2012 pu cpb 4 carbohydrates

7/25/2019 2012 PU CPB 4 Carbohydrates

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Class: JC1

Module: Concepts & Principles ofBiomedicine (CPB)

Code: CPB4

Lecturer: Prof. Tin TunDate: 1/10/2012

Carbohydrates


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Learning Outcomes

To understand the basic properties and functions of

carbohydrates.

Describe the key structural features of monosaccharides

( aldose/ketose, L&D isomeric forms and cyclisation).

Describe Glycosidic bonds and the structure of common

disaccharides.

Describe the structure and function of polysaccharides:

glycogen, starch and cellulose.

Describe constituents of the extracellular matrix:

glycosaminoglycans and proteoglycans and hereditarydisorders of glycosaminoglycan breakdown

(mucopolysaccharidoses).

Discuss glycoproteins.


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Carbohydrates

One of our most Important foodstuffs

One of the two ways our body has to store food (fuel)

Cell membranes

Intercellular communication

Empiric Formula

(CH2O)n

i.e. hydrate of carbon


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Carbohydrates

(CH2

O)n ????What are they?

Sugars / Sugar Polymers

What are Sugars:

Important Chemical groups to consider:

Hydroxyl group (-OH)Hydrogen linked to oxygen +

one spare valency for oxygen to link to another atom

Carbonyl group (-C=O)Carbon atom linked to oxygen

by a double bond, two carbon valencies free to link to

other atoms


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Sugars:

Carbon compounds :

At least two carbon atoms linked to anOH group and at least one

carbonyl group(not linked to anOH) at least three carbonatoms = triose

Carbonyl groupC

C

C

OH

OH

H

H

OH

O

C

H3CCH3

O

C

HH3C

O

C

H HAldehydeOne of

the two

spare

positions

on

carbonyl

carries a

H atom

Ketone

Both

Carbonyl

positions

linked to

other carbonatoms

formaldehyde

acetaldehyde

acetone

Glyceraldehyde

C

C

C

OHH

OHH

O

H

dihydroxyacetone

C3H6O3

H

H


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Monosaccharides simple sugars

37 carbon atoms

Each carbon atom contains a hydroxyl group

except the one that forms a carbonyl group

(either aldehyde or keto)

Classification:

Number of carbons

Nature of carbonyl group


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No. of Carbons Generic Names Examples

3 Carbons: Trioses Glyceraldehyde

4 Carbons: Tetroses Erythrose

5 Carbons: Pentoses Ribose

6 Carbons: Hexoses Glucose

7 Carbons: Heptoses Sedoheptulose

9 Carbons: Nonoses Neuraminic acid

Most Important sugars in Human Biology:

Pentoses & Hexoses


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Isomers, Epimers & Enantiomers

Isomers:

Same chemical formula but different structurese.g. C6H1206 glucose, fructose, mannose, galactose

C

C

C

OH

H

H OH

HO C

C

C

OH

OH

OH

H

H

H

H

Glucose

Isomers

Fructose

C

C

C

O

H

H

OH

HO C

C

C

OH

OH

OH

H

H

H

H

H

AldehydeKetone

CH2OH


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Epimerstwo monosaccharides differing in configuration

around one specific carbon atom

Glucose

C-4 Epimer

C

C

C

OH

H

H OH

HO C

C

C

HO

OH

OH

H

H

H

H

Galactose

C-2 Epimer

C

C

C

OH

H

H OH

HO C

C

C

OH

OH

OH

H

H

H

H

C

C

C

OH

H

HO H

HO C

C

C

OH

OH

OH

H

H

H

H

Mannose

e.g. glucose + galactose (C-4 epimers)

glucose + mannose (C-2 epimers)


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Enantiomers

Structuresmirror images D-and L-sugars

Humansvast majority D-sugars


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Cyclization of monosaccharides

Molecules can twist and rotate around their bonds,making possible a feature of sugars: Cyclization

>99.99% in ring form(Rapidly reversible so sugars can flick in & out of ring)

C1

C2

C4

OH

H

H H

HO C3

C5

OH

OHH

H

H

C6 OHH

D-Glucose

Aldehyde (or ketone) group reacts with an

alcohol group (hydroxyl attached to a carbon) on the

same sugarH

C6 OHH

C5

O

C1

OH

H

C4

OH

H

C2

OH

H

H

C3

HO

H

D-Glucopyranose


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Anomersring creates anomeric carbon at C-1 of an aldose (or

C-2 of a ketose) Designation or configuration

and anomers are in equilibrium and can be spontaneouslyinterconverted (mutarotation)

Importance: Enzymes are able to distinguish between anomers

Reducing sugarsoxygen on the anomeric carbon is not

attached to another structure

H

C6 OHH

C5 O

C1

OH

H

C4

OH

H

C2

OH

H

H

C3

HO

H

H

C6 OHH

C5 O

C1

H

HO

C4

OH

H

C2

OH

H

H

C3

HO

H


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Pentoses

Important Molecules in Biology:

Ribose Nucleotides Nucleic Acid:

Deoxyribose (e.g. ATP, NAD) DNA / RNA

Ribulose Hexose-monophosphate

Xylulose Shunt

Xylose Glycoproteins


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HexoseDietary Sources

Glucose: Fruit juices, starch, glycogen,

lactose, maltose, cane sugar

(sucrose)

