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CARBOHYDRATE STRUCTURES
Student Edition 5/24/13 Version
Pharm. 304 Biochemistry
Fall 2014
Dr. Brad Chazotte 213 Maddox Hall
Web Site:
http://www.campbell.edu/faculty/chazotte
Original material only ©2003-14 B. Chazotte
Goals• Review stereochemistry with emphasis on carbohydrates
• Learn the various projections & carbon numbering for carbohydrate structures
• Learn the structures of a few, selected biologically important aldoses & ketoses
• Understand that sugars are conformationally variable and this effects their properties.
• Understand some of the basic reactions of carbohydrate functional groups
• Become familiar with the difference types of monosaccharide derivatives
• Learn the differences and similarities among disaccharides, polysaccharides, glycoconjugates, peptidoglycans, proteoglycans, & glycoproteins
Stereochemistry and Carbohydrates: A Quick Review
• Optically active molecules rotate plane polarized light. D-dextrorotary (right, clockwise). L-levorotary (left, counterclockwise).
• Optically active molecules have an asymmetry such that they are not superimposable on their mirror image.
• This situation is characteristic of substances that contain tetrahedral carbons having four different substituents.
• Stereoisomers compounds that have the same molecular formula but differ in the configuration of their atoms in space, about one of more of their chiral centers.
• Enantiomers are stereoisomers, molecules, that are not superimpossible on their mirror images. Such molecule are physically and chemically indistinguishable by most techniques, except probing by plane polarized light
Chiral (Asymmetric) Carbons, Optical Activity, & Stereoisomers
Chiral (Asymmetric) Carbons, Optical Activity, & Stereoisomers
Berg, Tymoczko, & Stryer 2012 Fig 11.1
• Stereoisomers compounds that have the same molecular formula but differ in the configuration of their atoms in space, about one or more of their chiral centers.
• Enantiomers are stereoisomers, molecules, that are not superimposable on their mirror images. Such molecule are physically and chemically indistinguishable by most techniques, except probing by plane polarized light
• Optically active molecules rotate plane polarized light. D-dextrorotary (right, clockwise). L-levorotary (left, counterclockwise). [Small capital letters]
• Optically active molecules have an asymmetry such that they are not superimposable on their mirror image.
• This situation is characteristic of substances that contain tetrahedral carbons having four different substituents.
Configuration Sequence Rules about an Asymmetric Carbon Cahn-Ingold-Prelog System
Rule 1. If the four atoms attached to the asymmetric carbon are all different, priority depends on atomic number, with the atom of higher atomic number getting priority. If two atoms are isotopes of the same element, the atom of the higher mass number has the priority
Rule 2. If the relative priority of two groups cannot be decided by Rule 1, it shall be determined by a similar comparison of the atoms next in the groups (and so on, if necessary, working out from the asymmetric carbon).
Morrison & Boyd, 1966 Chapter 3; Voet & Voet 2003 Chapter 4;Matthew et al Fig 9.6
Designation:
R – Rectus (right) the order of the groups about the asymmetric centers is clockwise
S – Sinister (left) the order of the groups about the asymmetric center is counter clockwise
Fisher Convention for Viewing Carbohydrates
Barker 1971 Chaper 5
RULES
1. The carbon chain is vertical with the lowest numbered carbon at the top.
2. The numbering usually follows the convention that the most oxidized end of the molecule has the lowest number.
This “system” relates the configuration of the groups about an asymmetric center to that of glyceraldehyde. Glyceraldehyde has one asymmetric center.
In a Fisher projection on paper:
Horizontal bonds extend above the plane of the paper.
