Transcript Carbohydrates Structure

THE STRUCTURE OF CARBOHYDRATES
Dr. Ferchmin 2012
The objectives of this lecture are three:
a) To put you in “a molecular mind set”.
b) “Review” some concepts learned in organic chemistry.
c) Familiarize you with carbohydrate molecules involved in metabolism.
Summary of this handout:
1) Definition of carbohydrate.
2) Asymmetric carbon, Fischer projection formulas.
3) D and L series.
4) Mutarotation, Haworth formulas and anomers.
5) Examples of monosaccharides. Fructose, mannose, galactose, deoxysugars,
aminosugars, glucuronic and gluconic acids.
6) Glycosides and disaccharides. Lactose, maltose, isomaltose, cellobiose,
sucrose
7) Homo- and heteropolysaccharides. Glycogen !!!!
8) Glycosaminoglycans (formerly called mucopolysaccharides).
You will find two versions of this handout at http://www.ferchmin.org
Functions of carbohydrates
Energy Glucose is the circulating sugar in blood and the energy source for
most organs. Glycogen is one of the most important energy stores. Oxidation
of glucose to CO2 and H2O is the central energy yielding process.
Structural Polysaccharides are used as shock absorbers and lubricants in
joints and as adhesives between cells.
Signaling Sugars associated with proteins or lipids are involved in cell
signaling. Sugars are involved in cell-cell interactions, immunological
responses and determine the metabolic role of many proteins.
Carbohydrates are polyalcohols of ketones or aldehydes and simple
derivatives (like carboxylic acids or amino sugars), and polymers.
Carbohydrates can be considered as 'carbon hydrates', the empirical formula
is Cn(H2O)n. There is one water molecule per carbon atom.
Carbohydrates are also called sugars or saccharides.
The thousands of different carbohydrates found in nature are stereoisomers,
derivatives or polymers of a rather small number of monosaccharides. For
that reason, the concept of isomerism is important to understand
carbohydrates.
Stereoisomery of carbohydrates is produced by the asymmetric carbon.
The asymmetric carbon is tetrahedral and has 4 ≠ substituents.
These three pictures show molecules that are enantiomers or mirror images of each other
To make it easier to write Fischer
made the Fischer convention:
You must apply it to each and all
the asymmetric carbons of a
molecule.
Or to make it simpler you may
use the projection formula
The smallest sugars with an asymmetric carbons are shown below:
Conceptually speaking D-glyceraldehyde originates the series of D-carbohydrates,
and reciprocally L-glyceraldehyde the L series.
Aldoses are derivatives of glyceraldehyde
The asymmetric carbons in a hexose have to be viewed one by one.
Glucose is a carbohydrate of 6 carbons
Asymmetric carbons rotate polarized light: Ordinary light vibrates in all possible
planes. When ordinary light is filtered by certain crystals a single plane of
polarized light is obtained. Polarized light traveling through a solution of an
asymmetric compound, such as sugar, can rotate the plane of polarized light.
The degree of rotation is directly proportional to the concentration of the
asymmetric compound. Substances that rotate the plane of polarized light are
called "optically active."
Rotation to the left is indicated as l and to the right as d. Contrary to intuition the levo
or dextro rotation provides no clue whether a sugar is from the L or D series.
Confusion comes from the fact that D-glyceraldehyde was originally designated D
because it rotated the polarization plane +13.5º degrees and L-glyceraldehyde
because it rotated -13.8º degrees to the left. Each asymmetric carbon of a molecule
has its own contribution to the total rotation of polarized light.
Ketoses are derivatives of dihydroxyacetone
MUTAROTATION
Pyranoses and furanoses
The terms pyranose and furanose come from the ‘similarity’ to pyran and furan to
the rings formed by mutarotation.
- D-Glucopyranose
β- D-Fructofuranose
-D-Glucopyranose
β-D-Glucopyranose
63%
36%
<1%
β-D-Glucofuranose
<1%
0.1%
-D-Glucofuranose
There are three manners to write the formula of monosaccharides.
This actually represents how our concept of structure evolved
We will be repeating several concepts and practice them:
Enantiomers are mirror images of each other; see below D- and L-glucose.
We will need this concept to understand certain molecules
Chair model of glucose
showing the axial and
equatorial substituents.
β anomer
C5 is L. Therefore
C6 is below the ring
Since this is an
L series sugar
all is ≠ and
anomeric –OH
is above ring
and it is 
 anomer
Mutarotation in the case of fructose
The case of galactose
Ribose and “derivatives” of carbohydrates
2-[18-F] Fluoro-2-deoxy-D-glucose (FDG)
2-deoxy-D-glucose is a non metabolizable form
of glucose and its 18-F derivative is used for
imaging.
Reducing and nonreducing monosaccharides
C1 of aldoses or C2 of ketoses is prone to be oxidized at the expense of other
compounds including a reagents containing a cupric salt.
Monosaccharides are reducing when their reducing C is free or in the form of
hemiacetal
GLYCOSIDES
Acetals are not reducing because they are not in equilibrium with the open form
and there is no carbonyl group to be oxidized.
Acetals between monosaccharides and non-carbohydrate molecules are called
glycosides.
Acetals between monosaccharides are called mono, di, tri or polysaccharides
What can you say about this
monosaccharide?
Ouabain is an inhibitor of the sodium/
potassium pump
Ouabain
Sugar chains are often linked to proteins by glycosidic bonds as shown below:
This is an O glycosidic bond
This is a N glycosidic bond
All nucleosides and nucleotides are N-glycosides of ribose or deoxyribose
and the corresponding purine or pyrimidine.
Disaccharides: are dimers of monosaccharides, either aldoses or ketoses
You must be acquainted with: maltose, isomaltose, lactose, sucrose and cellobiose.
