Transcript SSM CH 07 - ::: 國立中正大學 National Chung Cheng

Chapter 7
Carbohydrates and the
Glycoconjugates of Cell Surfaces
Biochemistry
by
Reginald Garrett and Charles Grisham
Essential Question
• What is the structure, chemistry, and
biological function of carbohydrates?
• (CH2O)n or (C · H2O)n
• Breakdown of carbohydrates provides
energy.
• Glycolipids and glycoproteins are
glycoconjugates involved in recognition
between cell types or recognition of cellular
structures by other molecules.
Outlines
• 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?
7.1 – How Are Carbohydrates
Named?
Carbohydrates are hydrates of carbon.
• Monosaccharides (simple sugars) cannot
be broken down into simpler sugars
under mild conditions.
• Oligo = "a few" - usually 2 to 10
• Polysaccharides are 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 3C or more and ketoses with
4C or more are chiral.
• Review Fischer projections and D,L
system.
Stereochemistry Review
Read text on p. 204-207 carefully!
• D,L designation refers to the configuration
of the highest-numbered asymmetric center.
• D,L only refers the stereocenter of interest
back to D- and L-glyceraldehyde!
• D,L do not specify the sign of rotation of
plane-polarized light!
• All structures in Figures 7.2 and 7.3 are D.
• D-sugars predominate in nature.
More Stereochemistry
Know these definitions
•Stereoisomers that are mirror images of each
other are enantiomers.
•Pairs of isomers that have opposite
configurations at one or more chiral centers but
are NOT mirror images are diastereomers.
•Any 2 sugars in a row in Figures 7.2 and 7.3
are diastereomers.
•Two sugars that differ in configuration at only
one chiral center are epimers.
Cyclic monsaccharide structures
and anomeric forms
• Glucose (an aldose) can cyclize to form a
cyclic hemiacetal.
• Fructose (a ketose) can cyclize to form a
cyclic hemiketal.
• Cyclic form of glucose is mainly a
pyranose.
• Cyclic form of fructose is mainly a
furanose.
Cyclic monsaccharide structures
and anomeric forms
•Cyclic forms possess anomeric carbons.
•For D-sugars,  has OH down,  has OH up.
For L-sugars, the reverse is true.
•Mutarotation: The optical rotation of glucose
solution could change with time. It involves
interconversion of - and -D-glucose.
•[]D20 = 112.2 for -D-glucose
[]D20 = 18.7 for -D-glucose
Monosaccharide Derivatives
• Reducing sugars: sugars with free anomeric
carbons - they will reduce oxidizing agents, such
as peroxide, ferricyanide and certain metals
(Cu2+ and Ag+).
• Fehling’s reagent: CuSO4 (blue) + RC(=O)H 
Cu2O (red) + RCO2• Tollen’s reagent: Ag+  Ag0
• These redox reactions convert the sugar to a
sugar acid.
• Glucose is a reducing sugar --- so these
reactions are the basis for diagnostic tests for
blood sugar.
More Monosaccharide
Derivatives
• Sugar alcohols (alditols): sweet-tasting,
from 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
oligo- and poly-saccharides.
7.3 – What is the Structure and
Chemistry of Oligosaccharides?
It’s not important to memorize structures, but
you should know the important features.
• Be able to identify anomeric carbons and
reducing and nonreducing ends.
• Sucrose is NOT a reducing sugar.
• Browse the structures in Figure 7.19 and
Figure 7.20.
• Note carefully the nomenclature of links!
Be able to recognize (1,4), (1,4), etc.
7.4 – What is the Structure and
Chemistry of Polysaccharides?
Functions: storage, structure, recognition
• Nomenclature: homopolysaccharide vs.
heteropolysaccharide.
• Lower the osmotic pressure.
• Starch and glycogen are energy 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 7090% amylopectin.
• Amylose has (1,4) links and one
reducing end.
• Amylopectin has (1,6) branches in
every 12-30 residues.
Starch
• Amylose and amylopectin are poorly
soluble in water, but form micellar
suspensions.
• In these suspensions, amylose is helical
and iodine fits into the helices to
produce a blue color. Amylopectin
produces a red-violet color with I2.
• Salivary -amylase, an endoamylase, is
(14)-glucan 4-glucanhydrolase.
• -amylase is an exoamylase, cleaving
maltose units.
• (16)-glucosidase is required for
complete hydrolysis of amylopepctin.
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 provide a mechanism for quickly
releasing (or storing) glucose units for (or
from) metabolism.
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:
number of branches.
• (1,6) branches every 8-12 residues .
