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Fundementals I
8/22/08
11-12noon
Dr. David Pritchard
*Reading/Reviewing slides before class will be helpful
Slide 1:
Carbohydrate Basics
Slide 2
Carbohydrates (Overview):
 Carbohydrates are present in all living things, even the simplest virus. We know this because
RNA and DNA contain sugars; ribose and deoxyribose.
 There is more carbohydrates in the biosphere than anything.
 4 major classes of biological molecules
1. Carbohydrates
2. Proteins
3. Nucleic Acids
4. Lipids
 Carbohydrates can be very simple; from a 3-Carbon sugar to big, gigantic, complexes-some
even bigger than bacteria.
 In later lectures we will talk about Carbohydrates as metabolic intermediates, energy storers,
components of DNA and RNA, and major structural components.
 Sugars bound to proteins are called Glycoproteins, an especially important group of molecules.
(Will devote an entire lecture to glycoproteins later)
 Sugars bound to lipids are called glycolipids (Will be covered by other instructors)
 The Name Carbohydrate:
o When people first started isolating sugars and doing elemental analysis of them, they
discovered that in most sugars there was equal molar amounts of carbon and oxygen
and twice as much hydrogen.
o These people thought sugars were hydrates of carbon. This is where the name
“carbohydrate” came from.
Slide 3
Carbohydrates-Saccharides-Sugars:
 It turns out: sugars are actually polyhydroxy aldehydes and ketones
 Recall Aldehyde:
o an organic compound containing a terminal carbonyl group.
This functional group, which consists of a carbon atom bonded
to a hydrogen atom and double-bonded to an oxygen atom
(chemical formula O=CH-), is called the aldehyde group.

Recall Ketone:
o either the functional group characterized by a carbonyl group
(O=C) linked to two other carbon atoms or a chemical compound
that contains a carbonyl group. A ketone can be generally
represented by the chemical formula: R1(CO)R2.


(Complements of: http://en.wikipedia.org/wiki/Main_Page)
Pictures from Slide 2:
Aldehyde
Ketone

When carbohydrates have a lot of hydroxyl groups, they are sugars.
Slide 4
Optical Activity:
 Can’t talk about sugars without the idea of optical activity.
 Jean Baptist Biot discovered optical activity 200 years ago and thought he had discovered the
“secret of life” because it turns out:
o Naturally occurring compounds like sugar, amino acids, and even turpentine rotated a
beam of polarized light either to the right or the left-that was called optical activity.
o Nothing synthesized in the lab, anything that was manmade, had no optical activity-so
he thought only living things did. (not quite true)
Slide 5
Chirality and Optical Activity:
 Optically active molecules have chiral carbons
 “Chiro”- Greek for hand.
 “Chirality”-means it has a handedness-for right or left hand
 Right hand’s mirror image is a left hand (and vice versa)
 Whenever you have a carbon with 4 different things attached to it (4 substituents), they can be
linked two different ways. You can have a
o right-handed form
or a
o left-handed form
 If you have a pure solution of one or the other it will rotate light to the right or the left.
 Carbon with four different attachments (4 substituents) is a chiral carbon (or optically active
carbon)
 Sugar (like glucose)- there is actually 4 carbons that have four different things attached (4
substituents)
Slide 6
Carbohydrates-Saccharides-Sugars:

This molecule
is chiral:
Not a chiral carbon. Has two bonds to an oxygen.
1 chiral carbon
2 chiral carbon
3 chiral carbon
4 chiral carbon
Not a chiral carbon. Has bonds to two hydrogens.

This molecule is not chiral. There is no carbon with 4 different substituents.