Repeating unit in
starch and glycogen.
Notice the  bond
Repeating unit at
branching points
in starch and
glycogen. Notice
the  bond.
It is present in
milk
Glucose is the reducing
monosaccharide. Notice
the β bond.
Repeating unit in cellulose.
Notice the β bond.
Sucrose is not a reducing monosaccharide.
The bond is glucose 1 →fructose 2β.
Sucrose accounts for 15% of the calories in our
diet. It is the main cause of dental cavities,
contributes to obesity and diabetes
POLYSACCHARIDES
Homopolysaccharides are polymers of the same monosaccharide. Heteropolysaccharides are polymers of different
monosaccharides. Complex carbohydrates are important cell constituents. The cell membrane have oligosaccharides
that stabilizes protein conformation, protects against proteolysis, etc. In the erythrocyte, extracellular oligosaccharides
are responsible for the blood groups. The ABO blood group antigens are the product of presence of absence of
elongation enzymes (transferases).
HOMOPOLYSACCHARIDES:
In plants the main form of storage of carbohydrates is STARCH, a mixture of:
a) amylose: about 2,500 molecules of glucose bound by α(1-4) bonds forming a linear molecule.
b) amylopectin: about 50,000 molecules of glucose bound by α(1-4) bonds with α(1-6) branching bonds every
about 30 molecules of glucose. Amylopectin resembles glycogen although it is less branched.
Glycogen is a polymer of molecules of glucose bound by α(1-4) bonds with α(1-6) branching
bonds every about 4-5 glucose residues. It could be considered as a polymer of maltose and
isomaltose. You must know its structure because we will spend some time studying glycogen
synthesis and break down. There are several diseases of glycogen storage. Below are shown
two representations of glycogen.
Glycogen and starch are storage homopolysaccharides that contain -D-glucose and
form a helix in space.
Cellulose is a linear polymer of β-D-glucose that is stabilized by inter-chain hydrogen bonds that give stability to the molecule.
Cellulose forms a straight chain not a helix. Cellulose is not a source of calories for humans because the glycosidic
bond is β and not α.
Heteropolysaccharides
Glycosaminoglycans, formerly called mucopolysaccharides, are a group of
heteropolysaccharides composed of a repeating disaccharide unit usually formed by
an uronic acid and an aminated sugar (glucosamine or galactosamine). They are
variously substituted with negatively charged groups and are usually linked with
other macromolecules forming large molecular aggregates. Those long negatively
charged chains are hydrated and since the charges repel each other the chains are
separated by water making the glycosaminoglycans excellent lubricants and shock
absorbers.
Heparin and heparan sulfates: More than 70 % of heparin is a repeating
disaccharide unit of L-iduronic linked to D-glucosamine. It is sulfated on the N of the
glucosamine and on hydroxyl groups of both sugars. Heparin is the most acidic of all
glycosaminoglycans. Heparan sulfate is very similar but has D-glucuronic instead of Liduronic. Heparan is less acidic than heparin
Chondroitin sulfates 4S and 6S and dermatan sulfate. Chondroitin 4S and 6S are the
most abundant glycosaminoglycans. They are composed of D-glucuronic acid and N-acetylD-galactosamine. They are sulfated on position 4 or 6 respectively. Both structures can be
found on the same chain. Dermatan sulfate has L-iduronic acid in addition to D-glucuronic.
Chondroitin 6S has
the S03- on carbon 6
Chondroitin 4S
Keratan sulfate. Closely associated
with chondroitin sulfates in some
connective tissues. The remarkable
feature is the absence of glucuronic
or iduronic acids. It contains
galactose and N-acetyl-glucosamine.
Dermatan sulfate
Hyaluronic acid. Is the least acidic of all glycosaminoglycans. It is fairly homogeneous
containing N-acetyl-glucosamine and D-glucuronic. Does not contain sulfate
Attachment of glycosaminoglycans to proteins
Proteoglycan aggregate
The fig shows the macromolecular
structure formed by proteins and
glycosaminoglycans.
Intervertebral disk
Recommendations: You will be using the following formulas during the course.
The formulas of the monosaccharides you must be familiar with are shown below.
Those labeled with * are frequently used and you should memorize the formulas.
D-glucose*
D-fructose*
D-glucosamine*
D-galactosamine*
dihydroxyacetone*
D-erithrose
D-ribose*
maltose*
2-deoxy-D-ribose*
L-iduronic
D-galactose*
D-mannose
D-mannosamine
D-ribose*
D-glyceraldehyde*
lactose
sucrose
cellobiose
D-glucuronic*
sialic or neuraminic acid
Actually, you should only remember glucose and ribose. The rest is reasoning and
remembering basic concepts.
I will give you the Fischer projections of aldoses for the 1st exam and will test your
ability to reason rather than your short-term memory
You must have a good understanding of the structure of glycogen* (types of bonds)
because of its metabolic role and because you will use its structure to understand
several metabolic diseases.
You must have a general idea about the composition of heparin, heparan sulfate,
chondroitin and dermatan sulfates, keratan sulfate and hyaluronic acid. You must
relate the structure to the function.
New cell signaling functions of glycosaminoglycans are being discovered and the
new functions are quite “mysterious”. Remember that glycosaminoglycans were
previously called mucopolysaccharides. When associated with proteins they form
proteoglycans.
Things to remember:
The following concepts must be understood:
Isomer, stereoisomer, epimer, mutarotation, anomer (α and β), reducing carbohydrate,
conformation as different from configuration, glycoside, pyranose, furanose,
disaccharide, polysaccharide, homo-, and heteropolysaccharide, N-acetyl, deoxy,
amino, D and L.