Transcript Carbohydrates

Carbohydrates
Chapter 8
Carbohydrates
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Of the macromolecules that we will cover
in this class, those involving carbohydrates
are the most abundant in nature.
Via photosynthesis, over 100 billion metric
tons of CO2 and H2O are converted into
cellulose and other plant products.
The term carbohydrate is a generic one
that refers primarily to carbon-containing
compounds that contain hydroxyl, keto, or
aldehydic functionalities.
Carbohydrates can range in sizes, from
simple monosaccharides (sugars) to
oligosaccharides, to polysaccharides.
Carbohydrates
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Carbohydrates constitute more than 1/2 of organic molecules
Main role of carbos in nature
 Storage of energy
 Structural support
 Lipid and protein modification:
 membranes asymmetry, recognition by IgG/fertilization/virus
recognition/cell cell communication
Definition: Carbohydrates, Sugars and Saccharides- are all polyhydroxy
 (at least 2 OH) Cn(H20) n = hydrate of carbon
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Notice that there are two distinct types of monosaccharides, ketoses and
aldoses.
The number of carbons is important in general nomenclature (triose = 3,
pentose = 5, hexose =6,
Basic facts
Monosaccharides - Simple sugars
 Single polyhydroxyl
 Can’t be hydrolyzed to simpler form
Trioses - Smallest monosaccharides have three carbon atoms
Tetroses (4C) Pentose (5C) Hexoses (6C) Heptoses (7C) etc…
Disaccharide - two sugars linked together. Can be the same
molecule or two different sugars. Attached together via a
glycosidic linkage
Oligosaccharide - 2 to 6 monosaccharides
Polysaccharides - straight or branched long chain
monosaccharides. Bonded together by glycosidic linkages
The functional groups
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Aldehyde: Consists of a carbon atom
bonded to a hydrogen atom and doublebonded to an oxygen atom.
– Polar. Oxygen, more electronegative than carbon, pulls
the electrons in the carbon-oxygen bond towards
itself, creating an electron deficiency at the carbon
atom.
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Ketone: Characterized
by a carbonyl group
(O=C) linked to two other carbon atoms or a
chemical compound that contains a carbonyl
group
– A carbonyl carbon bonded to two carbon atoms
distinguishes ketones from carboxylic acids, aldehydes,
esters, amides, and other oxygen-containing compounds
Classification of monosaccharides
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Monosaccharides are classified according to
three different characteristics:
– the placement of its carbonyl group,
– the number of carbon atoms it contains
– its chiral handedness.
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If the carbonyl group is an aldehyde, the
monosaccharide is an aldose
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if the carbonyl group is a ketone, the
monosaccharide is a ketose.
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Monosaccharides with three carbon atoms
are called trioses, those with four are
called tetroses, five are called pentoses, six
are hexoses, and so on.
These two systems of classification are
often combined.
– For example, glucose is
an aldohexose (a six-carbon aldehyde)
carbonyl group
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A functional group composed of
a carbon atom double-bonded to
an oxygen atom: C=O.
The term carbonyl can also
refer to carbon monoxide as
a ligand in
an inorganic or organometallic
complex.
Classification of monosaccharides
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D-glucose
is an aldohexose with the formula
(C·H2O)6.
The red atoms highlight the
aldehyde group
the blue atoms highlight the
asymmetric center furthest from the
aldehyde; because this -OH is on the
right of the Fischer projection, this
is a D sugar.
Classification of monosaccharides
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The α and β anomers of glucose.
Note the position of the hydroxyl
group (red or green) on the anomeric
carbon relative to the CH2OH group
bound to carbon 5:
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Either on the opposite sides (α)
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Or the same side (β).
Steriochemistry
- optically active molecules
D or L as designated by furthest asymmetric carbon
from ketone or aldehyde
optical activity is independent of D or L designation D(-)
fructose
Increase in number of carbons increase possible
stereoisomers: Van’t Hoff’s Rule: A compound with n
asymmetric C atoms has a maximum of 2n possible
stereoisomers
Enantiomers: Stereoisomers that are non superimposable mirror
images
ex. L and D forms of sugars D-glyceraldehyde and Lglyceraldehyde
Chirality in Monosaccharides
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Most simple monosaccharides
have at least one chiral
center. As in the case of
amino acids, sugars are given
D or L designations based on
their similarity with D or L
glyceraldehyde (shown on
left).
