Dr. Saidunnisa Professor of Biochemistry Carbohydrates-II.

Dr. Saidunnisa Dr. Saidunnisa

Professor of BiochemistryCarbohydrates-II

Learning ObjectivesLearning ObjectivesAt the end of the session student shall

be able to:Define PolysaccharidesList homopolysaccharides and explains

the biomedical importance of each.List biologically important sugar

derivatives with its clinical importance. Define and lists various

Glycosaminoglycans and explains the biomedical importance of each and correlate to lysosomal storage disorders.

PolysaccharidesPolysaccharides They contain more than ten

monosaccharide units. These are of two types;1. Homo polysaccharides.2. Hetero polysaccharides. ( GAGS)

Homo polysaccharides.Homo polysaccharides.

Made up of same single monosaccharide units.

Examples:1. Starch2. Cellulose3. Glycogen4. Inulin5. Dextrans6. Chitin

StarchStarch

Carbohydrate reserve of the plants.

Important dietary source of man.

High content is present in cereals, roots, tubers.

It is made up of multiple units of alpha-D Glucose.

Structure of Starch Structure of Starch and its componentsand its components

H O

OH

H

OHH

OH

CH 2 OH

HO H

H

OHH

OH

CH 2 OH

H

O

HH H O

OH

OHH

OH

CH 2 OH

HH H O

H

OHH

OH

CH 2 OH

H

OH

HH O

OH

OHH

OH

CH 2 OH

H

O

H

1

6

5

4

3

1

2

a m y lo s e

H O

OH

H

OHH

OH

CH2OH

HO H

H

OHH

OH

CH2OH

H

O

HH H O

OH

OHH

OH

CH2

HH H O

H

OHH

OH

CH2OH

H

OH

HH O

OH

OHH

OH

CH2OH

H

O

H

O

1 4

6

H O

H

OHH

OH

CH2OH

HH H O

H

OHH

OH

CH2OH

HH

O1

OH

3

4

5

2

amylopectin

Amylose

water soluble,

unbranched,

gives blue colour with iodine

Amylopectin

Water insoluble,

branched,

gives violet colour with iodine

DegradationDegradation Starches are hydrolyzed by amylase to

liberate dextrin's.

Dextrin's are finally converted to Maltose and glucose

Cellulose Cellulose

Exclusively present in plant kingdom.

Totally absent in animal body.Made up of beta-D glucose units

linked by beta glycosidic linkages.

Cannot be digested in humans.Major constituent of dietary fiber.

c e l lu lo s e

H O

OH

H

OHH

OH

CH 2 OH

HO

H

OHH

OH

CH 2 OH

HO

H H O

O H

OHH

OH

CH 2 OH

HH O

H

OHH

OH

CH 2 OH

H

H

OHH O

O H

OHH

OH

CH 2 OH

HO

H H H H

1

6

5

4

3

1

2

Learning Check?Learning Check?Cellulose though not digested,

has great importance in human nutrition why?

1. Improves glucose tolerance2. Decresaes blood cholesterol 3. Relives constipation by

increasing the bulk of the feces.

GlycogenGlycogenAnimal reserve of the body.Present in high concentration in

liver, muscle and brain.Similar to Amylopectin, made up

of repeated units of alpha-D-Glucose linked by glycosidic linkages.

Structure of GlycogenStructure of Glycogen

InulinInulinPolymer of fructose.Present in garlic, onion, dahlia

bulbs etc.Low molecular weight easily

soluble in water.Not utilized by the body.Used for assessing kidney

function through GFR.

DextransDextransHigh molecular weight.Polymer of Alpha-D glucose

linked by glycosidic linkages.Used as an plasma expander.When given I.V in cases of blood

loss (Hemorrhage), it increase the blood volume.

Learning checkLearning checkDextrose, Dextrin, and Dextran

are same or different molecules?

ChitinChitinComposed of N-acetyl-D-

glucosamine.Found in exoskeleton of some

invertebrates.

HeteroHetero polysaccharides polysaccharides

Glycosaminoglycans (GAGs) important constituents of ECM (extra cellular matrix).

Extra cellular matrix Extra cellular matrix (ECM)(ECM)The ECM is often referred to as the

connective tissue made up of:Ground substancesCartilages, Tendons, ligaments, Vascular wall, Skin, LungCornea

FunctionsFunctions

Mechanical supportLubricationCushioning

Extracellular matrix (ECM)Extracellular matrix (ECM)The ECM is composed of 3 major

classes of biomolecules: 1. Structural proteins: collagen

and elastin.2. Specialized proteins: e.g.

fibrillin, fibronectin, and laminin.3. Proteoglycans: GAGS

Synthesis and Synthesis and Degradation Degradation These are synthesized in ER and

modifications like sulfation takes place in Golgi complex.

