What is the Difference Between Glycation and Glycosylation

The main difference between glycation and glycosylation is that glycation is the covalent attachment of free sugars to the proteins in the bloodstream whereas glycosylation is a post-translational modification of proteins in which a defined carbohydrate is added to a predetermined region of a protein. Furthermore, glycation affects both function and stability of proteins while glycosylation produces a mature protein, which is functional.

Glycation and glycosylation are two mechanisms which add carbohydrates to the proteins. Moreover, non-enzymatic glycosylation is another name for glycation while glycosylation is an enzymatic process.

Key Areas Covered

1. What is Glycation
     – Definition, Location, Process, Effect on Proteins
2. What is Glycosylation
     – Definition, Location, Process, Effect on Proteins
3. What are the Similarities Between Glycation and Glycosylation
     – Outline of Common Features
4. What is the Difference Between Glycation and Glycosylation
     – Comparison of Key Differences

Key Terms

Carbohydrates, Glycation, Glycosylation, Post-Translational Modifications, Protein maturation

What is Glycation

Glycations is a non-enzymatic process that occurs in the bloodstream. It covalently adds free sugars to proteins. Since glycation is not an enzymatic process, it is a spontaneous process, which is not under control. Moreover, due to the irreversible addition of sugars or sugar degradation products to the proteins, glycation is a type of protein damage. This means glycation reduces both stability and functionality of proteins.

Figure 1: Glycation

Furthermore, Glycation is a chemical cascade whose first step is condensation. This step is non-enzymatic as well as reversible. It occurs between the carbonyl group of a reducing sugar and the amine group of a protein or peptide. This type of reaction is known as Schiff base reaction. This step is time-consuming. Here, the end product is a non-stable Shiff base or aldimine. Then, this aldimine spontaneously rearranges more stable ketoamine, also known as the Amadori product. Moreover, it can undergo further degradation through various processes, forming furfurals, reductones, and fragmentation product. Finally, the polymorphic compounds formed by the glycation are collectively known as advanced glycation endproducts (AGEs).

Unfortunately, some AGEs are benign while the others are more reactive than the original sugars. Therefore, they implicate many age-related chronic diseases including, cardiovascular disease, Alzheimer’s disease, peripheral neuropathy, and cancer.

What is Glycosylation

Glycosylation is an important biological process, which occurs in both endoplasmic reticulum and Golgi apparatus. It is mainly a type of post-translational modification, which is responsible for the production of a functional protein from an immature protein. Therefore, glycosylation facilitates proper protein-folding; hence, this increases the stability of the protein. For instance, glycosylation is an enzyme-mediated process. Therefore, a defined carbohydrate is added to a predetermined region of a protein. Also, the process of glycosylation can be regulated by regulating the action of the enzyme.

Figure 2: N-Linked glycosylation

During glycosylation, the carbonyl group of a sugar (glycosyl donor) reacts with the hydroxyl or amine group of the protein (glycosyl accepter). Several types of glycosylations occur in the cell, including

• N-linked glycosylation – glycans attached to a nitrogen of asparagine or arginine side-chains
• O-linked glycosylation – glycans attached to the hydroxyl oxygen of serine, tyrosine, threonine, hydroxylysine, or hydroxyproline side-chains, or to oxygens on lipids such as ceramide
• Phosphoserine glycosylation – phosphoglycans including mannose, xylose or fucose linked through the phosphate of a phosphoserine;
• C-manosylation – sugar is added to a carbon on a tryptophan side-chain
• Glypiation – addition of a GPI anchor, linking proteins to lipids through glycan linkages.

Similarities Between Glycation and Glycosylation

• Glycation and glycosylation are two mechanisms which add carbohydrates to proteins.
• Covalent bonds are formed between carbohydrates and proteins in both processes.
• Also, both affect the functionality of proteins.

Difference Between Glycation and Glycosylation

Definition

Glycation refers to the bonding of a sugar molecule to a protein or lipid molecule without enzymatic regulation while glycosylation refers to the controlled enzymatic modification of an organic molecule, especially a protein, by addition of a sugar molecule. Thus, this is the main difference between glycation and glycosylation.

Significance

Moreover, glycation is the covalent addition of free sugars to the proteins in the bloodstream while glycosylation is a type of post-translational modification, which occurs either in endoplasmic reticulum or Golgi apparatus.

Enzymatic/Non-Enzymatic

Glycation is a type of non-enzymatic modification while glycosylation is a type of enzymatic modification. Hence, this is another difference between glycation and glycosylation.

Regulation

Also, since glycation is not an enzymatic process, it is not a regulated process. In contrast, glycosylation is a regulated process.

Types of Carbohydrates Added

Types of sugars added is also a significant difference between glycation and glycosylation. Glucose, fructose or galactose are the sugars added by glycation while glycans, mannose, xylose, fucose, etc. are the sugars added by glycosylation.

Type of Proteins Affected

One other difference between glycation and glycosylation is that glycation occurs in mature proteins while glycosylation occurs in immature or unmodified proteins.

Effect on the Protein

Furthermore, glycation makes the protein non-functional while glycosylation makes the protein functional. Furthermore, glycation decreases the stability of the protein while glycosylation increases the stability of the protein.

Conclusion

Glycation is the non-enzymatic addition of sugars to the proteins in the bloodstream. It drastically reduces the stability as well as the functionality of the protein. On the other hand, glycosylation is the enzymatic addition of sugars to immature proteins. It occurs inside the endoplasmic reticulum or Golgi apparatus. Most importantly, glycosylation is a post-translational modification responsible for the production of a functional protein. This is the main difference between glycation and glycosylation.

Reference:

1. Gkogkolou, Paraskevi and Markus Böhm. “Advanced glycation end products: Key players in skin aging?” Dermato-endocrinology vol. 4,3 (2012): 259-70. Available Here
2. Lodish H, Berk A, Zipursky SL, et al. Molecular Cell Biology. 4th edition. New York: W. H. Freeman; 2000. Section 17.7, Protein Glycosylation in the ER and Golgi Complex. Available Here

Image Courtesy:

1. “AGE accumulation” By Jasper Dijkstra –  (CC BY-SA 3.0) via Commons Wikimedia  
2. “N-linked glycosidic bond” By Tpirojsi – Own work (Public Domain) via Commons Wikimedia