Carbohydrates

1

• Carbohydrates

2
Carbohydrates

• Most abundant class of biological molecules on
  Earth
• Originally produced through CO2 fixation during
  photosynthesis

3
Roles of Carbohydrates

• Energy storage (glycogen,starch)
• Structural components (cellulose,chitin)
• Cellular recognition
• Carbohydrate derivatives include DNA, RNA,
  co-factors, glycoproteins, glycolipids

4
Carbohydrates

• Monosaccharides (simple sugars) cannot be broken
  down into simpler sugars under mild conditions
• Oligosaccharides "a few" - usually 2 to 10
• Polysaccharides are polymers of the simple sugars

5
Monosaccharides

• Polyhydroxy ketones (ketoses) and aldehydes
  (aldoses)
• Aldoses and ketoses contain aldehyde and ketone
  functions, respectively
• Ketose named for equivalent aldose ul
  inserted
• Triose, tetrose, etc. denotes number of carbons
• Empirical formula (CH2O)n

6
Monosaccharides are chiral

• Aldoses with 3C or more and ketoses with 4C or
  more are chiral
• The number of chiral carbons present in a ketose
  is always one less than the number found in the
  same length aldose
• Number of possible steroisomers 2n (n the
  number of chiral carbons)

7
Stereochemistry

• Enantiomers mirror images
• Pairs of isomers that have opposite
  configurations at one or more chiral centers but
  are NOT mirror images are diastereomers
• Epimers Two sugars that differ in configuration
  at only one chiral center

8
Cyclization of aldose and ketoses introduces
additional chiral center

• Aldose sugars (glucose) can cyclize to form a
  cyclic hemiacetal
• Ketose sugars (fructose) can cyclize to form a
  cyclic hemiketal

9
Glucopyranose formation
10
Fructofuranose formation
11
Monosaccharides can cyclize to form Pyranose /
Furanose forms
a 64 b 36
a 21.5 b 58.5
a 13.5 b 6.5
12
Haworth Projections
-OH up beta -OH down alpha
6
5
1
4
2
3
Anomeric carbon (most oxidized)
For all non-anomeric carbons, -OH groups point
down in Haworth projections if pointing right in
Fischer projections
13
Conformation of Monosaccharides
Pyranose sugars not planar molecules, prefer to
be in either of the two chair conformations.
14
Reducing Sugars

• When in the uncyclized form, monosaccharides act
  as reducing agents.
• Free carbonyl group from aldoses or ketoses can
  reduce Cu2 and Ag ions to insoluble products

15
Derivatives of Monosaccharides
16
Sugar Phosphates
17
Deoxy Acids
18
Amino Sugars
19
Sugar alcohols
20
Monosaccharide structures you need to know

• Glucose
• Fructose
• Ribose
• Ribulose
• Galactose
• Glyceraldehyde

21
Carbohydrates

• Monosaccharides (simple sugars) cannot be broken
  down into simpler sugars under mild conditions
• Oligosaccharides "a few" - usually 2 to 10
• Polysaccharides are polymers of the simple sugars

22
Glycosidic Linkage
23
Disaccharides
cellobiose
maltose
(a-D-glucosyl-(1-gt4)-b-D-glucopyranose)
(b-D-glucosyl-(1-gt4)-b-D-glucopyranose)
lactose
sucrose
(b-D-galactosyl-(1-gt4)-b-D-glucopyranose)
(a-D-glucosyl-(1-gt2)-b-D-fructofuranose)
24
Higher Oligosaccharides
25
Oligosaccharide groups are incorporated in to
many drug structures
26
Polysaccharides

• Nomenclature homopolysaccharide vs.
  heteropolysaccharide
• Starch and glycogen are storage molecules
• Chitin and cellulose are structural molecules
• Cell surface polysaccharides are recognition
  molecules

27
Starch

• A plant storage polysaccharide
• Two forms amylose and amylopectin
• Most starch is 10-30 amylose and 70-90
  amylopectin
• Average amylose chain length 100 to 1000 residues
  
