9. The following statements are made with reference to characteristics of glycosaminoglycans and proteoglycans, which are major constituents of
   extracellular matrix. Which one of them is INCORRECT?
   (1) Glycosaminoglycans are very long polysaccharide chains composed of repeating disaccharide units of an amino sugar and a uronic acid.
   (2) Except for hyaluronic acid, all glycosaminoglycans are covalently attached to protein as proteoglycans.
   (3) Glycoproteins contain less carbohydrate usually in the form of relatively short, branched oligosaccharide chains whereas proteoglycans contain more carbohydrate in the form of long unbranched glycosaminoglycan chains.
   (4) Like O-linked and N-linked glycoproteins, in proteoglycan also glycosaminoglycans are linked to serine or threonine and asparagine residues.

Introduction: Major ECM Macromolecules

Glycosaminoglycans (GAGs) and proteoglycans are central components of the extracellular matrix (ECM), responsible for matrix hydration, resisting compression, and supporting cell signaling and migration. Their structure and biochemical characteristics distinguish them clearly from standard glycoproteins.​

Correct Statements

Glycosaminoglycan Structure

GAGs are long unbranched polysaccharide chains composed of repeating disaccharide units: an amino sugar (such as N-acetylglucosamine or N-acetylgalactosamine) and a uronic acid (such as glucuronic acid or iduronic acid).​

Proteoglycan Linkage

Except for hyaluronic acid, all GAGs in ECM are covalently linked to a core protein, forming proteoglycans. Hyaluronic acid remains free and unlinked, despite its ECM importance.​

Carbohydrate Content in Glycoproteins vs Proteoglycans

Glycoproteins generally contain short, branched oligosaccharide chains, while proteoglycans have a much higher carbohydrate content, with long, unbranched GAG chains.​

Incorrect Statement: Proteoglycan Linkage

Linkage Chemistry

• Glycoproteins: O-linked glycans attach to serine or threonine residues, and N-linked glycans attach to asparagine.​

• Proteoglycans: GAG chains are almost always O-linked, attached to serine residues on the core protein through a tetrasaccharide bridge. N-linked attachment of GAGs to asparagine does NOT occur in proteoglycans.​

Thus, statement (4)—”Like O-linked and N-linked glycoproteins, in proteoglycan also glycosaminoglycans are linked to serine or threonine and asparagine residues.”—is incorrect, because in proteoglycans, GAG chains are not linked to asparagine (N-linked glycosylation).​

ECM Macromolecule Characteristics Table

Key Takeaways

• GAGs and proteoglycans are crucial matrix constituents, with unique linkages and structures that provide specialized functions.

• Proteoglycans feature GAG chains O-linked to serine, not N-linked to asparagine—this detail sets them apart from standard glycoproteins.​

• Understanding these distinctions is essential for appreciating extracellular matrix biochemistry and its medical relevance.