Since some sugars contain
many chiral centers, it is
necessary to designate one
chiral center that will act as
the reference. This chiral
center is designated as the
one that is most distant from
the carbon that bears the
carbonyl functionality.
Chirality in Monosaccharides
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Sugars are frequently written as
Fischer projections. Remember that
atoms that lie on horizontal bonds
are projecting towards you, while
those on vertical bonds are
projecting away from you.
Compare the top and bottom
structures for glyceraldehyde.
The numbering of carbons in sugars
begins at the end of the chain that
is closer to the carbonyl
functionality.
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If the carbonyl group is an aldehyde
the sugar is an aldose.
Arrows indicate Sterochemical
relationships
Configuration around C2 (red)
distinguishes the members of each
pair of monosaccharides
Most common aldoses:
– D-Ribose (Rib)
– D-Glucose (Glc)
– D-Mannose (Man)
– D-Galactose (Gal)
– D-Xylose (Xyl)
– D-Arabinose (Ara)
ALL BASED ON THE STRUCTURE
OF GLYCERALDEHYDE
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If the carbonyl group is an ketone
the sugar is an ketose
Arrows indicate Sterochemical
relationships
Configuration around C3 (red)
distinguishes the members of each
pair of monosaccharides
Most common Ketoses:
– D-Fructose (Fru)
– D-Ribulose (Rib)
ALL BASED ON THE STRUCTURE
OF Dihydroxyacetone
Epimers
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Epimers are two sugars that differ only in the
configuration around one carbon atom of their
structures.
D-Mannose differs from D-glucose only in its
configuration around carbon 2.
D-Galactose differs from D-glucose only in its
configuration around carbon 4.
D-Galactose and D-Mannose are not epimers.
Conformational Structures
Emil Fisher - Nobel Prize 1891
Organic chemist who found the
structure of D glucose
Fisher projections - place most
oxidized carbon on top
Haworth Structures: carbons
counted from anomeric C to
clockwise from the oxygen in the
ring (pyranose) or the #2 C for
furanose
– OH in down position - a form
– OH in up position - ß form
Cyclization of Monosaccharides
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Carbohydrates of four carbons and more are found
in cyclic forms. How?
Aldehydes and ketones react reversibly with -OH on
sugars
5 or 6 carbon rings most stable
 4 carbon membered ring furan - ribose
 5 carbon membered ring pyran - glucose
- straight chains form hemiacetals and hemi ketals
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Carbohydrates of four carbons and more are found in cyclic forms
How?
C=O at reference carbon is reduced to OH
Formation of ring structure leads to an additional chiral carbon
(anomeric carbon) This is the number one carbon in the pyranose
structures, #2 for the furanoses
Cyclization of Monosaccharides
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In hexoses, an attack of the
hydroxyl group at C-5 onto
the aldehyde functionality
generates a cyclic structure
containing six substituents.
One of the substituents is an
oxygen, which acted as the
nucleophile in the reaction.
Cyclization of Monosaccharides
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Notice that two different
stereochemical outcomes are
possible, at the new chiral center
that is generated (the
hemiacetal).
The hydroxyl group can be on the
same side (cis) of the ring as the
CH2OH moiety (beta
configuration), or it can be on
the opposite side (trans) of the
ring as the CH2OH moiety (alpha
configuration).
Notice the formal names for
each of the two possible
configurations.
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D sugar ring structures
form and reform so there is
an intra-conversion between
the a and ß form. This is
called mutarotation.
Mutorotation occurs
spontaneously or with the
help of an enzyme
(generally called a mutase)
The hemi groups are
ordinarily unstable and
revert back to the straight
chain form
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In solution: D-glucose (0.02%) a-D Glucopyranoside (37%) and ß-D
glucopyranoside (64%) less than 1% of the furans
pyranose and furanose are the basis for nomenclature; glucose
refers to the mixtures of the different forms.
