Carbohydrate Metabolism: Analyzing KEEG Pathways

The microbiome opens the pathway to understanding how the body works more and more every day. With a Thryve Gut Test, we have the ability to analyze your DNA and look deep into many physiological functions carried out by your system on a molecular level. Thanks to these advancements in technology and following KEGG pathway maps, we can determine how efficiently your body metabolizes carbs. Let’s take a look at the biomarkers for carbohydrate metabolism and how Thryve Inside can help you burn carbs easier.

What is Carbohydrate Metabolism?

Metabolism is a blanket term used to describe biological functions that happen, which are necessary for life to exist. Our body needs to break down carbohydrates because we use them as energy sources.

There are two types of carbohydrates that our body must metabolize:

• Complex Sugars (Carbs) – Starches, Cellulose
• Simple Sugars (Carbs) – Glucose, Fructose

During carbohydrate metabolism, our GI tract breaks down carbohydrates to simple sugars that are easily soluble. That way, these energy sources can penetrate the intestinal lining and join our bloodstream to power our cells.

Glycolysis and Carbohydrate Metabolism

One of the most common simple sugars in our diet (and that our breaks carbohydrates into) is glucose. During carbohydrate metabolism, glucose leaves the small intestine and makes its way to the liver [1]. Here, the liver either stores the energy to convert it into glycogen for future use.

Depending on insulin levels, cells will use the glucose for energy. As the glucose comes into contact with our cells, it causes a set of metabolic processes known as glycolysis.

During glycolysis, some of the glucose gets converted into Adenosine diphosphate (ADP). ADP is the precursor to Adenosine triphosphate (ATP). The end result of glycolysis is to create puvyrate. Puvyrate is the spark of energy necessary for our cells to complete the Krebs Cycle [2].

Krebs Cycle and Energy Production

Also known as the citrate cycle, the Krebs Cycle is the series of metabolic processes our cells go through. The end result is to create energy, such as ATP, Nicotinamide adenine dinucleotide (NADH), and Flavin adenine dinucleotide (FADH2).

Puvyrate gets converted into two energy sources — oxaloacetic acid and acetyl-CoA. Acetyl-COA is an essential catalyst for the Krebs Cycle [3].

This two-carbon compound gets transformed into a four-carbon compound, oxaloacetate. From there, the six-carbon compound, citrate, is formed. Hence, the citrate cycle.

Citrate is essential for many metabolic functions. However, it creates a waste product in the form of carbon dioxide. So, we breathe it out and release this gas through our stool. Therefore, testing a fecal sample can give a better indication of the ATP and puvyrate production in your gut biome.

Another result of the citrate cycle sees the production of Alpha-ketoglutarate (AKG). This metabolite essential for fueling gut lining cells [4]. It also plays a pivotal role in protein synthesis and maintaining bone strength.

Pentose Phosphate Pathway

While ATP is the primary source of energy for our cells, it’s not the only bank lender in town. NADH is another source of energy derived from glucose. Instead of going through the Krebs cycle, NADH travels along the pentose phosphate pathway for carbohydrate metabolism [5].

During glycolysis, six-carbon compounds are made. When phosphate is one of the factors that cause this transformation, it creates glucose-6-phosphate. This molecule can easily transport itself along the pentose phosphate pathway. Now, the compound will enter two phases.

Oxidative Phase

When glucose-6-phosphate comes into contact with oxygen that’s readily available in our system, it creates lactone. Subsequently, these chemical reactions release the byproduct, NADPH.

NADPH gives off electrons to cells. This transfer is known as oxidation. Once this happens, the energy source starts to fizzle out. It will inevitably lose one of its six carbon atoms. That will release carbon dioxide into the system. Meanwhile, the five-carbon molecule left behind kicks off the next phase.

Non-Oxidative Phase

The byproduct of NADPH oxidation is ribulose-5-phosphate [6]. This sugar is vital for the production of DNA and RNA. When ribulose-5-phosphate is in the system, it will hook up with another five-carbon ribulose-5-phosphate.

This 10-carbon chain transforms into a 7-carbon and 3-carbon mechanism. The 3-carbon mechanism is reused in glycolysis or converted into DNA and RNA.

