Biochemistry 1 Carbohydrate II

CARBOHYDRATE-II

Intended Learning Outcomes (ILOs):

This lecture will enable the students to:
▪ Describe the glycosidic linkage.
▪ Define oligosaccharides and polysaccharides.
▪ Understand nomenclature, structure & properties of disaccharides & polysaccharides.
▪ Classify disaccharides and polysaccharides
▪ List important disaccharides (e.g., maltose, lactose and sucrose).
▪ Distinguish between polysaccharides and their derivatives; glycosaminoglycans,
proteoglycans and glycoproteins

By:
Dr. Tamer A. Al-Shafie
Assoc. Professor of Medical Biochemistry

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Biochemistry 1 Carbohydrate II

Glycosidic Linkage:
Monosaccharides are joined by glycosidic bonds to form oligosaccharides and
polysaccharides. Glycosidic bonds are formed by enzymes known as: glycosyltransferases
and hydrolyzed to produce 2 monosaccharide molecules by enzymes known as:
glycosidases.
Glycosidic bonds between sugars are named according to the carbon atoms involved
in the bond.
For example, Lactose is synthesized by forming a glycosidic bond between C 1 of β-
galactose and C 4 of glucose. The linkage is, therefore, a β (1→ 4) glycosidic bond. Thus,
Lactose = galactosyl- β (1, 4)-glucose

Monosaccharides can also be attached by glycosidic bonds to non-carbohydrates. This

includes binding with:
– Purine and pyrimidine bases in nucleic acids
– Aromatic rings as in steroids and bilirubin
– proteins as in glycoproteins and proteoglycans
– lipids as in glycolipids

N- and O-glycosides:
If the sugar is attached to an –NH2 group, the structure is an N-glycoside and the bond
is called an N-glycosidic link.
If the sugar is attached to an –OH (as in sugar-sugar bond), the structure is an O-
glycoside, and the bond is an O-glycosidic link.

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Biochemistry 1 Carbohydrate II
B. Oligosaccharides
Oligosaccharides are molecules that are formed from few (3-10 units) different
monosaccharide units including: hexoses (e.g., glucose, fructose, mannose, and galactose)
and pentoses (e.g., ribose and xylose).

Disaccharides:
The simplest oligosaccharides are the disaccharides, which consist of two
monosaccharide units linked by a glycosidic bond. Each unit in an oligosaccharide is
termed: residue or moiety.
Classification: Disaccharides can be classified into:
# Homo-disaccharide: formed of 2 similar monosaccharide units, e.g., maltose,
isomaltose, cellobiose & trehalose (all consist of 2 glucose units but vary in bond type)
# Hetero-disaccharides: formed of 2 different monosaccharide units, including:
sucrose (glucose + fructose), lactose (galactose + glucose)
A. Nomenclature & Reducing Characteristics
Remember!! The Anomeric carbon is present in the ring form of the sugar and
represents the sugar carbonyl carbon responsible for its reducing properties.
In many disaccharides (e.g., Lactose and Maltose), the anomeric carbon of one unit
monosaccharide is involved in the glycosidic linkage while the other is free.
So, lactose and maltose are reducing sugars, as one of the two units may have an
open-chain form with an aldehyde group.
In some disaccharides, anomeric carbon of both monosaccharide units are involved in
the glycosidic linkage (e.g., Sucrose).
So, sucrose is a non-reducing sugar because neither of the two rings is capable of
opening.
1. Lactose (Milk sugar)
Chemistry: β-D-galactose and α-D-glucose linked by β-1, 4-galactosidic linkage. The
glucose residue has a free anomeric carbon atom, hence:
It exists in α- and β- forms.
− It is a reducing sugar
Sources: It is only found in milk.
Hydrolysis: it can be hydrolysed into D-
galactose and D-glucose by acid or
lactase enzyme in the intestine.

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Biochemistry 1 Carbohydrate II

2. Maltose (Malt sugar)

Chemistry: it contains two D-glucose residues linked by α-1-4 glucosidic bond. The
second glucose residue has a free anomeric carbon atom, hence:
− It exists in α- and β- forms.
− It is a reducing sugar
Sources:
− Germinating cereals and malt.
− The intermediate product of the action of amylases on starch.
Hydrolysis: it can be hydrolyzed into two D-glucose units by acid or maltase enzyme.

