TOPIC 2

PART 1 CARBOHYDRATES
Topic Brief Outline
➢ Basic Concepts
➢ Monosaccharide
o Reactions
o Derivatives
➢ Complex Carbohydrates
o Di / Oligosaccharides
o Polysaccharides
▪ Structural
▪ Storage
o Glycosaminoglycans
➢ Glycoproteins
o Proteoglycans
o Peptidoglycans
o Glycoproteins
o Glycolipids
➢ The Sugar Code
o Lectins
o Selectins
o Galectins
o Pentraxins

Learning Goals
1. Recognize the common features, function, and importance of carbohydrates.
2. Distinguish and explain the different configuration, stereochemistry and conformations.
3. Predict products of sugar reactions
4. Compare different polysaccharides according to their functions.
5. Make clear the types of glycoconjugates and their biological functions.
6. Familiarize the carbohydrate informational molecules.

CARBOHYDRATES

- also called ‘saccharide’; are the most abundant biomolecule on Earth on the basis of
mass and metabolic precursors of virtually all other biomolecules
- comes from the term “carbon hydrate” which describes the empirical formula for
carbohydrates, (CH2O)n in which n > 3. Some with nitrogen, phosphorus and sulfur.
- polyhydroxy aldehydes or ketones or substances that yield such compounds through
hydrolysis
- also called glycans – which is a term frequently used in the context of glycobiology
for carbohydrate polymer. It can refer to a polymer of identical sugars (homoglycan)
or of diff sugars (heteroglycan)
 Basic Concepts

Chemical Features

➢ The existence of at least one and often 2 or more asymmetric centers

➢ The ability to exist either in linear or ring structures
➢ The capacity to form polymeric structures via glycosidic bonds
➢ The potential to form multiple hydrogen bonds with water or other molecules in their
environment

Functions

a) Provide sources of metabolic energy in the form of dietary sugars;

b) (sugar & starch) are dietary staple in most parts of the world
c) The oxidation of carbohydrate is the central energy-yielding pathway in most non-
photosynthetic cells.
d) Insoluble carbohydrate polymers serve as structural and protective elements in the
cell walls of bacteria and plants and connective tissues of animals.
e) Other carbohydrate polymers lubricate skeletal joints and participate in recognition
and adhesion between cells.

3 Major Classes / Groups

1. Simple Sugars - Often functions as metabolic intermediates in energy conversion

pathways:
a. Monosaccharide
▪ ‘saccharide’ from the Greek word “sakcharon” meaning “sugar”
▪ can be a polyhydroxy aldehyde (aldose) or a polyhydroxy ketone
(ketose)
▪ the simplest contain 3C called trioses [glyceraldehyde – aldose with 3C
(aldotriose) and dihydroxyacetone – ketose with 3 C (ketotriose)]; four,
five, and six C atoms are called tetroses, pentoses, and hexoses,
respectively
▪ ex. glucose, galactose, mannose
b. Oligosaccharide
▪ are polymers with 2 to about 20 monosaccharide residues linked by
glycosidic bonds
▪ most abundant are disaccharides (2 monosaccharide units):
o sucrose – 6C D-glucose + D-fructose
o maltose – 6C D-glucose + D-glucose
o lactose – 6C D-glucose + 6C D-galactose

2. Polysaccharides – are sugar polymers containing more than 20 or so

monosaccharide units, and some have hundreds or thousands of units. Examples
are:
a. Glucose homopolymers – cellulose, starch, glycogen
b. Disaccharide heteropolymers – chitin, keratan sulfate
 3. Glycoconjugates – are carbohydrate derivatives in which one or more carbohydrate
chains are linked covalently to a peptide, protein or lipid which play a critical role in
cellular communication.
a. Glycoproteins – antibodies, viral coat proteins
b. Proteoglycans – aggrecan, syndecan, glypican
c. Glycolipids – blood antigens, membrane anchors.

Stereochemistry

Fisher projection – is a 2D representation of carbohydrate molecules. Prefix D and L

are used to relate the configuration of a given molecule to that of glyceraldehyde and
does not specify the sign of rotation of plane-polarized light.

Figure 1.Fischer projection (left: Garrett and Grisham, 2017; right: Nelson and Cox, 2004)

The L sugars are the mirror images of their D counterparts. Since L sugars are
biologically much less abundant than the D sugars, the D prefix is often omitted.