• Like amylopectin, glycogen gives a redviolet color with iodine.
• Hydrolyzed by -, -amylase, and
glycogen phosphorylase.
Dextrans
A small but significant difference from starch and
glycogen.
• If you change the main linkages between
glucose from (1,4) to (1,6), you get a new
family of polysaccharides – dextrans.
• Branches can be (1,2), (1,3), or (1,4).
• Dextrans formed by bacteria are components of
dental plaque.
• Cross-linked dextrans are used as "Sephadex"
gels in column chromatography.
• These gels are up to 98% water!
Structural Polysaccharides
Composition similar to storage polysaccharides,
but small structural differences greatly
influence properties.
• Cellulose is the most abundant natural polymer
on earth.
• Cellulose is the principal strength and support
of trees and plants .
• Cellulose can also be soft and fuzzy - in cotton.
Other Structural Polysaccharides
• Chitin - exoskeletons of crustaceans, insects
and spiders, and cell walls of fungi.
– similar to cellulose, but C-2s are N-acetyl
– cellulose strands are parallel, chitins can be
parallel or antiparallel.
• Alginates – Ca2+-binding polymers in algae.
• Agarose and agaropectin - galactose
polymers
• Glycosaminoglycans - repeating
disaccharides with amino sugars and
negative charges.
Bacterial Cell Walls
Composed of 1 or 2 bilayers and peptidoglycan shell
• To resist high internal osmotic pressure, to
maintain cell shape and size of bacteria.
• Gram-positive: One bilayer and thick
peptidoglycan outer shell.
• Gram-negative: Two bilayers with thin
peptidoglycan shell in between .
• Gram-positive: pentaglycine bridge connects
tetrapeptides.
• Gram-negative: direct amide bond between
tetrapeptides.
More Notes on Cell Walls
• Note the -carboxy linkage of isoglutamate
in the tetrapeptide
• Peptidoglycan is called murein - from Latin
"murus", for wall
• Gram-negative cells are hairy! Note the
lipopolysaccharide "hair" in Figures 7.35
and 7.36.
Cell Surface Polysaccharides
•
•
•
•
A host of important functions!
Animal cell surfaces contain an incredible diversity
of glycoproteins (on the dell surface) and
proteoglycans (in the extracellular matrix).
In glass dishes, heart myocytes “beat” and liver
cells avoid contact with kidney cells. Cancer cells
grow without contact inhibition.
These polysaccharide structures regulate cell-cell
recognition and interaction. They contain several
points for linkage (-OH) and are more informative
than linear proteins and nucleic acids.
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?
Many structures and functions!
• 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.
• See structures in Figure 7.39
O-linked Saccharides of
Glycoproteins
• Function in many cases is to adopt an
extended and relatively rigid conformation.
• These extended conformations resemble
"bristle brushes“.
• Bristle brush structure extends functional
domains up out of the glycocalyx.
• See Figure 7.40
N-linked Oligosaccharides
Many functions known or suspected
• N-glycosylation of proteins can alter the chemical
and physical properties of proteins, altering
solubility, mass, and electrical charges.
• N-linked oligosaccharide moieties can (1) stabilize
protein conformations, (2) protect against
proteolysis and (3) promote correct folding of
certain globular proteins (p. 239).
• Cleavage of monosaccharide units from N-linked
glycoproteins in blood targets them for degradation
in the liver. - see pages 238, 239
7.6 - Proteoglycans
--- Glycoproteins whose carbohydrates are
mostly glycosaminoglycans.
• Components of the cell membrane and
glycocalyx.
• Consist of proteins with one or two types
of glycosaminoglycan.
• See structures, Figure 7.44
7.6 – How Do Proteoglycans Modulate
Processes in Cells and Organisms?
• Proteoglycans are glycoproteins whose
carbohydrate moieties are predominantly
glycosaminoglycans.
• Example: syndecan - transmembrane protein inside domain interacts with cytoskeleton, outside
domain interacts with fibronectin.
• Highly sulfated glycosaminoglycans bind specific
proteins (e.g. fibronectin) at sites containing basic
amino acid residues. (charge interactions)
• A particular pentasaccharide sequence in heparin
finds to antithrombin III. (sequence-specific)
Proteoglycan Functions
• Modulation of cell growth processes
– Binding of growth factor proteins by
proteoglycans in the glycocalyx provides a
reservoir of growth factors at the cell surface.
• Cushioning in joints
– Cartilage matrix proteoglycans absorb large
amounts of water. During joint movement,
cartilage is compressed, expelling water!