Lecture 18 - Glycoconjugates

What are glycoconjugates?

Carbohydrates covalently linked to non-carbohydrate biomolecules.

Where are glycoconjugates commonly found?

On the exterior of the plasma membrane, though some are intracellular.

What are the main functions of glycoconjugates?

Cell-to-cell communication, signaling, protein labeling, and recognition of extracellular molecules.

What are the three main types of glycoconjugates?

Proteoglycans, glycoproteins, and glycolipids.

What are glycosaminoglycans (GAGs)?

Linear polymers of repeating disaccharide units found in proteoglycans.

What are proteoglycans?

Rod-shaped membrane proteins that are heavily glycosylated with GAGs.

What type of linkage connects carbohydrates to proteins in proteoglycans?

Covalent linkage.

What is the composition of glycosaminoglycans (GAGs)?

Repeating disaccharide units with one amine sugar and one uronic acid (except in keratan sulfate).

Which amine sugars are found in GAGs?

N-acetyl-glucosamine or N-acetyl-galactosamine.

What type of acid is commonly found in GAGs?

Uronic acid (oxidation of C6 carbon).

Which GAG does not contain uronic acid?

Keratan sulfate.

Which GAG lacks sulfate groups?

Hyaluronate.

What is the charge characteristic of GAGs?

Highly negatively charged.

Why are GAGs highly hydrated molecules?

Their negative charge attracts water and minimizes charge repulsion.

What structural role do GAGs play?

They form meshworks with fibrous proteins in the extracellular matrix (ECM).

Where are GAGs found in the body?

In connective tissues and as joint lubricants.

What is a unique property of hyaluronate?

It is unsulfated and not covalently bound to proteins.

Where is hyaluronate found?

In articular cartilage and synovial fluid.

What monomer does hyaluronate contain?

Glucuronic acid.

What distinguishes keratan sulfate from other GAGs?

It lacks uronic acid.

Where is keratan sulfate found?

In the cornea, cartilage, and bone.

What is dermatan sulfate sometimes composed of?

Iduronic acid.

What is the biological function of heparin?

Acts as an anticoagulant by activating antithrombin to inhibit thrombin.

What is heparin?

A highly sulfated, linear polysaccharide (3–40 kDa) with strong negative charge.

What is heparan sulfate?

A heparin-like polysaccharide covalently attached to proteins.

What is unique about heparin and heparan sulfate’s charge?

They have the highest negative charge density among biomolecules

Besides anticoagulation, what other roles do heparin and heparan sulfate play?

Regulate development, blood vessel formation, and reduce viral/bacterial virulence.

How are GAGs attached to the proteoglycan core protein?

Through a carbohydrate tetrasaccharide bridge.

What amino acid sequence is typically involved in GAG linkage to core proteins?

Ser–Gly–X–Gly (where X is any amino acid).

What is the linkage between the core protein and the GAG chain?

From the anomeric carbon of xylose to the hydroxyl of serine.

What is aggrecan?

A well-studied proteoglycan with chondroitin sulfate (CS) and keratan sulfate (KS) chains attached.

What are syndecans?

Proteoglycans with a single transmembrane domain (integral membrane proteins).

What are glypicans?

Proteoglycans anchored to the cell membrane via a glycosylphosphatidylinositol (GPI) anchor.

What is the function of proteoglycans in the ECM?

They regulate cell growth, tissue organization, and adhesion through receptor interactions.

How do proteoglycans bind to extracellular proteins?

Through electrostatic interactions.

What are proteoglycan aggregates?

Large assemblies of many proteoglycans bound noncovalently to hyaluronan.

What is the molecular mass of proteoglycan aggregates?

Greater than 2 × 10⁸ Daltons.

What physical property do proteoglycan aggregates have?

They retain large amounts of water (up to 1000× their weight) for lubrication.

Where are proteoglycan aggregates found in the body?

On articular cartilage surfaces in joints.

What function do proteoglycan aggregates serve in joints?

They reduce friction and distribute load during movement.

What is the extracellular matrix (ECM)?

A network of material outside cells providing structural strength, elasticity, and barriers in tissues.

What are the main components of the ECM?

Proteoglycan aggregates, collagen fibers, and elastin.

What is the role of the ECM in cancer invasion?

It acts as a barrier to tumor cells, though some tumors secrete heparinase to degrade it.

