Glycans are complex carbohydrate molecules found throughout all living organisms. They represent one of the four fundamental classes of macromolecules within cells, alongside DNA, proteins, and lipids. These intricate sugar structures participate in nearly every process within the human body, influencing how cells interact and function. Despite their widespread presence and significant roles, glycans are frequently overlooked compared to other biological molecules.
The Building Blocks of Glycans
Glycans are assembled from smaller sugar units called monosaccharides. Common examples include glucose, galactose, and sialic acid. These monosaccharides link together through glycosidic bonds. Unlike the uniform linkages in DNA or proteins, glycosidic bonds can vary in their connection points and spatial orientations, contributing to immense structural diversity.
When a few monosaccharides link, they form an oligosaccharide. If many monosaccharides join, they create a polysaccharide, which can be linear or extensively branched. This branching capability, combined with the variety of monosaccharides and linkage types, allows glycans to form complex three-dimensional structures, enabling them to carry vast amounts of biological information.
Where Glycans Reside
Glycans are prominently found on the cell surface, forming a dense, protective layer known as the glycocalyx. This “sugar coat” consists of glycans linked to proteins (glycoproteins) and lipids (glycolipids). These structures extend outwards from the cell membrane, acting as the cell’s interface with its external environment.
Glycans also contribute to the extracellular matrix, a network of molecules providing structural support and organization to tissues. Here, they are often part of proteoglycans, which are proteins heavily decorated with long, linear glycan chains. Most glycans in biological systems are covalently attached to proteins or lipids. For instance, antibodies are glycoproteins, and their attached glycans can influence their function and stability.
The Diverse Roles of Glycans
Glycans are fundamental in cell-cell recognition and communication, allowing cells to read and respond to signals from their neighbors. Their unique patterns on a cell’s surface serve as identity markers, influencing processes like cell adhesion and migration during development.
These sugar structures also modulate the immune system, helping to distinguish between the body’s own cells and foreign invaders. Immune cells recognize specific glycan patterns on pathogens, initiating defense responses. Glycans also regulate immune cell activation and migration.
Beyond recognition, glycans provide structural integrity and lubrication within tissues. For example, in connective tissues, proteoglycans with their associated glycan chains contribute to tissue resilience and ability to withstand compression. In the digestive and respiratory tracts, mucins, which are heavily glycosylated proteins, form a protective and lubricating barrier. Glycans also contribute to the proper folding and stability of newly synthesized proteins within cells. If proteins are not correctly glycosylated, they may fail to fold properly or exit the endoplasmic reticulum, leading to their degradation.
Glycans and Human Health
Understanding glycans is important for human health, as their alterations are linked to various diseases. A well-known example is the ABO blood group system, where differences between A, B, AB, and O blood types are determined by specific glycans on red blood cells. These glycan variations dictate compatibility for blood transfusions.
In cancer, changes in glycan expression on cell surfaces are a common hallmark. Cancer cells often display altered or truncated glycans, which can promote tumor growth, metastasis, and evasion of the immune system. Researchers are exploring these altered glycan patterns as potential targets for cancer diagnostics and therapies.
Glycans also serve as receptors for many infectious agents, enabling pathogens to enter host cells. For instance, the influenza virus binds to sialic acid glycans on respiratory tract cells to initiate infection. Similarly, Helicobacter pylori, which causes peptic ulcers, binds to specific Lewis type glycans in the stomach lining. Genetic defects in glycan synthesis can lead to Congenital Disorders of Glycosylation (CDGs). These disorders can affect multiple organ systems. The growing understanding of glycans also opens avenues for new therapeutics, including glycan-based drugs or diagnostic tools that target specific glycan structures involved in disease processes.