D isomer rotates plane polarized light to the right; the L isomer rotates it to the left.
Figure 2. Aldoses and ketoses in their
projection formulas (Garrett and
Grisham, 2017)
 Figure 3. Isomeric forms of carbohydrates (Berg, et. al., 2015).

Cyclic and Anomeric Formation

Sir Norman Haworth, a British chemist demonstrated that the linear form of glucose
undergo similar intramolecular reaction to form a cyclical structures known as Haworth
Projection formulas.

Sugars form cyclic structure with additional asymmetric center. Alcohol reacts with
aldehydes to form hemiacetals; while hemiketals form when alcohol reacts with ketones.
Cyclic hemiacetal with 6-member, oxygen containing ring is a pyran designated as
pyranose. On the other hand, cyclic hemiketal with 5-member ring is a furan referred as
furanose. The cyclic pyranose and furanose forms are preferred structures for
monosaccharides in aqueous solution.

Carbonyl groups attached to carbon atom forming hemiacetal and hemiketal makes
the carbon asymmetric. The carbon atom with isomeric configurations designated as α and β
is called the anomeric carbon while the isomeric formations are anomers (Figure 4).

α – hydroxyl group of the anomeric carbon is on the same side of the fischer projection and
is located at the right below the plane of the ring

β – hydroxyl group of the anomeric carbon is on the opposite side of the fischer projection
and is hydroxyl group is located above the ring of the plane
 Figure 4. Hemiacetal and hemiketal formations (Garrett and Grisham, 2017)

Mutarotation - the process of the interconversion α and β anomers in an aquesous solution

For a D sugar, any group that us written in the right of the carbon in a Fischer
projection has a downward direction in a Haworth projection; while any group at the left in a
Fischer projection has an upward direction in a Haworth projection.
Ring Conformations

Cyclic monosaccharide molecules are not planar in actual spatial arrangement. They
adopt different puckered conformations without breaking the covalent bonds.

Pyranose Rings – assumes two (2) conformations:

a) Chair conformation
➢ Minimizes steric repulsion among the ring substituents
➢ Generally more stable than boat conformation
➢ Can have two (2) orientations
i. Axial – nearly perpendicular to the plane of the ring or parallel to an
axis drawn though the ring.
ii. Equatorial – nearly parallel to the plane of the ring or approximately
coplanar with the ring. Bulky substituents in this orientation are more
stable (less crowded).
b) Boat conformation

Figure 5. Chair and boat conformations of pyranose sugar (left) Berg, et. al., 2015; (right)
Garrett and Grisham, 2017.

Furanose Rings – adopts envelope conformations as is resembles an opened envelope with

the back flap raised;

a) C2 – carbon 2 of the five carbon ring is out-of-plane and the remaining four are
approximately coplanar.
b) C3 – carbon 3 of the five carbon ring is out-of-plane and the remaining four are
approximately coplanar.
c) Twist – two (2) out of the five (5) atoms are out-of-plane (one on the either side of the
plane formed by the other three (3) atoms.
 Figure 6. Envelope conformations (left) Berg, et. al., 2015; (right) Moran and Horton 2012.

Monosaccharide Reactions

Oxidation – Reduction

Reducing sugars

- sugars with free carbonyl or aldehyde groups which are reactive and have the
ability to reduce and be oxidized by relatively mild oxidizing agents such as ferric
(Fe3+) or Cupric (Cu2+) ion
- sugars that are oxidized are being converted from a carbonyl group to a carboxyl
group (aldonic or uronic acid). Examples of oxidation of C6 glucose, galactose,
mannose to uronic acids – glucuronic acid, galacturonic acid, mannuronic acid.
Both aldonic and uronic acids form stable intramolecular esters called lactones.

Figure 7. (top) glucose is oxidized to gluconic acid and reduced cupric ion (Cu2+) to cuprous
ion (Cu1+ ) (Berg, et. al. 2015); (bottom) oxidation of sugar to form a lactone (Campbell and
Farrell, 2015).
Fehling’s Reaction

- a qualitative test for the presence of reducing sugar.

- concentration of sugar is estimated by measuring the amount of oxidizing agent
reduced by the sugar
- Ex. Glucose + hemoglobin; free amino group react with the free carbonyl group of
glucose forming a glycosylated hemoglobin. Changes of this formed molecule are
useful in diagnosing diabetes mellitus and also the effectiveness of any
treatments used to address this condition.

Esterification & Phosphorylation

The reactive hydroxyl groups of sugar react with acid and acid derivatives to form
esters. One important intermediate formed through esterification and phosphorylation is
phosphate esters (Figure 8). Phosphorylated sugars are the key intermediates in energy
generation and biosynthesis and also make it anionic.

