Transcript Chapter 7

Reginald H. Garrett
Charles M. Grisham
www.cengage.com/chemistry/garrett
Chapter 7
Carbohydrates and the
Glycoconjugates of Cell Surfaces
Reginald Garrett & Charles Grisham • University of Virginia
Outline
• How are carbohydrates named?
• What is the structure and chemistry of
monosaccharides?
• What is the structure and chemistry of
oligosaccharides?
• What is the structure and chemistry of
polysaccharides?
• What are glycoproteins, and how do they
function in cells?
• How do proteoglycans modulate processes in
cells and organisms?
• Do carbohydrates provide a structural code?
7.1 How Are Carbohydrates Named?
Carbohydrates are hydrates of carbon
with the general formula (CH2O)n
Carbohydrates are classified in three groups:
• Monosaccharides (simple sugars) - cannot be
broken down into simpler sugars under mild
conditions
• Oligosaccharides (oligo = "a few“) - usually 2 to
10 simple sugar residues
• Polysaccharides - polymers of the simple sugars
7.2 What Is the Structure and Chemistry
of Monsaccharides?
An organic chemistry review
• Aldoses and ketoses contain aldehyde and
ketone functions, respectively
• Triose, tetrose, etc. denotes number of carbons
• Aldoses with 3 or more carbon atoms and
ketoses with 4 or more carbon atoms are chiral
• Review Fischer projections and D,L system
7.2 What Is the Structure and Chemistry
of Monsaccharides?
Structure of a simple
aldose and a simple
ketose.
The Aldoses
The structure and
stereochemical
relationships of
D-aldoses with three
to six carbons. Know
the ones in the boxes
The Ketoses
The structure and
stereochemical relationships of
D-ketoses with three to six
carbons. Know the ones in the
boxes.
Cyclic monsaccharide structures and
anomeric forms
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Glucose (an aldose) can cyclize to form a cyclic
hemiacetal
Fructose (a ketose) can cyclize to form a cyclic
hemiketal
When hemiacetals and hemiketals are formed,
the carbonyl carbon atom becomes an
asymmetric center
Isomers of monosaccharides that differ only in
their configuration about that asymmetric carbon
are called anomers
Cyclic form of glucose is a pyranose
Cyclic form of fructose is a furanose
Monosaccharides Exist in Cyclic, Anomeric
Forms
7.2 What Is the Structure and Chemistry
of Monsaccharides?
Monosaccharides Can Be Converted to
Several Derivative Forms
• A variety of chemical and enzymatic reactions
produce derivatives of the simple sugars
• Some of the most common are:
• Sugar acids
• Sugar alcohols
• Deoxy sugars
• Sugar esters
• Amino sugars
• Acetals, ketals, and glycosides
Monosaccharide Derivatives
Reducing sugars are sugars with free anomeric
carbons - they will reduce oxidizing agents, such
as peroxide, ferricyanide and some metals (Cu2+
and Ag+).
These redox reactions oxidize the sugar to a
sugar acid.
Glucose is a reducing sugar - so these reactions
are the basis for diagnostic tests for blood sugar
Monosaccharides Can Be Converted to
Several Derivative Forms
More Monosaccharide Derivatives
• Sugar alcohols are formed by mild reduction of
sugars
• Deoxy sugars: constituents of DNA, etc.
• Sugar esters: phosphate esters like ATP are
important
• Amino sugars contain an amino group in place
of a hydroxyl group
• Acetals, ketals and glycosides: basis for oligoand polysaccharides
Sugar Alcohols
Deoxy Sugars
• Deoxy sugars are monosaccharides with one or more
hydroxyl groups replaced by hydrogens
• 2-Deoxy-D-ribose is a constituent of DNA
• Rhamnose is a component of ouabain, a toxic “cardiac
glycoside”
• Fucose is a component of some cell walls
Amino Sugars
• Sugars with an amino group at C-2 are amino sugars.
• They are found in many oligosaccharides and polysaccharides.
Muramic acid
Muramic acid is a component of the
polysaccharides of cell membranes
of higher organisms and also
bacterial cell walls.