Free anomeric carbon

(reducing end)

3. Sucrose: (Cane sugar = Table sugar = Beet sugar)

Chemistry: It contains β-D-fructose & α-D-glucose linked by (α-1, 2)-glucosidic linkage.
The anomeric carbon atoms of the two hexoses are linked to each other, thus,
sucrose contains no free anomeric carbon atom so:
– It does not occur in α- or β-forms.
– It is a non-reducing sugar.
Sources: Sugar cane and sugar beet.
Hydrolysis: it can be hydrolyzed into D-glucose and D-fructose by acids or sucrase
(invertase enzyme).

No Free anomeric carbon

no (reducing end)

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Biochemistry 1 Carbohydrate II
C. Polysaccharides
(Glycans)
"Polysaccharides (Poly- Many): >10 units"
Polysaccharides are sugars that contain tens to thousands of monosaccharide units
joined by glycosidic bonds to form linear chains or branched structures.
Polysaccharides differ according to:
1. Chain length and branching
2. Type of the constituting monosaccharide units.
1. Polysaccharide chains:
Polysaccharides chain lengths vary from tens to thousands of monosaccharide units.
Branches in polysaccharides involve (— OH) groups on the monosaccharide components.
←Linear Chain

Branched Chain↓

2. Type of the constituting monosaccharide units

The most common monosaccharide constituent of polysaccharides is D-glucose, but
D- fructose, D-galactose, L-galactose, D-mannose, L-arabinose, and D-xylose are also
common.

Polysaccharide Functions:
− Storage polysaccharides (e.g., Starch and glycogen), as readily metabolizable food,
provide energy reserves for cells.
− Tissue structural polysaccharides (e.g., Chitin and cellulose) provide strong support
for the skeletons of arthropods and green plants, respectively.
− Cell membrane structural polysaccharides (e.g., Mucopolysaccharides, such as
hyaluronic acids), form protective coats on animal cells and are involved in cellular
recognition & cellular communication events.

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Biochemistry 1 Carbohydrate II
According to type of monosaccharide units, polysaccharides can be classified into:
Homopolysaccharides & Heteropolysaccharides
1. HOMOPOLYSACCHARIDES
These are polysaccharides that contain only one type of monosaccharide molecule.
They contribute to two major functions:
Storage polysaccharides (e.g., Starch and Glycogen)
Structural Polysaccharides (e.g., Cellulose and Chitin)

▪ Starch
Starch is a glucose homopolymer of plant origin.
It is the major storage polysaccharide in our food and the most important dietary
carbohydrate in cereals, potatoes, and legumes
The glucose forming units are attached by α-glucosidic chain.
Starch includes two types: amylose and amylopectin:

– Amylose (MW 10,000-50,000 KD) consists of long, unbranched chains of glucose

residues connected by (α1→4) linkages.

– Amylopectin (MW 50,000-1,000,000 KD), unlike amylose, amylopectin is branched.

The glycosidic linkages join successive glucose residues in amylopectin chains via
(α1→4) linkages; the branch points occur every 24 - 30 residues via (α1→6) linkages.

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 Biochemistry 1 Carbohydrate II

▪ Glycogen
Glycogen is the main storage
polysaccharide in the human body.
Glycogen is a homopolymer of
(α1→4)-linked subunits of glucose, with
(α1→6)-linked branches.
Glycogen is more extensively
branched (on average, every 8 to 12
residues) than amylopectin.
Glycogen is especially abundant in
the liver and skeletal muscle.

2. HETEROPOLYSACCHARIDES = Glycosaminoglycans (GAGs)

General properties:
GAGs have a common structural feature:
They consist of linear chains of repeating disaccharides units either:

hexose (e.g. galactose), hexosamine (e.g. galactosamine, glucosamine) or hexuronic

acid (e.g. glucuronic acid and iduronic acid).

− They are also called: Mucopolysaccharides (MPS).

− They Contain a mixture of monosaccharides and their derivatives.
− Polar and gelatinous with high MW (up to 5×106 KD).
− Present mainly in the connective tissues extra-cellular matrix (ECM).
− Negatively-charged due to the presence of a sulfate residue, except hyaluronic acid.

Types of Glycosaminoglycans
(GAGs)

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Biochemistry 1 Carbohydrate II

Function of Glycosaminoglycans (GAGs):

▪ Hyaluronic acid HA
✓ Disaccharide unit: N-acetylglucosamine and glucuronic acid.
✓ Different from other GAGs: Unsulfated, not covalently attached to the protein, and
the only GAG not limited to animal tissue, but also found in bacteria.
✓ Occurrence: synovial fluid of joints, the vitreous humor of the eye, the umbilical
cord, connective tissue and cartilage serving as a lubricant and shock absorber.