Why do we care why things are chiral?
o Nature cares a lot. Molecules that are right-handed will not be recognized by an
enzyme if it was left-handed.
o Similarly: molecules that bind to hormone receptors, all kinds of situations in
biochemistry where chirality is critical.
o Drugs: right-handed drugs may be effective while left-handed drugs may have no effect
at all or even a bad effect.
Slide 7
Principle of the Three Point Landing:
 Slide shows a molecule and it’s mirror image (both have 4 different substituents)
 Suppose this molecule has to react with an enzyme or a receptor on the surface of the cell.
 Imagine dragging the first image to fit the dots (representing a receptor) on the bottom of the
slide. This sits down nicely on the receptor.
 There is no way to twist the mirror image to make it fit the receptor.
 This concept is called the “Principle of the Three Point Landing”
Slide 8
Geometric Formulas:
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Emil Fischer: Was around in the 1890s. Generally regarded as the father of carbohydrate
chemistry.
When talking about optical activity (and configuration of sugars), we need a way to illustrate it
conveniently.
Widely used in carbohydrate chemistry (for 100 years): Fischer convention.
Wedges represent substituents coming out of paper.
o (like hydroxyl group and hydrogen of 1st geometric formula)
Dotted line represents substituents going into the paper.
o (like aldehyde group and hydroxymethyl group of 1st geometric formula)
Mirror image of molecule is the image to the right.
With Fischer projections (a convention) the idea is that:
o Vertical lines correspond with dotted lines
On slide: Molecules to the left of the mirror plane are the same, and molecules on the right are
the same.
Students often don’t understand this concept:
o Although Fischer projections look the same as routine structural formulas seen in
organic chemistry, it is NOT the same.
o In organic chemistry, molecule could be rotated 90 degrees (put it on it’s side). This
can’t be done here. This rotation would produce a different molecule.
Slide 9
Absolute Configuration of Sugars:
 Another convention
 Some sugars are defined as L-sugars, and some as D-sugars
 Emil Fischer didn’t have powerful tools such as X-ray crystallography
 Fischer didn’t really know the configuration of glucose.
 Fischer broke down molecule step by step and figured out structure.
 Absolute configuration
o Refers to configuration of highest numbered asymmetric carbon
o Sugars are numbered:
1
2
3
4
5
6
o If hydroxyl group is on the right of the highest numbered asymmetric carbon (Carbon
#5 in this case), then the sugar is defined as D.

o Fischer decided: Any molecules with the same configuration of the highest numbered
asymmetric carbon as D-glyceraldehyde would be defined as D.
A naturally occurring molecule
Slide 10 and 11
Enantiomers and Diastereomers:
 When you have molecules with the same atoms attached to equivalent atoms of other molecules
but have different 3-D structures are called stereoisomers.
 2 different types of stereoisomers
o Enantiomers are mirror images
 Have almost identical chemical and physical properties and are difficult to
separate.
 If you were to go in the lab and make a simple molecule with a chiral carbon,
you would end up with about 50% D form and 50% L form. This is called a
racemic mixture.
 All chiral carbons are mirror images.
o Diastereomers (a stereoisomer that is not an enantiomer)
 Will have different chemical and physical properties.
 Will be able to be separated chromotographically.
 Have different solubilities and are on various chromatography columns.
 Similar structures but not mirror images.
Slide 12
Resolution of a Racemic Mixture:
 Enantiomers are difficult to separate and Louis Pasteur is the first person to separate a racemic
mixture.
 Seperation of a mixture of optical isomers is called resolution. (like resolving a racemic
mixture)
 Pasteur let tartaric acid crystallize and picked out left-handed crystals from right-handed
crystals. He dissolved them and found that one solution rotated the beam of light to the right
and the other solution rotated the light to the left.
 Pasteur had resolved a racemic mixture.
 He then found a better way by making derivatives of optically active compounds with another
optically active compound.
 Derivatives will almost always be diastereomers. (having different chemical and physical
properties) these are separated, then broken down to get the original molecule.
 This is what drug companies do. Almost every drug available today is optically active and can
be resolved various ways.