Vertical bonds extend below the plane of the paper
Lehninger Biochemistry 2000 Fig 9.2 a
Enantiomers and Epimer s
• D-Sugars predominate in nature
• Enantiomers –pairs of D-sugars and L-sugars (one type of stereoisomer)
• Epimers - sugars that differ at only one of several chiral centers
• Example: D-galactose is an epimer of D-glucose at C-4
Enantiomers (Mirror Images)
Lehninger Biochemistry 2000 Fig 9.2
Glucose and Two EpimersLehninger Biochemistry 2000 Fig 9.4
Carbohydrate Major Classes
• Carbohydrates (“hydrate of carbon”) have empirical formulas of (CH2O)n , where n ≥ 3
• Monosaccharides one monomeric unit Oligosaccharides ~2-20 monosaccharides
• Polysaccharides > 20 monosaccharides
• Glycoconjugates (carbohydrate derivative) linked to proteins or lipids
Horton et al 2002 Chapter 8
Number of Carbons in a Sugar is Indicated by a Prefix
All common monosaccharides and disaccharide names end in –”ose”
(e.g. glucose, sucrose, fructose, ribose, mannose)
The number of carbons in a sugar is indicated by a prefix:
C3 triose C4 tetrose C5 Pentose
C6 hexose C7 heptose C8 Octose
C9 Nonose
Most Monosaccharides are Chiral Compounds
O
• Aldoses - polyhydroxy aldehydes -C- CH
OH O OH
• Ketoses - polyhydroxy ketones –CH – C - CH2
• Most oxidized carbon: aldoses C-1, ketoses usually C-2
• Trioses (3 carbon sugars) are the smallest monosaccharides
Horton et al 2002 Chapter 8.1
Aldoses and Ketoses
• Aldehyde C-1 is drawn at the top of a Fischer projection
• Glyceraldehyde (aldotriose) is chiral (C-2 carbon has 4 different groups attached to it)
• Dihydroxyacetone (ketotriose) does not have an asymmetric or chiral carbon and is not a chiral compound
Horton et al 2002 Chapter 8
Fischer projections of: (a) L- and D-glyceraldehyde, (b) dihydroxyacetone
Horton et al 2012 Fig 8.1
Fisher projections of 3 to 6 carbon D-aldoses
• D-sugars have the same configuration, by convention, as D-glyceraldehyde when their chiral carbon most distant from the carbonyl carbon (highest number) is the same as C-2 of glyceraldehyde. That is, the –OH group is to the right in the Fisher projection.
• Aldoses those shown in blue (next slide) are the most important in biochemistry
Horton et al 2002 Fig 8.3
3, 4, & 5-Carbon D-Aldoses
Horton et al 2012 Fig 8.3
6-Carbon D-Aldoses
Horton et al 2012 Fig 8.3b
H O
C
H -- C -- OH
CH2OH
D-glyceraldehyde
Fisher projections of L- and D-glucose
Horton et al 2002 Fig 8.4
Fisher projections of the 3,4, & 5-Carbon D-ketoses (blue structures most common)
Horton et al 2012 Fig 8.5
6-Carbon D-Ketoses
Horton et al 2012 Fig 8.5b
Relevant Reactions of Aldehydes & Ketones
Lehninger 2000 Fig. 9.5Voet, Voet & Pratt 2013 Page 219
Cyclization of Aldoses and Ketoses
Reaction of an alcohol with:
(a) An aldehyde to form a hemiacetal
(b) A ketone to form a hemiketal
Horton et al 2002 Fig 8.6
alcohol
aldehyde
Voet, Voet & Pratt 2013 Page 219
Cyclization of D-glucose to form Glycopyranose Haworth Projection
• Fischer projection (top left)
• Three-dimensional figure (top right)
• C-5 hydroxyl close to aldehylde group (lower right)
Horton et al 2012 Fig 8.8
Cyclization of D-Glucose (continued) • Reaction of C-5 hydroxyl with
one side of C-1 gives a, reaction with the other side gives b
Horton et al 2002 Fig 8.8b
Anomers: Isomeric forms of monosaccharides that differ only about the hemiacetal or hemiketal carbon.
The hemiacetal or carbonyl carbon (the most oxidized carbon, i.e. attached to two oxygen atoms) is called the anomeric carbon.
The and anomers of D-glucose interconvert in solution by a process called mutarotation.
AnomersDefinition: Isomeric forms of monosaccharides that differ only about the hemiacetal or hemiketal carbon are called anomers
The hemiacetal or carbonyl carbon (the most oxidized carbon, i.e. attached to two oxygen atoms) is called the anomeric carbon.
The and anomers of D-glucose interconvert in solution by a process called mutarotation.
Voet, Voet & Pratt 2013 Figure 8.4
Pyran (a) and furan (b) ring systems
• (a) Six-membered sugar ring is a “pyranose”
• (b) Five-membered sugar ring is a “furanose”
Voet, Voet & Pratt 2013 p. 220
a b
Haworth Projections
Rules:
1. Cyclic monosaccharide is drawn with the anomeric carbon on the right.
2. Other carbons are numbered in a clockwise direction
3. Hydroxyl groups (-OH) on right of carbon skeleton in Fischer projection point down in Haworth projection (and vice versa).
4. (For D sugars) Anomeric carbon is if its hydroxyl group is trans to the CH2OH at the carbon atom that determine whether the sugar is designated (D or L).
