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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