BIOC2600 Study Guide - Carbohydrates and Glycobiology

Carbohydrates and Glycobiology
 a single polyhydroxyl aldehyde or ketone unit
 the most abundant naturally-occurring monosaccharide is D-glucose/ dextrose (D-form of
Oligosaccharides (oligo refers to few, scanty in Greek)
 Short chains or monosaccharide units/ residues joined by glycosidic linkages
 The most abundant naturally-occurring form is disaccharide Sucrose: D- glucose + D-fructose
In cells, most oligosaccharides consisting of three or more units joined to non-sugar molecules
(lipids or proteins) to form glycoconjugates instead of occurring as free entities
 Sugar residues > 20
Cellulose VS Glycogen:
o Both have the same monomer of D-glucose
o However, the D-glucose residues are bonded with different types of glycosidic linkages →
different properties → different biological roles
Stereospecificity of monosaccharides (reaction mechanism only generates one specific stereoisomer)
o The C atoms to which the hydroxyl groups attach to are chiral centres
o Stereoisomerism is biologically significant because the enzymes acting on these stereoisomeric
monosaccharides are also stereoisomeric in nature
Nomenclature of monosaccharides:
Chemical nature:
o Aldehydes→ aldose
o Ketones→ ketose
 `Simplest monosaccharides: glyceraldehyde and dihydroxylacetone (triose that are functional
group isomers)
 Food for thought: why is the simplest triose instead of ‘diose’? Since ketones must have at least
2 Cs
The number of C atoms in the backbone
Stereoisomerism of monosaccharides:
 Enantiomerism at the reference Carbon
Reference carbon: the chiral carbon most distant from the carbonyl carbon
–OH located on the R.H.S of reference C in Fischer projection → D (dextro)
–OH located on the L.H.S of reference C in the Fischer projection→ L (levo)
By natural selection, most of the hexoses of living organisms are D isomers
 Epimers (Diastereomer)
o Two sugars that only differ in configuration around one
chiral carbon atom
D-glucose and D-mannose are epimers at C-2
D-glucose and D-galactose are epimers at C-4
Remarks: Sugars with configurations only different at the reference carbon → L/D Enantiomers.
Sugars that only differ in configuration at one chiral carbon atom → Epimers
Naming of Ketoses:
o For 4/5 carbon ketoses, they are named by inserting ‘ul’ into the name of the corresponding aldose
Triose, tetrose, pentose, hexose
Triulose, tetrulose, pentulose, hexulose
Cyclization of monosaccharides:
o Enantiomeric at the anomeric carbon:
● Alpha-anomes: the –OH attached to the anomeric C is opposite to the the C-6
● Beta-anomers: the –OH attached to the anomeric C is on the same side as the C-6
o Six-membered ring compounds are called pyranoses as they resemble pyran
o Five-membered ring compounds are called furanoses
o Mutarotation:
● The ring opens briefly to the linear form so that the two anomeric forms can
● Equilibrium mixture: 1/3 alpha anomer, 2/3 beta anomer, very small amount of linear
form and glucofuranose (glucose with five-membered ring)
● Food for thought: why is the ratio of alpha anomers and beta anomers = 1:2? Reason:
Hexose Derivatives:
 Substitution
 Substitution of hydroxyl group at C-2 of glucosamine, galactosamine and mannosamine by amino
group that is commonly condensed with acetic acid (N-acetyl)- “……”
Glucosamine is part of the many structural polymers, including bacterial cell walls
Substitution of –OH with H at the C-6 of L-galactose → L-fucose
(found in complex oligosaccharide components of glycoproteins and glycolipids)
Substitution of –OH with H at the C-6 of L-mannose → L-rhamnose
(found in plant polysaccharides)
 Oxidation of Hexose into acids (aldehyde/alcohol group)
 Oxidation of aldose’s carbonyl C to carboxylic forms aldonic acids (glucose→ gluconic acid)
(used as innocuous counterion when administering cations in medicine)
Oxidation of –OH group at the C-6 (terminal carbon) of glucose, galactose and mannose form
corresponding uronic acid (glucuronic acid, galacturonic acid, mannuronic acid)
These acids form intramolecular esters (with adjacent –OH) called lactones
NB: Aldonic acids themselves cannot be cyclic, they can only be cyclic after becoming lactones (intramolecularly esterified)
 Sialic acids (mostly referred as N-acetylneuraminic acid)
o Generic names of the N-, O- substituted neuraminic acid (nine-carbon back bone)
 Sialic acid occurs in many glycoproteins and glycolipids on animal cell surfaces, providing sites of
