Glycosaminoglycans, Proteoglycans & Glycoprotein

Hi, after long time

Today, we will explain Glycosaminoglycans, Proteoglycans and Glycoprotein but before we start, we will make a quick revision for basics of carbohydrates.

Revision:

Carbohydrates have general formula (CH2O)n, where n ≥ 3.

They are classified into monosaccharides (simple sugar such as glucose), disaccharides and polysaccharides.

They can also be classified into aldoses (-CHO) and ketoses (-CO) where:

Enantiomers are special type of isomerism is found in the pairs of structures that are mirror images of each other where the two members of the pair are designated as a D- and an L-sugar. In the D isomeric form, the –OH group on the asymmetric carbon (a carbon linked to four different atoms or groups) farthest from the carbonyl carbon is on the right, whereas in the L-isomer, it is on the left.

Cyclization:

You can see anomeric carbon in the image (referred by arrow).

Alpha anomer where OH on anomeric carbon is trans to CH2OH group in Haworth projection (opposing sides) where beta anomers OH is cis to CH2OH (in the same side as you see in the image).

Joining of monosaccharides:

They are joined by a bond called Glycosidic bond, let’s give example to know how to name the bond.

To name the bond:

a)    Take into consideration numbers of carbons shared in formation of bond and position of anomeric (-OH) of sugar involved in bond (beta or alpha).

So, for example: Lactose, the bond is formed between C1 of galactose and C4 of glucose and the anomeric (-OH) is beta, then the bond is β(1→4) glycosidic bond.

Now, let’s begin our principal topic:

Monosaccharides Derivatives:

a)    Amino sugar: (Monosaccharide + (-NH2))

To get amino sugar, replace hydroxyl group with amino group (-NH2) such as glucose with replacing (-OH) with (-NH2), it will be amino glucose or glucosamine.

b)   Acidic sugar: (Monosaccharide + (-COOH))

There are 3 possibilities for replacement if we take glucose as example:

1)    (-CHO) will become (-COOH) and this will be called Aldonic acid such as Gluconic acid.

To memorize the name quickly, Glucose with aldose while gluconic acid with aldonic (the others are the same)

2)    Terminal (-CH2OH) will become (-COOH) and this will be called Uronic acid such as Glucuronic acid.

3)   
(-CHO) and terminal (-CH2OH) will become (-COOH) and this will be called Aldaric acid such as Glucaric acid.

 

 

Polysaccharides are classified into homo- and hetero- polysaccharides and we will talk about heteropolysaccharides which are glycosaminoglycans, Proteoglycans and Glycoprotein.

You can see the difference in the following image:

First: Glycosaminoglycans:

are large complexes of negatively charged heteropolysaccharide chains. They are generally associated with a small amount of protein (“core protein”), forming proteoglycans, which typically consist of up to 95% carbohydrate

General Structure:

are long, unbranched, heteropolysaccharide chains composed of a repeating disaccharide unit [acidic sugar–amino sugar]n.

Amino Sugar:

D-Glucosamine or D-Galactosamine and amine group is acetylated which means acetyl group (-COCH3) is attached to (-NH2). As you see in the image

Sulfated at C4 or C6 or non-acetylated nitrogen except Hyaluronic acid.

Acidic sugar: D-Glucuronic acid or L-iduronic acid.

The single exception is Keratin sulphate where galactose is rather than an acidic sugar.

Note: These acidic sugars contain carboxyl groups that are negatively charged at physiologic pH as (-COOH) loses one proton and become (-COO^-) and, together with the sulfate groups, give GAGs their strongly negative nature.

Function:

1)    Have the special ability to bind large amounts of water, thereby producing the gel-like matrix that forms the basis of the body’s ground substance, which, along with fibrous structural proteins such as collagen, elastin, and fibrillin-1, and adhesive proteins such as fibronectin, make up the extracellular matrix (ECM).

2)    The hydrated GAGs serve as a flexible support for the ECM, interacting with the structural and adhesive proteins, and as a molecular sieve, influencing movement of materials through the ECM.