Figure 8. Esterification and phosphorylation of sugar which forms an intermediate that plays
an important role in metabolism: (top) Campbell and Farrell, 2015; (bottom) Berg, et. al.,
2015.

Glycoside Formation

Glycosidic bond
- is the primary structural linkage in all polymers of monosaccharides and the basis
for the formation of oligosaccharides and polysaccharides
 - is an acetal linkage in which the anomeric carbon of a sugar is condensed with
another anomerc carbon, alcohol, an amine, or a thiol.
- R-OH to R’-O-R (hydroxyl group of the anomeric carbon react with other hydroxyl
group)
- Can be an α- or β-glycosidic linkage bonded together at different carbon
number of the anomeric carbon

Glycosides
- compounds containing glycosidic bonds
- compound in which one or more sugars is bonded to another molecule
o Furanosides - glycosides derived from furanoses
o Pyranosides - glycosides derived from pyranoses
o O-glycosides - sugar bonded with another sugar
o N-glycosides - sugar is bonded to a nitrogen atom of a base or the bond
between an anomeric carbon and an amine

Figure 9. Examples of formation of glycosides; (top) –OH group of the the hemiacetal is
replaced by an –OCH3 group (Moran and Horton, 2012); (middle) methyl alcohol reacts
with a hemiacetal (Campbell and Farrell, 2015) and (bottom) α and β glycosidic
linkages of glucose with methanol (Voet, et. al., 2016).
Figure 10. α-glycosidic bond formation from 2 molecules of α-D-glucose linked at α(1→4)
and at α(1→ 6) (Campbell and Farrell, 2015).

Figure 11. β-glycosidic bond formation from 2 molecules of β-D-glucose linked at β(1→1)
(Campbell and Farrell, 2015).

Figure 12. N-glycosidic bond formation

between an anomeric carbon and an
amine (Voet, et.al., 2016).
Monosaccharide derivatives

A. Sugar Phosphates - as discussed above, are important metabolic intermediates

Figure 13. Several sugar esters important in metabolism phosphorylated at the 5’-
position (Garrett and Grisham, 2017).

B. Deoxy Sugars – are monosaccharide units in which one or more of its hydroxyl (-OH)
groups are replaced by hydrogen (-H). The biologically most important of these are:
a. 𝛃-D-2-deoxyribose, the sugar component of DNA’s sugar–phosphate
backbone
b. L-Fucose is one of the few L sugar components of polysaccharides widely
distributed in plants, animals, and microorganisms.

Figure 14. Deoxy sugar at their “deoxy”

positions (Voet, et. al., 2016)

C. Amino Sugars – are monosaccharide units in which one or more of its hydroxyl (-OH)
groups have been replaced by an amino group at the C-2 position and is often
acetylated.

Figure 15. Amino sugars β-D-Glucosamine and β-D-Galactosamine found in many

oligo- and polysaccharides (left: Voet, et.al., 2016, right: Garret and Grisham, 2017).

D. Sugar Alcohols – also known as alditols are polyhydroxyl alcohols formed when
carbonyl groups of aldoses and ketoses reduced by treatment with NaBH 4 or similar
agents.
- naming is through replacement of –ose with suffix –itol to the parent aldose.
 - are characteristically sweet, in fact used as sugarless sweetener is some
candies, gums and mint (sorbitol, mannitol, xylitol)
- Glycerol and myo-inositol are important components of lipids

Figure 16. Structures of some sugar alcohols. (myo-inositol is a polyhydroxy cyclohexane,

not a sugar alcohol.) Garrett and Grisham, 2017

Figure 17. Some commercial sugar

alcohols; “sugarless” gums and candies
(https://www.healthbenefitstimes.com/nu
trition/sugar-alcohol/)

BOX 1. SORBITOL BUILD-UP and CATARACT FORMATION

Manageable amount of sorbitol are

converted to fructose with sorbitol
dehydrogenase. However, the cells in the
eyes have limited sorbitol dehydrogenase
enzyme to convert them, thus causing
build-up. The build-up of sorbitol causes
Tarr, et. al., 2013 osmotic damage and eventually cell death.
Cataracts and other damage to visual
pathway damages are formed
(https://www.stomponstep1.com/pku-
phenylketonuria-galactosemia-hereditary-
fructose/).

https://www.mayoclinic.org/healthy-lifestyle/adult-
health/multimedia/vision-problems/sls-20076758
 E. Sugar Acids – are carbonyl groups of free anomeric carbons reduced to carboxyl
groups as discussed in monosaccharide reactions (reducing sugars). Sugar acids are
important components in polysaccharides.