recognition by other cells or extracellular carbohydrate- binding proteins
 Phosphorylated Sugars (intermediate in synthesis and metabolism of carbohydrates)
 Phosphoric acid forms phosphate ester with one hydroxyl group of a sugar (e.g. glucose-6-phosphate)
One function is to trap sugar within the cell for respiration because most cells do not have plasma
membrane transporters for phosphorylated sugars
Phosphorylation also activates sugar for subsequent chemical transformation
Reducing Properties of Monosaccharides:
Prerequisite: a. Able to interconvert between cyclized state and open ring form
b. Is an aldose (ketose as ketones cannot be further oxidized/act as reducing agent)
Fehling’s reaction: monosaccharides are able to reduce mild oxidizing agent cupric ion (Cu2+) while being
oxidized to be aldonic acids
Glycosidic bonding
i. O- glycosidic bond
o Anomeric carbon condensed with a hydroxyl group of another sugar molecule, typically in
cyclic form
o Hemiacetal (the anomeric carbon) + alcohol (from another sugar molecule) → acetal
o Hydrolysed in acidic but not basic conditions
ii. N-glycosyl bonds
o The anomeric carbon condenses with a nitrogen atom in glycoproteins and nucleotides
 Naming of disaccharides
1) Arrange the disaccharide such that the non-reducing end is on the left.
2) Give the configuration at the anomeric carbon joining the first monosaccharide unit to the
3) Name the D/L enantiomerism succeeding the anomeric configuration, then the reducing
residue. Add ‘furano’ for five membered ring and ‘pyrano’ for 6-membered rings. Change
the suffix of the non-reducing residue to ‘syl’
4) Indicate in parenthesis the 2 carbon atoms involved in the glycosidic bond with an arrow
connecting the two numbers
5) Name the reducing residue in the same fashion as its counterpart
● Food for thought: why isn’t the reducing residue named for its configuration around
the anomeric Carbon? Reason: because the reducing residue can undergo
mutarotation, the reducing end can interconvert between the α and β configuration.
Therefore, there is no need to distinguish it; the parenthesis is essentially a mirror
with the double-headed arrow serving as the plane of symmetry; for disaccharides
with no reducing ends, replace the suffix with ‘side’.
Examples of Disaccharides
1. Maltose
o α−D-glucopyranosyl-(1→4) - D-glucopyranose / Glc (α1→4) Glc
o Reducing
2. Lactose
o β-D-galactospyranosyl-(1→4) -D-glucopyranose/ Gal (β1→4) Glc
o Reducing in nature
o Occurs naturally in milk, gives milk the taste of sweetness
o Lactase digests lactose by hydrolyzes the (β1→4) bond into galactose and glucose which
is absorbed from the small intestines
o In lactose-intolerant individuals (where lactase is missing), the undigested lactose passes
into the large intestines. The osmolarity increases owing to the dissolved lactose which
opposes the absorption of water from the large intestines into the bloodstream. As a result,
watery, loose stools are formed. In addition, fermentation (anaerobic respiration) of the
lactose by the intestinal bacteria produces large volumes of CO2 which leads to the
bloating, cramps and gas.
3. Sucrose
o β-D-fructofuranosyl α−D-glucopyranoside/ Glu(α1←➔2β) Fru/ Fru (2β←➔1α) Glu
o Non-reducing in nature, because both anoemric carbons involved in glycosidic bond
o Because it is resistant to oxidation, it is stable→ a suitable molecule for the storage and
transportation of energy in plants; major intermediate product of photosynthesis)
o Table sugar
4. Trehalose
o α−D-glucopyranosyl α−D-glucopyranoside/ Glc(α1←➔1α) Glc
o Non-reducing in nature, because both anoemric carbons involved in glycosidic bond
o Because it is resistant to oxidation, it is stable→ major constituent of the circulating
fluid(hemolymph) of insects, energy-storage compound
o Commercially used as a sweetener
Polysaccharides (Glycans)
Classification of polysaccharides
1. Identity of monomer
● Homopolysaccharides: a single monomeric species
● Heteropolysaccharides: 2 or more different kinds of monomers
The length of chains
The types of glycosidic bonds linking the monomers together
The degree of branching
Unlike proteins, the repeating unit for polysaccharides is a variable. This is because the
program for polysaccharide synthesis is intrinsic to the enzymes doing so and there is no
specific stopping points. As for proteins, they are synthesized on a template of defined
sequence and length by enzymes that follow such a template.
