Carbohydrates Lecture 4

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CarbohydratesLecture 4
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Lecture Outline

• Lecture 1 Monosaccharides
• Definition
• Nomenclature
• Fischer projections
• Lecture 2 Monosaccharides
• Haworth projections
• Furanose Pyranose rings
• Modified Sugars
• Sugars in DNA

• Lecture 3 Disaccharides Energy storage
• Glycosidic bond
• Glycolysis
• Lecture 4 Complex Carbohydrates Function
• Starch glycogen
• Cellulose
• Blood groups
• Glycoproteins

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Lecture Outline

• Polysaccharides
• Glycogen, starch, cellulose,murein
• Glycosaminoglycans
• Blood group antigens
• Glycoproteins - role of ER and Golgi
• N-linked
• O-linked
• Lectins proteins that bind specific
  carbohydrates
• Carbohydrates on the WWW

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1.
2.
3.
1. Which classification does NOT apply to this
sugar? a. Disaccharide c. Sucrose b. Lactose d.
?-D-glucopyranosyl(1-gt2)-?-D-fructofuranose
2. Name the ring structure in this
carbohydrate 3. Name the enzyme that catalyses
this reaction and name the protein fold it
exhibits. 4. How many ATP molecules are used and
generated during glycolysis and hence what is the
net gain in ATP?
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Polysaccharides

• Join 2 monosaccharides to form a disaccharide
• Oligosaccharides built by linkage of 2 or more
  monosaccharides
• Polysaccharides built by linkage of multiple
  monosaccharides

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Disaccharides
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Glycogen

• Polysaccharide homopolymer
• Most common homopolymer in animal cells
• Storage form of glucose

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Glycogen

• Large branched polymer
• Most glucose units linked by ?-1,4 glycosidic
  bonds
• Branches formed by ?-1,6 glycosidic bonds every
  10 glucose units

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Glycogen

• 2 major sites of storage are liver skeletal
  muscle
• Glycogen present in the cytosol in form of
  granules

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Starch

• Starch storage form of glucose in plants
• Two forms of starch
• Amylose unbranched
• glucose units linked by ?-1,4 glycosidic bonds
• Amylopectin branched
• 1 ?-1,6 glycosidic bond per 30 ?-1,4 glycosidic
  bonds
• lower degree of branching compared to glycogen

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Cellulose

• Cellulose major structural polymer in plants
• 1015kg of cellulose synthesized and degraded on
  earth each year
• Unbranched polymer of glucose
• Linked through ?-1,4 glycosidic bonds

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Cellulose

• ?-1,4 glycosidic bonds long straight chains
• Fibrils fomed when parallel chains interact
  through hydrogen bonds
• Fibres have a high tensile strength

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Murein

• Murein found in cell walls of bacteria
• Linear polymer of N-acetylglucosamine
• Cross-linked with peptide units

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Glycoaminoglycans

• Most abundant hetero-polysaccharides
• Long unbranched chains with repeating
  disaccharide units
• N-acetylgalactosamine (GalNAc) or
  N-acetylglucosamine (GlcNAc)
• Uronic acid
• At least one sugar has a negatively charged
  carboxylate or sulphate group

Glucosamine
Uronic acid
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Glycosaminoglycans

• Heparin glucosamine and uronic acid units
• Acts as an anticoagulant by binding antithrombin
• Heparin/antithrombin complex increases rate of
  inhibition of two procoagulant proteases factor
  Xa and thrombin

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Glycosaminoglycans

• Resemble carbohydrates more than proteins as the
  carbohydrate makes up 90 of molecule by weight
• Function as lubricants and structural components
  in connective tissue
• Bind factors that stimulate cell proliferation
• Usually bound to proteins - proteoglycans

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Human Blood Groups

• Carbohydrates attached to glycoproteins and
  glycolipids on the surface of red blood cells
• For one type of blood group one of three
  different structures are present
• Each of three structures have in common an
  oligosaccharide foundation called O antigen

Fuc fucose, Gal galactose, GalNAc
N-acetylgalactosamine GlcNAc N-acetylglucosamine
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Blood Groups

