Meet the Sugars

Sugars, also known as glycans, play big and small roles in everything from growth & development to energy metabolism to cell signaling. Whether they impact us positively or negatively depends entirely on context – that is, what kind of protein or lipid they happen to be attached to.

The GlycoGang

Click on each sugar to learn more about them!

GlcNAc

GlcNAc

IdoA

IdoA

GalNAc

GalNAc

Fuc

Fuc

Glc

Glc

Meet N-Acetylglucosamine
aka GlcNAc

Many proteins are modified by N-glycosylation, and all N-glycans begin with GlcNAc. N-glycans have been connected to many different diseases. You can even use the appearance of certain N-glycans in the blood to diagnose cancer. This knowledge could lead to improved treatment outcomes and prevention. In fact, we already use N-glycans in many drugs, including those used to treat rheumatoid arthritis, type 2 diabetes, and Crohn’s disease. O-GlcNac is vital to maintaining homeostasis, but too much of it is linked to cardiovascular disease.

Meet Iduronic acid
aka IdoA

IdoA is a major part of two kinds of glycosaminoglycans (GAGs), dermatan sulfate and heparin. GAGs are one part of the glycocalyx, a gel-like layer that surrounds the cell membrane. It plays a role in the immune system, the movement of molecules, and cell adhesion. Heparin is the most commonly used drug in preventing the formation of harmful blood clots. Dermatan sulfate also plays a role in coagulation and wound repair. However, too much of either causes problems that affect the skin, muscles, and blood vessels.

Meet N-Acetylgalactosamine
aka GalNAc

GalNAc is the first sugar to attach to a protein in O-glycosylation. Most glycoproteins in mucus, called mucins, are O-glycosylated. They form a physical barrier around cells and play important roles in cell adhesion and cell signaling. The simplest mucin-type O-glycan is the Tn antigen, composed of a single GalNAc linked to a serine or threonine residue. However, it’s only seen when the cell can’t extend the glycan any further, as is the case in multiple cancer types. GalNAc is also critical to our nervous system and is what differentiates blood type A from other blood types.

Meet Fucose
aka Fuc

In N-glycans, Fuc acts as an attachment point for adding other sugars or as an end unit. Because of this, it plays a role in many biological functions including cell-cell interactions, host-microbe interactions, and development. For example, ABO blood type is determined by what sugars are attached to the end of the blood group antigen, or H antigen. An unmodified H antigen, as seen in people with O blood type, is characterized by the presence of a terminal Fuc. In medicine, therapeutic monoclonal antibodies are used for the treatment of various cancers. Some of these antibodies rely on Fc-mediated immune effector function to deplete tumor cells. Interestingly, the absence of fucose in the Fc region of the antibody enhances its tumor cell killing activity.

Meet Glucose
aka Glc

Glc is the most abundant sugar in nature and the primary source of energy for every cell in our bodies. In people with diabetes, the body can’t regulate Glc levels in the blood either because not enough insulin is produced or their response to it is weak. This results in hyperglycemia, or high blood sugar. If left untreated, hyperglycemia can damage the nerves, blood vessels, tissues and organs. Insulin facilitates the entry of Glc into muscle, adipose and several other tissues from the blood to prevent these harmful effects.

Meet Galactose
aka Gal

Gal is critical on the ends of N-glycans and at the core of O-glycans – it plays a role in numerous biological functions. It’s also important to human nutrition. After consumption, Gal is converted to glucose-1-phosphate in the liver and subsequently stored as glycogen or converted to glucose and released into circulation. Gal is essential to the early developmental stages of infants as it combines with glucose to form lactose, a major part of milk. Galactosemia, a disorder that affects the ability to convert Gal to glucose, is fatal in most infants if left untreated. Gal is also what differentiates blood type B from other blood types.

Meet N-Acetylneuraminic acid
aka Neu5Ac

Many viruses infect cells by binding to sialic acids, a class of sugars. Neu5Ac is the predominant sialic acid in humans. For example, influenza virus attaches to our mucus membranes by binding to Neu5Ac. Therefore, it’s an important antiviral target. Neu5Ac is also found in gangliosides, a type of glycolipid. Gangliosides help regulate cell signaling, proliferation and differentiation. There’s evidence that gangliosides are involved in brain health, but our understanding of the role they play is limited.