Properties and the biological significance of polysaccharides
o In general, homopolysaccharides:
1. Serve as storage forms of monosaccharides that are used as fuels (starch in plants and
glycogen on animals)
2. Serve as structural elements in plant cell walls and animal skeletons (cellulose and
o In general, heteropolysachharides:
1. Provide extracellular support for organisms of all kingdoms
▪ The rigid layer of the bacterial cell envelope (peptidoglycan) is composed of a
heteropolysaccharide built from two alternating monosaccharide units
▪ In animal tissues, the extraceulluar space is occupied by several types of
heteropolysaccharides which form a matrix that holds individual cells together and
provides protection, shape and support to cells, tissues and organs.
o Steric and Hydrogen Bonding in homopolysaccharide folding
● Folding of subunits in a homopolysaccharide chain is stabilized hydrogen bonds,
hydrophobic interactions, van der waal’s forces and ionic interactions
● Because a lot of polyscahharides composed of glucopyranose, there are any hydroxyl
groups along the polysaccharide chain. Therefore, hydrogen bond is especially
important in folding
● Rotation about the glycosidic bond
1. (α1→4) linkages of starch and glycogen (trans- configuration)
Each residue is rotated to 60 degrees→ six residues in each turn
The core of the helix is of precisely right dimensions to accommodate iodine
complex ions (I3- and I5-), giving an intensely blue complex
2. (β1→4) linkages of cellulose (trans-configuration)
Each chair residue is rotated to 180 degrees→ straight and extended chain
All –OH groups are available for hydrogen bonding with neighboring
chains→ chains lying side by side form a stabilizing network of interchain and
intrachain hydrogen bonds producing straight stable supramolecular (well-defined
complex of molecules held together by non-covalent bonds) fibres of great tensile
Water content is low because the hydrogen bonds are used for intra- and intermolecular hydrogen bonding→ no more hydrogen bonds to interact with water
Storage forms of fuels
1. Starch
● Storage for fuels in plants
● Occur intracellularly as large clusters or granules
● Most plant cells have the ability to form starch
● Starch storage is especially abundant in tubers (underground stems) such as potatoes,
and in seeds
● Heavily hydrated, because there are many exposed hydroxyl groups available for
hydrogen-bond with water
● Contains two types of glucose of polymers:
I. Amylose
● Long unbranched chains of D-glucose connected by (α1→4) linkages (as in
● Vary in length
II. Amylopectin
● Highly branched
● Successive D-glucose residues within the amylopectin joined by (α1→4)
● Branching points (where amylopectin connects with amylose as branches)
occur every 24 to 30 residues, occurs as (α1→6) linkages between the
hydroxyl group at C-6 of D-glucose monomer of and C-1(anomeric carbon) of
the D-glucose of amylopectin
● Amylose forms double helix with the branches of amylopectin
2. Glycogen
● Storage for fuels in animals
● Occur intracellularly as large clusters or granules
● Heavily hydrated, because there are many exposed hydroxyl groups available for
hydrogen-bond with water
● Structure similar to amylopectin, except that glycogen is more extensively branched
(branching points every 8 to 12 residues) → stronger intramolecular forces→ more
compact than starch
● Especially abundant in liver (constituting 7% of wet weight)
● In hepatocytes (liver cells), glycogen is found in large granules which are clusters of
smaller granules composed of single, highly branched glycogen molecules with an
average weight of several million; in tightly bond form contains enzymes responsible
for the synthesis and degradation of glycogen
● The number of non-reducing ends in each glycogen molecule is (n+1), where n is the
number of branches since for each branch the two ends are non-reducing in nature
(one end for the (α1→6) linkages, another end is originally non-reducing; +1 for the
non-reducing end of the parent chain)
● When glycogen is used as energy source, glucose units are removed one at a time
from the non-reducing ends; degradative enzymes act only at nonreducing ends can
work simultaneously on different branches, speeding the conversion of
polysaccharide to many monosaccharides
● Why is glucose stored as glycogen instead of in its monomeric form?
● Hepatocytes store glycogen equivalent to a glucose concentration of 0.4M.
