Glycan Metabolism: Analyzing KEGG 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. This is even more important when it comes to glycan metabolism. Thanks to these advancements in technology and following KEGG pathway maps, we can determine how efficiently your body burns carbohydrates to create energy. Let’s take a look at the biomarkers for glycan metabolism and how Thryve Inside can help you feel your best!

What is Glycan Metabolism?

Glycans (or polysaccharides) are chains that are composed of single sugar molecules known as monosaccharides. These are the byproducts of the carbohydrate metabolism process.

glycan metabolism
Plenty of glycans in fruit!

Common monosaccharides include:

  • Glucose
  • Fructose
  • Galactose

These simple sugars get chained together by chemical compounds known as O-glycosidic or N-glycosidic linkages. What is in this chain will dictate how body breaks down the particles, uses them for energy, and gets rid of the waste. That entire process is known as glycan metabolism.

N-Linked Glycan Biosynthesis

N-linked glycans are formed in either the formed the endoplasmic reticulum of microbe cells [1].

It’s comprised of 14 simple molecules:

  • 3 Glucose
  • 9 Mannose
  • 2 N-acetylglucosamine

When a monosaccharide come into contact with nitrogen. Then, they come into contact with two N-acetylglucosamine molecules. These are byproducts of glucose metabolism.

Next, the intermediate comes into contact with a fat, dolichol monophosphate. Then, five mannose residues are added, creating the primary structure of the glycan.

The glycan moves across the endoplasmic reticulum and into reticular lumen. Essentially, these are the soft tissues that create the structure of vial organs.

immune system and gut biome
Your immune system relies on glycans

Now, four more mannose residues get added to the structure. It then meets up with the enzyme glycosyltransferase. This enzyme creates the links of the chain to turn the monosaccharides into an oligosaccharide. It then attaches itself to proteins and used as energy to power cells that influence important body parts and systems.

N-glycans are crucial for a healthy immune system. For instance, the CD337 receptor on Natural Killer (NK) immune system cells use N-glycans as a mode of communication [2]. N-glycans interact with the receptor to let the immune system know that a cell has become cancerous.

Various Types of N-glycan Biosynthesis

Once the oligosaccharides entire the peptide chain, a number of reactions transpire. First, the chain gets stripped of its three glucose molecules. This action is followed up by the removal of several mannose residues.

Many interchangeable factors can alter the outcome of this process. Proteins get folded in that influence the overall structure. From there, various phosphates and acetyls may cause unique interactions. It’s all case-by-case.

Mucin Type O-glycan Biosynthesis

An o-glycan is usually formed from residues of threonine and serine during the amino acid metabolism process. O-glycan production begins with the residues come into contact with N-acetylgalactosamine (GalNAc).

From there, sugars get added to GalNAC, including:

  • Galactose
  • N-acetylglucosamine
  • Fucose
  • Sialic Acid

There are eight common o-glycan structures, with four being predominant to mammals. Mucin oglycans are typically adhered to proteins that live in the mucus of cells. They may be branched to add many sugars.

Mannose Type O-glycan Biosynthesis

Mannose is a simple sugar that is present in many fruits, which makes it relative to glucose. This monosaccharide is essential for carbohydrate metabolism. It’s also used to treat Urinary Tract Infections (UTIs) [3].

O-mannosyl glycans are produced when mannose interacts with serine or threonine residude. The chain that grows by inclusions of
N-acetylglucosamine (GlcNAc) and galactose (Gal).

Depending on the compound, mannose o-glycans that form are called:

  • M1 – Attaches to Fucose Residues, Sialic Acid Terminals, Sulfatded Glucuronic Acid Terminals
  • M2 -Attaches to Fucose Residues, Sialic Acid Terminals, Sulfatded Glucuronic Acid Terminals
  • M3 – Cofactor in Synthesizing Protein for Muscles and Brains

M3 is an essential byproduct of glycan metabolism. It plays as a catalyst for the production of alpha-dystroglycan [4]. This protein is essential for the structure of connective tissue that powers our muscles and our brains. That’s why defected M3 glycans are associated with muscular dystrophy.

Glycosaminoglycan Biosynthesis

no dairy boost your immune system
Many have trouble metabolizing lactose, so be sure to have your glycan metabolism in check!

Glycosaminoglycans (GAGs) are chains of sugars that have repeated disaccharides. Disaccharides are a chain of monosaccharides.

Common disaccharides include:

  • Sucrose
  • Maltose
  • Lactose

When these disaccharides adhere to core proteins it creates a new compound. These byproducts are known as proteglycans.

Chrondroitin Sulfate and Dermatan Sulfate

One of the most common proteglycans is chrondroitin sulfate (CS). This compound is made up of disaccharides beta-D-galactosamine (GalNAc) and beta-D-glucuronic acid (GlcA). Chrondroitin sulfate can be modified depending on the ester-linked sulfate that interacts with the molecule and where that reaction takes place.

