glycosaminoglycans and glycoproteins

where are glycosaminoglycans (GAGs) found?

in the extracellular spaces of connective tissue. These spaces contain collagen and elastin fibres embedded in a gel like matrix, which is mainly made up of GAGs

properties of glycosaminoglycan solutions

slimy and mucous like as a result of high viscosity and elasticity

GAG structure

linear chains of repeating disaccharides where at least one of the monosaccharide monomers has 1+ negatively charged functional group

How many disaccharide units do hyaluronic acid molecules contain?

250 to 25,000

viscosity of hyaluronate solutions at low shear rates

Molecules form tangled masses that impede flow (high viscosity)

Heparin structure

2 to 3 sulfates per repeat disaccharide unit so it’s one of the most negative biopolymers

What is the function of heparin, found in the arterial wall lining?

Inhibits blood clotting, is released upon injury and is used clinically in post surgical patients

keratan sulfate structure and function

Variable sulfate content and contain several monosaccharides. Component of cartilage, bone, hair, nails, horn and cornea

cartilage structure

Mesh of collagen fibres combined with glycoproteins containing keratan sulphate and chondroitin sulphate. Highly hydrated due to sulphate groups

cartilage, water and mechanical compression

Mechanical compression displaces water until sulphate groups repel significantly and resist further compression. Releasing pressure → water molecules return

dermatan sulfate

Found mainly in skin and connective tissue. Epimer of chondroitin-4-sulfate - enzymatic epimerisation occurs after chondroitin formation

bacterial cell walls and GAGs

Contain linear chains of 1,4’ beta linked NAG (N-acetylglucosamine) and NAM (N-acetylmuramic acid). Polypeptide chains covalently cross-linked via polysaccharides

amide bonds in bacteria

Linkage between polysaccharide & polypeptide chains occurs through an amide functional group. Amide formed by COOH of NAM and amine from Ala residue

how does penicillin kill bacteria?

Inhibits cell wall biosynthesis by binding the enzyme responsible for crosslinking peptidoglycan strands of bacterial cell walls

why is there large variability in glycoprotein structure?

due to way synthesis occurs as there’s not always enzymes present to create regularity

glycoprotein formation

Polypeptide part synthesised by translation. Carbohydrate component enzymatically generated. Carbohydrate can makes up 1 to 90% of the biomolecule mass

different roles of glycoproteins in HUMAN biology

structural protein components (part of ground substance), mucous secretions, immunoglobulins, interferons, blood plasma proteins

functions of glycoproteins in different areas of biology

Infection, infection prevention, egg fertilisation, inflammatory disease, septic shock, clotting

O linked carbohydrate structure

carbohydrate is often linked to the polypeptide chains via the -OH of the following amino acid side groups: serine, threonine or hydroxylysine

O linked glycoproteins in mucus

Usually clustered in heavily glycosylated segments.. Contain sulfate groups in mucus which repel one another, preventing protein secondary structure developing.

antigenic determinants as glycoproteins

Carbohydrate structure on cell surface glycoprotein determines blood type (O/A/B/AB). If donor and acceptor don’t have compatible blood types RBC agglutination occurs → fatal blood vessel blockage

N-linked glycoproteins

oligosaccharides attached to N acetylglucosamine via the amide nitrogen of asparagine

Sialyl Lewis^x acids

cell-surface carbohydrates which contain a sialic acid group. Involved in cell-to-cell recognition in the immune response

Sialic acid and injury

Cells at the trauma site display proteins that signal the injury site. These selectins bind sialyl Lewisx acid → leukocyte adhesion

How to combat the overactive inflammatory cascade which has led to conditions eg rheumatoid arthritis and stroke

disrupt leukocyte adhesion by blocking selectin binding of sialyl Lewisx acid.

What happens as more sialic acid galactose units are exposed?

Protein binds more tightly with the asialoglycoprotein receptor in the liver. The complex is absorbed and degraded. Therefore slow cleavage of sialyl acid residues from *N*-linked glycoproteins in the blood

sialic acid and viruses

Receptors that viruses bind to are sometimes carbohydrate portions of cell-surface glycoproteins. The virus binds these sugars, and cleaves them from the glycoprotein so the virus can enter and infect

anti flu treatments and sialic acid

Neuramidase inhibitors that cleave sialic acid’s glycoside bond are used as anti flu treatments.

viscosity of hyaluronate solutions at high shear rates

Less resistance to flow so there’s potential for movement (low viscosity)

structure of new serum proteins

New serum proteins have *N*-linked oligosaccharides with chains terminated with 3 strands that have sialic acid end caps covering a galactose.

What happens as new serum proteins circulate?

Sialic acid groups are slowly cleaved off by enzymes in blood vessel walls, exposing the galactose units. The liver asialoglycoprotein receptor binds to the exposed galactose units.

What have synthetic mimetic sialyl Lewisx acids helped to identify?

key groups for recognition and binding in overactive inflammatory cascades.

Future hopes for treating chronic inflammatory disease

It’s hoped tighter binding derivatives can result to provide new therapies for chronic inflammatory disease.

How do mucins protect and lubricate mucous membranes?

They form inter-tangled networks that act as viscoelastic gels