Because glycogen is insoluble in water, it does not contribute to the osmolarity of
cytosol. If the cytosol contains 0.4M of glucose, the osmolarity would increase.
Thus, water would enter into the cell down the water potential gradient., leading
to the rupturing of the cell.
● With an intracellular glucose concentration of 0.4M and external concentration of
about 5nM(blood-glucose concentration), the free energy change for glucose
uptake into the cells against this steep concentration gradient would be
prohibitively large.
3. Dextrans
● Bacterial and yeast polysaccharides
● Made up of (α1→6) linked poly-D-glucose
● All have (α1→3) branches, some in addition have either (α1→2) or (α1→4)
● Dental plaque, formed by bacteria, is rich in dextrans which are adhesive and
allow the bacteria to stick to teeth and to each other.
● Provides source of glucose for bacterial metabolism
● Synthetic dextrans are components of several commercial products used in the
fractionation of products by size-exclusion chromatography and are chemically
cross-linked to form insoluble materials of various size
Structural roles(intracellular)
1. Cellulose
● Tough, fibrous, water-insoluble substances found in the cell walls of plants,
particularly in stalks, stems, trunks, and all the woody portions of the plant body
● Cellulose constitutes much of the mass of wood; cotton is almost pure cellulose
● Linear, unbranched homopolysaccharide
● Consists of 10,000 to 15,000 D-glucose units that are bonded by (β1→4)
glycosidic bonds
● Because glycogen and starch ingested in diet are hydrolyzed by α amylases and
glycosidases, enzymes in saliva and the small intestine that break (α1→4)
glycosidic bonds between glucose units. Most verterbrate animals cannot utilize
cellulose for energy because they lack the enzyme to catalyze (β1→4)
glycosidic bonds. Exception: Ruminant animals such as cattle, sheep and goats
harbour symbiotic microorganisms in the rumen (the first of their four stomach
compartments) that can hydrolyze cellulose, allowing the animal to degrade
dietary cellulose from soft grass, but not from woody plants. Fermentation in the
rumen yields acetate, propionate and β-hydroxybutyrate, which the animal uses
to synthesize the sugars in the milk.
● Most abundant naturally-occuring polysaccharide
2. Chitin
● Linear homopolysaccharide
● Composed of N-acetylglucosamine linked by (β1→4) glycosidic bonds
● Similar to cellulose, vertebrates cannot digest chitin due to the lack of enzymes
degrading (β1→4) glycosidic bonds
● Principal component of the hard exoskeletons of nearly a million species of
anthropods (invertebrates having exoskeleton) such as insects, lobsters and
● Probably the second most abundant polysaccharide in nature
3. Peptidoglycan
● Rigid component of bacterial cell walls
● Heteropolymer of alternating (β1→4) linked N-acetyl-gluocsamine and Nacetylmuramic acid residues
● Cross-links between adjacent chains by the peptides extending from the C-3 of
the N-acetylmuramic acid→ weld the chains into a strong sheath that envelopes
which is responsible for preventing the osmotic entry of water and consequent
cell swelling and lysis
● The enzyme lysozyme kills bacteria by hydrolyzing the (β1→4) linkages.