• A and B antigen differ by addition of one extra
  monosaccharide N-acetylgalactosamine or
  galactose

Fuc fucose Gal galactose GalNAc
N-acetylgalactosamine GlcNAc
N-acetylglucosamine
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Blood Groups

• Glycosyltransferases catalyse formation of
  glycosidic bonds
• Specific glycosyltransferases add the extra
  monosaccharide to the O antigen
• Individuals inherit gene for one transferase from
  each parent
• Type A transferase adds N-acetlygalactosamine
• Type B transferase adds galactose
• Important implications for blood transfusions

Karl Lansteiner 1930
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Blood Groups
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Glycoproteins

• Carbohydrate groups attached to different
  proteins
• Carbohydrates much smaller of the weight of
  glycoproteins than proteoglycans
• Carbohydrates either attached to
• amide N atom in the side chain of asparagine
  (N-linked)
• O atom in side chain of serine or threonine
  (O-linked)

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N-linked Oligosaccharide

• All N-linked oligosaccharides have a common
  pentasaccharide core

GlcNAc N-acetylglucosamine
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N-linked Oligosaccharide

• All N-linked oligosaccharides have a common
  pentasaccharide core

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Glycoproteins

• An asparagine can only accept oligosaccharide if
  it is part of specific sequence
• Asn-X-Ser
• Asn-X-Thr
• Potential glycosylation sites can be detected
  within protein sequences
• Which sites are actually glycosylated depends on
  aspects of protein structure and cell type in
  which the protein is expressed

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Glycoproteins
Aspartylglucosaminidase (PDB 1apy) (Rasmol
NAG,MAN)
Elastase (PDB 1b0F) (Rasmol NAG,FUC,SEI)
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Glycoproteins

• Glycosylation takes place in ER and Golgi complex
• N-linked glycosylation begins in ER and continues
  in Golgi
• O-linked glycosylation only occurs in the Golgi
• N-linked glycoproteins acquire initial sugars in
  the ER

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Glycoproteins

• Golgi complex involved in glycosylation and
  sorting
• N-linked sugars elaborated modified
• O-linked sugars created
• Glycoproteins sorted according to signals encoded
  in amino acid sequence and structure

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Lectins

• Proteins that bind specific carbohydrate
  structures
• Ubiquitous found in animals plants
• Facilitate cell-cell contacts
• Binding sites of lectins on surface of one cell
  interact with arrays of carbohydrates on surface
  of another cell

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Lectins
Coral Tree Lectin PDB 1AXO (Rasmol
FUC,NAG, MAN,XYS,NGA)
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Exam Questions - 2004
A
B
C
D

• Identify the carbohydrates (A, B, C or D) for
  which the following classifications apply.
• Note there may be more than one carbohydrate for
  each classification. 6 
• Ketose 2
• Aldose 2
• Furanose 2
•  
• Answer the following questions about the 4
  carbohydrates in the diagram.
• Identify the carbohydrates using the letters (A,
  B, C or D). 4
• Which structures are drawn as Haworth projections
  ? 1
• Which pair of structures are enantiomers, and
  identify which is the D form enantiomer ? 3

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Carbohydrates on the WWW

• CCSD Complex carbohydrate structure database
  (CarbBank)
• SUGABASE carbohydrate NMR database combines CCSD
  data with NMR data
• http//www.boc.chem.uu.nl/sugabase/sugabase.html
• GLYCAN part of KEGG project pathway database
  at Kyoto university in Japan.

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GLYCAN Database

• http//www.genome.ad.jp/ligand
• KEGG ligand database - carbohydrate as ligands
• 10,000 complex carbohydrates
• Carbohydrate structures represented as a
  mathematical representation known as a graph
• Enables users to search for similar structures in
  the database

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Lecture 4 Summary

• Polysaccharides
• Glycogen, starch storage forms of glucose
• Cellulose structural fibres
• Blood group antigens
• Glycoproteins sugar attached to
• N atom in asparagine (N-linked)
• O atom in serine or threonine (O-linked)
• Lectins proteins that bind specific
  carbohydrates
• Carbohydrates on the WWW GLYCAN database