carbohydrates:

The definition of carbohydrates in chemistry is as follows: “Optically active polyhydroxy

aldehydes or polyhydroxy ketones or substances which give these on hydrolysis are termed as
carbohydrates

monosacharides: Monosaccharides, also called simple sugar, is a mixture of sugar and

are the simplest form of sugar and the most basic units of carbohydrates. They cannot be further
hydrolyzed to simpler chemical compounds. The general formula is CnH2nOn. They are usually
colorless, water-soluble, and crystalline solids. Some monosaccharides have a sweet taste.

The structure of monosaccharides

Monosaccharides are the basic unit of carbohydrates, an organic class of molecules made of carbon,
hydrogen, and oxygen atoms, usually in a respective ratio of 111:222:111. When in their linear chain
form, these molecules are polyhydroxylated aldehydes and ketones. The name carbohydrate reflects the
presence of one water molecule for every carbon atom in the general formula. Monosaccharide naming
further distinguishes both the highest priority functional group and number of carbon atoms as well as the
chirality of the highest numbered chiral carbon. The functional group determines the molecule’s prefix,
while the suffix “ose” is applied generally to all molecules in this class of sugars. For example, a six-
carbon monosaccharide with an aldehyde functional group is an aldohexose, of which glucose is a notable
example. Fructose is also a six-carbon monosaccharide, however it differs from glucose in that its
functional group is a ketone at carbon 222 making it a ketohexose. Lastly, the stereochemistry of the
highest numbered carbon atom is distinguished as D or L. Figure 1 represents the eight possible D-
aldohexoses.

types of monosaccharides:
On the base of functional group:
Monosaccharides have two broad classifications on the basis of the functional group present in them.
  So if they contain an aldehyde group they are known as “aldose”.

Let us examine the case of aldotetroses (aldoses with 4 carbon atoms). We can apply the rule we have just
enunciated, but the situation is somewhat complicated by the fact that there are two asymmetric carbon
atoms. We will have the 2 configurations D and L of erythrose (E 1 and E2) forming a couple of
enantiomers because they are mirror images of each other, and we will also have the 2 configurations D
and L of threose forming a couple of enantiomers (T 1 and T2).
On the contrary, E1 and T1, E1 and T2, E2 and T1, E2 and T2 do not form couples of enantiomers; they are
diastereo-isomers; their physical and chemical properties are distinctly different, so that it is easier to
separate 2 diastereo-isomers than 2 enantiomers

 Now considering aldopentoses, one finds 3 asymmetric carbon atoms, and therefore 8 possible stereo-
isomers. Only the 4 D-forms are shown in figure 4-4 (to each one of them corresponds a L-form, i.e., its
mirror image).

As regards aldohexoses, which have 4 asymmetric carbon atoms, there are 16 possible stereo-isomers (i.e.
8 couples of enantiomers). Figure 4-5 shows only the 3 isomers most frequently found in living
organisms.

It is observed that these 3 isomers are all of the D-series. In fact, natural monosaccharides, whether
aldoses or ketoses, are mostly of the D-series (the only notable exceptions are L-arabinose and L-fucose).

Ketoses:
Regarding the D- or L-configuration of ketoses, the same rule — given earlier — applies. Figure 4-6
shows the structure of some ketoses which play an important role in carbohydrate metabolism. It will be
observed that they all have the ketone group in position 2 and – excepting fructose – their names are
appended with the suffix -ulose which is characteristic of ketoses.

It may be noted that the 2 ketopentoses represented, D-ribulose and D- xylulose differ only by the
configuration of a single carbon atom (carbon 3), they are epimers. D-glucose and D-galactose (see fig. 4-
5) are also epimers (they differ only by the configuration of carbon 4) and so also D- glucose and D -man-
nose (the difference in configuration is exclusively on carbon 2); on the contrary, D-mannose and D-
galactose axe not epimers.

The Different Types of Monosaccharides:

Monosaccharides are divided into four categories: “neutral” monosaccharides, osamines, uronic acids and
sialic acids (or neuraminic acids).
1. “Neutral” Monosaccharides:
The “neutral” monosaccharides include carbohydrates which possess only alcoholic groups in addition to
the aldehyde or ketone group: D-glucose, D-galactose, D-mannose, D-xylose, etc. may be cited as
examples.

This group also comprises the deoxyoses, which are monosaccharides having lost 1 or 2 oxygen atoms.
Among them, can be mentioned the 6-deoxyhexoses which may be considered, either as aldohexoses, the
terminal — CH2OH of which is replaced by a — CH3, or as aldopentoses in which one hydrogen of
carbon 5 is replaced by a methyl (examples: L-rhammose or 6-deoxy-L-man- nose, L-fucose or 6-deoxy-
L-galactose).
The most important is a pentose, the 2-deoxy-D-ribose, which is the monosaccharide found in
deoxyribonucleic acids and derives from D-ribose (see fig. 4-9) by simple replacement of the hydroxyl of
carbon 2, by a hydrogen.