Muramic acid is a glycosamine
linked to a 3-carbon acid at C-3.
(Murus is Latin for “wall”.)
Sialic acids
The N-acetyl and N-glycolyl derivatives of neuraminic acid are
known as sialic acids.
Acetals and Ketals
Acetals and ketals can be formed from hemiacetals and
hemiketals, respectively.
Glycosides
The pyranose and furanose forms
of monosaccharides react with
alcohols in dehydration synthesis
reactions to form glycosides, with
retention of the α- or βconfiguration at the C-1 carbon.
The new bond formed is called a
glycosidic bond.
7.3 What is the Structure and Chemistry
of Oligosaccharides?
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Disaccharides are the simplest oligosaccharides
Two monosaccharides linked by a glycosidic bond
Each unit in an oligosaccharide is termed a residue
Each of the structures in Figure 7.18 is a “mixed
acetal”, with one hydroxyl provided intramolecularly
and one hydroxyl from the other monosaccharide
• Each of these (except for sucrose) possesses one
free unsubstituted anomeric carbon, and is thus a
reducing sugar
• Sucrose is not a reducing sugar – it does not have a
free anomeric carbon
7.3 What is the Structure and Chemistry
of Oligosaccharides?
7.3 What is the Structure and Chemistry
of Oligosaccharides?
Know the important features
• Be able to identify anomeric carbons and
reducing and nonreducing ends
• Note carefully the nomenclature of links. Be
able to recognize alpha(1,4), beta(1,4)
linkages, etc., in structures.
7.4 What is the Structure and Chemistry
of Polysaccharides?
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Functions: storage, structure, recognition
Nomenclature for polysaccharides is based on
their composition and structure
Homopolysaccharide – a polysaccharide that
contains only one kind of monosaccharide
Heteropolysaccharide – a polysaccharide
made of several monosaccharides
Starch and glycogen are storage molecules
Chitin and cellulose are structural molecules
Cell surface polysaccharides are recognition
molecules
Starch
A plant storage polysaccharide
• Two forms: amylose and amylopectin
• Most starch is 10-30% amylose and 70-90%
amylopectin
• Branches in amylopectin every 12-30 residues
• Amylose has alpha(1,4) links, one reducing
end
• The branches in amylopectin are α(1→6).
Amylose and Amylopectin are energy
storage molecules in plants
The Structure of Amylose
• Amylose is poorly soluble
in water, but forms
micellar suspensions
• In these suspensions,
amylose is helical
• Iodine fits into the helices
to produce a blue color
Why Branching in Starch?
Consider the phosphorylase reaction
• Phosphorylase releases glucose-1-P products
from the amylose or amylopectin chains
• The more branches, the more sites for
phosphorylase attack
• Branches in amylopectin provide a mechanism
for quickly releasing (or storing) glucose units
for (or from) metabolism
The Phosphorylase Reaction Releases
Glucose Units for Metabolic Energy
Glycogen
The glucose storage device in animals
• Glycogen constitutes up to 10% of liver mass
and 1-2% of muscle mass
• Glycogen is stored energy for the organism
• Only difference from amylopectin: even more
highly branched
• Alpha(1,6) branches every 8-12 residues
• Like amylopectin, glycogen gives a red-violet
color with iodine
Structural Polysaccharides
• The composition of structural polysaccharides
is similar to storage polysaccharides
• But small structural differences greatly
influence properties
• Starch and glycogen linkages consist primarily
of α(1→4) linkages.
• Cellulose consists of β(1→4) linkages
Cellulose Provides Physical Structure and
Strength to Plants
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Cellulose is a structural polysaccharide
It is the most abundant natural polymer in the world
It is found in the cell walls of nearly all plants
The wood and bark of trees are insoluble, highly
organized structures formed from cellulose and lignin
• Cotton is almost pure cellulose
• Cotton acetates, made from the action of acetic
anhydride on cellulose, are used in dresses, lingerie,
and other clothing
The Structural Difference Between
Amylose and Cellulose
(a) Amylose prefers a helical conformation (due to its bent α(1→4) linkages.