15 years ago many drugs were mixtures of D and L forms, but it turns out it is much more
effective to find which optical isomer is working and resolve the mixture.
Slide 13:
 Do not learn all of this slide.
 Slide has one main point: When there are several chiral carbons in a molecule, you get many
different combinations.
 With 6-membered sugars, (what we will be dealing with most of the time) you can get 8
different sugars. –these are just the D-sugars. You will also get the mirror images of these Dsugars (will be the L-Sugars). This gives you a total of 16 different hexoses.
 Although these hexoses look very similar, the body can tell them apart in a “flash”.
 We can use D-glucose, mannose, and galactose although they are used quite differently
 Most of the other sugars: If we ate them they would “go right through us” because we don’t
have the enzymes to handle them.
Slide 14
Lobry de Bruyn-van Ekenstein reaction:
 One of the reactions worth knowing so that you don’t do it.
 (Dilute Base) If you were to have a bottle of pure glucose dissolved in sodium carbonate, stir it
up and come back and analyze for different sugars, you won’t have D-glucose exclusively
anymore. You will have loads of mannose and fructose. (under alkaline conditions)
o What happens here is D-glucose can form the straight chain form and when the double
bond gets rearranged again the result is a mannose, fructose, or a glucose. (all changes
occurring in Carbon2) C2 epimerization. (Epimer differs only by the configuration of
one carbon)
 (Strong Base) Every one of the hydroxyl groups can epimerize. The result is a big mixture of
dozens of things.
Slide 15
Oxidation:
 A mild method for oxidizing things is bromine water. Put an aldose in bromine water and the
aldehyde group gets oxidized to an acid. This is referred to as an aldonic acid.
 Useful in the past for identifying whether the sugar was a ketose or an aldose because this
reaction doesn’t work in ketoses.
 This is another way to oxidize sugars: in an alkaline solution.
 In an alkaline solution the ketoses get oxidized too. Why?
o Because in alkaline solution ketoses can interconvert to aldoses and then they get
oxidized. This drives to equilibrium.
Slide 16
Another oxidation:
 A stronger oxidizing agent.
 Converts both the aldehyde group and hydroxymethyl group to an acid. These are called alderic
acids.
Slide 17
Reduction:

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A common reagent used is sodium borohydride
Turns the aldehyde group into an alcohol. Called an alditol
With a ketose, the hydroxyl group can then be on either side, producing two different alditols.
Slide 18
The Maillard Reaction:
 Responsible for the flavor of all kinds of interesting foods.
 When you heat up a sugar with an amino compound around (like an amino acid in proteins) the
sugar and the amino acid will react together forming a complex series of compounds and the
whole process is called the Maillard Reaction.
o Heat sugar up with butter = caramel
o Browning meat on BBQ is a Maillard Reaction
o Bread that is toasted brown is a Maillard Reaction.
o Sunless tanning lotion (active ingredient is a small 3-Carbon sugar called
dihydroxyacetone) Dihydroxyacetone reacts with amino groups of proteins on skin,
turning it brown (or tan).
Slide 19:
 Turns out: when you have an alcohol and an aldehyde, these can spontaneously react with each
other forming a hemiacetal.
o To recognize a hemiacetal structure, look for carbon with 2 oxygens on it, one of the
oxygens has to be hydroxyl.
 Notice there is no loss of water in this reaction.
 Sugars have alcohol and aldehyde groups in them. They can spontaneously fold up and make a
cyclic structure.
o Notice when this folding occurs, the hydroxyl group can be either below the plane of
the paper or above.
Slide 20:
 Hexagons with bold edges. Bold side means it is coming toward you, and the opposing side
going away from you.
o These are not flat structures, just represented that way.
 For the 1st 60 years after Fischer figured out the structure of glucose, everyone thought that
glucose looked like D-glucose (1st image on slide). It usually doesn’t. Most of the time
glucose occurs in a cyclic form.
 These are called Haworth projections.
 There really is no space in the “center” of a cyclic sugar molecule.
 6-membered ring is pyranose
Slide 21
Fischer Projection Formulas:
 Slide shows cyclic forms of Fischer projections.
Slide 22:
 Shows a more realistic cyclic structure.
 A space-filling model
Slide 23:

You can get the same type of reaction with ketoses as you do with aldoses.
Slide 24:
 This slide shows how you get Fructose.
 5-membered ring is furanose
 Point of slide is to show you rings can fold up in a couple different ways
o If it folds up with hydroxyl on C5- you get 6 membered ring (pyranose)
o If it folds up with hydroxyl on C4- you get a furanose.
 Both forms have an alpha and beta form. (can get 4 total different things)
Slide 25:
 Alpha form of D-Fructofuranose
Slide 26:
 Beta form of D-Fructofuranose
Slide 27:
 Shows a space-filling model of the Beta form
Slide 28:
 Shows pyranose and furanose again.
Slide 29
Anomeric Configurations:
 NOTE: if you draw sugars with Haworth projections, if the hydroxymethyl group is pointing
up, it is a D-sugar. (on this slide, the hydroxymethyl group is located on C5, both are pointing
up, so both are D-sugars)
 Alpha vs. Beta
o If hydroxyl group (on C2) is on opposite side as hydroxymethyl group, it is referred to
as alpha (alpha=opposite)
o If hydroxyl group (on C2) is on same side as hydroxymethyl group it is referred to as
beta
Slide 30
Anomeric Configurations continued:
 Positions refer to the relative positions, not whether it is up or down.
 Will be different in D verses L sugars.
Slide 31
Mutarotation:
 Should be familiar with this term
 If you were to have a fresh bottle of ά-D-glucose, make a solution of it, and stick it in a
polarimeter tube, and make it 1 gram per milliliter (for example). Measure the optical rotation
and you would start out getting a high optical rotation, about 112 degrees. If you let it sit
overnight or added a tiny bit of acid or base, you will see it convert to a lower optical rotation,
it would go down by half.
 Similarly, if you started with β-D-glucose, it would have a much lower optical rotation, then it
would gradually change to this, too.
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This is called mutorotation
Way it works: These sugars spend almost all their time in the cyclic form but can momentarily
form straight-chain sugars which can fold up either way.
At equilibrium, with glucose (is different with different sugars), you get about 1/3 of the alpha
and 2/3 of the beta, and only a trace of straight-chain.
Slide 32
Conformation of Cyclic Sugars:
 Configuration-how different substituents are linked to a carbon
 Conformation-how these things are folded
 Haworth Structure- This is a more modest way to express things. (used when they don’t really
know what the conformation is)
 Modern NMR techniques, however, allow you to easily tell what the conformation is.
 Top right molecule (conformational structure) is shown in a chair conformation.
o To get a better “feel” for this, get some ball-and-stick models so that you can actually
flip the molecule into the various positions.
o There are 2 possible chairs, 4 boats, 6 skews (twisting it), and 12 half-chairs.
 Sugars will almost always be in one form or another.
Slide 33
Major Sugar Residues of Mammalian Glycoconjugates:
 Glucose
 Mannose (glucose and mannose are very similar but vary at C2 configuration. Glucose’s
hydroxyl is below and mannose is above)
 Galactose (very similar to glucose except hydroxyl on C4 is different.)
 N-Acetylglucosamine (looks just like glucose except at C2 instead of a hydroxyl we have a NAcetyl group)
Slide 35
Honey:
 1st self-preserving sweetener. Was self-preserving because it only contains a little bit of water.
 High osmolarity keeps bacteria and molds from growing in it
 Honey is mainly fructose (and glucose).
Slide 36:
 Publishers of textbooks usually like to show fructose as a furanose but in honey the major form
of the fructose is this pyranose 6-membered ring.
Slide 37
Common Alditols:
 Recall: if you reduce sugars you get an alditol
 Reduce glucose you get glucitol (common name- Sorbitol)
 Reduce mannose you get mannitol (used in sugarless gum sometimes)
 Reduce xylose, you get xylitol (also used in sugarless gum)
 Glyceral is in all kinds of things we eat. (a sweet, sticky, gooey molecule)
 Inositol is an “honorary” sugar because there is no oxygen in the ring. Looks like a sugar and
has a lot of properties of sugars. (has a lot of hydroxyl groups)
Slide 38
Phytate:
 Phytate is an inositol that also has phosphates.
 Normal storage compound for phosphate in many grains and beans
 Humans lack the enzymne, phytase, which cleaves the phosphate. People can’t use this then.
 Cows can use this because their 1st stomach contains bacteria which cleave the phosphate.
 Pigs can’t cleave molecule, phosphate goes right through the pig. Same with chickens.
 Chicken/pig farms cause an environmental problem because all the phytate ends up in lakes and
streams.
 To solve this: some people genetically engineered pigs to secrete phytase in their saliva, so pigs