2. Osamines:
They derive from the neutral monosaccharides by replacement of a hydroxyl (generally the one carried by
carbon 2) by an amine group. They are often found in polysaccharides which are described in the
following. The amino group is frequently acetylated. Figure 4-10 shows the structure of the 4 most
common hexosamines (the structures of glucosamine and muramic acid are represented in the N-
acetylated form).
3. Uronic Acids:
Uronic acids derive from aldoses by oxidation of the primary- alcohol group into a carboxylic group (and
therefore maintain the aldehyde group). D-glycuronic (also called “glucuronic”) acid is one of the most
widely distributed uronic acids; it is found in various polysaccharides; furthermore, it participates in
detoxification processes: some compounds are eliminated by the higher organisms in the form of
heterosides called glucuronides (or glucorono- conjugates). Its structure is shown in figure 4-11.

4. Sialic Acids:
Sialic (or neuraminic) acids are derivatives (generally acetylated) of neuraminic acid which itself consists
of a molecule of pyruvic acid (carbons 1, 2,3) condensed with a molecule of D-mannosamine (carbons 4
to 9). N-acetyl- neuraminic acid (see fig. 4-11) is obtained if the amino group of this osamine is
acetylated.

The other acetylations, leading to various sialic acids, occur on hydroxyls (especially in positions 4 and
7). Sialic acids are constituents of various glycoproteins and glycolipids. There are also N-glycolyl-
neuraminic acids (the OH of which can also be acetylated).

Compounds Derived from Monosaccharides:

1. L-Ascorbic Acid (Vitamin C):
A study of its structure (see fig. 4-11) reveals that it is the γ-lactone of an hexonic acid (which itself
derives from an aldohexose by oxidation of the aldehyde group to acid). It is further characterised by a
double bond between 2 carbon atoms, each carrying a hydroxyl (ene-diol). This substance readily
oxidises to dehydroascorbic acid (reversible reaction), which enables its participation in cellular
oxidation-reduction processes.

2. Polyalcohols (or Polyols):

Polyalcohols are obtained by reduction of the aldehyde or ketone group to alcohol group. For example, by
reduction, D-glucose gives D-glucitol (usually known as sorbitol), D-galactose gives D-galactitol (usually
known as dulcitol), D-mannose gives mannitol, D-ribose gives ribitol (found in the molecule of
riboflavin, see fig. 2-17).

The compound with 3 carbon atoms, glycerol, which may be considered as the reduction product of
glyceraldehyde or dihydroxyacetone (and which in fact, derives from the latter) is a trialcohol which has a
considerable metabolic importance.

Lastly, let us mention the existence of cyclic polyalcohols, called cyclitols. The representative of this
group most frequently found in nature is myo-inositol (see fig. 4-12); it is present either in the free state,
or hexa-esterified by phosphoric acid (phytic acid, which exists in the form of a complex salt of Ca 2+ and
Mg2+ — called phytin — in the envelope of cereal grains), or as constituent of certain phospholipids, the
phosphatidyl-inositols

Role of Monosaccharide:
Biological Forms of Monosaccharides

Monosaccharides are characterized by the number of carbon atoms their molecules contain.
Monosaccharides with the formula C6H12O6 include glucose, galactose and fructose, which are sugars
used by organisms for energy. Xylose is a five-carbon monosaccharide, called a pentose, found in plant
cells; this monosaccharide combines with xylan to form woody materials, such as those that make up
trees. Similarly, arabinose is found in coniferous trees. Ribose and deoxyribose are components of
ribonucleic and deoxyribonucleic acids, commonly known as RNA and DNA.

Fuel for Metabolism

One major function of a monosaccharide is its use for energy within a living organism. Glucose is a
commonly known carbohydrate that is metabolized within cells to create fuel. In the presence of
oxygen, glucose breaks down into carbon dioxide and water, and energy is released as a byproduct.
Glucose is a product of photosynthesis, and plants obtain energy from glucose through respiration.
Humans acquire glucose from food, and the body transforms this monosaccharide into energy

Building Blocks

Monosaccharides are also the foundation for more complex carbohydrates, or they serve as components
to amino acids. The ribose and deoxyribose monosaccharides are vital elements of RNA and DNA,
which are the building blocks of life. While monosaccharides cannot be broken down into smaller
sugars, disaccharides and polysaccharides are broken down into monosaccharides in processes like
digestion. For example, the disaccharide lactose is degraded into monosaccharides, which can be
absorbed into the human body.

