SN5 SHORT NOTE 5M

Describe the structure and functions of glycoproteins. Add a note on the blood group antigens.

Biochemistry · 1st Professional — Pre-Clinical

Glycoproteins = proteins covalently linked to carbohydrate chains, usually short and branched, forming less than 40% of the molecule by weight.

Distinguished from proteoglycans, in which the carbohydrate is a long unbranched glycosaminoglycan and predominates by weight
Most secreted and membrane proteins are glycosylated

Type	Linked to	Sugar attached	Site of synthesis
N-linked	Asparagine (in Asn-X-Ser/Thr)	N-acetylglucosamine	Endoplasmic reticulum, then Golgi
O-linked	Serine or threonine (also hydroxylysine in collagen)	N-acetylgalactosamine	Golgi

Dolichol phosphate carries the preassembled oligosaccharide for N-linked glycosylation
The sugars commonly found are mannose, galactose, N-acetylglucosamine, fucose and sialic acid
Sialic acid is usually terminal and gives the negative charge

Protein folding and stability; protection from proteolysis
Cell–cell recognition and adhesion — selectins, integrins
Blood group antigens — A, B and O differ only in their terminal sugar
Determining plasma half-life — loss of terminal sialic acid exposes galactose, and the asialoglycoprotein receptor of the liver removes the molecule
Lubrication and protection — mucins of gastric and respiratory mucus
Receptors and transporters; hormones — TSH, FSH, LH, hCG, erythropoietin
Targeting — the mannose-6-phosphate tag for lysosomal enzymes

The entire ABO system rests on a single terminal sugar — a striking illustration of how much biological information carbohydrate structure can carry
Bombay phenotype — absence of the H substance itself, so neither A nor B can be added

Congenital disorders of glycosylation — a growing group causing developmental delay, hepatopathy, coagulopathy and abnormal fat distribution; screened for by transferrin isoform analysis
Influenza virus neuraminidase cleaves sialic acid to release new virions — the target of oseltamivir and zanamivir
Tumour markers are largely glycoproteins — CA-125, CA 19-9, CEA, AFP, hCG
Recombinant erythropoietin must be correctly glycosylated to have a useful half-life, which is why it is made in mammalian rather than bacterial cells
Selectin-mediated leucocyte rolling depends on glycoprotein recognition; its failure causes leucocyte adhesion deficiency

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