Lecture #8
Carbohydrates
Slide 1. In this lecture we will consider another major class of biomolecules,
the carbohydrates.
Slide 2. Most carbohydrates are polyhydroxy aldehydes or ketones. They
often have the general empirical formula: [CH2O]n Their name derives from
that formula which has the proportions of one carbon atom and one water
molecule—carbo for carbon—hydrate for water. Early chemists thought
that this might have some significance. Even though that is not the case, the
name has stuck.
Slide 3. Monosaccharides are the basic building blocks from which all
carbohydrate polymers are constructed. The term aldose is used to describe
those monosaccharides that have an aldehyde functional group. The term
ketose is used for monosaccharides that have a ketone group.
Carbohydrates are also classified by the number of carbon atoms that they
contain. Trioses have three carbons, tetroses have four, pentoses have five,
hexoses have six and heptoses have seven.
These terms are combined to give a more complete description of a
monosaccharide. For example, glucose is an aldohexose.
Slide 4. There are specific terms that describe the number of monomer units
that are covalently linked to each other. Monosaccharides have one residue,
Oligosaccharides have 2-10 residues, and Polysaccharides can have up to
1000 or more residues.
Within the oligosaccharide range one commonly encounters disaccharides
that have two monosaccharide units, trisaccharides that have three, and
tetrasaccharides that have four.
Slide 5. As with amino acids, many carbohydrates have centers of
asymmetry (chiral centers). Enantiomers are isomers that are exact mirror
images of each other. In reference to carbohydrate enantiomers, the
designators D- and L- are used. The trioses, D- and L-glyceraldehyde are
the simplest carbohydrate enantiomers. Most, but not all of the naturally
occuring carbohydrates are D-isomers.
Carbohydrates with chiral centers often rotate the plane of polarized light.
This property was used by early carbohydrate chemists to help characterize
various carbohydrates and to track the reactions they undergo. When two
enantiomers of the same compound are mixed in equal amounts the effects
on polarized light are canceled out, and no rotation occurs. A mixture of
equal amounts of two enantiomers is called a racemic mixture.
Slide 6. Perspective formulas designate D- and L-isomers. With
perspective formulas the two bold groups radiating from a central carbon are
coming out of the plane of the screen, and the two groups in regular type are
going into the plane of the screen.
When Fischer projection formulas are used, these same orientations of the
carbon atoms are assumed even though they are not shown.
Slide 7. The 3-dimensional arrangements of substituent groups in space
about a chiral center are referred to as configurations. The different spatial
arrangements of a molecule, resulting from free rotation about carboncarbon single bonds, are called conformations.
Slide 8. Epimers are monosaccharides that differ in stereochemistry at only
one chiral carbon. Epimers are generally not mirror images of each other
(except for trioses) and are not chemically equivalent to each other. That is,
epimers generally are different compounds with specific names and varying
chemical reactivities.
Slide 9. A monosaccharide will have 2N isomers, where N equals the
number of centers of asymmetry. In the example shown here an
aldohexose will have four chiral centers corresponding to the middle four
carbons, which each are attached to four different substituents. (The top and
bottom carbons are not chiral because they do not have four different
substituents.) In the example of aldohexoses there will be 2N isomers
(equaling 24), which is 16 isomers or 8 D- and 8 L-pairs.
-Aldotrioses have one asymmetric center and 2 possible isomers.
-Aldotetroses have two asymmetric centers and 4 possible isomers. (22)
-Aldopentoses have three asymmetric centers and 8 possible isomers. (23)
-Aldohexoses have four asymmetric centers and 16 possible isomers. (24)
Slide 10. Here we see the chiral centers in aldo trioses and aldo tetroses.
The prefix D- or L- for these compounds is derived from the lowest center of
asymmetry in the Fischer projection. According to convention the most
oxidized functional group (in this case the aldehyde) is placed at the top of
the compound. If the –OH group is to the right in the lowest center of
asymmetry, then the compound is designated “D”. If the –OH group is to
the left in the lowest center of asymmetry, then the compound is designated
“L”.
Slide 11. Shown here on the lower half of the slide, are the four D-isomers
of aldopentoses. There are also four possible L-isomers.
Slide 12. This slide shows the eight D-isomers of aldohexoses. Again,
there are also eight L-isomers. The structures of the shaded compounds
glucose, galactose and mannose should be firmly deposited into our memory
bank, because these compounds are very common in nature. (I personally
like the sound of gulose because it has a sort of horror show ring to it—
however, that is probably not a good reason to learn it’s structure.)
Slide 13. In water glucose spontaneously reacts to form two cyclic (six
membered pyranose ring) products. These - and -glucopyranose
compounds are referred to as - and -anomers.