What are syndecans in relation to the ECM?

Integral membrane proteoglycans that link the cytoskeleton to the ECM.

What are integrins?

Membrane receptors that connect the cytoskeleton to ECM proteoglycans.

What processes do syndecans and integrins regulate?

Cell growth, mobility, apoptosis, and wound healing.

Which group of carbohydrates are strong anions containing carboxylate and sulfate?

Glycosaminoglycans.

Which characteristic is not true of glycosaminoglycans?

They do not always contain sulfates.

Which glycosaminoglycan is found in synovial fluid of joints?

Hyaluronate.

How does an informational carbohydrate become biologically active?

By being covalently linked to a protein or lipid.

What are glycoproteins?

Proteins with one or more covalently bound oligosaccharide chains.

Where are glycoproteins located?

On the outer plasma membrane, in the ECM, in blood, or inside cells.

How are carbohydrates linked to glycoproteins?

Through O-linkages (Ser/Thr) or N-linkages (Asn).

What proportion of mammalian proteins are glycoproteins?

About half.

Do bacteria glycosylate proteins?

Only a few bacterial proteins are glycosylated.

What is the functional role of glycoprotein carbohydrates?

Mediating protein–protein recognition.

Why are viral proteins heavily glycosylated?

To help them evade the immune system.

What proteins bind to glycoprotein carbohydrates with high affinity?

Lectins.

What are glycolipids?

Lipids covalently linked to oligosaccharides.

Where are glycolipids located?

In plant and animal cell membranes.

What are glycosphingolipids?

Glycolipids composed of oligosaccharides attached to a sphingolipid backbone.

What roles do glycolipids play?

Cell recognition, nerve conduction, myelin formation, and signal transduction.

How do glycolipid oligosaccharides function?

They act as recognition sites for lectins.

What determines blood groups in vertebrates?

The carbohydrate composition of gangliosides (a type of glycolipid).

What are gangliosides?

Glycolipids that determine cell recognition and blood type.

What bacterial structure contains glycolipids?

The outer membrane of gram-negative bacteria.

What are lipopolysaccharides (LPS)?

Glycolipid components of gram-negative bacterial membranes.

What regions make up lipopolysaccharides?

Lipid A, core polysaccharide, and O-specific chain.

Why is Lipid A significant in bacteria?

It can be endotoxic and cause toxic effects in hosts.

What identifies gram-negative bacteria to the immune system?

The O-specific chain of lipopolysaccharides.

How are glycoconjugates analyzed in research?

Using mass spectrometry.

What are proteoglycans composed of?

Core proteins covalently attached to sulfated GAGs.

What functions do proteoglycans serve?

Adhesion, recognition, and information transfer.

What are glycoproteins composed of?

Proteins covalently linked to short, branched oligosaccharides.

Where are glycoproteins commonly found?

On the cell surface, extracellularly, and in secreted proteins.

What are glycolipids and glycosphingolipids composed of?

Lipids with oligosaccharide chains exposed on the outer cell surface.

What is the main function of glycolipids in cells?

Cell recognition and signaling.

What are lipopolysaccharides in bacteria responsible for?

Structural support and immune recognition.

Which amino acids are analyzed for glycosylation on glycoproteins?

Serine, threonine, and asparagine.

Which lipids are commonly modified with oligosaccharides?

Sphingolipids and phospholipids

Are glycoproteins always extracellular?

No, some can be cytoplasmic or nuclear.

What amino acid residues can glycoprotein oligosaccharides attach to?

Asparagine (N-linked), serine, or threonine (O-linked).

What fraction of total proteins are glycoproteins in humans?

Approximately half of all proteins.

Which molecule is dominant in the outer membrane of gram-negative bacteria?

Lipopolysaccharides.

What is the function of proteoglycans in cell signaling?

They bind growth factors and influence signaling pathways.

What property allows proteoglycans to act as tissue organizers?

Their ability to interact with cell receptors and ECM components.

How do proteoglycan aggregates reduce friction in joints?

They bind water and create a lubricating gel-like matrix.

What enzyme can degrade the ECM to promote tumor invasion?

Heparinase.

How do integrins and syndecans link the ECM to cell function?

By connecting the extracellular matrix to the cytoskeleton and transmitting regulatory signals.

What is the overall biological role of glycoconjugates?

They mediate recognition, communication, and structural stability at the cell surface.