Meet Glucuronic acid
aka GlcA

GlcA is key to many glycosaminoglycans (GAGs) like heparin, chondroitin sulfate and dermatan sulfate. This means it’s found in basically every part of our bodies from our lungs to the cartilage in our joints. They are essential to our health and wellbeing. However, GlcA can also interact with the immune system in a way that harms us – it aggravates both acute and chronic inflammatory conditions, increasing the pain patients feel. Despite this, GlcA is included in fermented foods like Kombucha tea as an antioxidant.

Meet Xylose
aka Xyl

Xylose is the first sugar added onto glycosaminoglycans (GAGs). Pathogens use GAGs to invade cells but once inside, they face a new problem – GAGs trap them there. To counteract this, they make enzymes that break down their backbone. This exposes the remaining molecules on the cell surface, causing our immune system to overreact and harm us. Using Xyl in treatment may be able to prevent this, as it promotes the synthesis of new GAGs. Xyl is also used to test for malabsorption – it’s normally easily absorbed by the intestines so if it shows up in the blood or urine, there’s a problem with the body’s ability to absorb nutrients.

Meet Mannose
aka Man

High-mannose glycans contain multiple terminal mannose sugars. They play an important role in protein folding by protecting against degradation during intracellular transport. The mannose residues are then cleaved sequentially once they reach the Golgi and replaced by other sugars to form complex and hybrid glycans. Because of this, it’s not common to see high-mannose glycans in serum. A number of pathogenic microorganisms display high-mannose glycans on their surfaces. These residues act as markers of non-self that trigger an immune response. O-mannose, on the other hand, is critical for muscle development in animals. Breaks in the O-mannosylation pathway result in congenital muscular dystrophies (CMD) like Walker-Warburg syndrome (WWS).

Gal

Gal

Neu5Ac

Neu5Ac

GlcA

GlcA

Xyl

Xyl

Man

Man

The GlycoGang

Click on each sugar to learn more about them!

GlcNAc

GlcNAc

Meet N-Acetylglucosamine
aka GlcNAc

Many proteins are modified by N-glycosylation, and all N-glycans begin with GlcNAc. N-glycans have been connected to many different diseases. You can even use the appearance of certain N-glycans in the blood to diagnose cancer. This knowledge could lead to improved treatment outcomes and prevention. In fact, we already use N-glycans in many drugs, including those used to treat rheumatoid arthritis, type 2 diabetes, and Crohn’s disease. O-GlcNac is vital to maintaining homeostasis, but too much of it is linked to cardiovascular disease.

IdoA

IdoA

Meet Iduronic acid
aka IdoA

IdoA is a major part of two kinds of glycosaminoglycans (GAGs), dermatan sulfate and heparin. GAGs are one part of the glycocalyx, a gel-like layer that surrounds the cell membrane. It plays a role in the immune system, the movement of molecules, and cell adhesion. Heparin is the most commonly used drug in preventing the formation of harmful blood clots. Dermatan sulfate also plays a role in coagulation and wound repair. However, too much of either causes problems that affect the skin, muscles, and blood vessels.

GalNAc

GalNAc

Meet N-Acetylgalactosamine
aka GalNAc

GalNAc is the first sugar to attach to a protein in O-glycosylation. Most glycoproteins in mucus, called mucins, are O-glycosylated. They form a physical barrier around cells and play important roles in cell adhesion and cell signaling. The simplest mucin-type O-glycan is the Tn antigen, composed of a single GalNAc linked to a serine or threonine residue. However, it’s only seen when the cell can’t extend the glycan any further, as is the case in multiple cancer types. GalNAc is also critical to our nervous system and is what differentiates blood type A from other blood types.