Pentose Interconverstions

Our bodies are very smart. Depending on the chain of reactions leading up to the non-oxidative phase, the 10-carbon chain might not follow the 7:3 ratio. For instance, it can break into a 6:4 carbon ratio, where the six carbons enter glycolysis, and the extra four-carbon compounds promote amino acid production.

Fructose and Mannose Carbohydrate Metabolism

Another pathway in carbohydrate metabolism is the fructose and mannose. Here, the simple sugar fructose is used as energy, as well as fructose that’s gone through glycolysis, known as fructose-6-phosphate.

Following down the metabolic pathway, these sugars are responsible for GDP-D-mannose and GDP-L-fucose. GDP-L fucose, in particular, is essential for healthy immune system cells [7].

Subsequently, a drop in fucose is correlated with cancer development. While there are benefits to mannose, our body absorbs it slowly. So, irregularities along fructose and mannose pathways can cause complications with diabetes.

Galactose Metabolism

When our body breaks carbohydrates into simple sugars (monosaccharides), one of the byproducts might be galactose. Typically your body creates galactose when the small intestines break down lactose. That’s why this precursor to glucose is known as Also known as “milk sugar.”

Galactose enters the Leloir pathway, where it encounters three important enzymes:

• galactokinase (GALK)
• Galactose-1-phosphate uridyltransferase (GALT)
• UDP-galactose-4’-epimerase (GALE)

Here, galactose gets converted into glucose [8]. Our liver then stores the energy for future use. When we are low on galactose, our body reacts negatively. Usually, this deficiency is caused by a lack of GALT to perform the conversion of galactose into glucose. When some develops galactosemia, they are at an increased risk of developing Escherichia coli (E.coli) sepsis.

Starch and Sucrose Metabolism

Starches are polysaccharides, meaning they are a cluster of plant sugars. They are longer-chained compounds. Therefore, it takes longer for our body to break them down. Also known as complex carbs and resistant starches, good sources of this energy include sweet potatoes and oats.

Since starches are long, many of them get stored in the liver. Here, it converts the starch into glycogen.

As our small intestine digests starches, it might release sucrose into the system. However, a majority of us get our sucrose intake from candy and baked goods.

Sucrose is what we know as table sugar. This simple sugar gets burned through quickly. However, too much sucrose can cause fatty tissue buildups around the gut.

If our body uses starch and sucrose for immediate energy, it relies on amylase enzymes to break these sugars down.

Amino Sugar and Nucleotide Metabolism

When monosaccharides become activated, they also become known as nucleotide sugars. These sugars power the proteins and fats to produce metabolites. This reaction is important in repairing gut lining, cell proliferation, and improving the immune system.

Amino sugars are also sugar donors. They are a group of monosaccharides that transformed from a hydroxyl to an amino. There are over 60 known to humankind, most notably N-Acetyl-d-glucosamine. These potent molecules regulate protein function. They also serve as natural antibiotics [9].

Glyoxylate and Dicarboxylate Metabolism

This pathway is closely related to the Krebs Cycle. When acetyl-coenzyme-A enters the system, it will interact with enzymes within the environment.

To kickstart the glyoxylate cycle, the sugars most come into contact with:

• Isocitrate Lyase
• Malate Synthase

What sets this carbohydrate metabolism cycle apart from the citrate cycle is that it doesn’t produce carbon dioxide in the end [10]. That’s because this cycle produces two oxaloacetates that balance each other. Whereas, the Krebs cycle produces one oxaloacetate, which gets burned off and released as carbon dioxide.

Propionate Metabolism

Propionate is an ester that’s essential for many functions. It’s a short-chain fatty acid that acts as quick and efficient bursts of energy for your cells. It gets converted into propionyl-CoA. Once this compound comes into contact with the carbon, it becomes d-methylmalonyl-CoA.

Next, this molecule transforms into L-methylmalonyl-CoA. Now, it must come into contact with Vitamin B12 to create succinyl-CoA. Humans can’t make Vitamin B12, so they must get it from food sources. However, most Vitamin B12 food sources are animal-based, making it harder for vegans to regulate propionate metabolism.