Figure 18. Carbonyl to carboxyl with the help of an oxidizing agent Cu2+
(R-OH to R-O-OH / R-OO-) (Garrett and Grisham, 2017).

Figure 19. Oxidation of D-glucose to sugar acids (Garrett and Grisham, 2017).

Complex Carbohydrates

Disaccharides are the simplest oligosaccharides which consist of two

monosaccharide units linked by a glycosidic bond. Oligosaccharides range in complexity
from ~3 to ~20 branched and unbranched sugar residues. Oligosaccharides containing three
or more residues are relatively rare, occurring almost entirely in plants. Disaccharides, the
simplest polysaccharides, are more common.
Most common naturally occurring disaccharides

Figure 20. Common disaccharide structures (Campbell and Farrell, 2015).

A. Maltose

➢ the unambiguous name is α-D-glucopyranosyl-(1→4)-D-glucopyranose

➢ two (2) glucose units are linked by an α-1,4-glycosidic bond
➢ is a homodisaccharide – contain only one (1) kind of disaccharide
➢ produced from the hydrolysis of starch and glycogen and in turn hydrolyzed back into
units of glucose by enzyme maltase – located on the other surfaces of epithelial cells
lining the small intestine together with sucrase and lactase.
➢ present in malt used in beverages (malted milk, beer), because it is fermented readily
by yeast

B. Sucrose

➢ the unambiguous name is α-D-glucopyranosyl-(1→2)-β-D-fructofuranoside

➢ most abundant disaccharide found in nature
➢ disaccharide of glucose and fructose formed by plants but not animals
➢ commonly known as table sugar commercially obtained from sugar cane or beets.
➢ a non-reducing sugar since it contains no free anomeric carbon atom
➢ major intermediate product of photosynthesis
➢ can be cleaved into glucose and fructose by enzyme sucrase and hydrolyzed by
invertase.
➢ Excessive consumption can lead to health problems, thus other sweeteners (natural
and artificial) are produced to mimic its taste but still pose health risks. Some are;
o High-fructose corn syrup – produce from fructose itself which is sweeter than
sucrose but can change food product texture
o Saccharin – has been found to cause cancer in laboratory animals
o Aspartame – has been suspected of causing neurological problems,
especially in individuals whose metabolisms cannot tolerate phenylalanine.
o Acesulfame – commonly used in combination with aspartame since they
perform synergistically.
o Sucralose – cannot be metabolized in the body, thus does not provide
calories. (Ex. Splenda, etc.)
 Figure 21. Difference in structure between sucralose and sucrose
(https://jakefood.com/2019/sucralose/)

o Stevia – is a natural sweetener from a the leaves of the plant species Stevia
rebaudiana with an active compound called steviol glycosides, which have 30
to 150 times the sweetness of sugar. Increase amount of stevia to food and
beverage introduces a bitter aftertaste.

C. Lactose

➢ the unambiguous name is β-D-galactopyranosyl-(1→4)-β-D-glucopyranose

➢ occurs naturally in milk with concentration ranges from 0 to 7% depending on the
species; has critical nutritional importance to mammals in their life stages
➢ hydrolyzed by enzyme lactase in humans and broken down to galactose and glucose
before being absorbed into the bloodstream; and by β-galactosidase in bacteria
➢ reducing disaccharide since the anomeric carbon of glucose is free for oxidation;
glucose is not involved in the glycosidic linkage and can be in either be in α or in the
β form

BOX 2. LACTOSE INTOLERANCE

𝒍𝒂𝒄𝒕𝒂𝒔𝒆
𝒍𝒂𝒄𝒕𝒐𝒔𝒆 → 𝒈𝒍𝒖𝒄𝒐𝒔𝒆 + 𝒈𝒂𝒍𝒂𝒄𝒕𝒐𝒔𝒆

Lactose needs to be hydrolyzed first to their component

monosaccharides glucose and galactose before they can be
absorbed into the bloodstream with the help of the enzyme https://reference.jrank.org/diets/Lactose_I
lactase or β-D-galactosidase. ntolerance_Diet.html