Derivatives of Monosaccharides
Derivatives of monosaccharides are found in nature. One example of a monosaccharide derivative is
vitamin C, also called ascorbic acid, which is derived from glucose. Sugar substitutes, such as sorbitol
and mannitol, are used as sweeteners, and they form naturally in plants and berries from
monosaccharides like glucose and mannose. Amino sugars, such as glucosamine, a derivative of
glucose, produce cartilage, connective tissue and chitin, a component of an insect’s exoskeleton.

oligosaccharides:
An oligosaccharide  is a saccharide polymer containing a small number (typically three to ten)
of monosaccharides (simple sugars). Oligosaccharides can have many functions including cell recognition
and cell binding.] For example, glycolipids have an important role in the immune response.
They are normally present as glycans: oligosaccharide chains linked to lipids or to compatible amino
acid side chains in proteins, by N- or O-glycosidic bonds. N-Linked oligosaccharides are always
pentasaccharides attached to asparagine via a beta linkage to the amine nitrogen of the side chain.
[7]
 Alternately, O-linked oligosaccharides are generally attached to threonine or serine on the alcohol
group of the side chain. Not all natural oligosaccharides occur as components of glycoproteins or
glycolipids. Some, such as the raffinose series, occur as storage or transport carbohydrates in plants.
Others, such as maltodextrins or cellodextrins, result from the microbial breakdown of
larger polysaccharides such as starch or cellulose.
N-Linked oligosaccharides

An example of an N-linked oligosaccharide, shown here with GlcNAc. X is any amino acid except
proline.

N-Linked glycosylation involves oligosaccharide attachment to asparagine via a beta linkage to the amine
nitrogen of the side chain.[7] The process of N-linked glycosylation occurs cotranslationally, or
concurrently while the proteins is being translated. Since it is added cotranslationally, it is believed
that N-linked glycosylation helps determine the folding of polypeptides due to the hydrophilic nature of
sugars. All N-linked oligosaccharides are pentasaccharides: five monosaccharides long.
In N-glycosylation for eukaryotes, the oligosaccharide substrate is assembled right at the membrane of
the endoplasmatic reticulum.[9] For prokaryotes, this process occurs at the plasma membrane. In both
cases, the acceptor substrate is an asparagine residue. The asparagine residue linked to an N-linked
oligosaccharide usually occurs in the sequence Asn-X-Ser/Thr, [7] where X can be any amino acid except
for proline, although it is rare to see Asp, Glu, Leu, or Trp in this position.
O-Linked oligosaccharides

An example of an O-linked oligosaccharide with β-Galactosyl-(1n3)-α-

N-acetylgalactosaminyl-Ser/Thr.Oligosaccharides that participate in O-linked glycosylation are attached
to threonine or serine on the hydroxyl group of the side chain.[7] O-linked glycosylation occurs in
the Golgi apparatus, where monosaccharide units are added to a complete polypeptide chain. Cell surface
proteins and extracellular proteins are O-glycosylated.[10] Glycosylation sites in O-linked oligosaccharides
are determined by the secondary and tertiary structures of the polypeptide, which dictate
where glycosyltransferases will add sugars.
Dietary oligosaccharides:
Fructo-oligosaccharides (FOS), which are found in many vegetables, are short chains
of fructose molecules. They differ from fructans such as inulin, which as polysaccharides have a much
higher degree of polymerization than FOS and other Oligiosaccharides, but like inulin and other fructans,
they are considered soluble dietary fibre. Galactooligosaccharides (GOS), which also occur naturally,
consist of short chains of galactose molecules. Human milk is an example of this and contains
oligosaccharides, known as human milk oligosaccharides (HMOs), which are derived from lactose.[17]
[18]
 These oligosaccharides have biological function in the development of the gut flora of infants.
Examples include lacto-N-tetraose, lacto-N-neotetraose, and lacto-N-fucopentaose. [17][18] These
compounds cannot be digested in the human small intestine, and instead pass through to the large
intestine, where they promote the growth of Bifidobacteria, which are beneficial to gut health

Cell recognition
All cells are coated in either glycoproteins or glycolipids, both of which help determine cell
types. Lectins, or proteins that bind carbohydrates, can recognize specific oligosaccharides and provide
useful information for cell recognition based on oligosaccharide binding
An important example of oligosaccharide cell recognition is the role of glycolipids in determining blood
types. The various blood types are distinguished by the glycan modification present on the surface of
blood cells.[15] These can be visualized using mass spectrometry. The oligosaccharides found on the A, B,
and H antigen occur on the non-reducing ends of the oligosaccharide. The H antigen (which indicates an
O blood type) serves as a precursor for the A and B antigen. [7] Therefore, a person with A blood type will
have the A antigen and H antigen present on the glycolipids of the red blood cell plasma membrane. A
person with B blood type will have the B and H antigen present. A person with AB blood type will have
A, B, and H antigens present. And finally, a person with O blood type will only have the H antigen
present. This means all blood types have the H antigen, which explains why the O blood type is known as
the "universal donor".[citation needed]
How do transport vesicles know the final destination of the protein that they are transporting?
Vesicles are directed by many ways, but the two main ways are:

1. The sorting signals encoded in the amino acid sequence of the proteins.
2. The Oligosaccharide attached to the protein.
The sorting signals are recognised by specific receptors that reside in the membranes or surface coats of
budding vesicles, ensuring that the protein is transported to the appropriate destination. 
Cell adhesion
Many cells produce specific carbohydrate-binding proteins known as lectins, which mediate cell adhesion
with oligosaccharides.[16] Selectins, a family of lectins, mediate certain cell–cell adhesion processes,
including those of leukocytes to endothelial cells. [7] In an immune response, endothelial cells can express
certain selectins transiently in response to damage or injury to the cells. In response, a reciprocal selectin–
oligosaccharide interaction will occur between the two molecules which allows the white blood cell to
help eliminate the infection or damage. Protein-Carbohydrate bonding is often mediated by hydrogen
bonding and van der Waals forces.
polysaccharides
Polysaccharides or polycarbohydrates, are the most abundant carbohydrate found in food. They are long
chain polymeric carbohydrates composed of monosaccharide units bound together by glycosidic linkages.
This carbohydrate can react with water (hydrolysis) using amylase enzymes as catalyst, which produces
constituent sugars (monosaccharides, or oligosaccharides). They range in structure from linear to highly
branched. Examples include storage polysaccharides such as starch, glycogen and galactogen and
structural polysaccharides such as cellulose and chitin.
Polysaccharides are often quite heterogeneous, containing slight modifications of the repeating unit.
Depending on the structure, these macromolecules can have distinct properties from their monosaccharide
building blocks. They may be amorphous or even insoluble in water.[1] When all the monosaccharides in a
polysaccharide are the same type, the polysaccharide is called a homopolysaccharide or homoglycan, but
when more than one type of monosaccharide is present they are
called heteropolysaccharides or heteroglycans.[2][3]
Natural saccharides are generally composed of simple carbohydrates called monosaccharides with general
formula (CH2O)n where n is three or more. Examples of monosaccharides are glucose, fructose,
and glyceraldehyde.[4] Polysaccharides, meanwhile, have a general formula of C x(H2O)y where x is usually
a large number between 200 and 2500. When the repeating units in the polymer backbone are six-carbon
monosaccharides, as is often the case, the general formula simplifies to (C 6H10O5)n, where typically 40
≤ n ≤ 3000.
As a rule of thumb, polysaccharides contain more than ten monosaccharide units,
whereas oligosaccharides contain three to ten monosaccharide units; but the precise cutoff varies
somewhat according to convention. Polysaccharides are an important class of biological polymers.
Their function in living organisms is usually either structure- or storage-related. Starch (a polymer of
glucose) is used as a storage polysaccharide in plants, being found in the form of both amylose and the
branched amylopectin. In animals, the structurally similar glucose polymer is the more densely
branched glycogen, sometimes called "animal starch". Glycogen's properties allow it to be metabolized
more quickly, which suits the active lives of moving animals. In bacteria, they play an important role in
bacterial multicellularity[5].
Cellulose and chitin are examples of structural polysaccharides. Cellulose is used in the cell walls of
plants and other organisms, and is said to be the most abundant organic molecule on Earth.[6] It has many
uses such as a significant role in the paper and textile industries, and is used as a feedstock for the
production of rayon (via the viscose process), cellulose acetate, celluloid, and nitrocellulose. Chitin has a
similar structure, but has nitrogen-containing side branches, increasing its strength. It is found
in arthropod exoskeletons and in the cell walls of some fungi. It also has multiple uses, including surgical
threads. Polysaccharides also
include callose or laminarin, chrysolaminarin, xylan, arabinoxylan, mannan, fucoidan and galactomannan.
Structure:
Nutrition polysaccharides are common sources of energy. Many organisms can easily break down
starches into glucose; however, most organisms cannot metabolize cellulose or other polysaccharides
like chitin and arabinoxylans. These carbohydrate types can be metabolized by some bacteria and
protists. Ruminants and termites, for example, use microorganisms to process cellulose.
Even though these complex polysaccharides are not very digestible, they provide important dietary
elements for humans. Called dietary fiber, these carbohydrates enhance digestion among other benefits.
The main action of dietary fiber is to change the nature of the contents of the gastrointestinal tract, and to
change how other nutrients and chemicals are absorbed. [7][8] Soluble fiber binds to bile acids in the small
intestine, making them less likely to enter the body; this in turn lowers cholesterol levels in the blood.
[9]
 Soluble fiber also attenuates the absorption of sugar, reduces sugar response after eating, normalizes
blood lipid levels and, once fermented in the colon, produces short-chain fatty acids as byproducts with
wide-ranging physiological activities (discussion below). Although insoluble fiber is associated with
reduced diabetes risk, the mechanism by which this occurs is unknown. [10]
Not yet formally proposed as an essential macronutrient (as of 2005), dietary fiber is nevertheless
regarded as important for the diet, with regulatory authorities in many developed countries recommending
increases in fiber intake

