GAGS

2. Glycosaminoglycans
(Heteropolysaccharides)

3. Learning Objectives
 To identify the components of heteropolysaccharides
 To know about some of the individual heteropolysaccharides
 To understand the functions of heteropolysaccharides
 To know about the disorders related to heteropolysaccharides

4.  Also known as Glycosaminoglycans (GAGs)
 Heteropolysaccharides are polysaccharides which yield
10 or more different types of monosaccharides or their
derivatives on hydrolysis
Heteropolysaccharides

5.  Present as polysaccharide chains of proteoglycans
 Linked to the protein core via serine or threonine
(O-glycosidic linkage)
 The chains are linear (unbranched)
Heteropolysaccharides

6.  These are mostly composed of alternating units of
amino sugars and uronic acids
 Subclassified as
 Mucopolysaccharides (Hyaluronic acid, Heparin)
 Mucilages (Agar, vegetable gum, pectins, hemicellulose)
Heteropolysaccharides

7. Chondroitin
Sulfate
N-Acetyl -
D-
Galactosamine
D-Glucuronate Cartilage, bone,
skin, cornea, blood
vessel walls
Glycosaminoglycan Amino Sugar Uronic Acid Tissue Distribution
Hyaluronic Acid N-Acetyl -
Glucosamine
D-Glucuronate Connective tissues
cartilage, synovial
fluid, Vitreous
humor, umbilical
cord
Heteropolysaccharides
Dermatan Sulfates N-Acetyl -
Glucosamine
L-Iduronate,
D-Glucuronate
Skin, heart valve,
tendon, blood
vessel wall.

8. Heparan Sulfate D-Glucosamine D-Glucuronate
(major)
L-Iduronate
(minor)
Lung, blood vessel
walls, many cell
surfaces
Heteropolysaccharides
Glycosaminoglycan Amino Sugar Uronic Acid Tissue Distribution
Keratan sulfate N-Acetyl
Glucosamine
None (but
contains
D-Galactose)
Cartilage , Cornea,
Inter vertebral Discs
Heparin D-Glucosamine L-Iduronate
(major)
D-Glucuronate
(minor)
Lung, liver, skin,
intestinal mucosa
(mast cells)

9.  As structural components of the extracellular (EC) matrix
 Have specific interactions with collagen, elastin, fibronectin,
laminin, and other proteins of the matrix
 As poly-anions, bind with poly-cations and cations
 Contribute to the characteristic fullness/strength of various
tissues
Heteropolysaccharides
Functions

10.  Act as sieves in the EC matrix
 Facilitate cell migration (Hyaluronic acid)
 Have role in compressibility of cartilage in weight–bearing
(Hyaluronic acid, Chondroitin sulfate)
Heteropolysaccharides
Functions

11.  Play role in corneal transparency
(Karatan sulfate and Dermatan sulfate)
 Have structural role in sclera (Dermatan sulfate)
 Act as anticoagulant (heparin)
Heteropolysaccharides
Functions

12.  Are components of plasma membranes,
where they may act as receptors and participates in
cell adhesion and cell interaction (e.g. Heparan sulfate)
 Determine charge selectiveness of renal glomerulus
(Heparan sulfate)
Heteropolysaccharides
Functions

13. Mucopolysaccharidoses
Storage diseases related to glycosaminoglycans (GAGs)
 Rare, inborn errors of metabolism
 Deficiencies / defects of enzymes that degrade GAGs
result in a group of disorders called
mucopolysaccharidoses

14.  These disorders are accompanied by one or more of the
following:
 Somatic Skeletal changes
 Mental retardation
 Cardio Pulmonary problems
 Hepato-splenomegaly
 Corneal Clouding
 Hearing loss
Mucopolysaccharidoses
Storage diseases related to glycosaminoglycans (GAGs)

15. Types of Mucopolysaccharidoses
Types Enzyme Defect Urinary MPS
MPS-1
(Hurler’s syndrome)
-L-Iduronidase
(a lysosomal hydrolase)
Dermatan SO4
Heparan SO4
MPS-II
(Hunters syndrome)
Iduronate Sulfatase - Do -
MPS-III
(San Filippo syndrome)
A.B. & C.
A. Sulfamidase
B. -N-acetyl-
Glucosaminidase
C. Acetyl-Transferase
Heparan SO4

16. Types Enzyme Defect Urinary MPS
MPS-IV
(Morquio syndrome)
N – Acetyl –
Galactosamine – 6 –
sulfatase
Keratan SO4
Types of Mucopolysaccharidoses
MPS-V
(Scheie’s syndrome)
 -L - Iduronidase Dermatan SO4
MPS-VI
(Maroteaux Lamy
syndrome)
N – Acetyl –
Galactosamine – 4 –
sulfatase
(Aryl sulfatase B)
Dermatan SO4
MPS-VII
(Sly syndrome)
 - Glucuronidase Dermatan SO4
Heparan SO4
Chondroitin SO4

17. Hyaluronic acid derivatives
 Several products are used in the management of
osteoarthritis symptoms
 Others are used as ophthalmic surgical procedures
Gums
 Widely used in the food and pharmaceutical industry
 Used as: suspending agents, gelling agents, thickening
agents, emulsifiers, adhesives

18. Pectins
 Pectins are heteropolysaccharides found in the pulp of
fruits (citrus, apples)
 On hydrolysis pectins yield galacturonic acid, galactose,
arabinose, methanol and acetic acid
 Used as gelling agents (to make jellies)