Carbohydrate Biochemistry
Objectives
-Recognize the features and functions of different classes of
“carbohydrates”
-Understand the concept of asymmetric carbons and other
diastereoisomers, epimers and enantiomers and anomers
-Recognize the structure of glucose and its relationship with
other monosaccharides
-Understand the different reactions of monosaccharide
-Understand the nature of glycosidic bond and recognize the
structure of the common disaccharides
-Recognize the different types and classes of polysaccharides
-Understand the basic differences between amylose and cellulose
-Understand the digestion of carbohydrates process, and
recognize cases of abnormal degradation of disaccharides
*Functions of Carbohydrates
* Classification of CHO
- Monosaccharides
- aldoses and ketoses
* Structure of Monosaccharides
-isomers, epimers and enantiomers
-cyclic structure, hemiacetal and hemiketal
*Reactions of monosaccharides
* Derivatives of Hexoses
-amino sugars
-acidic sugars
-Glycosides
* Disaccharides
-disaccharide formation and hydrolysis
-nomenclature of disaccharides
-glycosides
* Polysaccharides (Glycans)
-homo and hetero polysaccharides
-Storage polysaccharides; starch & Glycogen
-Structural polysaccharides, cellulose & chitin
Biochemistry of Carbohydrate
Carbohydrates (CHO) are the most abundant biomolecules in nature
CHO are the photosynthesis product
nCO2 +H2O
(CH2O)n + nO2
light
Originally thought to have the formula (CH2O)n.
Now known that only simple monosaccharides obey this rule.
Carbohydrate- polyhydroxy aldehyde or ketone or a larger molecule which
can be hydrolyzed to a polyhydroxy aldehyde or ketone.
Functions of Carbohydrates
1.
2.
3.
4.
5.
Energy source for plants and animals
Source of carbon in metabolic processes
Storage form of energy
Structural elements of cells and tissues
Some CHO participate in recognition and adhesion between cells and mediate
some forms of inter cellular communications
Classes of Saccharides
Monosaccharides
= single polyhydroxy aldehyde or ketone unit,
(eg. 6-carbon glucose, most abundant in nature)
Oligosaccharides
= short chain of 2- ~20 monosaccharides joined by “glycosidic bonds”
(eg. disaccharide sucrose = glucose-fructose)
- oligosaccharides > 3 residues are usually joined to protein or lipid
in “glycoconjugates”
Polysaccharides
- chains > ~ 20 to 1000’s of monosaccharides in length
- linear: eg. cellulose (glucose)n or chitin (N-acetylglucosamine)n
- branched: eg. glycogen & starch (glucose)
- depending on the sugar residues in a polysaccharide and the linkages
between them, polysaccharides can have very different biological roles
Monosaccharides
- Backbone = un-branched carbon chains in which all C atoms are linked by single bonds
- Colorless, crystalline, solid freely soluble in water, insoluble in organic solvents
- If it has keto group as the most oxidized functional group = Ketose
- If it has aldehyde group as the most oxidized functional group = aldose
According to the number of carbon atoms
- 3 C = triose, 4 C = tetrose, 5 C = pentose, 6 C = hexose (eg. aldo- or ketohexoses)
Simplest monosaccharides are 3 carbon...
Aldotriose
ketotriose...
Common monosaccharides are 6 carbon...