Lysozyme is found in human tears against bacterial infections, produced by
viruses so as to release themselves from the host bacteria during hijacking
● Penicillin and related antibiotics kill bacteria by preventing the synthesis of
peptidoglycan crosslinks→ density of the chains decrease→ osmotic entry of
water→ cell swelling and lysis
Structural roles (Extra-cellular)
1. Extracellular Matrix (ECM)
● Extracellular space is filled with gel-like material called the extracellular matrix
which is a collection of extracellular materials/ ground substances
● Holds cell together and provides a porous pathway for the diffusion of nutrients
and oxygen to individual cells
● ECM= glycosaminoglycans (a family of linear polymers composed of repeating
disaccharide units) + fibrous proteins (specialized collagens, elasticins,
● Glycosaminoglycans = (N-acetylglucosamine/ N-acetylgalactosamine + Dglucuronic acid/ L-iduronic acid)n , sometimes contains esterified sulphate
● Combination of esterified sulphate groups and carboxylate groups of uronic
acids produce a very high density of negative charge→ extended conformation
in solution by forming a rod-like helix in which the negatively charged
carboxylate groups occur on alternate sides of the helix whilst the negativelycharged sulphate group has maximized separation to reduce charge repulsion→
the specific patterns of sulphated and non-sulphated sugar residues allow
specific recognition by a variety of protein ligands that bind electrostatically to
these molecules→ proteoglycans
▪ Hyaluronan
● (D-glucuronic acid + N-acetylglucosamine) <50,000
Forms clear, highly viscous, noncompressible solutions that serve as lubricants in the
synovial fluid of joints and give vitreous humour of the vertebrate eye its
jelly-like consistency
● Also, a component of the ECM of the cartilage and tendons→ contribute
tensile strength and elasticity as a result of strong noncovalent interactions
with other components of the matrix
● Other glycosaminoglycans differ from hyaluronan by
Shorter polymeric length
Covalent attachment to specific proteins to form proteoglycans (no
such an attachment for hyaluronan)
Identity of monomers
Presence of sulphate (no such an attachment for hyaluronan)
▪ Chondroitin sulphate
● GlcA (β1→3) GalNAc4S
● Contributes to the tensile strength of cartilage, tendons, ligaments, heart
valves and the walls of aorta
▪ Dermatan sulphate
● IdoA (α1→3) GalNAc4S; IdoA is essentially the same as GlcA, just that
the carboxyl group (at C-5) is below the ring structure→ alpha
● Contributes to the pliability of skin and also present in the blood vessels
and heart valves
▪ Keratan sulphates
● Gal (β1→4) GlcNAc6S
● Have no uronic acids
● Sulphate content is variable
● Present in cornea, cartilage, bone, and a variety of horny structures
formed dead cells: horn, hair, hoofs, nails and claws
▪ Heparan sulphate
● Produced by all animal cells and contains variable arrangements of
sulphated and nonsulphated sugars
● Sulphated segments of the chain allow it to interact with a large number
of proteins, including growth factors and ECM components, various
enzymes and factors present in plasma
▪ Heparin
● IdoA2S (α1→4) GlcNS36S
● Highly sulphated, intracellular form of heparan sulphate produced
primarily by mast cells (a type of leukocyte or immune cell)
● Purified heparin used as a therapeutic agent to inhibit the coagulation of
blood through its capacity to bind the protease inhibitor antithrombin
Information carriers
● For communication between cells and their extracellular surroundings (the
glycocalyx which is a layer formed from specific oligosaccharide chains attach to
components of the plasma membrane to form a carbohydrate layer; in such a case
these informational carbohydrates are covalently attached to either proteins or
lipids to form glycoconjugates) label proteins for transport to and localization of
specific organelles, for destruction when protein is malformed and superfluous
(unnecessary), recognition sites for extracellular signal molecules or extracellular
● Glycoconjugates:
1. Glycoproteins
● Have one or several oligosaccharides(heterogenous and rich in information→
forming highly specific sites for recognition and high-affinity binding by
carbohydrate-bindingg proteins called lectins of varying complexity) joined
covalently to a protein
● Usually found on the outer surface of the plasma membrane( a part of
glycocalyx), in the ECM, and in the blood
● Inside cells, they are found in specific organelles such as the Golgi complexes,
secretory granules and lysosomes
2. Glycosphingolipids
● Plasma membrane components in which the hydrophilic head groups are
● Specific sites for recognition by lectins
● Neurons are rich in glycosphingolipids which help in nerve conduction and
myelin formation
● Also play a role in signal transduction in cells
3. Proteoglycans
Macromolecules of the cell surface of ECM in which one or more sulphated
glycosoaminoglycans are joined covalently to a membrane protein or secreted
protein by electrostatic interactions between the protein and the negatively
charged sugar moieties on the proteoglycan
● Major components of ECM
Mechanisms of Proteglycan
● Proteoglycan= ‘core protein’ + glycosaminoglycans