Fuc

Fuc

Meet Fucose
aka Fuc

In N-glycans, Fuc acts as an attachment point for adding other sugars or as an end unit. Because of this, it plays a role in many biological functions including cell-cell interactions, host-microbe interactions, and development. For example, ABO blood type is determined by what sugars are attached to the end of the blood group antigen, or H antigen. An unmodified H antigen, as seen in people with O blood type, is characterized by the presence of a terminal Fuc. In medicine, therapeutic monoclonal antibodies are used for the treatment of various cancers. Some of these antibodies rely on Fc-mediated immune effector function to deplete tumor cells. Interestingly, the absence of fucose in the Fc region of the antibody enhances its tumor cell killing activity.

Glc

Glc

Meet Glucose
aka Glc

Glc is the most abundant sugar in nature and the primary source of energy for every cell in our bodies. In people with diabetes, the body can’t regulate Glc levels in the blood either because not enough insulin is produced or their response to it is weak. This results in hyperglycemia, or high blood sugar. If left untreated, hyperglycemia can damage the nerves, blood vessels, tissues and organs. Insulin facilitates the entry of Glc into muscle, adipose and several other tissues from the blood to prevent these harmful effects.

Gal

Gal

Meet Galactose
aka Gal

Gal is critical on the ends of N-glycans and at the core of O-glycans – it plays a role in numerous biological functions. It’s also important to human nutrition. After consumption, Gal is converted to glucose-1-phosphate in the liver and subsequently stored as glycogen or converted to glucose and released into circulation. Gal is essential to the early developmental stages of infants as it combines with glucose to form lactose, a major part of milk. Galactosemia, a disorder that affects the ability to convert Gal to glucose, is fatal in most infants if left untreated. Gal is also what differentiates blood type B from other blood types.

Neu5Ac

Neu5Ac

Meet N-Acetylneuraminic acid
aka Neu5Ac

Many viruses infect cells by binding to sialic acids, a class of sugars. Neu5Ac is the predominant sialic acid in humans. For example, influenza virus attaches to our mucus membranes by binding to Neu5Ac. Therefore, it’s an important antiviral target. Neu5Ac is also found in gangliosides, a type of glycolipid. Gangliosides help regulate cell signaling, proliferation and differentiation. There’s evidence that gangliosides are involved in brain health, but our understanding of the role they play is limited.

GlcA

GlcA

Meet Glucuronic acid
aka GlcA

GlcA is key to many glycosaminoglycans (GAGs) like heparin, chondroitin sulfate and dermatan sulfate. This means it’s found in basically every part of our bodies from our lungs to the cartilage in our joints. They are essential to our health and wellbeing. However, GlcA can also interact with the immune system in a way that harms us – it aggravates both acute and chronic inflammatory conditions, increasing the pain patients feel. Despite this, GlcA is included in fermented foods like Kombucha tea as an antioxidant.

Xyl

Xyl

Meet Xylose
aka Xyl

Xylose is the first sugar added onto glycosaminoglycans (GAGs). Pathogens use GAGs to invade cells but once inside, they face a new problem – GAGs trap them there. To counteract this, they make enzymes that break down their backbone. This exposes the remaining molecules on the cell surface, causing our immune system to overreact and harm us. Using Xyl in treatment may be able to prevent this, as it promotes the synthesis of new GAGs. Xyl is also used to test for malabsorption – it’s normally easily absorbed by the intestines so if it shows up in the blood or urine, there’s a problem with the body’s ability to absorb nutrients.

Man

Man

Meet Mannose
aka Man

High-mannose glycans contain multiple terminal mannose sugars. They play an important role in protein folding by protecting against degradation during intracellular transport. The mannose residues are then cleaved sequentially once they reach the Golgi and replaced by other sugars to form complex and hybrid glycans. Because of this, it’s not common to see high-mannose glycans in serum. A number of pathogenic microorganisms display high-mannose glycans on their surfaces. These residues act as markers of non-self that trigger an immune response. O-mannose, on the other hand, is critical for muscle development in animals. Breaks in the O-mannosylation pathway result in congenital muscular dystrophies (CMD) like Walker-Warburg syndrome (WWS).

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