Biosynthesis of Keratan Sulfate Carbohydrate Chain and Corneal Abnormality led by Its Impairment

Abstract

Keratan sulfate glycosaminoglycans are negatively charged linear carbohydrate chains consisting of poly-N-acetyllactosamine with sulfate modification. The glycans are found in the extracellular matrix of the cornea, cartilage, and brain of vertebrates, and those function in the cornea has been extensively studied. The biosynthetic pathway of keratan sulfate glycosaminoglycans in the cornea is mainly catalyzed by four enzymes (β1,3-N-acetylglucosaminyltransferase-7, β1,4-galactosyltransferase-4, CHST1, CHST6) in the cooperative manner. In human, genetic mutations in CHST6 cause a hereditary eye disease, macular corneal dystrophy. In this disease, abnormal glycoproteins are synthesized due to impaired sulfation step in keratan sulfate biosynthesis, which may be aggregated and deposited in the corneal stroma, resulting in corneal opacity.