probably be swee...