Question

Fucose and sialic acid A. are both derivatives of UDP- \(N\) -acetylglucosamine. B. are the parts of the carbohydrate chain that are covalently linked to the protein. C. can be found in the core structure of certain O-linked glycoproteins. D. are transferred to a carbohydrate chain when it is attached to dolichol phosphate. E. are the repeating unit of proteoglycans.

Short answer

A) They are both derivatives of UDP-\(N\)-acetylglucosamine. B) They are the parts of the carbohydrate chain that are covalently linked to the protein. C) They can be found in the core structure of certain O-linked glycoproteins. D) They are transferred to a carbohydrate chain when it is attached to dolichol phosphate. E) They are the repeating unit of proteoglycans. Answer: B, C

Step-by-step solution

Evaluate Option A

A. are both derivatives of UDP-\(N\)-acetylglucosamine. Fucose is indeed synthesized from GDP-fucose, derived from GDP-mannose, which in turn comes from UDP-\(N\)-acetylglucosamine. However, sialic acid has its own biosynthetic pathway, starting from UDP-GlcNAc (UDP- \(N\) -acetylglucosamine) and forming CMP-sialic acid as an intermediate. Hence, option A is not entirely correct, as it does not apply to both fucose and sialic acid.

Evaluate Option B

B. are the parts of the carbohydrate chain that are covalently linked to the protein. Both fucose and sialic acid can be covalently linked to proteins, often found as terminal residues of a glycan chain in N-linked and O-linked glycoproteins. Thus, option B is correct.

Evaluate Option C

C. can be found in the core structure of certain O-linked glycoproteins. Fucose and sialic acid are commonly found in the core structures of some O-linked glycoproteins. This statement is correct.

Evaluate Option D

D. are transferred to a carbohydrate chain when it is attached to dolichol phosphate. The dolichol phosphate pathway is crucial for the synthesis of N-linked glycoprotein structures. It does not involve the direct transfer of fucose or sialic acid to the carbohydrate chain. Therefore, option D is not correct.

Evaluate Option E

E. are the repeating unit of proteoglycans. Proteoglycans consist of a core protein and glycosaminoglycan (GAG) chains. The GAG chains contain repeating disaccharide units consisting of an amino sugar and a uronic acid or galactose. Fucose and sialic acid are not part of these repeating units. Thus, option E is incorrect. In conclusion, the correct options are: B. are the parts of the carbohydrate chain that are covalently linked to the protein. C. can be found in the core structure of certain O-linked glycoproteins.

Key concepts

UDP-N-acetylglucosamine

UDP-N-acetylglucosamine (UDP-GlcNAc) serves as a fundamental building block in the biosynthesis of glycoproteins and other glycoconjugates. It is an activated form of N-acetylglucosamine, a monosaccharide that plays a crucial role in the structure of glycoproteins, as well as in signal transduction processes.

During glycosylation, the enzymatic process of attaching carbohydrates to proteins or lipids, UDP-GlcNAc is a substrate for various glycosyltransferases. These enzymes catalyze the transfer of N-acetylglucosamine to specific proteins or lipids, forming a glycosidic bond and thereby extending the developing carbohydrate chain.

Importantly, the synthesis of UDP-GlcNAc itself is an intricate pathway that involves the conversion of glucose to amino sugar derivatives. This conversion is crucial for the production of numerous glycostructures that are fundamental to cellular communication, adhesion, and the immune response. Within the context of fucose and sialic acid, as mentioned in the original exercise, understanding UDP-GlcNAc's role helps clarify how these sugars are integrated into glycoproteins, although they have distinct biosynthetic pathways.

Carbohydrate Chain Covalent Linkage

The attachment of carbohydrate chains to proteins is a covalent linkage essential for forming glycoproteins. This attachment happens through a process called glycosylation, which can take two primary forms: N-linked and O-linked glycosylation.

N-linked glycosylation involves attaching a carbohydrate chain to the nitrogen atom on the side chain of an asparagine amino acid residue in a protein, whereas O-linked glycosylation involves the attachment to the oxygen atom on the side chain of serine or threonine. The biosynthesis of these glycosidic bonds requires enzyme-mediated catalysis, ensuring the carbohydrate chains are correctly attached to the appropriate protein residues.

As detailed in the exercise solutions, fucose and sialic acid are often found at the terminal ends of these carbohydrate chains. Their presence affects the physical properties and biological functions of the glycoproteins, such as stability, solubility, and recognition by other biomolecules. Understanding the specific covalent linkage of carbohydrates to proteins highlights the diversity and specificity of these molecules' roles within biological systems.

O-linked Glycoproteins Core Structure

O-linked glycoproteins possess a core structure characterized by the attachment of carbohydrate chains to the hydroxyl group of serine or threonine amino acids within the protein. This core is the foundation upon which more complex glycan structures are built.

The glycosylation process begins in the Golgi apparatus, where the core glycan linkage is initiated, often involving the addition of N-acetyl galactosamine (GalNAc) to the protein. Subsequent sugars, including fucose and sialic acid as mentioned in the exercise, are often added to this foundation to form the full glycan structure. These additions frequently occur through the sequential action of various glycosyltransferases, each adding a specific sugar residue.

It is pivotal to recognize that the core structure of O-linked glycoproteins can be varied, leading to a diverse array of possible glycan compositions. This diversity plays a significant role in the function of the glycoproteins, affecting processes like cell-cell recognition, protein stability, and immune responses. The correct identification of components present in this structure, such as fucose and sialic acid, can provide insights into the glycoprotein's biological roles and interactions.