● Tetrasaccharide bridge (GlcA (β1→3) Gal (β1→3) Gal (β1→4) Xyl) connects the
glycosaminoglycans to the ‘-Ser-Gly-X-Gly- ’ residue of the core protein
● Two types of proteoglycans:
1. Syndecans
● Have a single transmembrane domain and a extra-cellular domain
● Bears 3 to 5 heparan sulphate chains, and sometimes chondroitin sulphate
2. Glypicans
● Attached to the plasma membrane by lipid anchor, a derivative of the
membrane lipid phosphatidylinositol
● Shedding of syndecans and glypicans:
● Protease in the ECM cuts proteins close to the surface of the cell membrane to
release syndecan ectodomains (outside of the plasma membrane)
● Phospholipase breaks the connection of the glypican to the membrane lipid
which releases glypicans
● These mechanisms provide a way for a cell to change its surface features
● Highly regulated and activated in proliferating cells such as cancer cells
● Involved in cell-cell recognition and adhesion, the proliferation and
differentiation of cells
● Glycosaminoglycans chains bind to a variety of extracellular ligands by NS
domains→ modulate the ligand’s interactions with specific receptors of the cell
● The domains (3 to 8 disaccharides units long) differ from neighbouring domains by
its sequence and ability to bind to specific proteins: highly-sulphated (by
esterification) (NS domains for N-sulphated domains) alternate with unmodified
GlcNAc and GlcA residues (N-acetylated, or NA domains)→ depends on the
particular type of proteoglycan
● Heparan sulphate molecule with precisely organized NS domains bind specifically
to extracellular proteins and signaling molecules to alter their activities:
1. Conformational change in the ligand that is induced by binding with NS
2. Enhanced protein-protein interaction when adjacent domains of heparin sulphate
bind to two different proteins→ close proximity→ enhance protein-protein
3. Co-receptor for extracellular ligands: binding of extracellular signal molecules
to heparin sulphate which increases the local concentrations and enhance their
interaction with signal receptors on the cell surface
Example: Fibroblast Growth Factors (FGF) for stimulating cell division
4. NS domains (heparin sulphate being negatively charged due to sulphate and
carboxylate groups) interact electrostatically or otherwise with a variety of
soluble molecules outside the cell, maintaining high local concentrations at the
cell surface
Example: Protease thrombin, which is essential to blood coagulation, is inhibited by
another blood protein called antithrombin which prevents premature blood
clotting. Antithrombin only bids to thrombins to inhibit it in the presence of
heparan sulphate or heparin which increases such a binding affinity. The binding
sites of both thrombins and antithrombins, to which hepraan sulphate and
heparins bind to are rich in positively-charged Arg and Lys residues which
interact with the negatively-charged hepearn sulphate/ heparin, causing
allosteric change that inhibits thrombin’s protease activity.
● Importance of correctly synthesizing sulphated domains in heparan sulphate:
1. In mutant mice lacking enzymes that sulphates the C-2 hydroxyl of iduronate,
they are born without kidneys and with severe developmental abnormalities of
the skeletons and eyes.
2. Important in the liver for clearing lipoproteins from the blood
3. Provide directional cues for axon outgrowth, influencing the path taken by
developing axons in the nervous system
● Proteoglycan aggregates
● Enormous supramolecular assemblies of many aggrecan core proteins bound
to a single molecule of hyaluronan (heparan sulphate bind to aggrecan core
protein through trisaccharide linkers to Ser residues of the aggrecan core proteins
*100 bind to a single, extended molecule of hyaluronate→ proteoglycan
aggregate and its associated water of hydration occupies a volume about equal to
that of bacterial cell
● Interacts strongly with collagen in the ECM of cartilage, contributing to the
development, tensile strength and resilience of this connective tissue
● Fibrous matrix proteins such as collagen, elastin and fibronectin interweave
with proteoglycans aggrecans→ gives the whole ECM strength and resilience
● Some of these proteins are multi-adhesive, ie a single protein could have
binding sites for several different matrix molecules
◊ Fibronectin has separate domains that bind fibrin, heparan sulphate, collagen
and a family of plasma membrane proteins called integrins that mediate
signalling between the cell interior and the ECM
● In other words, these fibrous matrix proteins connect proteoglycan aggregates
with the cells
● The interactions between the fibrous matrix proteins, proteoglycan aggregates
and integrins anchor the cells to ECM which provides strength and elasticity of
skin and joints, provide paths that direct the migration of cells in developing
tissues and serve to convey information in both directions across the plasma
● Carbohydrate-protein conjugates where glycans are branched and smaller and more
structurally diverse (not restricted to the certain types of monomers) than
● Carbohydrate attached at its anomeric carbon through a O-linked glycosidic bond
to the –OH of Ser (Mucins contain large number of such glycoproteins) or Thr
residue/ N-glycosyl link to the amide nitrogen of an Asn residue.