Thankfully, vegans can still make use of this energy source. When we lack Vitamin B12, the body converts propionate into 3-hydroxypropionate, before becoming acetate. While acetate isn’t the best energy source for colon cells, it plays a monumental role in building muscle.

Butanoate Metabolism

Butyrate is another essential short-chain fatty acid. It is produced as a byproduct of intestinal flora fermenting sugars. When these metabolites are released, they play a role in the promotion of ketosis.

Ketosis is an autonomous way for our body to create energy. When we don’t consume carbs in our diet, our liver produces ketone bodies. This all-natural energy source is ideal for losing weight.

That’s why people who follow a Keto Diet adhere to a low-carb, high-fat diet plan. They want the butyrate found in healthy fats and don’t want the sugars available in carbs. In turn, ketone bodies produce energy while simultaneously burning fat.

Analyze Your Carbohydrate Metabolism

Feeling low on energy? Your carbohydrate metabolism might be a bit off. The best way to find out if this is happening is to get your gut tested. Using KEEG pathways, we can map out where the deficiencies are. That way, we can get your gut health on the right track. From there, you will produce natural energy that will sustain you throughout the day!

Resources

[1] Naifeh J, Varacallo M. Biochemistry, Aerobic Glycolysis. [Updated 2018 Dec 20]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK470170/.

[2] Schroeder, M. A., Atherton, H. J., Ball, D. R., Cole, M. A., Heather, L. C., Griffin, J. L., Clarke, K., Radda, G. K., & Tyler, D. J. (2009). Real-time assessment of Krebs cycle metabolism using hyperpolarized 13C magnetic resonance spectroscopy. FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 23(8), 2529–2538. https://doi.org/10.1096/fj.09-129171.

[3] “Oxidation of Pyruvate and the Citric Acid Cycle – Biology 2e.” OpenStax, openstax.org/books/biology-2e/pages/7-3-oxidation-of-pyruvate-and-the-citric-acid-cycle.

[4] Hou, Yongqing, et al. “Alpha-Ketoglutarate and Intestinal Function.” Frontiers in Bioscience (Landmark Edition), U.S. National Library of Medicine, 1 Jan. 2011, www.ncbi.nlm.nih.gov/pubmed/21196226.

[5] Cho, E. S., Cha, Y. H., Kim, H. S., Kim, N. H., & Yook, J. I. (2018). The Pentose Phosphate Pathway as a Potential Target for Cancer Therapy. Biomolecules & therapeutics, 26(1), 29–38. https://doi.org/10.4062/biomolther.2017.179.

[6] Dringen R., Hoepken H.H., Minich T., Ruedig C. (2007) 1.3 Pentose Phosphate Pathway and NADPH Metabolism. In: Lajtha A., Gibson G.E., Dienel G.A. (eds) Handbook of Neurochemistry and Molecular Neurobiology. Springer, Boston, MA.

[7]Michael Schneider, Esam Al-Shareffi, Robert S Haltiwanger, Biological functions of fucose in mammals, Glycobiology, Volume 27, Issue 7, July 2017, Pages 601–618, https://doi.org/10.1093/glycob/cwx034.

[8] Stern, E S, and R S Krooth. “Studies on the Regulation of the Three Enzymes of the Leloir Pathway in Cultured Mammalian Cells. I. Effect of Substitution of Galactose for Glucose as the Sole Hexose in the Medium in Human Diploid Cell Strains and in a Rat Hepatoma Line.” Journal of Cellular Physiology, U.S. National Library of Medicine, Aug. 1975, www.ncbi.nlm.nih.gov/pubmed/170294.

[9] Zeng, Lin, et al. “Amino Sugars Enhance the Competitiveness of Beneficial Commensals with Streptococcus Mutans through Multiple Mechanisms.” Applied and Environmental Microbiology, American Society for Microbiology, 15 June 2016, aem.asm.org/content/82/12/3671.

[10] Ahn, S., Jung, J., Jang, I. A., Madsen, E. L., & Park, W. (2016). Role of Glyoxylate Shunt in Oxidative Stress Response. The Journal of biological chemistry, 291(22), 11928–11938. https://doi.org/10.1074/jbc.M115.708149.

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