What Are Glycosaminoglycans (GAGs)?

Definition and chemistry

Glycosaminoglycans, or GAGs for short, are long, unbranched sugar chains built from repeating pairs of sugar units. Each pair contains an amino sugar (glucosamine or galactosamine) together with, in most cases, a uronic acid unit. In older terminology these molecules were called mucopolysaccharides; the scientific literature now uses the name glycosaminoglycan.

The chains carry a dense array of sulfate and carboxyl groups. These groups give the molecule a strong negative charge, and that charge is the key to GAG chemistry: it attracts water molecules and positively charged ions, so the chains create a water rich, gel like environment. The same charge makes the chains repel one another, so they extend and occupy a large volume.

In most tissues GAGs are not found on their own; they attach to a core protein to form larger structures called proteoglycans. Proteoglycans are among the main components of the extracellular matrix, the material that fills the space between cells and gives a tissue its shape.

Main types

Hyaluronic acid (hyaluronan) is the only member of the family that carries no sulfate, and it exists as a single very long chain without binding to a core protein. It is abundant in joint fluid, in skin and in the vitreous body of the eye, and is known for holding many times its own weight in water.

Chondroitin sulfate is the most abundant glycosaminoglycan in cartilage and is also present in bone and in vessel walls. Dermatan sulfate is concentrated in skin, tendons and heart valves, while keratan sulfate is found in the cornea, in cartilage and in the discs between the vertebrae.

Heparan sulfate occurs on the surface of almost every cell and in the basement membranes that support tissues; what sets it apart is its role in communication between cells, achieved by binding growth factors. Heparin, found in the granules of mast cells, is the member with the highest density of negative charge.

Where they are found

In cartilage, proteoglycans hold water like a sponge. When the joint is loaded, part of that water is pushed out and it is drawn back when the load is removed; the ability of cartilage to withstand pressure depends largely on this movement of water. The hyaluronic acid in joint fluid is associated with the ease with which joint surfaces glide over one another and with the damping of impact.

In the skin, GAGs determine the water content and fullness of the dermis. In the cornea, the ordered arrangement of keratan sulfate contributes to the transparency of the tissue. On the inner surface of the bladder there is a thin, slippery GAG layer covering the urothelial cells; this layer forms a boundary between substances in the urine and the bladder wall, and it is discussed in detail in the article on pentosan polysulfate.

What they do

Their first role is to hold water and meet pressure. The water loaded proteoglycan network behaves like a cushion that keeps tissue from being crushed when compressed; cartilage, the spinal discs and the layer beneath the skin all work on this principle.

Their second role is to provide lubrication. GAGs in joint fluid and on tissue surfaces reduce friction. The third is a covering or boundary function: as on the inner surface of the bladder, they form a protective interface between a cell layer and the outside environment.

The fourth role is communication between cells. Heparan sulfate in particular binds growth factors and certain proteins and releases them at the right moment, acting as a regulator in cell division, migration and tissue repair. The rise in hyaluronic acid during the early stages of wound healing is a well known example of this regulatory role.

Relationship with health

The GAG content of tissues does not stay constant throughout life. With age the amount of hyaluronic acid in the skin decreases and the proteoglycan structure of cartilage changes. These changes in the cartilage matrix are among the main topics of research into osteoarthritis, the most common joint disease; measuring GAGs, however, is not a diagnostic tool in everyday clinical practice.

The integrity of the protective layer on the inner surface of the bladder is one of the subjects examined in studies of painful bladder complaints. Among inherited diseases are the mucopolysaccharidoses: in these rare conditions one of the enzymes that break down GAGs does not work well enough and the chains accumulate inside cells. Diagnosis and follow-up are carried out by physicians experienced in this field.

Hyaluronic acid and chondroitin sulfate are ingredients widely used in food supplements and cosmetics with the aim of supporting skin and joint health, and research on them continues. For health-related questions, consult your physician or pharmacist.

This page is intended as general information; for diagnosis and treatment consult your physician, and for questions about medicines consult your pharmacist.

Frequently asked questions

What does GAG stand for?

GAG is the abbreviation of glycosaminoglycan. The same molecules were formerly called mucopolysaccharides. They are long sugar chains built from repeating pairs of sugar units and carrying a dense negative charge.

Is hyaluronic acid a glycosaminoglycan?

Yes. Hyaluronic acid is the only member of the family that carries no sulfate, and it exists as a single chain without binding to a core protein. It is abundant in joint fluid, in skin and in the vitreous body of the eye.

What is chondroitin sulfate?

It is the most abundant glycosaminoglycan in cartilage and is also present in bone and vessel walls. It is widely used in food supplements and cosmetics with the aim of supporting joint health, and research on it continues. The For health-related questions, consult your physician or pharmacist.

What happens when glycosaminoglycans are taken by mouth?

These long sugar chains are largely broken down into smaller fragments in the digestive system. How much of the amount taken is absorbed and how it reaches the tissues is still an open question in research; it would not be correct to state a definite conclusion.

What is the GAG layer of the bladder?

It is a thin, slippery covering that lies on the urothelial cells lining the inner surface of the bladder. It forms a boundary between substances in the urine and the bladder wall. The article on pentosan polysulfate covers it in detail.

What is mucopolysaccharidosis?

It is a group of rare inherited diseases in which one of the enzymes that break down glycosaminoglycans does not work well enough, so the chains accumulate inside cells. Diagnosis, follow-up and the treatment plan are determined by physicians experienced in this field.

Aymed İlaç Sanayi manufactures authorised medicinal products in urology and nephrology. This page does not contain diagnostic or treatment advice; it is intended as general health information.