Keratan sulfate is a complex carbohydrate molecule found naturally within the human body. This molecule is a type of glycosaminoglycan. It serves as a significant component within various biological structures, contributing to their physical properties and functions. Keratan sulfate is a building block in the intricate architecture of human tissues.
Understanding Keratan Sulfate
Keratan sulfate (KS) is a linear polysaccharide chain characterized by its repeating disaccharide unit. This unit consists of galactose and N-acetylglucosamine. The sulfation patterns on these disaccharide units can vary, contributing to the molecule’s structural heterogeneity.
As a glycosaminoglycan (GAG), KS is known for its repeating disaccharide units and sulfation. KS associates with core proteins to form proteoglycans. These proteoglycans are integral components of the extracellular matrix, which provides structural support and regulates cellular processes. Three forms of KS are identified by their linkage to the proteoglycan core protein: KS I, KS II, and KS III.
Biological Functions and Tissue Distribution
Keratan sulfate plays various roles across different tissues, contributing to their properties. It is found in the cornea, where it is a component of corneal proteoglycans. In this transparent tissue, keratan sulfate maintains corneal clarity by influencing tissue hydration and regulating the spacing and organization of collagen fibrils. This allows light to pass through without scattering, enabling clear vision.
In articular cartilage, which covers the ends of bones in joints, keratan sulfate contributes to its elasticity and ability to withstand compressive forces. Its presence helps maintain hydration, important for absorbing shock and facilitating smooth joint movement. The ability of cartilage to deform under pressure and then return to its original shape is partly due to the water-binding capacity of molecules like keratan sulfate.
The central nervous system also contains keratan sulfate, particularly within structures known as perineuronal nets that surround neurons. Here, it is involved in neuronal plasticity, which is the brain’s ability to reorganize itself by forming new neural connections. It also contributes to brain development and the regulation of synaptic function, influencing how nerve cells communicate with each other.
Keratan sulfate is also present in bone and other connective tissues. In these locations, it contributes to their structural integrity and participates in various cellular processes. Keratan sulfate exerts its effects through its capacity to bind water, interactions with other extracellular matrix components, and involvement in cell signaling pathways that regulate cell behavior.
Keratan Sulfate and Human Health
Abnormalities in keratan sulfate synthesis, degradation, or structure can have implications for human health. Lysosomal storage disorders, such as Morquio Syndrome (Mucopolysaccharidosis Type IVA and IVB), are examples. In these genetic conditions, defective enzymes lead to the abnormal accumulation or breakdown of keratan sulfate, resulting in severe skeletal dysplasias, clouding of the cornea, and other systemic issues impacting organ systems.
Corneal dystrophies, including Macular Corneal Dystrophy, are directly linked to defects in keratan sulfate sulfation or production. These defects cause the progressive accumulation of abnormal deposits in the cornea, leading to opacity and impaired vision. Precise sulfation patterns are important for keratan sulfate’s role in maintaining corneal transparency.
Changes in the content, structure, and sulfation patterns of keratan sulfate in cartilage are observed in the progression of osteoarthritis. As cartilage degrades in this degenerative joint disease, the extracellular matrix composition, including keratan sulfate, is altered. These changes make keratan sulfate a potential biomarker for assessing the severity of joint degradation and monitoring disease progression.
Keratan sulfate also has clinical relevance as a biomarker in certain cancers, where its levels or specific forms may correlate with tumor development or progression. Its involvement in wound healing processes is also being explored, suggesting a broader role in tissue repair and regeneration.