Beta form - OH above plane of ring
Alpha form - OH below plane of ring
Reactions of monosaccharides
Reducing sugars - a reduction reaction at the aldehyde or ketone groups of the
sugar molecules. As sugar is being oxidized, something else is being
reduced:
Only those anomeric carbons that can mutorotate are available for
reduction. ie. disaccarides only contain 1 reducing sugar
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Formation of a carboxylic acid from an aldehyde
is a 2-electron oxidation.
Notice that the sugar acts as the reductant of
copper. Copper is reduced from the +2 state to
the +1 state; however, the sugar is oxidized by 2
electrons.
In the presence of Benedict’s reagent (sodium
citrate, sodium carbonate, and copper sulfate,
reducing sugars will produce a brick-red
precipitate of cuprous oxide.
There are enzymatic methods that can be used to
quantify reducing sugars such as glucose, which
forms the basis of blood sugar detection by
diabetics.
Reactions of monosaccharides
Phosphorylation
- can form
anhydride phosphoester bond.
phosphorylation alters ionic
character.
– Locks molecule in cell.
– Nucleotides are
phosphorylated (ATP, GTP…)
Reactions of monosaccharides
Deoxy sugars
- without oxygen common case ribose RNA vs. DNA
Reactions of monosaccharides
Amino sugars - Sugars with OH replaced by NH2. Amination usually occurs at
C2 and often is acetylated
Glycosaminoglycans both amino and sulfated sugars.
Heparin inhibits action of thrombin in blood clotting
- sugars as this will often have added C chains (acylated), sulfur groups
(sulfanated) and aminated
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Important monosaccharides
Glucose - preferred source of energy for brain cells and
cells without mitochondria
Fructose - ketose, 2x as sweet as sucrose. Sperm use
this as major sugar/energy source for motility
Galactose - important for lacotose and glycolipid
production
 galactosemia - genetic disorder in galactose
metabolism leads to accumulation of galactose-1phosphate in liver results in liver damage. Another
version of the disease results due to lack of
galactose metabolism. Galactose concentration
builds up in blood leading to cataracts.
- Can result in severe mental retardation.
Identification and galactose free diet helps
Modification of monosaccharides
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A uronic acid is a sugar acid with both a
carbonyl and a carboxylic acid function.
It is best thought of as a sugar in which the
terminal carbon's hydroxyl function has been
oxidized to a carboxylic acid
Some of these compounds
biochemical functions; for
wastes in the human body
urine as their glucuronate
have important
example, many
are excreted in the
salts
D-glucose
Yes – peeing on plants is good for them!!!!!!!!!
a-D-glucuronic acid
Disaccharide Nomenclature
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When named, structures are considered to have
their reducing ends on the right. Locate the
reducing ends of the structures on the left if
appropriate.
The configuration of the anomeric carbon joining
the first monosaccharide unit to the second is
given (reading left to right).
The non-reducing residue is named, and five-and
six-membered ring structures are distinguished
by using “furano” or “pyrano” prefixes.
Non-reducing disaccharides are named as glycosides rather than
glycoses. Note that a double-headed arrow is used to denote sugars
that are joined by their anomeric carbons, AND, it is necessary to
specifiy the stereochemistry at both anomeric carbons.
Disaccharide Nomenclature
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The two carbons joined by the glycosidic bond
are indicated in parentheses, with an arrow
connecting the two numbers.
The second residue is then named.
If there are subsequent residues, the
subsequent glycosidic bonds are described by the
same conventions.
Non-reducing disaccharides are named as glycosides rather than
glycoses. Note that a double-headed arrow is used to denote sugars
that are joined by their anomeric carbons, AND, it is necessary to
specifiy the stereochemistry at both anomeric carbons.