Structural polysaccharides

Arabinoxylans
Arabinoxylans are found in both the primary and secondary cell walls of plants and are the copolymers of
two sugars: arabinose and xylose. They may also have beneficial effects on human health. [22]
Cellulose
The structural components of plants are formed primarily from cellulose. Wood is largely cellulose
and lignin, while paper and cotton are nearly pure cellulose. Cellulose is a polymer made with repeated
glucose units bonded together by beta-linkages. Humans and many animals lack an enzyme to break
the beta-linkages, so they do not digest cellulose. Certain animals such as termites can digest cellulose,
because bacteria possessing the enzyme are present in their gut. Cellulose is insoluble in water. It does not
change color when mixed with iodine. On hydrolysis, it yields glucose. It is the most abundant
carbohydrate in nature.
Chitin
Chitin is one of many naturally occurring polymers. It forms a structural component of many animals,
such as exoskeletons. Over time it is bio-degradable in the natural environment. Its breakdown may be
catalyzed by enzymes called chitinases, secreted by microorganisms such as bacteria and fungi, and
produced by some plants. Some of these microorganisms have receptors to simple sugars from the
decomposition of chitin. If chitin is detected, they then produce enzymes to digest it by cleaving
the glycosidic bonds in order to convert it to simple sugars and ammonia.
Chemically, chitin is closely related to chitosan (a more water-soluble derivative of chitin). It is also
closely related to cellulose in that it is a long unbranched chain of glucose derivatives. Both materials
contribute structure and strength, protecting the organism.
Pectins
Pectins are a family of complex polysaccharides that contain 1,4-linked α- D-galactosyl uronic acid
residues. They are present in most primary cell walls and in the non-woody parts of terrestrial plants.

Acidic polysaccharides
Acidic polysaccharides are polysaccharides that contain carboxyl groups, phosphate groups
and/or sulfuric ester groups.
Bacterial polysaccharides
Pathogenic bacteria commonly produce a thick, mucous-like, layer of polysaccharide. This "capsule"
cloaks antigenic proteins on the bacterial surface that would otherwise provoke an immune response and
thereby lead to the destruction of the bacteria. Capsular polysaccharides are water-soluble, commonly
acidic, and have molecular weights on the order of 100,000 to 2,000,000 daltons. They are linear and
consist of regularly repeating subunits of one to six monosaccharides. There is enormous structural
diversity; nearly two hundred different polysaccharides are produced by E. coli alone. Mixtures of
capsular polysaccharides, either conjugated or native are used as vaccines.
Bacteria and many other microbes, including fungi and algae, often secrete polysaccharides to help them
adhere to surfaces and to prevent them from drying out. Humans have developed some of these
polysaccharides into useful products, including xanthan gum, dextran, welan gum, gellan gum, diutan
gum and pullulan.
Most of these polysaccharides exhibit useful visco-elastic properties when dissolved in water at very low
levels.[23] This makes various liquids used in everyday life, such as some foods, lotions, cleaners, and
paints, viscous when stationary, but much more free-flowing when even slight shear is applied by stirring
or shaking, pouring, wiping, or brushing. This property is named pseudoplasticity or shear thinning; the
study of such matters is called rheology.

Viscosity of Welan gum

Viscosity (cP or
Shear rate (rpm)
mPa⋅s)

0.3 23330

0.5 16000

1 11000

2 5500

4 3250

5 2900

10 1700
 20 900

50 520

100 310

Aqueous solutions of the polysaccharide alone have a curious behavior when stirred: after stirring
ceases, the solution initially continues to swirl due to momentum, then slows to a standstill due to
viscosity and reverses direction briefly before stopping. This recoil is due to the elastic effect of the
polysaccharide chains, previously stretched in solution, returning to their relaxed state.
Cell-surface polysaccharides play diverse roles in bacterial ecology and physiology. They serve as a
barrier between the cell wall and the environment, mediate host-pathogen interactions.
Polysaccharides also play an important role in formation of biofilms and the structuring of complex
life forms in bacteria like Myxococcus xanthus[24].
These polysaccharides are synthesized from nucleotide-activated precursors (called nucleotide
sugars) and, in most cases, all the enzymes necessary for biosynthesis, assembly and transport of the
completed polymer are encoded by genes organized in dedicated clusters within the genome of
the organism. Lipopolysaccharide is one of the most important cell-surface polysaccharides, as it
plays a key structural role in outer membrane integrity, as well as being an important mediator of
host-pathogen interactions.
The enzymes that make the A-band (homopolymeric) and B-band (heteropolymeric) O-antigens have
been identified and the metabolic pathways defined.[25] The exopolysaccharide alginate is a linear
copolymer of β-1,4-linked D-mannuronic acid and L-guluronic acid residues, and is responsible for
the mucoid phenotype of late-stage cystic fibrosis disease. The pel and psl loci are two recently
discovered gene clusters that also encode exopolysaccharides found to be important for biofilm
formation. Rhamnolipid is a biosurfactant whose production is tightly regulated at
the transcriptional level, but the precise role that it plays in disease is not well understood at present.
Protein glycosylation, particularly of pilin and flagellin, became a focus of research by several groups
from about 2007, and has been shown to be important for adhesion and invasion during bacterial
infection.[26]