✓ The medical importance of Hyaluronic Acid (HA)

1. Age-related disturbances:
− Age-related pains: As age advances hyaluronic acid is replaced by dermatan
sulfate in synovial fluid which is not a good lubricant; whivh leads to joint pain.
− Age-related vision affections: Vitreous is a clear elastic gel in which
hyaluronic acid is associated with collagen. As age advances vitreous elasticity is
reduced due to decreased association between collagen and hyaluronic acid.
− Age-related scar formation HA content of skin decreases as age advances
facilitating the formation of scars of the skin.
2. Hyaluronic acid is involved in wound healing. In the initial phase of wound
healing, hyaluronic acid concentration increases many fold at the wound site to
allow rapid migration of the cells to the site of connective tissue development.
3. It has a role in the migration and metastasis of tumor cells.
4. Some pathogenic bacteria (e.g. pneumonia and meningitis) contain hyaluronate
lyase which facilitates invasion of a host by these bacteria through hydrolysis of
HA by this enzyme.

▪ Chondroitin Sulfates CS
✓ Disaccharide unit: N-acetylgalactosamine with sulfate on either C4 or C6, and
glucuronic acid.
✓ Occurrence: Most abundant GAGs in the body; found in cartilage, tendons,
ligaments, and aorta.
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 Biochemistry 1 Carbohydrate II

Chondroitin-4-sulfate Chondroitin-6-sulfate

▪ Dermatan Sulfate DS
✓ Disaccharide unit: N-acetylgalactosamine and L-iduronic acid
✓ Occurence: skin, blood vessels, and heart valves.

▪ Heparin/Heparan sulfate
✓ Disaccharide unit: Glucosamine and glucuronic or iduronic acid.
✓ Glucosamine residues are mostly bound in sulfamide linkages.
✓ Sulfate is also found on C-3 or C-6 of glucosamine and C-2 of uronic acid.
✓ Occurrence: heparin is an intracellular component of mast cells that line arteries,
especially in the liver, lungs, and skin.
✓ Used as an anticoagulant. It binds to antithrombin III (a protein involved in the
termination of the clotting process).

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 Biochemistry 1 Carbohydrate II

▪ Keratan Sulfate KS
✓ Disaccharide unit: N-acetylglucosamine and galactose (KS DOESN'T contain uronic a.)
✓ Sulfate content is variable and may be present on C-6 of either sugar.
✓ Most heterogeneous GAGs because they contain monosaccharides such as L-fucose,
N-acetyl-neuraminic acid, and mannose.
✓ Occurrence: Cornea, Cartilage, Bone, horny structures

Summary of Glycosaminoglycans (GAGs)

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Biochemistry 1 Carbohydrate II
Derived Polysaccharides
▪ Proteoglycans
Except for hyaluronic acid, ALL glycosaminoglycans are covalently attached to a core
protein forming Proteoglycans
They represent a subclass of Glycoproteins.
▪ Proteoglycan = Glycosaminoglycans (GAGs) + protein
Structure of Proteoglycans
The linkage between GAG chain and core protein is most commonly through a
trihexoside (gala-gala-xyl) and a serine residue respectively. A glycosidic bond is formed
between the xylose and the hydroxyl group of the serine.

The function of proteoglycans:

1. Many proteoglycans are components of the connective tissue (extra-cellular matrix
(ECM) (e.g., Aggrecan).
2. Some are integral membrane proteins (e.g., Syndecan).

▪ Glycoproteins
Glycoproteins are found in mucous fluids, tissues, blood, and cell membrane.
They are proteins containing short chains of carbohydrates, usually
oligosaccharides. These oligosaccharide chains are attached to proteins by O-glycosidic
and N-glycosidic bonds.

▪ Glycoprotein = Carbohydrate + Protein

The oligosaccharide chains of glycoproteins have important functions:
1. They present on the surface of erythrocytes and determine blood groups; they are
responsible for the classification of blood groups.
2. Cell-cell communication depends on oligosaccharide chains of glycoproteins.

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Biochemistry 1 Carbohydrate II
Extracellular matrix (ECM)
It is a component of the connective tissue that holds the cells together and provides a
porous pathway for the diffusion of nutrients and oxygen to individual cells.

The ECM is composed of two major classes of biomolecules:

✓ Proteoglycans: Glycosaminoglycans (GAGs) are covalently linked to protein.
✓ Fibrous proteins: include collagen, elastin, fibronectin, and laminin.

…End of Lecture…
Thank You

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