SN6 SHORT NOTE 5M

Classify glycosaminoglycans with their functions. Add a note on the mucopolysaccharidoses.

Biochemistry · 1st Professional — Pre-Clinical

Definition

Glycosaminoglycans (GAGs, mucopolysaccharides) = long unbranched polysaccharides of repeating disaccharide units, each containing an amino sugar and a uronic acid, usually sulphated.

They are strongly negatively charged, so they bind large amounts of water and cations
Bound to a core protein they form proteoglycans — the ground substance of connective tissue

The Important Glycosaminoglycans

Gag	Site	Special feature
Hyaluronic acid	Synovial fluid, vitreous humour, loose connective tissue	The only one that is not sulphated and not protein-bound; a lubricant and shock absorber
Chondroitin sulphate	Cartilage, bone, cornea	The most abundant in the body
Keratan sulphate	Cornea, cartilage, intervertebral disc	Contains galactose instead of uronic acid
Dermatan sulphate	Skin, blood vessels, heart valves	Gives skin its pliability
Heparin	Mast cell granules	Anticoagulant — the most highly charged molecule in the body
Heparan sulphate	Basement membranes, cell surfaces	Charge barrier of the glomerulus

Functions

Structural — ground substance of connective tissue, cartilage and bone
Lubrication and shock absorption — hyaluronic acid in synovial fluid
Charge-selective filtration — heparan sulphate in the glomerular basement membrane repels albumin
Anticoagulation — heparin activates antithrombin III
Corneal transparency — regular arrangement of keratan sulphate with collagen
Cell signalling and adhesion; binding of growth factors
Clearing of chylomicrons — heparin releases lipoprotein lipase

Mucopolysaccharidoses

Inherited lysosomal storage disorders in which GAGs cannot be degraded and accumulate in tissues, with excess excretion in urine.

Disease	Enzyme deficient	Inheritance	Features
Hurler (MPS I)	α-L-iduronidase	Autosomal recessive	Coarse facies (gargoylism), corneal clouding, mental retardation, hepatosplenomegaly, dwarfism; death in childhood
Hunter (MPS II)	Iduronate sulphatase	X-linked	Milder; NO corneal clouding — the key distinction from Hurler
Sanfilippo (MPS III)	Heparan sulphate degradation	Autosomal recessive	Severe neurological disease with mild somatic features
Morquio (MPS IV)	Galactose-6-sulphatase	Autosomal recessive	Skeletal deformity with normal intelligence

Diagnosis — urinary gag screening, then enzyme assay and genetic testing
Treatment — enzyme replacement therapy for several types; haematopoietic stem cell transplantation in Hurler if done early

Applied Aspects

Heparin is used clinically as an anticoagulant; unfractionated heparin is monitored by APTT, low molecular weight heparin usually needs no monitoring
Loss of glomerular heparan sulphate is one mechanism of the proteinuria of diabetic nephropathy and minimal change disease
Hyaluronic acid injections are used in osteoarthritis of the knee and in ophthalmic surgery
Osteoarthritis involves loss of cartilage proteoglycan, reducing its capacity to hold water and resist compression

All questions in Carbohydrate Metabolism II: Glycogen, HMP & Diabetes

Every Biochemistry chapter →