These are degraded by lysosomal enzymes.

Inability to degrade leads to a set of disease known as Lysosomal storage disease or mucopolysaccharidoses.

ClassificationClassification

1. Hyaluronic acid2. Chondroitin sulfate3. Heparin4. Dermatan sulfate.5. Keratan sulfate All gags are covalently attached

to protein forming proteoglycan.

Resilience of GAGS Resilience of GAGS

There are negatively charged COO- and SO4

– groups on the GAG which bind to positively charged hydrogen ions of water molecules thereby creating a hydrated gel.

Negative charge imparts high viscosity and low compressibility which makes them ideal for lubricating fluid in the joints.

Constituents of GAGS are Constituents of GAGS are repeating sugar derivatives repeating sugar derivatives

These units contain a

1. Amino sugar:

(N acetyl glucosamine / galactosamine)

&

2.Uronic acid:

(Glucuronic / iduronic acid).

1. Hyaluronic Acid1. Hyaluronic Acid

• Disaccharide unit-N-acetyl glucosamine & Glucuronic acid.

• Found in Synovial fluid; vitreous humor of eyes connective tissue, and forms gel around ovum.

• Only GAG not sulfated.• Serves as a lubricant

and shock absorbent in joints.

Learning CheckLearning CheckWhat is Hyaluronidase? (hint:

fertilization)

2. Chondroitin 4-and 6 2. Chondroitin 4-and 6 sulfatesulfate

• Most abundant GAG in the body.

• Found in cartilage (Chondros); tendons ligaments; and aorta.

• Disaccharide unit-N-acetyl galactosamine (with sulfate on either C-4;C-6)and Glucuronic acid.

• Loss of Chondroitin sulfate from the cartilage causes osteoarthritis.

3. Heparin3. HeparinDisaccharide unit

(glucosamine sulfated at C2;C6 & Glucuronic sulfated at C2).

Found as an intracellular component of mast cells that line arteries of liver; lung & skin.

Acts as an anticoagulant.

CaseCaseA 76-year old woman who is bed

bound in a nursing home begins to develop swelling of her left leg. She is evaluated for deep vein thrombosis; she is immediately started on heparin to further prevent the clot.

What is Heparin and its components ?

What is its action?

4. Dermatan sulfate4. Dermatan sulfate

Disaccharide unit (N-acetyl galactosamine and L- iduronic acid).

Found in skin; blood vessels and heart valves.

Learning checkLearning checkWhat is the difference between

Dermatan sulfate and Chondroitin sulfate?

5. Keratan sulfate5. Keratan sulfate

Disaccharide unit (N acetyl glucosamine& galactose; sulfate may be present on C6 of either sugar) does not contain uronic acid.

Found in cornea responsible for transparency of cornea.

Summary Summary GAG Repeating Disaccharide Tissue

distribution

Hyaluronic Acid

N-acetyl glucosamine (Not sulfated)

Glucuronic acid.

Synovial fluid

Chondroitin 4-and 6 sulfate

N-acetyl galactosamine(sulfated)

Glucuronic acid

Cartilages

Heparin glucosamine (sulfated )

Glucuronic sulfated

line arteries

Dermatan sulfate

N-acetyl galactosamine

L- iduronic acid

Skin

Keratan sulfate

N acetyl glucosamine& galactose; sulfate

does not contain uronic acid

cornea

Pathogenesis of Pathogenesis of hypothyroidism hypothyroidism

The characteristic finding is the accumulation of glycosaminoglycans (mostly hyaluronic acid) in interstitial tissue. This results in interstitial edema (e.g. in skin, heart muscle etc.).

The accumulation is due to decreased destruction of glycosaminoglycans.

Pathogenesis of Pathogenesis of hypothyroidism hypothyroidism

The characteristic finding is the accumulation of glycosaminoglycans (mostly hyaluronic acid) in interstitial tissue. This results in interstitial edema (e.g. in skin, heart muscle etc.).

The accumulation is due to decreased destruction of glycosaminoglycans.

Structure of ProteoglycansStructure of Proteoglycans

The Proteoglycans are essential parts of extracellular matrix,

The majority of GAGs in the body are linked to core proteins, forming Proteoglycans .

The linkage of GAGs to the protein core involves a specific trisaccharide composed of two Galactose residues and a xylose residue (GAG-GalGalXyl-O-CH2-protein). This is linked to the protein core through an O-glycosidic bond.

Proteoglycan structure Proteoglycan structure The GAGs extend

perpendicularly from the core in a brush-like structure.

Lysosomal storage disorders or MPS

DiagnosisDiagnosisWide spread

deposits in tissues of a particular GAGS.

Excessive excretion of GAG in Urine.

Detection of GAG in urine:

Cetyl trimethyl ammonium bromide test.