You can see here the convention for coverting from the linear Fischer
formula to the cyclic Halworth formula. The convention is to have the
number 6 carbon (hydroxymethyl group) radiating up for D-aldohexoses.
The hydroxyl groups at carbons 2 and 4 which are to the right in the Fischer
formula radiate down in the Halworth formula. The hydroxyl group at
carbon 3 which is to the left in the Fischer formula radiates up in the
Halworth formula. The hydroxyl group at position 5 becomes the ring
oxygen and so has no chirality.
The aldehyde group, at position 1 in the open chain Fischer projection, is
converted to a new (anomeric) hydroxyl group which has chirality. If the
anomeric hydroxyl radiates down it is called an -anomer. If it radiates up
it is referred to as a -anomer.
Slide 14. The - and -anomers at position 1 differ only in their
configuration about the new asymmetric (anomeric) center that is
formed when the open chain form of a monosaccharide reacts to form cyclic
products.
Slide 15. This process of interconversion of - and -anomers through
the intermediate formation of an open chain form is called mutarotation.
In solution Monosaccharides in the open chain form are constantly
equilibrating with the cyclic - and -anomers.
Slide 16. The cyclization of an aldose such as glucose occurs when an
alcohol group reacts with an aldehyde group in the same molecule. This is
the chemical equivalent of the formation of a hemiacetal..
Slide 17. The cyclization of a ketose such as fructose occurs when an
alcohol group reacts with a ketone group in the same molecule. This is the
chemical equivalent of the formation of a hemiketal..
Slide 18. After reaction of a hemiacetal with a second alcohol molecule,
the product is an acetal. When two cyclized carbohydrates react to form a
disaccharide it is the equivalent of the formation of an acetal. Unlike
hemiacetals which are constantly equilibrating with the aldehyde and alcohol,
the acetal derivatives are generally very stable.
Slide 19. There is a classic test (Fehling’s reagent) for the identification of
carbohydrates that can mutarotate through the open chain form to produce an
aldehyde. Such open chain aldehydes can reduce Cu2+ and in the process
are oxidized to a carboxylic acid. Most monosaccharides are reducing
compounds, but if the anomeric hydroxyl group is methylated or locked in
an acetal structure they become non-reducing compounds.
Slide 20. Ketoses have the carbonyl carbon at the #2 position of the
monosaccharide. They have one less asymmetric center than the equivalent
aldose molecule. You should learn the structure of fructose.
Slide 21. As with aldoses, ketose compounds such as fructose can
mutarotate to form cyclic derivatives. In the example shown, fructose
cyclizes to form a -fructofuranose (a five-membered furanose ring)
anomer. Fructose can also cyclize to form a six-membered pyranose ring.
The distribution of fructose between the open chain form and the various
possible cyclic structures depends on the relative energy levels of those
structures. The form with the lowest energy level will have the greatest
concentration at equilibrium.
Slide 22. In this slide you can see the various pyranose (six-membered) and
furanose (five-membered) ring forms of fructose. As with aldoses the
designators  and  refer to the anomeric position which is the new
hydroxyl group produced when the cyclic derivative is formed. If the
anomeric -OH goes down it is an  anomer, and if the -OH goes up it is
a  anomer.
Slide 23. Carbohydrate molecules also equilibrate between various
conformations--different arrangements of the molecule in space resulting
from rotation about C-C bonds. The preferred conformation of a
carbohydrate is the one with the lowest energy level. For aldohexoses the
distribution between various chair and boat conformation depends on which
conformation exhibits the least steric hinderance.
Slide 24. The term steric hinderance refers to negative interactions that can
occur between two functional groups in a molecule. This slide shows two
bulky groups in proximity to one another. If the groups are very large
certain conformations might be impossible, because the two groups would
be competing for the same space. Even when that is not the case, it is
generally true that bulky groups are more stable when they are not in close
proximity. In general conformations that minimize steric hindrance tend
to predominate. In monosaccharides that can exist in various
conformations, the distance between bulky groups is often greater if they
occur in the equatorial position.
Slide 25. Here we see the two common carbohydrate conformations which
are designated chair and boat forms. Groups that radiate out toward the
midline of these conformations are referred to as occupying the equatorial
position (designated e). The groups that radiate up or down are said to
occur in the axial position (designated a). Again, the distribution of a
monosaccharide into various chair and boat forms favors the form with the
lowest energy level, which in turn is dependent on minimizing steric
hinderance.
Slide 26. Carbohydrates can be selectively methylated at the anomeric
hydroxyl. The methylation of a sugar locks the cyclic forms into either the
 and  anomer so there is no mutarotation. In addition the methylated
sugar becomes non-reducing because it cannot achieve the open chain form.
That is, the methylated sugar cannot react with oxidizing agents because
these reactions need a free aldehyde group in order to proceed.