(b) Cellulose, with β(1→4) linkages, can adopt a fully extended conformation.
The Structure of Cellulose
The structure of
cellulose,
showing the
hydrogen
bonds (blue)
between the
sheets, which
strengthen the
structure.
Intrachain Hbonds in red;
interchain Hbonds in
green.
Other Structural Polysaccharides
• Chitin – found in the exoskeletons of
crustaceans, insects and spiders, and cell
walls of fungi
• It is similar to cellulose, but C-2s are N-acetyl
• Cellulose strands are parallel; chitins can be
parallel or antiparallel
Structures of cellulose, chitin and mannan
Like cellulose, chitin and mannan form extended ribbons and pack
together efficiently, taking advantage of multiple hydrogen bonds.
Glycosaminoglycans – Linear Chains of
Repeating Disaccharides
Glycosaminoglycans are
linear chains of repeating
disaccharides in which
one unit is an amino sugar
and one or both is
negatively charged.
Functions of Glycosaminoglycans
• Heparin, with a very high negative charge, is a
natural anticoagulant.
• Hyaluronates (consisting of up to 25,000
disaccharide units) are components of the vitreous
humor of the eye and of synovial fluid, the lubricant
fluid of the body’s joints
• Chondroitins and keratan sulfate are found in
tendons, cartilage, and other connective tissue
• Dermatan sulfate is a component of the extracellular
matrix of skin
• Glycosaminoglycans are constituents of
proteoglycans (discussed later in this chapter)
Bacterial Cell Walls
Composed of 1 or 2 bilayers and peptidoglycan shell
• Gram-positive: One membrane phospholipid bilayer
and thick peptidoglycan outer shell
• Gram-negative: Two membrane phospholipid
bilayers with thin peptidoglycan shell in between
• Gram-positive: pentaglycine bridge connects
tetrapeptides
• Gram-negative: direct amide bond between
tetrapeptides
The Structure of Peptidoglycan
The Structure of Gram-positive
Peptidoglycan
The Cell Wall of Gram-positive Bacteria
The Cell Wall of Gram-negative Bacteria
Animals Display a Variety of Cell Surface
Polysaccharides
• Animal cell surfaces contain an incredible
diversity of glycoproteins and proteoglycans
• These polysaccharide structures regulate cellcell recognition and interaction
• The uniqueness of the "information" in these
structures is determined by the enzymes that
synthesize these polysaccharides
7.5 What Are Glycoproteins, and How Do
They Function in Cells?
• May be N-linked or O-linked
• N-linked saccharides are attached via the
amide nitrogens of asparagine residues
• O-linked saccharides are attached to
hydroxyl groups of serine, threonine or
hydroxylysine
The Structure of O-Linked Saccharides
O-linked Saccharides of Glycoproteins
The O-linked
saccharides
often adopt
extended
conformations
to lift the
functional
domains of
these proteins
above the
membrane
surface.
The Structure of N-Linked Saccharides
Figure 7.32 The carbohydrate moieties of glycoproteins may
be linked to the protein via asparagine residues (in N-linked
saccharides).
The Structure of N-Linked Saccharides
Figure 7.32 N-linked glycoproteins are of three types: high mannose,
complex, and hybrid, the latter of which combines structures found in the
high mannose and complex saccharides.
Functions of N-linked Oligosaccharides
Many functions known or suspected
• Oligosaccharides can alter the chemical and
physical properties of proteins
• Oligosaccharides can stabilize protein
conformations and/or protect against
proteolysis
• Cleavage of monosaccharide units from Nlinked glycoproteins in blood targets them for
degradation in the liver
Structures of Proteoglycans
Structure of rat cartilage matrix
proteoglycan. This molecule is highly
hydrated. Compression of cartilage (as in
walking) squeezes water out of the
cartilage tissue to cushion the joint.
Water is reabsorbed when the stress and
compression diminishes.
Lectins are proteins that bind carbohydrates with
high specificity and high affinity
Sugars are the “letters” of the sugar code. Lectins are the
translators of the sugar code. Many processes, such as cell
migration, cell-cell interactions, immune responses, and blood
clotting, depend on information transfer using this code.