Monosaccharides have asymmetric centers
- All monosaccharides (except dihydroxyacetone) have one or more asymmetric carbons
- eg. glyceraldehyde: middle C is a chiral center, so molecule has 2 different optical isomers
or enantiomers (= stereoisomers that are non-super imposable mirror images of one another)
By convention, one enantiomer = the D isomer, the other is L,
HORIZONTAL:
PROJECTS OUT
FROM PLANE
Configurations of glyceraldehyde:
VERTICAL:
PROJECTS
BEHIND PLANE
D and L configurations of monosaccharides
- Stereoisomers of monosaccharides > 3 C divided into 2 groups:
differ in the configuration about the chiral center most distant from the carbonyl C
In biochemistry, we use the D-L system (similar principle to the R-S system usually used in
organic, but everything is compared with glyceraldehyde
- In general, a molecule with n chiral centers can have 2n stereoisomers
-OH GROUP ON RIGHT,
CONFIGURATION = D
-OH GROUP ON LEFT,
CONFIGURATION = L
1
2
3
IN ALDOHEXOSES, C-2,
C-3, C-4, AND C-5
= CHIRAL CENTERS,
SO 24 = 16 POSSIBLE
ALDOHEXOSES:
8 D AND 8 L
4
5
MIRROR
6
- Most of the hexoses in living organisms are D-isomers
Epimers
- 2 sugars that differ only in the configuration around one carbon = epimers
Series of D-ketoses
- Have 1 less chiral center than aldoses
- C-4 and C-5 ketoses designated by adding “ul”
into the name of their corresponding aldose,
eg. D-ribulose = ketopentose corresponding to D-ribose
Stereochemistry
The D and L designation of sugars with n > 3 are taken from the
chiral carbon furthest from the carbonyl carbon.
Other important terminology:
Enantiomers- D- and L-sugars are enantiomers (mirror image
molecules)
Diastereomers- nonsuperimposable, non mirror image
Epimers- differ in arrangement about one chiral carbons.
Conformational isomers:
Formation of the two cyclic forms of D-Glucose
Interconversion between anomers
Anomers: Isomeric forms of monosaccharides that differ only in their
configuration at the anomeric carbon.
Mutarotation: The interconversion of α and β anomers of the monosaccharide
- α and β anomers interconvert in solution via the linear form: = mutarotation
- D-glucose solution forms an equilibrium mixture of ~ 64% β, 36% α
α-D- Mannose
α -D Galactose
Reactions of Monosaccharides
Reducing sugars.
Reduction to polyols (Alditols).
Reduction of Erythrose Æ Erythritol
Mannose Æ Mannitol
Glucose Æ Sorbitol
Oxidation into acidic sugars
Oxidation the –OH group at C6 Æ -uronic acid derivative
Glucose Æ Glucuronic acid (COOH at C6)
Oxidation the aldehyde group at C1 Æ -onic acid
Glucose Æ Gluconic acid (COOH at C1)
Reduction of hydroxyl group into deoxy sugars
Ribose Æ 2-deoxyribose
Formation of acetals, also called glycosides
Glycosidic bond- bond between a sugar and an alcohol (another sugar) or
amine (a base) through an O- or N- linkage
Reducing sugars
-The anomeric carbon of Glc and other
sugars can be oxidized by mild
oxidizing agents such as Cu2+ , providing
the sugar is in its open chain form, with a
“free” carbonyl carbon at C-1
-Sugars capable of reducing Cu2+ are
called “reducing sugars”
-The end of a chain of sugars that has a
free anomeric (C-1) carbon is called
the reducing end
This principle was used to detect
qualitatively the presence of the
reducing sugars these tests are not
specific for Diabetes mellitus
RED
COLOR
Blood glucose concentration is commonly determined by measuring the amount
of H2O2
Complex carbohydrates
Carbohydrate can be attached by glycosidic bond to non- carbohydrate structure
through an O- or N- linkage to form “complex carbohydrates”
-The non-carbohydrate portion is called Aglycone
-The entire molecule is called Glycoside
Glycosidic bond- bond between the anomeric carbon of a sugar and an alcohol
(can be another sugar) or amine (a base) through an O- or N- linkage.