Another common proteglycan is dermatan sulfate (DS). DS is a derivative from CS. It gets transformed when glucuronate residues become epimerized to L-iduronates (IdoA).

Both DS and CS can be linked serine residues found in core proteins. They immerse with protein sources by linking up with xylose, and three residues to create a tetrasaccharide.

Heparan Sulfate and Heparin

What separates these proteglycans from others is that they consist of disaccharides intertwined with resiudes of alpha-D-glucosamine (GlcN) and uronic acid. Biosynthesis of heparan sulfate (HS) and heparin (Hep) require the uronic acid to be derived from beta-D-glucuronic acid (GlcA) or alpha-L-iduronic acid (IdoA).

Sulfation occurs when lead sulfur crystals conjugate on compounds. It seems Hep goes through more sulfation than HS.

GlcNAc residue links up with enzyme EXTL3 glycosyltransferase. It attaches onto a region of serine residue to create a long-chain. This chain gets catalyzed by the enzymes EXT1 and EXT2 transferases.

From there, a new chain of reactions within this division of glycan metabolism occurs, including:

  • N-deacetylation
  • N-sulfation
  • Epimerization
  • O-sulfation

In the end, HS is attached to a core protein, making it a proteoglycan. However, Hep remains a sugar chain without a core protein present. Both of these molecules bind onto other molecules in our system, including growth factors. Therefore, these compounds might be helpful for rejuvenating skin. Furthermore, low levels of HS are indicative of cancerous growth [5].

Keratan Sulfate

This compound is a glycosaminoglycan (GAG), which plays a significant role in the synthesis of connective tissue [6]. It contains repeating disaccharides that are mixed with an amino sugar. Then keratan sulfate (KS) will contain either uronic sugar or galactose.

The two types of KS are distinguished by protein links. Type 1 are N-linked glycans. Meanwhile Type 2 denotes an O-glycan base.

Glycosaminoglycan Degradation

Whatever our body synthesizes, it must used up, broken down, and expelled. This process is different based on the GAG being used. These rules are dependent on the residues within the polysaccharide chain. They become catalyzed by either lyases or hyrolases. Enzymes are also dependent on the structures within the chain [7].

Analyze Your Glycan Metabolism

Want to make sure your body is creating and breaking down glycans efficiently? The best way to find out if this is happening is to get your gut tested. Using KEGG 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 metabolize glycans efficiently to support connective tissue, improve your skin health, and create the protein needed to power you through the day!

Thryve Probiotics Gut Health

Resources

[1] Bieberich E. (2014). Synthesis, Processing, and Function of N-glycans in N-glycoproteins. Advances in neurobiology9, 47–70. https://doi.org/10.1007/978-1-4939-1154-7_3.

[2] Martin, T. C., Ilieva, K. M., Visconti, A., Beaumont, M., Kiddle, S. J., Dobson, R., Mangino, M., Lim, E. M., Pezer, M., Steves, C. J., Bell, J. T., Wilson, S. G., Lauc, G., Roederer, M., Walsh, J. P., Spector, T. D., & Karagiannis, S. N. (2020). Dysregulated Antibody, Natural Killer Cell and Immune Mediator Profiles in Autoimmune Thyroid Diseases. Cells9(3), 665. https://doi.org/10.3390/cells9030665.

[3] Domenici, L, et al. “D-Mannose: a Promising Support for Acute Urinary Tract Infections in Women. A Pilot Study.” European Review for Medical and Pharmacological Sciences, U.S. National Library of Medicine, July 2016, www.ncbi.nlm.nih.gov/pubmed/27424995.

[4] Sheikh, M. O., Halmo, S. M., & Wells, L. (2017). Recent advancements in understanding mammalian O-mannosylation. Glycobiology27(9), 806–819. https://doi.org/10.1093/glycob/cwx062.

[5] Nagarajan, Arvindhan, et al. “Heparan Sulfate and Heparan Sulfate Proteoglycans in Cancer Initiation and Progression.” Frontiers, Frontiers, 3 Aug. 2018, www.frontiersin.org/articles/10.3389/fendo.2018.00483/full.

[6] Caterson, Bruce, and James Melrose. “Keratan Sulfate, a Complex Glycosaminoglycan with Unique Functional Capability.” OUP Academic, Oxford University Press, 11 Jan. 2018, academic.oup.com/glycob/article/28/4/182/4798945.

[7] Ernst, S, et al. “Enzymatic Degradation of Glycosaminoglycans.” Critical Reviews in Biochemistry and Molecular Biology, U.S. National Library of Medicine, 1995, www.ncbi.nlm.nih.gov/pubmed/8575190.