Haworth
FischerHaworth projection indicates sterochemistry and is easily related to Fischer projection
11
Berg, Tymoczko, & Stryer 2012 Fig 11.3
Conformations of Monosaccharides
Horton et al 2002 Chapter 8.3
Conformation:
Three-dimensional shape having the same configuration.
Sugars are conformationally variable!
Conformations of b-D-glucopyranose
(b) Stereo view of chair (left), boat (right)
Horton et al 2012 Fig 8.11Voet, Voet & Pratt 2013 Figure 8.3
Conformations of b-D-glucopyranose
• Conformer on the left is more stable because it has the bulky hydroxyl substituents in equatorial positions (less steric strain)
Voet, Voet & Pratt 2013 Figure 8.5 Berg, Tymoczko, & Stryer 2012 p.334
Conformations of b-D-ribofuranose
Horton et al 2012 Fig 8.10
Derivatives of Monosaccharides
• Many sugar derivatives are found in biological systems
• Some are part of monosaccharides, oligosaccharides or polysaccharides
• These include sugar phosphates, deoxy and amino sugars, sugar alcohols and acids
Horton et al 2012 Table 8.1
Abbreviations for some Monosacchardies and their Derivatives
Monosaccharide Derivatives
A. Sugar Phosphates
Some important sugar phosphates
Horton et al 2012 Fig 8.13
B. Deoxy Sugars
• In deoxy sugars an H replaces an OH
Deoxy sugars
Horton et al 2012 Fig 8.14
C. Amino Sugars
• An amino group replaces a monosaccharide OH
• Amino group is sometimes acetylated
• Amino sugars of glucose and galactose occur commonly in glycoconjugates
Horton et al 2002 Chapter 8
Several amino sugars
• Amino and acetylamino groups are shown in red
Horton et al 2012 Fig 8.15
D. Sugar Alcohols (polyhydroxy alcohols)
• Sugar alcohols: carbonyl oxygen is reduced
Horton et al 2012 Fig 8.16
E. Sugar Acids
• Sugar acids are carboxylic acids • Produced from aldoses by:
(1) Oxidation of C-1 to yield an aldonic acid
(2) Oxidation of the highest-numbered carbon to an alduronic acid
Lehninger Biochemistry 2000 Fig 9.9
Some Biologically Important Hexose Derivatives
Disaccharides and Other Glycosides
• Glycosidic bond - primary structural linkage in all polymers of monosaccharides
• An acetal linkage - the anomeric sugar carbon is condensed with an alcohol, amine or thiol
• Glucosides - glucose provides the anomeric carbon
Glucopyranose + methanol yields a glycoside
Voet, Voet & Pratt 2013 Figure 8.7
Structures of Disaccharides
Structures of (a) maltose, (b) cellobiose
Horton et al 2012 Fig 8.20a,b
Systematic name
Systematic Description: The linking atoms, the configuration of the glycosidic bond, and the name of each monosaccharide, including its designation as a pyranose or furanose, MUST be specified.
Structures of Disaccharides (cont.)
Structures of (c) lactose, (d) sucrose
Horton et al 2012 Fig 8.20c,d
Rules for Disaccharide Structures1. The structure is written starting with the non-reducing end at the
left and standard accepted abbreviation are used. (see Table 8.1 in Horton et al.,)
2. Anomeric and enantiomeric forms are designated by prefixs, e.g. - and D-.)
3. The ring structure is indicated by a suffix (p for pyranose and f for furanose)
4. The atoms between which glycosidic bonds are formed are indicated by numbers in parentheses between residue designations (e.g., (14) means a bond from carbon 1 of the residue on the left to carbon four of the residue on the right.)
Example : -D-Glcp(12)--D-Fruf Matthews et al, 2000 Chap 9
Reducing vs Nonreducing SugarsReducing:
• Monosaccharides and most disaccharides are hemiacetals with a reactive carbonyl group.
• Carbonyl group can be readily oxidized to diverse products; will reduce metal ions, e.g.,Cu2+ or Ag+ to precipitates.
Non reducing:
• Carbohydrates that are acetals cannot reduce metals, sucrose with both anomeric carbons in a glycosidic bond is one example.
Oligo- and poly-saccharides: with a linear polymer they show only one reducing end. All the glycosidic bonds are acetals which are not in equilibrium with the open chain structure and therefore cannot reduce metal ions.
Polysaccharides
• Homoglycans - homopolysaccharides containing only one type of monosaccharide
• Heteroglycans - heteropolysaccharides containing residues of more than one type of monosaccharide
• Lengths and compositions of a polysaccharide may vary within a population of these molecules
Horton et al 2002 Chapter 8
Horton et al 2012 Table 8.2
The nature of a polysaccharide’s biological role is commonly used to classify them, such
as: structural or (energy) storage.