Classification:

They are classified according to monomeric composition, type of glycosidic linkages (alpha or beta), and degree and location of sulfate unit.

a)    Chondroitin 4- and 6-sulphates:

They are composed of: N-acetyl galactosamine with sulfate group on C4 or C6 and glucuronic acid lined by β(1→3) glycosidic bond.

They are the most abundant GAGs in the body.

They are found in cartilage, tendons, ligaments and aorta.

b)   Dermatan sulphate:

It is composed of: N-acetyl galactosamine with sulfate at C4 and L-iduronic acid linked by β (1→3) glycosidic bond.

It is found in skin, blood vessels and heart valves.

c)    Keratin Sulphates I and II:

They are composed of N-acetyl glucosamine and galactose sugar (no uronic acid) lined by β (1→4) glycosidic bond.

KSI is found in Cornea while KSII is found in loose connective tissue.

d)   Heparin:

It is composed of Glucosamine and Glucuronic or Iduronic acid linked by α (1→4) glycosidic bond.

It is intracellular component of mast cells that lines arteries in lung, liver and skin.

It acts as anticoagulant.

e)    Heparin sulfate:

It is the same as heparin except some glucosamines are acetylated with fewer sulfate groups.

It is extracellular GAGs which is found in basement membrane.

f)     Hyaluronic acid:

It is composed of N-acetyl glucosamine and glucuronic acid linked by β (1→3) glycosidic bond.

It is also found in bacteria.

It is found in synovial fluid of joints, vitreous humor of eye, umbilical cord and cartilage.

Second: Proteoglycans:

Structure:

A proteoglycan monomer found in cartilage consists of a core protein to which up to 100 linear chains of GAGs are covalently attached.

These chains, which may each be composed of up to 200 disaccharide units, extend out from the core protein and remain separated from each other because of charge repulsion.

The resulting structure resembles a “bottle brush”.

In cartilage proteoglycan, the species of GAGs include chondroitin sulfate and keratan sulfate.

The proteoglycan monomers associate with a molecule of hyaluronic acid to form proteoglycan aggregates.

The association is not covalent but occurs primarily through ionic interactions between the core protein and the hyaluronic acid.

The association is stabilized by additional small proteins called link proteins.

Third: Glycoprotein:

Characteristics:

1)    are proteins to which oligosaccharides are covalently attached.  

2)    differ from the proteoglycans in that the length of the carbohydrate chain in glycoproteins is relatively short (usually 2 to 10)

3)    GAGs have repeating disaccharide units, the carbohydrates of glycoproteins do not have serial repeats.

4)    Carbohydrate chains are often branched and may or may not be negatively charged.

Function:

Participate in a broad range of cellular phenomena:

1)    cell-surface recognition (by other cells, hormones, and viruses),

2)    cell-surface antigenicity (such as the blood group antigens),

3)    As components of the ECM and of the mucins of the gastrointestinal and urogenital tracts, where they act as protective biologic lubricants.

Extracellular matrix component:

a)    Intracellular proteins (IC) are found inside cell skeleton to maintain the shape of the cell such as actin.

b)    Extracellular proteins (EC) such as collagen, elastin and proteoglycans to help cell adhesion to other surrounding cells to make tissues and interact with others to do different functions.

IC connect to EC by other proteins such as Dystrophin, Fibronectin and Integrin with the help of linker proteins so that it allows mobility of ECM and IC proteins.

Elastin:

a)    Is the key protein of ECM.

b)    Is connective tissue protein with rubber like properties.

c)    Is found in lungs, the walls of large arteries, elastic ligaments and ciliary zonules of the eye.  

d)    Can be stretched to several times than its original length but recoil when stretching force is removed.

e)    Is synthesized from Tropoelastin.

Fibrillin:

a)    Is glycoprotein secreted by fibroblasts in ECM.

b)    Interacts with Tropoelastin which functions as scaffold onto which Tropoelastin is deposited.

c)    Is important for integrity of connective tissue.

d)    Fibrillin-1 protein is encoded by FBN-1 gene, located on Chromosome 15.

e)    Mutation in the previous gene leads to Marfan Syndrome and associated with Adolescent Idiopathic Scolisois and may be inhibit formation of functional microfibrils with tissue weakness.

Wait for another post in Biochemistry!!!!