Important Disaccharides
– sucrose = table sugar - glucose and fructose
(alpha linkage)
– lactose = milk sugar - galactose and glucose
(beta linkage)
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Maltose - malt sugar, from breakdown of
starch - 2 glucoses
Lactose intolerance
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inability to metabolize lactose
lack of the required enzyme lactase in
the digestive system.
estimated that 75% of adults worldwide
show some decrease in lactase activity
during adulthood.
The frequency of decreased lactase
activity ranges from as little as 5% in
northern Europe, up to 71% for Sicily,
to more than 90% in some African and
Asian countries
Lactose intolerance
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Disaccharides cannot be absorbed
through the wall of the small intestine
into the bloodstream
so in the absence of lactase
lactose present in ingested dairy products
remains uncleaved and passes intact into
the colon.
Remember that there are bacteria in
the human digestive system!
Remember the LAC operon?
Lactase
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Part of the β-galactosidase family of enzymes, is a glycoside hydrolase
involved in the hydrolysis of the disaccharide lactose into
constituent galactose and glucose monomers.
Lactase is present predominantly along the brush border membrane of
the differentiated enterocytes lining the villi of the small intestine.
The LAC operon
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beta-galactosidase:
This enzyme hydrolyzes the bond
between the two sugars, glucose and
galactose.
It is coded for by the gene LacZ.
Lactose Permease:
This enzyme spans the cell membrane and
brings lactose into the cell from the
outside environment. The membrane is
otherwise essentially impermeable to
lactose. It is coded for by the gene LacY.
Thiogalactoside transacetylase:
The function of this enzyme is not
known. It is coded for by the gene LacA.
Lactose intolerance
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The operons of enteric bacteria quickly
switch over to lactose metabolism, and
results in in vivo fermentation.
– produces copious amounts of gas (a
mixture of hydrogen, carbon dioxide,
and methane).
This, in turn, may cause a range of
abdominal symptoms, including
stomach cramps, nausea, bloating, acid
reflux and flatulence.
In addition, as with other unabsorbed
sugars (such as sorbitol, mannitol,
and xylitol), the presence of lactose and
its fermentation products raises
the osmotic pressure of the
colon contents.
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Symptoms
Lactose intolerance
Abdominal bloating
Abdominal cramps
Diarrhea
Floating stools
Foul-smelling stools
Gas (flatulence)
Malnutrition
Nausea
Slow growth
Weight loss
Lactose intolerance
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Most people with low lactase levels can tolerate 2
- 4 ounces of milk at one time (up to one-half
cup). Larger (8 oz.) servings may cause problems
for people with some amount of milk intolerance.
These milk products may be easier to
digest:
Buttermilk and cheeses (they have less lactose than
milk)
Fermented milk products, such as yogurt
Goat's milk (but drink it with meals, and make sure
it is supplemented with essential amino acids and
vitamins if you give it to children)
Ice cream, milkshakes, and aged or hard cheeses
Lactose-free milk and milk products
Lactase-treated cow's milk for older children and
adults
Soy formulas for infants younger than 2 years
Soy or rice milk for toddlers
Sucralose
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zero-calorie artificial sweetener
Approximately 600 times as sweet as sucrose
It is stable under heat and over a broad range
of pH conditions
Belongs to a class of compounds known
as organochlorides (or chlorocarbons). Some
organochlorides, particularly those that
accumulate in fatty tissues, are toxic to plants
or animals, including humans.
Sucralose, however, is not known to be toxic in
small quantities and is extremely insoluble in
fat; it cannot accumulate in fat like
chlorinated hydrocarbons.
In addition, sucralose does not break down or
dechlorinate
Sucralose
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Some concern has been raised about the
effect of sucralose on the thymus.
Two studies on rats, both of which found
"a significant decrease in mean thymus
weight" at high doses.
The sucralose dose which caused the
effects was 3000 mg/kg/day for 28 days.
For a 150 lb (68.2 kg) human, this would
mean an intake of nearly 205 grams of
sucralose a day, which is equivalent to
more than 17,200 individual Splenda
packets/day for approximately one month
Important Polysaccharides:
Starch - energy
reservoir in plants made of two
polysaccharides
Amylose -long
unbranched glucose a
(1,4) with open
reducing end large
tight helical forms.