Glycosaminoglycans
Glycosaminoglycans[1] (GAGs) or mucopolysaccharides[2] are long linear polysaccharides consisting of
repeating disaccharide units (i.e. two-sugar units). The repeating two-sugar unit consists of a uronic
sugar and an amino sugar, with the exception of keratan, where in the place of the uronic sugar it
has galactose.[3] Because GAGs are highly polar and attract water, they are used in the body as a lubricant
or shock absorber.
Production
Glycosaminoglycans vary greatly in molecular mass, disaccharide construction, and sulfation. This is
because GAG synthesis is not template driven like proteins or nucleic acids, but constantly altered by
processing enzymes.[4]
GAGs are classified into four groups based on core disaccharide structures. [5] Heparin/heparan
sulfate (HSGAGs) and chondroitin sulfate/dermatan sulfate (CSGAGs) are synthesized in the Golgi
apparatus, where protein cores made in the rough endoplasmic reticulum are post-translationally modified
with O-linked glycosylations by glycosyltransferases forming proteoglycans. Keratan sulfate may modify
core proteins through N-linked glycosylation or O-linked glycosylation of the proteoglycan. The fourth
class of GAG, hyaluronic acid is synthesized by integral membrane synthases which immediately secrete
the dynamically elongated disaccharide chain.

 HSGAG and CSGAG

HSGAG and CSGAG modified proteoglycans first begin with a consensus Ser-Gly/Ala-X-Gly motif in
the core protein. Construction of a tetrasaccharide linker that consists of -GlcAβ1–3Galβ1–3Galβ1–
4Xylβ1-O-(Ser)-, where xylosyltransferase, β4-galactosyl transferase (GalTI),β3-galactosyl transferase
(GalT-II), and β3-GlcA transferase (GlcAT-I) transfer the four monosaccharides, begins synthesis of the
GAG modified protein. The first modification of the tetrasaccharide linker determines whether the
HSGAGs or CSGAGs will be added. Addition of a GlcNAc promotes the addition of HSGAGs while
addition of GalNAc to the tetrasaccharide linker promotes CSGAG development. [5] GlcNAcT-I transfers
GlcNAc to the tetrasaccahride linker, which is distinct from glycosyltransferase GlcNAcT-II, the enzyme
that is utilized to build HSGAGs. EXTL2 and EXTL3, two genes in the EXT tumor suppressor family,
have been shown to have GlcNAcT-I activity. Conversely, GalNAc is transferred to the linker by the
enzyme GalNAcT to initiate synthesis of CSGAGs, an enzyme which may or may not have distinct
activity compared to the GalNAc transferase activity of chondroitin synthase. [5]
With regard to HSGAGs, a multimeric enzyme encoded by EXT1 and EXT2 of the EXT family of genes,
transfers both GlcNAc and GlcA for HSGAG chain elongation. While elongating, the HSGAG is
dynamically modified, first by N-deacetylase, N-sulfotransferase (NDST1), which is a bifunctional
enzyme that cleaves the N-acetyl group from GlcNAc and subsequently sulfates the N-position. Next, C-5
uronyl epimerase coverts d-GlcA to l-IdoA followed by 2-O sulfation of the uronic acid sugar by 2-
O sulfotransferase (Heparan sulfate 2-O-sulfotransferase). Finally, the 6-O and 3-O positions of GlcNAc
moities are sulfated by 6-O (Heparan sulfate 6-O-sulfotransferase) and 3-O (3-OST) sulfotransferases.
Chondroitin sulfate and dermatan sulfate, which comprise CSGAGs, are differentiated from each other by
the presence of GlcA and IdoA epimers respectively. Similar to the production of HSGAGs, C-5 uronyl
epimerase converts d-GlcA to l-IdoA to synthesize dermatan sulfate. Three sulfation events of the
CSGAG chains occur: 4-O and/or 6-O sulfation of GalNAc and 2-O sulfation of uronic acid. Four
isoforms of the 4-O GalNAc sulfotransferases (C4ST-1, C4ST-2, C4ST-3, and D4ST-1) and three
isoforms of the GalNAc 6-O sulfotransferases (C6ST, C6ST-2, and GalNAc4S-6ST) are responsible for
the sulfation of GalNAc.[6]