Due to congenital errors, infants may lack or has defective Lactose Free Milk Substitutes
lactase enzyme where breaking down of lactose is difficult. Soy Milk
Lactose ingested moves from digestive tract to the colon Almond Milk
where bacterial fermentation takes place resulting to Coconut Milk
formation of organic acids, CO2, and H2 which lead to Oat Milk
experiences of flatulence, bloating, intestinal pain and Rice Milk
diarrhea. Cashew Milk
Macadamia Milk
Problem also exists even enzyme lactase is present. This is
when galactose is build up due to missing enzyme in sub-
Hemp Milk
-sequent reactions in lactose breakdown. This is called galactosemia. As galactose is build-up in cells, it
is converted to galacitol, a hydroxyl sugar that cannot escape. Water is then accumulated within the
cells causing swelling and edema. Damage in the brain cells that will lead to irreversible retardation
will happen if build-up occurs in the brain tissues (Campbell and Farrell, 2015 & Voet, et.al, 2016).
Other naturally occurring disaccharides

D. Trehalose

➢ the unambiguous name is α-D-glucopyranosyl-(1→1)-α-D-glucopyranoside

➢ a non-reducing sugar; major component in insects’ circulating fluid called
hemolymph, that function as energy-storage compound.

E. Cellobiose

➢ the unambiguous name is β-D-glucopyranosyl- (1→4)-D-glucose

➢ obtained from the aid hydrolysis or degradation of cellulose
➢ differ in maltose on the linkage; maltose is α while cellobiose β glucose-glucose bond
➢ can’t be digested by mammals unlike maltose

F. Isomaltose

➢ the unambiguous name is α-D-glucopyranosyl-(1-6)-α-D-glucopyranoside

➢ obtained in the hydrolysis of polysaccharide such as dextran
➢ also contains two (2) glucose units like maltose and cellobiose (homodisaccharide)
but the bond is between C1 and C6 and the configuration is α.

Polysaccharides

Polysaccharides also known as ‘glycans’, consists of several linear and/or branched

monosaccharide units linked together by glycosidic bonds. They can be distinguished from
proteins and nucleic acids with their ability to form branched structures since the former
biomolecules cannot.
They generally provide protection, serve as energy storage and function as physical
structure and strength. They are also classified as:

a. Homopolysaccharides - only one type of monosaccharide

b. Heteropolysaccharides - more than one type of monosaccharide

Figure 22. Representation of homo

and heteropolysaccharides
(Nelson and Cox, 2004).
Structural polysaccharides

A. Cellulose

➢ major structural component of plant cell walls especially of woods and plant fibers
particularly in stalks, stems, trunks, and all the woody portions of the plant body.
➢ most abundant natural organic polymer in the world accounting for over half of the
carbon in the biosphere
➢ linear homopolymer of up to 10,000 - 15,000 repeating units of cellobiose; D-glucose
residues linked by β(1→4) glycosidic bonds making it not digestible by humans or by
most animals
➢ the β configuration allows cellulose to from very long straight chains. In which
glucose residue is rotated 1800 relative to its neighbors
➢ held cohesively together by hydrogen bonds and van der Waals interaction that gives
exceptional strength and makes them water insoluble.
➢ Animals and human cannot digest cellulose because cellulase enzyme is not found in
the digestive tracts. But ruminant animals (deer, cattle, giraffe, etc.) have a stomach
compartment called the rumen that has symbiotic relationship with bacteria present;
and they are able to secrete cellulases that hydrolyze cellulose to glucose. This is
primarily why these animals can live on grass.
➢ Cotton – almost 100% pure cellulose

Figure 23. Cellulose structure (Miesfeld and McEvoy,

2017); ruminant animals stomach (Garrett and
Grisham, 2017).
 BOX 2. DIETARY FIBER
Getty images
(https://www.menshealth.com/nutritio
n/g19663803/best-sources-of-fiber/)
Cellulose is a component in dietary
fiber. Fiber, colloquially termed as roughage.
It is highly insoluble for human but they
stimulate eristaltic action that assists in the
transport of digested food to the instestine
which prevents accumulation and
eventually other intestinal problems. It is
also established that toxins bind to fiber and
are then expeled from the body decreasing
chances of lower intestinal damage.
Fiber also binds to carcinogens that
lower risks of colon and other types of
cancer. Thus high-fiber diet is beneficial for
a healthy digestive system (Campbell and
Farrell, 2015)

B. Chitin

➢ similar with cellulose in both structure and function and the second most abundant
➢ is a linear homopolysaccharide of β(1→4)-linked N-acetyl-D-glucosamine residues
➢ differs from cellulose only on the C2 where the –OH group is replaced by an
acetykated amino group.
➢ hexosamine polysaccharide which is a principal structural component of nearly
million species of anthropods and invertebrates – insects, crustaceans, spiders. But
also present in cell walls of most fungi and algae (mushroom, etc.)
➢ Arrangement of chains occur inn three (3) forms:
o α-Chitin - is an all-parallel arrangement of the chains
o β-Chitin - is an antiparallel arrangement
o δ-Chitin - involves pairs of parallel sheets separated by single antiparallel
sheets.