utilize phosphate in their seeds so extra phosphate doesn’t have to be added to the feed.
Slide 39:
 Recall: Hemiacetal formed by linking an alcohol and aldehyde.
 Hemiacetal is still fairly reactive. So hemiacetal can react with an alcohol and produce an
acetal.
o You know it is an acetal because you see a carbon with two oxygens linked to it, both
with some other substituent.
Slide 40
Sugar acetals are called glycosides:
 You can get sugars to form acetals.
o If you heat up glucose in methanol with a little acid catalyst, you can end up producing
methyl-glycosides.
Slide 41:
 This slide illustrates several different disaccharides. (we have been talking about
monosaccharides until now)
 Lactose- major sugar in milk (both human and cow)
 Maltose- breakdown product of starch
 Cellobiose- breakdown product of cellulose
 Sucrose- common table sugar. A glucose linked to a fructose.
o Sucrose fundamentally different from others.
Slide 42:
 Lactose is a galactose linked to a glucose. Linked head to tail. Reducing end is side with
HOH. This is a latent aldehyde. Can react and reduce things like metallic silver ion to silver
metal, or copper to copper I. This is called reducing.
 Sucrose is different from all the others because anomeric carbon of a glucose is being linked to
the anomeric carbon of fructose.
Slide 43:
 Disaccharide Amygdalin is responsible for the bitter taste of almonds and the pits of peaches.
Slide 44:
 Laetrile (several years ago it was thought to be an anticancer agent because the theory was that
glucose molecules could be taken out by cancer molecules and cyanide would poison the
cancer cell).
Slide 45:
 Interesting molecule because it happens from the natural breakdown of starch and it forms a
nice ring. Widely used to separate molecules chromatographically.
Slide 46:
 Mentioned because it is one of the few tetrasaccharides we have in our diet. Notice you have a
sucrose alpha linked to a galactose, alpha-linked to a glucose, alpha linked to another glucose.
 We don’t have alpha galactostachyase in our small intestine. We can’t digest this. This
molecule goes through our small intestine and ends up in the large intestine which is filled with
bacteria. The bacteria then start breaking it down, make carbon dioxide and hydrogen and
cause gas.
o In foods like beans, broccoli and onions, there is a lot of stachyose.
o Beano- a coffee bean that supposedly clips off the galactose in the small intestine,
leaving only sucrose, which can be easily digested.
Slide 47
Some Human Milk Oligosaccharides:
 Cow milk and human milk are different.
 One main difference is there are twenty oligosaccharides in human milk. (often 4-7 sugars
long). Cow milk doesn’t have these.
 What do oligosaccharides do in human milk?
o Not nutritional. May have 2-3 grams in urine per day. Also appear in urine in nursing
mothers. People suspect they play an important role of preventing colonization of GI
tract with pathogenic material. Structures of many of these are similar to structures on
the surface of many human pathogenic bacteria.
o Some companies synthesize these oligosaccharides and adds them to baby formula
Slide 48
Glycosyl Transferases and Sugar Nucleotides:
 In making oligosaccharides, you can’t make them enzymatically add a sugar to another sugar.
You must activate the sugar. (routinely activated by making sugar nucleotide)
o Example: UDP (contains Uricil (ribose), and a couple phosphates) linked to a galactose
(in this slide) Activated sugar can connect galactose and glucose to produce lactose.
Slide 49:
 Depending on the sugar there might be a different nucleotide involved. Usually it is UDP but
with Fucose and Mannose it is GDP and with Sialic Acid it is CMP.
Slide 50
Lactose Biosynthesis:
 Lactose synthase- a heterodimer of 2 proteins
o β-D-galactosyl transferase (Men and women have this) it catalyzes this reaction:
o ά-lactalbumin (lactating mammory gland) proteins called alpha-lactobumin is made and
binds to β-D-galactosyl transferase and changes it’s specificity. This is an example of a
modifier protein.
Slide 51
Lactose Degradation:
 How do you break down lactose?
 Almost all children have an enzyme called β-galactosidase in small intestine. Children can
breakdown lactose into galactose and glucose and then use them.
 As people get older, you make less and less β-galactosidase. Some people completely stop
making it. These people can’t break down lactose, so they become lactose-intolerant. Lactose
builds up and changes osmolarity of intestine. This produces bloating and gas (carbon dioxide
and hydrogen gas)
Slide 52:
 If people come from a familial history of consuming a lot of lactose, these groups are normally
lactose tolerant.
ARS question:
Glycoside is a sugar-acetal!