A. Starch and Glycogen• D-Glucose is stored intracellularly in polymeric forms
• Plants and fungi - starch
• Animals - glycogen
• Starch is a mixture of amylose (unbranched) and amylopectin (branched)
(a) Amylose is a linear polymer
(b) Assumes a left-handed helical conformation in water
Horton et al 2002 Fig 8.22Voet, Voet & Pratt 2013 p.227
Glycogen• Storage polysaccharide for animals: greatest in skeletal muscle and liver cells, but present
in all cells.
• Primary structure resembles amylopectin but more highly branched, i.e. every 8-14 residues.
• In the cell degraded for use by glycogen phosphorylase cleaving (1-4) bonds working from the nonreducing end onward.
• Highly branched structure provides rapid access.
• Debranching enzyme cleaves the (1-6) bonds at the branch points.
Stryer et al., 2002 Fig 21.1
B. Cellulose and Chitin (structural homopolysaccharidies)
Structure of cellulose
(a) Chair conformation
(b) Haworth projection
Horton et al 2002 Fig 8.25
O
- NH-C-CH3
substituted in chitin
Voet, Voet & Pratt 2013 Figure 8.9
A linear, unbranched polymer of 10 –50 thousand glucose units. One key difference is that cellulose is in the beta configuration and has (1-4) glycosidic bonds compared to amylose & glycogen
Lehninger Biochemistry 2000 Fig 9.17a
Structure of Cellulose: 2 Chain Units
intrachain
interchain
Glycoconjugates
• Heteroglycans appear in three types of glycoconjugates:
Proteoglycans
Peptidoglycans
Glycoproteins
Horton et al 2012 Chapter 8
Proteoglycans• Proteoglycans - glycosaminoglycan-protein complexes
• Glycosaminoglycans - unbranched heteroglycans of repeating disaccharides (many sulfated hydroxyl and amino groups)
• Disaccharide components include:
(1) amino sugar (D-galactosamine or D-glucosamine), (2) an alduronic acid
Horton et al 2012 Chapter 8Voet, Voet & Pratt 2013 Figure 8.15
Repeating disaccharide of hyaluronic acid
• GlcUA =D-glucuronate
• GlcNAc= N-acetylglucosamine
Horton et al 2012 Fig 8.28
Peptidoglycans• Peptidoglycans - heteroglycan chains linked to peptides
• Major component of bacterial cell walls
• Heteroglycan composed of alternating GlcNAc and N-acetylmuramic acid (MurNAc)
• b-(1-4) linkages connect the units
Glycan moiety of peptidoglycan
Horton et al 2012 Fig 8.30
Bacterial Cell Walls
Matthews et al, 2000 Fig 9.25
Voet, Voet & Pratt 2013 Figure 8.16
Peptodiglycan Layer of Gram
Positive Bacteria
Matthews et al, 2000 Fig 9.26
Glycoproteins• Proteins that contain covalently-bound
oligosaccharides
• “Class” includes: enzymes, hormones, transport & structural proteins
• O-Glycosidic and N-glycosidic linkages
• Oligosaccharide chains exhibit great variability in sugar sequence and composition
• Glycoforms - proteins with identical amino acid sequences but different oligosaccharide chain composition
Horton et al 2012 Chapter 8
Diversity in Glycoprotein Oligosaccharide Chains1. Chain can contain several different sugars (predominant in eukaryotes) such as: (6
carbon) L-fucose, D-galactose, D-glucose, D-mannose; N-acetyl-galactosamine, N-acetyl-glucosamine; (9-carbon) sialic acids; (5 carbon) D-xylose.
2. Sugars can be joined by either or glycosidic linkages
3. Linkages can join various carbon atoms. In 6 carbon all involve C-1 of one sugar, but C-2,3,4, or 6 of another hexose or C-3,4 or 6 of hexosamines; C-2 not C-1 of sialic acid links to other sugars.
4. Chains can contain up to four branches
Horton et al 2012 Chapter 8
IMPORTANT: The addition of one or more oligosaccharide chains affects a protein’s PHYSICAL PROPERTIES (size, shape, charge, stability, etc.) which, in turn, affects the BIOLOGICAL PROPERTIES such as: secretion rate, circulation ½-life, immunogenicity, targeting within the cell, cell signaling.
Stryer et al., 2002 Fig 11.X
Blood Groups & Glycoproteins
End of Lectures