Figure 24. Chitin structure and invertebrates and fungi with chitin
(Miesfeld and McEvoy, 2017).
 Figure 25. Colored identification of chitin structure (Voet, et. al. 2016 and
Nelson and Cox, 2004)

Storage polysaccharides

Starch

➢ principal nutritional and energy reservoir in plants

➢ homopolymer of α-D-glucose in plants cells particularly deposited in the chloroplast
and appear as insoluble starch granules in the cytosol
➢ digestion of starch start in the mouth upon macerating, α-amylase in our saliva
hydrolyze the 1→4 linkages, then transported to the small intestine where the
pancreatic amylase continues to hydrolyze the bonds. Further hydrolysis cleaving
each glucose residues at a time with α-glucosidase enzyme and debranching
enzyme breaking down the 1→6 linkages. Monosaccharides produced from several
hydrolysis are then absorbed in the intestine and transported to the bloodstream
➢ composed of 10% to 30% α-amylose and 70% to 90% amylopectin;
o Amylose
▪ linear, unbranched glucose residues in α(1→4) linkage
▪ hydrolyzed by α-amylase, an enzyme secreted by the salivary glands
and the pancreas
▪ Isomer of cellulose
▪ Adopt a stable and irregular left-handed helical structure as a result of
intramolecular hydrogen bonding
o Amylopectin
▪ branched chain polymer, with the branches starting at α(1→6)
linkages along the chain of α(1→4) linkages at every 24 to 30 glucose
residues on average.
▪ approx. contains 106 glucose residues making them some of the
largest molecules in nature.

Glycogen

➢ storage homopolymer in animal cells found

in cytoplasmic granules
➢ storage for of glucose abundant in muscle
and liver tissues
➢ large, branched polymer linked by α(1→4)
glycosidic bonds while the branches are

Figure 26. Glycogen structure and

branched point (Berg, et. al., 2015)
 Figure 27. Amylose and amylopectin (Campbell and Farrell, 2015).

formed by α-1,6-glycosidic bonds, present about once in 10 units.

➢ stored glycogen can be used for future energy requirement.
➢ glycogen phosphorylase enzyme cleaves the glycosidic bonds and removes glucose
one at a time from the non-reducing ends producing glucose-1-phosphate which then
enters to the metabolic pathways of carbohydrate breakdown
➢ can be hydrolyzed by both α and β amylases, breaking down to glucose and maltose
respectively.

Figure 28. degree of branching comparison between amylopectin and glycogen

(Campbell and Farrell, 2015)
Dextran

➢ are bacterial and yeast branched polysaccharide linked by α(1→6) D-glucose

glycosidic bonds with branch points at either α(1→2), α(1→3) or α(1→4).
➢ The degree of branching and mean length of the chains depends on the species and
strain of the organism.
➢ bacteria forming dental plaque on the surface of the teeth is an accumulation of
extracellular dextrans

Heteropolysaccharides

Agarose

➢ Isolated from marine red algae (Rhodophyceae), agar is used mostly in

microbiological cultivation.
➢ Polysaccharide where the 3-dimensional structure is a double helix with a threefold
screw axis. Central cavity is large enough to trap up to 99.5% water molecules
forming gels.
➢ Consists of two components:
o Agarose – chain of alternating D-galactose and 3,6-anhydro-L-galactose, with
side chains of 6-methyl-D-galactose.
o Agaropectin – same with agarose but contains sulfate ester side chains and
D-glucuronic acid.