• Branches in amylopectin every 25 residues (15-25
  residues) a-1-gt6 linkages
• Amylose has a-1-gt4 links, one reducing end

28
Amylose and Amylopectin
29
Starch

• Amylose is poorly soluble in water, but forms
  micellar suspensions
• In these suspensions, amylose is helical

30
Glycogen

• Storage polysaccharide in animals
• Glycogen constitutes up to 10 of liver mass and
  1-2 of muscle mass
• Glycogen is stored energy for the organism
• Only difference from starch number of branches
• Alpha(1,6) branches every 8-12 residues
• Like amylopectin, glycogen gives a red-violet
  color with iodine

31
Dextrans

• If you change the main linkages between glucose
  from alpha(1,4) to alpha(1,6), you get a new
  family of polysaccharides - dextrans
• Branches can be (1,2), (1,3), or (1,4)
• Dextrans formed by bacteria are components of
  dental plaque
• Cross-linked dextrans are used as "Sephadex" gels
  in column chromatography
• These gels are up to 98 water!

32
Dextrans
33
Cellulose

• Cellulose is the most abundant natural polymer on
  earth
• Cellulose is the principal strength and support
  of trees and plants
• Cellulose can also be soft and fuzzy - in cotton

34
Cellulose vs Amylose
amylose
cellulose
Glucose units rotated 180o relative to next
residue
35
Cellulose

• Beta(1,4) linkages make all the difference!
• Strands of cellulose form extended ribbons
• Interchain H-bonding allows multi-chain
  interactions. Forms cable like structures.

36
Chitin

• exoskeletons of crustaceans, insects and spiders,
  and cell walls of fungi
• similar to cellulose, but instead of glucose uses
  N-acetyl glucosamine (C-2s are N-acetyl instead
  of OH)
• b-1-gt4 linked N-acetylglucosamine units
• cellulose strands are parallel, chitins can be
  parallell or antiparallel

37
Chitin vs Cellulose
38
Peptidoglycan

• N-acetylglucosamine and N-acetylmuramic acid
  groups linked b-1-gt4
• Heteroglycan linked to a tetrtapeptide
  (Ala-IsoGlu-Lys-Ala)
• Gram (-) have petanta- glycine linker to next
  strand
• Gram () have directly cross links to next strand

39
Peptidoglycan
40
Peptidoglycan is target of antibacterial agents

• Lysozyme enzyme that cleaves polysaccharide
  chain of peptidoglycan
• Penicillin inhibits linking of peptidoglycan
  chains.
• Inhibits bond formation between terminal alanine
  and pentaglycine linker
• Penicillian looks like an Ala-Ala

41
Peptidoglycan and Bacterial Cell Walls

• Composed of 1 or 2 bilayers and peptidoglycan
  shell
• Gram-positive One bilayer and thick
  peptidoglycan outer shell
• Gram-negative Two bilayers with thin
  peptidoglycan shell in between
• Gram-positive pentaglycine bridge connects
  tetrapeptides
• Gram-negative direct amide bond between
  tetrapeptides

42
(No Transcript)
43
Glycoproteins

• May be N-linked or O-linked
• N-linked saccharides are attached via the amide
  nitrogens of asparagine residues
• O-linked saccharides are attached to hydroxyl
  groups of serine, threonine or hydroxylysine

44
(No Transcript)
45
O-linked Glycoproteins

• Function in many cases is to adopt an extended
  conformation
• These extended conformations resemble "bristle
  brushes"
• Bristle brush structure extends functional
  domains up from membrane surface

46
O-linked Glycoproteins
47
N-linked Glycoproteins

• Oligosaccharides can alter the chemical and
  physical properties of proteins
• Oligosaccharides can stabilize protein
  conformations and/or protect against proteolysis
• Cleavage of monosaccharide units from N-linked
  glycoproteins in blood targets them for
  degradation in the liver
• Involved in targeting proteins to specific
  subcellular compartments