 Keratan sulfate types

Unlike HSGAGs and CSGAGs, the third class of GAGs, those belonging to keratan sulfate types, are
driven towards biosynthesis through particular protein sequence motifs. For example, in the cornea and
cartilage, the keratan sulfate domain of aggrecan consists of a series of tandemly repeated hexapeptides
with a consensus sequence of E(E/L)PFPS.[7] Additionally, for three other keratan sulfated
proteoglycans, lumican, keratocan, and mimecan (OGN), the consensus sequence NX(T/S) along with
protein secondary structure was determined to be involved in N-linked oligosaccharide extension with
keratan sulfate.[7] Keratan sulfate elongation begins at the nonreducing ends of three linkage
oligosaccharides, which define the three classes of keratan sulfate. Keratan sulfate I (KSI) is N -linked via
a high mannose type precursor oligosaccharide. Keratan sulfate II (KSII) and keratan sulfate III (KSIII)
are O-linked, with KSII linkages identical to that of mucin core structure, and KSIII linked to a 2-
O mannose. Elongation of the keratan sulfate polymer occurs through the glycosyltransferase addition of
Gal and GlcNAc. Galactose addition occurs primarily through the β-1,4-
galactosyltransferase enzyme (β4Gal-T1) while the enzymes responsible for β-3-Nacetylglucosamine
have not been clearly identified. Finally, sulfation of the polymer occurs at the 6-position of both sugar
residues. The enzyme KS-Gal6ST (CHST1) transfers sulfate groups to galactose while N-
acetylglucosaminyl-6-sulfotransferase (GlcNAc6ST) (CHST2) transfers sulfate groups to terminal
GlcNAc in keratan sulfate.[8]

 Hyaluronic acid
The fourth class of GAG, hyaluronic acid, is not sulfated and is synthesized by three transmembrane
synthase proteins HAS1, HAS2, and HAS3. HA, a linear polysaccharide, is composed of repeating
disaccharide units of →4)GlcAβ(1→3)GlcNAcβ(1→ and has a very high molecular mass, ranging from
105 to 107 Da. Each HAS enzyme is capable of transglycosylation when supplied with UDP-GlcA and
UDP-GlcNAc.[9][10] HAS2 is responsible for very large hyaluronic acid polymers, while smaller sizes of
HA are synthesized by HAS1 and HAS3. While each HAS isoform catalyzes the same biosynthetic
reaction, each HAS isoform is independently active. HAS isoforms have also been shown to have
differing Km values for UDP-GlcA and UDPGlcNAc.[11] It is believed that through differences in enzyme
activity and expression, the wide spectrum of biological functions mediated by HA can be regulated, such
as its involvement with neural stem cell regulation in the subgranular zone of the brain.

Function
CSGAGs
Endogenous heparin is localized and stored in secretory granules of mast cells. Histamine that is present
within the granules is protonated (H2A2+) at pH within granules (5.2–6.0), thus it is believed that heparin,
which is highly negatively charged, functions to electrostatically retain and store histamine. [12] In the
clinic, heparin is administered as an anticoagulant and is also the first line choice for thromboembolic
diseases.[13][14] Heparan sulfate (HS) has numerous biological activities and functions, including cell
adhesion, regulation of cell growth and proliferation, developmental processes, cell surface binding of
lipoprotein lipase and other proteins, angiogenesis, viral invasion, and tumor metastasis. [12]CSGAGs
interact with heparin binding proteins, specifically dermatan sulfate interactions with fibroblast growth
factor FGF-2 and FGF-7 have been implicated in cellular proliferation and wound repair [15] while
interactions with hepatic growth factor/scatter factor (HGF/SF) activate the HGF/SF signaling pathway
(c-Met) through its receptor. CASGAGs are important in providing support and adhesiveness in bone,
skin, and cartilage. Other biological functions for which CSGAGs are known to play critical functions in
include inhibition of axonal growth and regeneration in CNS development, roles in brain development,
neuritogenic activity, and pathogen infection.[16]

Keratan sulfates
One of the main functions of the third class of GAGs, keratan sulfates, is the maintenance of
tissue hydration.[17] Keratan sulfates are in the bone, cartilage, and the cornea of the eye. [18] Within
the normal cornea, dermatan sulfate is fully hydrated whereas keratan sulfate is only partially
hydrated suggesting that keratan sulfate may behave as a dynamically controlled buffer for
 hydration.[17] In disease states such as macular corneal dystrophy, in which GAGs levels such as
KS are altered, loss of hydration within the corneal stroma is believed to be the cause of corneal
haze, thus supporting the long-held hypothesis that corneal transparency is a dependent on proper
levels of keratan sulfate. Keratan sulfate GAGs are found in many other tissues besides the
cornea, where they are known to regulate macrophage adhesion, form barriers to neurite growth,
regulate embryo implantation in the endometrial uterine lining during menstrual cycles, and affect
the motility of corneal endothelial cells.[17] In summary, KS plays an anti-adhesive role, which
suggests very important functions of KS in cell motility and attachment as well as other potential
biological processes.
Dermatan sulfates
Dermatan sulfates function in the skin, tendons, blood vessels, and heart valves. [18]
Hyaluronic acid
Hyaluronic acid is a major component of synovial tissues and fluid, as well as the ground
substance of other connective tissues. Hyaluronic acid binds cells together, lubricates joints, and
helps maintain the shape of the eyeballs.[18]:The viscoelasticity of hyaluronic acid make it ideal
for lubricating joints and surfaces that move along each other, such as cartilage. A solution of
hyaluronic acid under low shear stress has a much higher viscosity than while under high shear
stress.[19] Hyaluronidase, an enzyme produced by white blood cells, sperms cells, and some
bacteria, breaks apart the hyaluronic acid, causing the solution to become more liquid. [18]
In vivo, hyaluronic acid forms randomly kinked coils that entangle to form a hyaluronan network,
slowing diffusion and forming a diffusion barrier that regulates transport of substances between
cells. For example, hyaluronan helps partition plasma proteins between vascular and
extravascular spaces, which affects solubility of macromolecules in the interstitium, changes
chemical equilibria, and stabilizes the structure of collagen fibers. [19]
Other functions include matrix interactions with hyaluronan binding proteins such as
hyaluronectin, glial hyaluronan binding protein, brain enriched hyaluronan binding
protein, collagen VI, TSG-6, and inter-alpha-trypsin inhibitor. Cell surface interactions involving
hyaluronan are its well-known coupling with CD44, which may be related to tumor progression,
and also with RHAMM (Hyaluronan-mediated motility receptor), which has been implicated in
developmental processes, tumor metastasis, and pathological reparative processes. Fibroblasts,
mesothelial cells, and certain types of stem cells surround themselves in a pericellular "coat", part
of which is constructed from hyaluronan, in order to shield themselves from bacteria, red blood
cells, or other matrix molecules. For example, with regards to stem cells, hyaluronan, along with
chondroitin sulfate, helps to form the stem cell niche. Stem cells are protected from the effects of
growth factors by a shield of hyaluronan and minimally sulfated chondroitin sulfate. During
progenitor division, the daughter cell moves outside of this pericellular shield where it can then
be influenced by growth factors to differentiate even further.