Fructose: Fruit juices, honey, cane sugar

Galactose: Lactose

Mannose: Plants and gums


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Complex carbohydrates

Monosaccharides joined together by o-glycosidic bonds

May be or (o refers to -OH group of next molecule)

n = 2 disaccharides

e.g. maltose glu 1-4 glu

cellobiose glu 1-4 glu

lactose gal 1-4 glu

sucrose glu 1-2 fru

n = 3-12 oligosaccharides

n > 12hundreds polysaccharides


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Disaccharides


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Polysaccharides

n > 12hundreds

Variation:Monosaccarides

Glycosidic bonds

Branch points

Sturcture Amylopectin

branched every 24-30 residues

1-4,

1-6

F ti


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Functions:Storage: Plantsstarch. Homopolymer of glucose

Amylopectin (80-85%) branched every 24-30 residues (

1-4, 1-6)

Amylose (15-20%) non branched helical structure (

1-4)

AnimalsGlycogen. Homopolymer of glucose. Branched every

12-14 residues(

1-4, 1-6)

Structural: Plantscellulose. Homopolymer of glucose. Long straight chains

(1-4).

Insoluble & Indigestible by humans

Invertebrateschitin

Homopolymer of n-acetyl-glucosamine


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Glycosaminoglycans (GAGs)

Heteropolysaccharides

repeating disaccharide units of

(acidic sugaraminosugar)n

COO-

at physiological pH

COOH

O

OH

OH

O

NH

OH

CH2OH

O

O

C=O

CH3

Amino group

Acetyl Group

Acidic Sugar N-Acetylated amino sugar

D-Glucuronic

acid

OrC5 epimer:

L-Iduronic acid

D-Glucosamine

or

D-Galactosamine

Eliminates +ve Charge

May also be

sulfated on

C4, C6 or on

Amino Group


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GAGs CNTD

Large number of negative charges:Repel each other, slip past each other

Surrounded by a shell of water molecules

Therefore forming gel-like matrix

Lubrication properties

Mucous secretions / synovial fluid

Gave them their original name: Mucopolysaccarides


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GAGs CNTD Extracellular:Hyaluronic acid:

Lubricant & Shock abosrber

Synovial Fluid of joints, vitreous humor of eye, looseconnective tissue , cartilage

Chondroitin 4- and 6- sulphate:

Hold fibres in strong network

Cartilage, Aorta, Tendons, Ligaments

Keratan sulphates I & II

Loose Connective issue associated with Chrondroitin

Cornea of eye

Dermatan sulphate:

Skin, Blood vessels, Heart valvesHeparan sulphate:

Basement Membrane, component of cell surfaces

Heparin:

Intracellular, Anticoagulant

Mast cells that line arteries in Liver, Lungs,Skin

P t l (PG)


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Proteoglycans (PG)

Allglycosaminoglycans (except hyaluronic acid)covalently bonded to protein

Proteoglycan aggregatesPG monomers associate with a

molecule of hyaluronic acid = Bottle Brush


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Proteoglycans - Functions

Found in extra cellular matrix (ground substance)

Structural properties

PolyanionsBind cations (eg Na+, K+)

Attract water into extracellular matrix.

Molecular sieves restricting passage of

macromolecules

M l h id


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Mucopolysaccharidoses

(Lysosomal storage diseases)

Clinically progressive Hereditary disordersGAGs accumulate in tissues

Skeletal deformities, mental retardation

Deficiency of lysosomal hydrolayses normally involved in thedegradation of heparan slulphate or dermatan sulfate

Oligosaccarides in Urine used to identify specific disease

Mainly Autosomal Recessive

e.g. Hurlers syndrome Iduronidase deficiency

Hunters syndrome - X linkdedIduronate sulphatasedeficiency


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Glycoproteins

Proteins with attached oligosaccharides (2-10 sugars)

often branched

Membrane glycoproteins

Cell surface recognition

Cell surface antigenicity e.g. blood groups

Extracellular matrix

Mucins (80% carbohydrate) of GI and GU tractsactas protective lubricants

Globular proteins in human plasma


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Glycoprotein Oligosaccharides:Generally branched heteropolymers

Do not have serial repeatsOligosaccharide attachment to protein through

a) N-glycosidic link (amide group of asparagine)

b) O-glycosidic link (hydroxyl group of serine orthreonine

Contain no glucose

Degradation: by Lysosomal enzymes

Glycoprotein Storage diseases

(oligosaccharidoses)


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Study Questions

Following a bout of gastroenteritis a 4-monthold infant was found to be intolerant to milk.Which of the following disaccharides is likely

to be the cause of the problem?

A. Sucrose

B. Lactose

C. MaltoseD. Isomaltose

E. Cellobiose


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Study Questions (Contd.)

Choose the ONE correct answer:

Mucopolysaccharidoses are inherited storage

diseases. They are caused by:A. An increased rate of synthesis of proteoglycans.

B. The synthesis of polysaccharides with an alteredstructure.

C. Defects in the degradation of proteoglycans.

D. The synthesis of abnormally small amounts ofprotein cores.

E. An insufficient amount of proteolytic enzymes.


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Refs:

Lippincott

- Chapter 7 Carbohydrates

- Chapter 14 Glycosaminoglycans and

Glycoproteins

2012 pu cpb 4 carbohydrates

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