Glucosaminoglycan

➢ Unbranched heteropolysaccharide with repeating disaccharide units that form highly

hydrated gels found on the extracellular spaces, particularly those of connective
tissues such as cartilage, tendon, skin, and blood vessel walls
➢ One of the monosaccahride units is an amino sugar with amino group of either D-
galactosamine or D-glucosamine
➢ One of the monosaccharide units has a negatively charged carboxylate or sulfate
group
➢ major glycosaminoglycans;
i. chondroitin sulfate
▪ chondroitin comes from the Greek word “chondros”, meaning
“cartilage”
▪ components of the connective tissue sulfated at the C4 or C6 of the N-
acetylgalactosamine
▪ are sold over-the-counter as supplements to help repair cartilage
especially in knees.
▪ contributes to the tensile strength of cartilage, tendons, ligaments,
heart valves, and the walls of the aorta.
ii. keratan sulfate
▪ comes from the Greek word “keras” meaning “horn”
▪ also component of connective tissue found in tendons, cartilage,
cornea and horny structures: horn, hair, hoofs, nails and claws.
▪ the most heterogeneous glycosaminoglycan with no uronic acid, has
variable sulfate, and contains small amounts of mannose and sialic
acid.
iii. Heparin
▪ Greek work “hēpar”, meaning “liver” since originally isolated from
dog’s liver
 ▪ also variably sulfated but nor a component of connective tissue like
other glycosaminoglycans but is a cell surface component and an
extracellular substance in blood vessel walls and brain
▪ acts as a natural anticoagulant that inhibits blood clotting
▪ critical role in development and in wound healing
iv. Dermatan sulfate
▪ component of the extracellular matrix of the skin
▪ derived from the C-5 enzymatic epimerization of chondroitin
glucuronate residue forming L-iduronate
▪ contributes to skin pliability and is also found in blood vessels and
heart valves
v. hyaluronate
▪ composed of 80 to 8000 and as many as 25,000 disaccharide units
▪ disaccharide units that β(1→4)-linked which consist of D-glucuronic
acid and N-acetyl-D-glucosamine linked by a β(1→3) bond
▪ important component of the connective tissue, fluid joints lubricant
(synovial fluid) and vitreous humor of the eye

Figure 29. Structures of major glycosaminoglycans (Garrett and Grisham, 2017).

 BOX 3. NAKED MOLE RAT

Naked mole rat has higher life span than any other
rodents (>30 years). Their cells excrete large
amount of hyaluronate up to 32,000 disaccharide
residues. This obstructs formation of malignant
cells leading to cancer, where other type of
rodents is prone to (Voet, et. al., 2016).
https://hero.fandom.com/wiki/Ruf
us_(Kim_Possible)

Glycoconjugates

Glycoconjugates are heterpolysaccharides composed of different monosaccharide

covalently linked to proteins or peptides or lipids used for various biological functions

Glycoproteins

➢ Contains one or several oligosaccharides covalently linked to protein where is it

larger by mass
➢ Often found on the outer surface of the plasma membrane, extracellular matrix and in
the blood.
➢ Diverse group and functions of proteins that includes enzymes, hormones, structural
proteins, and transport proteins.
➢ Glycoprotein erythropoietin (EPO) – present in the blood serum secreted by the
kidneys that improves treatment for anemia, particularly that induced by cancer
chemotherapy.

A. Proteoglycan

➢ type of glycoprotein where the protein is covalently linked to a glycosaminoglycan

where carbohydrate has the larger weight as much as 95%
➢ major components of extracellular matrix, also function as lubricant
➢ major component of cartilage where its collagen fibrils is filled in by proteoglycans
that contributes to its high resilience and flexibility
o proteoglycan aggrecan
▪ a key component of cartilage serves as a shock absorber; can cushion
compressive forces because the absorbed water enables it to spring
back after having been deformed
 ▪ its repetitive amino acid sequence are sites for keratan and
chondroitin sulfate attachment
o mucin
- also called mucuproteins
- glycoprotein components of mucus
- extensively glycosylated at serine or threonine residues by N –
acetylgalactosamine
- overexpression causes adenocarcinomas—cancers of the glandular cells
of epithelial origin
- functions;
o coat and protects mucous membranes in the respiratory and
gastrointestinal tracts
o as lubricant (abundant in saliva)
o adhere to epithelial cells and serves as protective barrier
o hydrate underlying cells
o fertilization
o immune response
o cell adhesion

Figure 30. Bottlebrush model of

proteoglycan with attached
glycosaminoglycans
(Voet, et. al. 2016)

Peptidoglycan

➢ Cross-link of polysaccharide to peptides

➢ Found in bacterial cell walls, generally a class of peptidoglycan with a heteroglycan
component attached to 4C or 5C peptide residue. The heteroglycan consists of
alternating β-linked N-Acetylglucosamine and N-acetylmuramic acid residue.
➢ Due to cross-linking of peptide chains to the polysaccharide, it forms a strong
peptidoglycan that encloses the cell that protects from swelling and lysis from water
though osmosis
➢ Peptidoglycan difference between Gram Negative and Gram-Positive Bacteria;

Gram Negative
▪ Have thin (2-3 nm) cell wall of single layer peptidoglycan between inner and
outer lipid bilayer membrane
▪ stains red upon gram staining
 ▪ due to its thin peptidoglycan layer, it can’t retain the crystal violet initial
staining solution when decolorized but reflects red, mimicking the safranin
solution when the counterstained.