Slide 27. Deoxysugars lack a hydroxyl group at one of their carbons.
Ribose and deoxy-ribose are components of RNA and DNA. You should
probably know the structures of these compounds, because where would you
and your future children be with these essential materials? In addition 2deoxy-ribose is the prime example of a deoxysugar. It lacks a hydroxyl
group at carbon 2.
Slide 28. Phosphorylated sugar derivatives have at least one covalently
bound phosphate residue. The three phosphorylated compounds shown here
are all components of the glycolysis pathway. In general phosphorylated
sugars occur in side of cells where they function as intermediates in
biochemical pathways.
Slide 29. In sugar acids there is at least one carboxyl group. Galacturonic
acid is a common sugar acid. The sugar acids tend to be components of
complex carbohydrate polymers that serve as structural materials in
connective tissues and other extracellular polysaccharides.
Slide 30. In sugar alcohols the aldehyde or ketone group is replace by an
additional hydroxy group. The commercial sweetener sorbitol is an example
of a sugar alcohol. Another sugar alcohol is the cyclic polyalcohol, inositol.
Inositol serves as a component of phosphoglycerols, and in a phosphorylated
form it also functions as a biological second messenger.
Slide 31. In nucleic acids and nucleotides a nitrogen atom of an organic
base (purine or pyrimidine) is covalently linked to the anomeric group of
ribose or deoxy-ribose. Such a linkage is referred to as an N-glycosidic
bond.
Slide 32. In disaccharides, oligosaccharides and polysaccharides the
monosaccharide units are linked to each other by glycosidic bonds. In
maltose two glucopyranose units are joined together in an -1,4glycosidic bond. The glycosidic linkage in maltose is referred to as -1,4
because it connects the 1 (anomeric) carbon of the glucose unit on the left to
the 4 carbon of the glucose unit on the right. The linkage from the anomeric
carbon radiates in a downward direction so it is an -linkage.
Slide 33. Common disaccharides include sucrose, lactose and maltose.
-Sucrose is the usual food that we purchase when we buy a bag of “sugar” in
the store. It is a non-reducing sugar because its two anomeric carbons are
linked together so that neither of the anomeric positions can mutarotate into
the open chain form.
-Lactose is the disaccharide present in mammalian milk. It contains
galactose and glucose units joined by a -1-4 linkage. It is a reducing sugar
because the glucose component can mutarotate into the open chain form.
-Maltose contains two glucose units connected by an -linkage. It is a
reducing sugar because the glucose residue on the right can mutarotate.
Maltose units are present in the 1,4-linked regions of the polysaccharides,
glycogen and starch.
Slide 34. The human storage polysaccharide glycogen contains about
90% -1,4 linkages and 10% -1,6 linkages. The -1,6-linkages are
responsible for the branch points in glycogen.
Slide 35. The structural plant polysaccharide
-1,4
linkages. It forms a sheet-like structure. It is not digestible by humans
because we lack the appropriate enzyme for hydrolyzing -1,4-linked
glucose units. Starch and glycogen contain  -1,4-linked glucose units (and
-1,6-linked glucose units) and form spiral structures. These linkages are
digestable by human enzymes.
Slide 36. Proteoglycans are proteins attached to
polysaccharides called glycosaminoglycans.
-Glycosaminoglycans are anionic polysaccharide chains made of repeating
disaccharide units.
-They resemble polysaccharides more than proteins because their
carbohydrate component typically makes up 95% of the molecular weight.
-Glycosaminoglycans contain derivatives of amino sugars and of other
monosaccharides containng negatively charged carboxylate or sulfate
groups.
Slide 37. Amino sugars have an amino group substituted for one hydroxyl
group. The N-acetyl derivatives of glucose and galactose are very common
components of proteoglycans.
Slide 38. Chondroitin 6-sulfate and the other disaccharides shown are
common components of Glycosaminoglycans. The negatively charged
carboxylate and sulfate components are highlighted in red.
Slide 39. The structure shown in the electron micrograph is a
proteoglycan from cartilage.
Slide 40. The proteoglycan has the chemical structure shown in figure
11.16b.
Slide 41. The synthesis of carbohydrate polymers is catalyzed by
enzymes called glycotransferases and is accomplished using a variety of
nucleotide sugars as the donors. The cleavage of phosphoester linkages
helps to drive the process in the direction of polysaccharide synthesis.
Slide 42. Figure 11.9 shows a variety of modified monosaccharides.
These compounds are often found as components of polysaccharide
structures on cell surfaces.
Slide 43. Figure 11.18 shows the structure of A,B, and O antigens that are
found in humans. These carbohydrate structures are present on cell surfaces,
attached to proteins and lipids. They are responsible for variations in human
blood types. The use of the proper ABO group in blood transfusions is
critical.