Typical Aglycone
- Purines, Pyrimrdines fo form Nucleotides
- Aromatic rings (steroids)
- Proteins to form glycoproteins, the polypeptide is joined to the sugar moiety
via Asparagine to form N-glycoside and via serine to form O-glycosides
- lipids to form and glycolipids
Complex carbohydrates
N-glycoside
O-glycosides
Joining of sugars via glycosidic bonds
- O-glycosidic bonds are
formed when the -OH group of
one sugar reacts withthe
anomeric carbon of the other
- Reaction = formation of an
acetal from a hemiacetal (eg. C1 of gluco pyranose) and an
alcohol (-OH group on C-4 of
second glucopyranose molecule)
Joining of sugars via glycosidic bonds
- When an anomeric carbon participates in a glycosidic bond, it cannot exist in linear form,
and can no longer act as a reducing sugar (ie. it can’t reduce Cu2+)
- The end of a di- or polysaccharide chain with a free anomeric carbon (ie. not involved in a
glycosidic bond) = the “reducing end”
- In maltose, the configuration of the anomeric carbon in the glycosidic linkage is α
- Glycosidic bonds are readily hydrolyzed by mild acid
REDUCING
END
NONREDUCING
END
a
a OR b
b/c
MUTAROTATION
The name describes the sugar
with its reducing end
Glycosidic bonds are readily
hydrolyzed by acids
Non-reducing sugars named as
Glycosides
Trehalose: non-reducing sugar, a major
constituents of the circulating fluid od
insects
Polysaccharides:
are polymers of monosaccharides units of medium to high molecular weight.
Homopolysaccharides contain only a single type of monomers, as starch, glycogen, cellulose
Heterpolysaccharides contain two or more different kinds monomers, as
glycosaminoglycans
Polysaccharides could be branched or un-branched
Function: storage of energy, structural elements, animal exoskeleton and provide support
+-
- Important cell surface components, eg.
in holding cells together in tissues
- Important in molecular recognition events
Polysacchs. usually don’t have precisely defined molecular weights, unlike proteins
Storage polysaccharides: glycogen and starch
Glycogen:
polymer of α (1Æ4) linked glucoses with α (1Æ6) branches (one every 8-12 glucoses),
average mol. wt. = several millions. Can be ≤ 7 % wet wt. of liver
Starch:
= mixture of amylose, a linear polymer of α (1Æ4) linked glucoses, and amylopectin,
a linear polymer of α (1Æ4) linked glucoses with α (1Æ6) branches (one every 4-30
glucoses)
Liver cells (hepatocytes) store glycogen
equivalent to a [glucose] of 0.4 M
Storage polysaccharides are essentially
insoluble in the cell, so they don’t raise
the intracellular [glucose], which would
set up a very high [glucose] gradient.
Structure of Amylose
Rotation is permitted about the two C-O
bonds in a glycosidic linkage:
most stable conformation for α (1Æ4)
linked glucose = curved chain of rigid
“chairs”
- Conformation of a α (1Æ4) )-linkages
in amylose and glycogen causes
polymers to assume tightly coiled
helical structures that form dense
granules in cells.
- Molecules heavily hydrated, b/c many
–OH groups available to H-bond to
water.
Structural polysaccharides: cellulose
In β(1Æ4)-linked polysaccharides,
each residue is rotated 180° relative
to its neighbors. The intra-chain H-bonds can form
between ring O and the -OH of C-3 on
adjacent glucoses:
H-bonds also form between -OH’s on
residues on neighboring chains…..
…..the stabilizing network of intra-chain
and inter-chain H-bonds gives straight
stable fibers with great tensile strength.
Cellobiose
Glc β(1Æ4)-Glc
Extensive H-bonding within molecule
results in little H-bonding to water, hence
fibers have low water content
Structural polysaccharides: chitin
- Polymer of β(1Æ4)-)-linked N-acetylglucosamine
- Each residue rotated 180° relative to its neighbors
- Intra-chain H-bonds can form between ring O and C-3’s -OH’s on adjacent sugars
(as in cellulose)
- Inter-chain -NH --- O=C- H-bonds between aminoacyl groups
CH3
O=C
H- N
|
O
O
CH2OH
O
The End