Gram Positive
▪ Have thick (approx. 25 nm) cell wall made up of peptidoglycan
▪ No outer membrane
▪ Stains purple upon gram staining
▪ Since have thicker peptidoglycan layer, crystal violet solution are retained
even after decolonization

Figure 31a. Gram positive and negative bacteria cells (Voet, et. al., 2016)

BOX 4. PENICILLIN
Penicillin binds irreversibly to transpeptidase enzyme
leaving the structure of the cell wall open and weak
for cell lysis and further blocking peptidoglycan
synthesis.

But other bacteria release penicillin enzyme that

resists its antibiotic effect. The enzyme penicillinase
or β-lactamase cleaves the amide group of the lactam
ring (red color) making penicillin limited as an
antibiotic drug (Campbell and Farrel, 2015 and Voet,
et.al. 2016).
Figure 31b. Cell wall and membrane structures of Gram positive and Gram-negative bacteria
(Garrett and Grisham, 2017)
 The Sugar Code

Lectins

➢ Translators of sugar code

➢ a class of proteins that bind carbohydrates with high specificity and affinity. The link
is a weak non-covalent bond but the composition is strong where unlinking is
possible.
➢ Functions:
o facilitate cell-cell contact or interaction
o immune response
o blood clotting

A. Selectins

➢ members of the C-type family

➢ bind immune-system cells to sites of injury in the inflammatory response
➢ found both on the rolling leukocytes and on the endothelial cells of the vascular walls

B. Galectins

➢ conserved family of proteins with

carbohydrate recognition
➢ mediators of inflammation, immunity and
cancer
➢ mediate the attachment between
leukocytes
➢ consists of about 135 amino acids linked
to β-galactosidase
➢ participate in:
o cell adhesion
o growth regulation
o inflammation
o immunity Figure 32. The selectin family of adhesion
o cancer metastasis proteins (Garrett and Grisham, 2017).
➢ forms
o L-selectins - expressed on leukocytes, monocytes, neutrophils, and
eosinophils, adhesion receptor in leukocytic cells
o E-selectins - expressed on endothelial cells plays in mediating leukocyte
rolling, it contributes to firm adhesion
o P-selectins – are expressed on platelets and leukocytes for cell adhesion
molecule

C. Pentraxins

➢ lectins with quarternary structure in which five identical subunits combine to form a
planar ring with a central hole
➢ to limit tissue damage, acute inflammation, and autoimmune reactions
 Thank you
For clarifications and other discussions regarding the topic, we will meet on December 12,
2020 at 9:45 AM, google meet ID: meet.google.com/oqd-pehw-nkh. Write down some
questions and others for us to discuss. This will be a recorded meeting for other students
who will not be able to participate.

After our discussion, I will give study questions for you to answer and submit. Date of
submission will be posted together with the questions. Thank you everyone.

Note:

Kindly be resourceful in searching videos regarding the topic for you to fully comprehend all
about Carbohydrates. I believe this is just a review for all of you, but I encourage you to
relate this to your field and its practical application to medicine. My exams are usually
practical questions. Thank you again.

REFERENCES

Berg, J. M., et al. 2015, Biochemistry 8th edition. W. H. Freeman and Company

Campbell, M.K. and Farrel, S. O. 2015. Biochemistry 8th edition. Cengage Learning

Garret, R.H. and Grisham, C.M. 2017. Biochemistry 6th edition. Brooks/Cole
Cengage Learning

Miesfeld, R. L. and McEvoy, M. M., 2017. Biochemistry. W. W. Norton & Company,

Inc.

Moran, L.A. et al. 2012. Principles of Biochemistry 5th Edition. Pearson Education Inc.

Nelson, D. L. and Cox, M. M., 2004 Lehninger Principles of Biochemistry 4th edition.
W. H. Freeman and Company

Nelson, D. L. and Cox, M. M., 2017 Lehninger Principles of Biochemistry 7 th edition.

W. H. Freeman and Company

Voet, D., et. al. 2016. Fundamentals of Biochemistry: Life at the Molecular Level.
John-Wiley & Sons, Inc.