● About half of the proteins of mammals are glycosylated whilst about 1% of all
mammalian genes encode enzymes involved in the synthesis and attachment of
these oligosaccharide chains
● Glycoproteins can have one or multiple oligosaccharide chains
● One unique class of glycoproteins in the cytoplasm and the nucleus: the
glycosylated sites of the protein only carry single residues of GlcN-Ac in Oglycosidic bond to the hydroxyl group of Ser side chains. Such a modification is
reversible and often occurs on the same Ser residues that are phosphorylated at
some stage in protein’s activities. NB: these two modifications are mutually
exclusive. This type of glycosylation is important in the regulation of protein
● Many of the proteins secreted by eukaryotic cells are glycoproteins
▪ Antibodies: Immunoglobin
▪ Hormones: follicle-stimulating hormone, luteinizing hormone, thyroidstimulating hormones
▪ Milk proteins: Major whey protein α−lactalbumin
▪ Proteins secreted by the pancreas (ribonucleases)
● Biological advantages of adding oligosaccharides:
● Hydrophillic carbohydrate clusters due to presence of numerous hydroxyl
group alter the polarity and solubility of glycoproteins
● Oligosaccharides attach to the newly synthesized proteins in the endoplasmic
reticulum and elaborated in the Golgi Apparatus serve as destination labels and
also act as protein quality control, targeting misfolded proteins for degradation
● When numerous oligosaccharide chains are clustered in a single region of a
protein, charge repulsion amongst them favours the formation of an extended, rod
like structure in that region. The bulkiness and negative charge of
oligosaccharides protect some proteins from the attack of proteolytic
● As information code
● Gangliosides are membrane lipids of eukaryotic cells where the polar head group
facing the extracellular liquid is a complex oligosaccharide containing sialic acid
● Since some of the oligosaccharide moieties in ganglioside=those found in certain
glycoproteins→ both sets of moieties contribute to blood group type, also found at
the same location: outer face of the plasma membrane
Example of glycoproteins in mediating biological processes: Lectin
● Lectins, found in all organisms, are proteins that bind carbohydrates with high
specificity and with moderate to high affinity.
● Serve in a wide variety of cell-cell recognition, signaling, and adhesion processes and in
intracellular targeting of newly synthesized proteins:
1. Peptide hormones that circulate in the blood have oligosaccharide moieties that
strongly influence their circulatory half-life. Luteinizing hormones and thyrotropin
(polypeptide hormones produced in the pituitary glands) have N-linked
oligosaccharides that end with the disaccharide GalNAC4S(β1→4) GlcNAc, which
is recognized by a lectin(receptor) of hepatocytes. Receptor-hormone interaction
mediates the uptake and destruction of luteinizing hormone and thyrotropin,
reducing their concentration in blood→ blood levels of these hormones rise
periodically (pulsatile secretion then degradation)
2. The residues of Neu5Ac (a sialic acid) situated at the ends of the oligosaccharide
chains of many plasma glycoproteins protect these proteins from uptake and
degradation in the liver. When the Neu5A are removed somehow, the lectin
receptors of the plasma membrane of hepatocytes bind with the oligosaccharide
chains and triggers endocytosis which results in the destruction of these plasma
glycoproteins. This is similar for the removal of old enthrocytes in mammalian
3. Selectin, a family of plasma membrane lectins, mediates the movement of immune
cells(leukocytes) through the capillary wall, from blood to tissues, at the site of
infection or inflammation. At the site of infection, P-selectin on the surface of
capillary endothelial (internal lining) cells interacts with a specific oligosaccharide
of the surface glycoproteins of circulating leukocytes, slowing down the leukocytes
as they roll along the endothelial lining of capillaries. A second interaction between
integrin molecules in the leukocyte plasma membrane and an adhesion protein on the
endothelial cell surface stops the leukocyte and allow it to move through the
capillary wall into the infected tissues to initiate the immune attack.
4. Sorting proteins for transporting to specific cellular compartments by recognizing
oligosaccharide chain containing mannose-6-phosphate which marks the newly
synthesized proteins in the golgi complex for transfer to the lysosome.
● Specificity of carbohydrate-lectin interactions
complementarity→ highly specific
Affinity may be modest, but effective due to lectin multivalency, in which one
lectin has multiple Carbohydrate-binding domain (CBD)
Specificity: Polar side of the sugar hydrogen –bonds with the lectin whilst the
non-polar side undergoes interactions with non-polar amino acid residues through
the hydrophobic effect→ complimentary for the binding force
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