Objectives IX and X

Where does synthesis of N-linked polysaccharide cores occur?

On Dolichol phosphate embedded in the ER membrane.

Describe the synthesis of the core structure of N-linked polysaccharides.

Begins on cytosolic face of ER → sugars added to dolichol phosphate → flips to luminal side → further sugar additions complete core

What are the activated forms of the monosaccharides used?

UDP-GlcNAc, UDP-GalNAc, GDP-mannose, and UDP-glucose.

What is the function of Translocase?

Flips the dolichol-linked oligosaccharide from the cytoplasmic to luminal side of the ER membrane.

What is the function of the Oligosaccharide Transferase Complex?

Transfers the pre-assembled oligosaccharide to the asparagine residue of the growing polypeptide.

What is the function of the Asialoglycoprotein receptor?

Binds glycoproteins missing terminal sialic acid and mediates their clearance from circulation by receptor-mediated endocytosis.

Describe the synthesis of O-linked polysaccharides.

Sugars are sequentially added to the hydroxyl group of serine or threonine residues in the Golgi apparatus using glycosyltransferases.

What is ubiquitin?

A small 76-amino acid protein that tags proteins for degradation.

Why is a protein ubiquitinated?

To mark it for degradation by the 26S proteasome, often due to damage, misfolding, or regulation.

How is a protein ubiquitinated?

Via a 3-enzyme cascade:

• E1 activates ubiquitin

• E2 conjugates it

• E3 ligates it to a lysine residue on the substrate protein.

What happens after a protein is polyubiquitinated?

It is recognized and degraded by the proteasome, yielding peptides and free ubiquitin for reuse.