Classification
Members of the glycosaminoglycan family vary in the type of hexosamine, hexose or hexuronic acid unit
they contain (e.g. glucuronic acid, iduronic acid, galactose, galactosamine, glucosamine).
They also vary in the geometry of the glycosidic linkage.
Examples of GAGs include:

Hexuronic acid or Linkage geometry between

Name hexose (for kerata Hexosamine predominant monomeric Unique features
n) units

Chondroitin sulfa GlcUA or GalNAc or GlcUAβ(1→3)GalNAcβ(1 Most prevalent

te GlcUA(2S) GalNAc(4S) →4) GAG
or
GalNAc(6S)
or
GalNAc(4S,6
S)

Dermatan sulfate GlcUA or GalNAc or 'IdoUAβ1-3'GalNAcβ1-4 Distinguished

IdoUA or GalNAc(4S) from
IdoUA(2S) or chondroitin
GalNAc(6S) sulfate by the
or presence
GalNAc(4S,6 of iduronic acid,
S) although some
hexuronic acid
monosaccharide
s may
be glucuronic
acid.[15]

Keratan sulfate Gal or GlcNAc or -Gal(6S)β1- Keratan sulfate

Gal(6S) GlcNAc(6S) 4GlcNAc(6S)β1-3 type II may
be fucosylated.
[20]

Heparin GlcUA or GlcNAc or -IdoUA(2S)α1- Highest

IdoUA(2S) GlcNS or 4GlcNS(6S)α1-4 negative charge
GlcNAc(6S) density of any
or known
GlcNS(6S) biological
molecule

Heparan sulfate GlcUA or GlcNAc or -GlcUAβ1-4GlcNAcα1-4 Highly similar

IdoUA or GlcNS or in structure to
IdoUA(2S) GlcNAc(6S) heparin,
or however
 GlcNS(6S) heparan
sulfate's
disaccharide
units are
organised into
distinct sulfated
and non-
sulfated
domains.[21]

Hyaluronan GlcUA GlcNAc -GlcUAβ1-3GlcNAcβ1-4 The only GAG

that is
exclusively non-
sulfated

Glycoconjugate
Glycoconjugates is the general classification for carbohydrates – referred to as glycans – which
are covalently linked with other chemical species such as proteins, peptides, lipids and other compounds.
[1]
 Glycoconjugates are formed in processes termed glycosylation.
Glycoconjugates are very important compounds in biology and consist of many different categories such
as glycoproteins, glycopeptides, peptidoglycans, glycolipids, glycosides and lipopolysaccharides. They
are involved in cell–cell interactions, including cell–cell recognition; in cell–matrix interactions; in
detoxification processes.
Generally the carbohydrate part(s) play an integral role in the function of a glycoconjugate; prominent
examples of this are NCAM and blood proteins where fine details in the carbohydrate structure determine
cell binding or not or lifetime in circulation.
Although the important molecular species DNA, RNA, ATP, cAMP, cGMP, NADH, NADPH,
and coenzyme A all contain a carbohydrate part, generally they are not considered as glycoconjugates.
Glycocojugates is covalent linking of carbohydrates antigens to protein scaffolds with goal of achieving a
long term immunological response in body. Immunization with glycoconjugates successfully induced
long term immune memory against carbohydrates antigens. Glycoconjugate vaccines was introduced
since the 1990s have yielded effective results against influenza and meningococcus.[2]