Sialic acid

Where are white blood cells found

White blood cells patrol the circulatory system and interstitial spaces ready for mobilisation at a trauma site.

What are frontline scouts for these leukocytes called

Cell-surface carbohydrates called sialyl Lewis^x acids and contain a sialic acid group.

What do cells do upon injury?

Upon injury, cells at the trauma site display proteins (selectins) that signal the site of injury.

Function of selectins

These selectins bind sialyl Lewis^x acid. This binding causes adhesion of leukocytes at the infected area.

what is leukocyte recruitment central to

Leukocyte recruitment is central to the inflammatory cascade.

What can result of over enthusiastic leukocyte recruitment

Some diseases result from the over enthusiastic leukocyte recruitment (e.g. rheumatoid arthritis and strokes).

How can oevr active inflammatory cascade be combated

Disrupt leukocyte adhesion by blocking selectin binding of sialyl Lewis^x acid.

What have synthetic mimetic sialyl Lewis^x acids helped

Synthetic mimetic sialyl Lewis^x acids have helped to identify the key functional group for recognition and binding.

What is hoped to occur as result of preparing sialyl Lewis^x acid analogues

It is hoped that tighter binding derivatives can result, so providing new therapies for chronic inflammatory diseases.

What do new serum proteins contain

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 glycoproteins circulate

As the glycoproteins circulate, sialic acid groups are slowly cleaved from the glycoprotein by enzymes in the blood vessel walls. This exposes the galactose units.

What binds to exposed galactose units as result of glycoproteins circulating

The asialoglycoprotein receptor in the liver bonds to the exposed galactose units.

What sugar is usually found at the N-link in glycoproteins?

N-acetylgalactosamine

What other sugars can be used for N-linked glycoproteins

• mannose

• galactose

• xylose

What are oligosaccharides attached to in N-linked glycoproteins

Oligosaccharides are attached to N-acetylglucosamine via the amide nitrogen of asparagine.

What does the cleavage of sialic acid expose

Cleavage of sialic acid exposes galactose units.

What happens as more galactose units are exposed

• As more galactose units are exposed, the protein binds more tightly with the asialglycoprotein receptor in the liver.

• The receptor-asiaglycoprotein complex is absorbed and degraded by the cell.

• Thus, it is the slow cleavage of sialyl acid residues from N-linked glycoproteins in the blood that controls the degradation of glycoproteins.

What is the ability of viruses to infect cells dictated by

Dictated partly by their ability to bind particular structures or receptors on the cell surface.

How are glycoproteins related to viral infections

In some cases, receptor on cell surface are carbohydrate portions of cell- surface glycoproteins.

The virus binds to these sugars and cleaves them from the glycoprotein

This allows the virus to infect the cell.

What are neuramidases?

enzymes that cleave the sialic acid glycoside bond

What are inhibitors of neuramidases used as

Anti-flu treatments

How does inhibition occur

Inhibitors bind to an enzyme more tightly than the usual substrate, giving an inhibitor-enzyme complex.

Give examples of transition state analogue inhibitors of influenza neuramidase

• tamiflu

• relenza

What type of reaction is the cleaving of the sialic acid glycoside bond?

glycoside hydrolysis