Test by iodination..
Important Polysaccharides:
Starch - energy reservoir in plants - made of two polysaccharides
– Amylose -long unbranched glucose a (1,4) with open reducing end large
tight helical forms. Test by iodination.
– Amylopectin - polymer of a(1,4) and a (1,6) branches. Not helical.
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Glycogen - storage of carbohydrates in vertebrates greatest
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Similar to amylopectin with more branch points - takes up less
space
conc. in muscles and liver.
Cellulose
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Linear glucan chains of
unbranched (1-4)-b-linkedD-glucose in which every
other glucose residue is
rotated 180° with respect to
its two neighbors and
contrasts with other glucan
polymers such as:
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starch (1-4-a-glucan)
callose (1-3-b-glucan).
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Cellulose
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This means that cellobiose, and not glucose, is the basic repeating
unit of the cellulose molecule. Groups of 30 to 40 of these chains
laterally hydrogen-bond to form crystalline or para-crystalline
microfibrils.
Chitin
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Chitin is a linear homopolysaccharide composed of Nacetylglucosamine residues in b linkages.
Chitin differs chemically from cellulose only in the acetylated amino
substituent at carbon 2.
It forms extended fibers that are similar to those of cellulose, and
is found principally in hard exoskeletons of arthropods.
Also occurs naturally in both parallel and antiparallel stacking
arrangements.
Glycoproteins
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proteins that contain oligosaccharide chains covalently
attached to polypeptide side-chains.
The carbohydrate is attached to the protein in
a cotranslational or posttranslational modification. This
process is known as glycosylation.
– In proteins that have segments extending extracellularly,
the extracellular segments are often glycosylated.
Glycoproteins are often important integral membrane
proteins, where they play a role in cell-cell interactions.
Glycoproteins also occur in the cytosol, but their functions
and the pathways producing these modifications in this
compartment are less well-understood
Glycoproteins
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There are two types of glycoproteins:
In N-glycosylation , the addition of
sugar chains can happen at the amide
nitrogen on the side chain
of asparagine.
In O-glycosylation, the addition of
sugar chains can happen on
the hydroxyl oxygen on the side chain
of hydroxylysine, hydroxyproline, serin
e, or threonine.
asparagine
hydroxyproline
Glycoproteins
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The principal sugars found in
human glycoproteins
β-D-Glucose
Glc
β-D-Galactose
Gal
β-D-Mannose
Man
α-L-Fucose
Fuc
N-Acetylgalactosamine GalNAc
N-Acetylglucosamine GlcNAc
N-Acetylneuraminic acid NeuNAc
Xylose
Xyl
Glycoproteins
examples of glycoproteins found in the body
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Mucins
secreted in the mucus of the respiratory and
digestive tracts. The sugars attached to
mucins give them considerable water-holding
capacity and also make them resistant
to proteolysis by digestive enzymes.
In the immune system
white blood cell recognition molecules such
as antibodies which interact directly
with antigens
molecules of the major histocompatibility
complex (or MHC), which are expressed on
the surface of cells and interact with T
cells as part of the adaptive immune response.
examples of glycoproteins found in the body
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glycoprotein IIb/IIIa
– an integrin found on platelets that is
required for normal platelet aggregation
and adherence to the endothelium.
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The zona pellucida
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which surrounds the oocyte, and is
important for sperm-egg interaction.
connective tissue.
– These help bind together the fibers,
cells, and ground substance
of connective tissue. They may also
help components of the tissue bind to
inorganic substances, such
as calcium in bone.
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Glycoprotein-41 (gp41) and
glycoprotein-120 (gp120)
– HIV viral coat proteins.
examples of glycoproteins found in the body
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Hormones that are glycoproteins include:
Follicle-stimulating hormone
– Stimulates the follicle to produce
estrogen
Luteinizing hormone
– Stimulates the corpus leuteum to
produce progesterone.
Thyroid-stimulating hormone
Human chorionic gonadotropin
– maintains the corpus luteum and
allows the production of
progesterone and estrogen until the
placenta takes over this task
The End.
Any Questions?