Wednesday, June 24, 2009

FERTILIZATION AND IMPLANTATION




FERTILIZATION AND IMPLANTATION











IMPLANTATION




GAMETOGENESIS





SPERMATOGENESIS















OOGENESIS






Monday, June 8, 2009

Glycosaminoglycans and glycoproteins


Glycosaminoglycans and glycoproteins

A. Hyaluronic acid 


As constituents of proteoglycans ,
the glycosaminoglycans—a group of acidic
heteropolysaccharides—are important structural
elements of the extracellular matrix.
Glycosaminoglycans contain amino sugars
as well as glucuronic acid and iduronic acid as
characteristic components . In addition,
most polysaccharides in this group are
esterified to varying extents by sulfuric acid,
increasing their acidic quality. Glycosaminoglycans
can be found in free form, or as components
of proteoglycans throughout the organism.
Hyaluronic acid, an unesterified glycosaminoglycan
with a relatively simple structure,
consists of disaccharide units in which Nacetylglucosamine
and glucuronic acid are
alternately β14-linked and β13-linked.
Due to the unusual β13 linkage, hyaluronic
acid molecules–which may contain several
thousand monosaccharide residues—are
coiled like a helix. Three disaccharide units
form each turn of the helix. The outwardfacing
hydrophilic carboxylate groups of the glucuronic
acid residues are able to bind Ca2+
ions. The strong hydration of these groups
enables hyaluronic acid and other glycosaminoglycans
to bind water up to 10 000 times
their own volume in gel form. This is the
function which hyaluronic acid has in the vitreous
body of the eye, which contains approximately
1% hyaluronic acid and 98% water.

B. Oligosaccharide in immunoglobulin G(IgG) 


Many proteins on the surface of the plasma
membrane, and the majority of secreted proteins,
contain oligosaccharide residues that
are post-translationally added to the endoplasmic
reticulum and in the Golgi apparatus
. By contrast, cytoplasmic proteins
are rarely glycosylated. Glycoproteins can
contain more than 50% carbohydrate; however,
the proportion of protein is generally
much greater.
As an example of the carbohydrate component
of a glycoprotein, the structure of one of
the oligosaccharide chains of immunoglobulin
G (IgG; is shown here. The
oligosaccharide has an N-glycosidic link to
the amide group of an asparagine residue in
the Fc part of the protein. Its function is not
known.
Like all N-linked carbohydrates, the oligosaccharide
in IgG contains a T-shaped core
structure consisting of two N-acetylglucosamines
and three mannose residues (shown
in violet). In addition, in this case the structure
contains two further N-acetylglucosamine
residues, as well as a fucose residue
and a galactose residue. Glycoproteins show
many different types of branching. In this
case, we not only have β14 linkage, but
also β12, α13, and α16 bonds.


C. Glycoproteins: forms 

On the cell surface of certain glycoproteins,
O-glycosidic links are found between the carbohydrate
part and a serine or threonine residue,
instead of N-glycosidic links to asparagine
residues. This type of link is less common
than the N-glycosidic one.
There are two types of oligosaccharide
structure with N-glycosidic links, which arise
through two different biosynthetic pathways.
During glycosylation in the ER, the protein is
initially linked to an oligosaccharide,which in
addition to the core structure contains six
further mannose residues and three terminal
glucose residues . The simpler
from of oligosaccharide (the mannose-rich
type) is produced when only the glucose residues
are cleaved from the primary product,
and no additional residues are added. In other
cases, the mannose residues that are located
outside the core structure are also removed
and replaced by other sugars. This produces
oligosaccharides such as those shown on the
right (the complex type). At the external end
of the structure, glycoproteins of the complex
type often contain N-acetylneuraminic acid
residues,which give the oligosaccharide components
negative charges.

Plant polysaccharides


Plant polysaccharides


Two glucose polymers of plant origin are of
special importance among the polysaccharides:
β14-linked polymer cellulose
and starch, which ismostly α14-linked.

A. Cellulose 


Cellulose, a linear homoglycan of β14-
linked glucose residues, is the most abundant
organic substance in nature. Almost half of the
total biomass consists of cellulose. Some
40–50% of plant cell walls are formed by cellulose.
The proportion of cellulose in cotton
fibers, an important raw material, is 98%. Cellulose
molecules can contain more than 104
glucose residues (mass 1–2 106 Da) and can
reach lengths of 6–8 μm.
Naturally occurring cellulose is extremely
mechanically stable and is highly resistant to
chemical and enzymatic hydrolysis. These
properties are due to the conformation of
the molecules and their supramolecular organization.
The unbranched β14 linkage results
in linear chains that are stabilized by
hydrogen bonds within the chain and between
neighboring chains (1). Already during
biosynthesis, 50–100 cellulose molecules associate
to form an elementary fibril with a
diameter of 4 nm. About 20 such elementary
fibrils then form a microfibril (2), which is
readily visible with the electron microscope.
Cellulose microfibrils make up the basic
framework of the primary wall of young plant
cells (3), where they form a complex network
with other polysaccharides. The linking polysaccharides
include hemicellulose, which is a
mixture of predominantly neutral heteroglycans
(xylans, xyloglucans, arabinogalactans,
etc.). Hemicellulose associates with the cellulose
fibrils via noncovalent interactions. These
complexes are connected by neutral and
acidic pectins, which typically contain galacturonic
acid. Finally, a collagen-related
protein, extensin, is also involved in the formation
of primary walls.
In the higher animals, including humans,
cellulose is indigestible, but important as
roughage . Many herbivores (e. g.,
the ruminants) have symbiotic unicellular organisms
in their digestive tracts that break
down cellulose and make it digestible by the
host.

B. Starch 


Starch, a reserve polysaccharide widely distributed
in plants, is the most important carbohydrate
in the human diet. In plants, starch
is present in the chloroplasts in leaves, as well
as in fruits, seeds, and tubers. The starch content
is especially high in cereal grains (up to
75% of the dry weight), potato tubers (approximately
65%), and in other plant storage
organs.
In these plant organs, starch is present in
the form of microscopically small granules in
special organelles known as amyloplasts.
Starch granules are virtually insoluble in cold
water, but swell dramatically when the water
is heated. Some 15–25% of the starch goes
into solution in colloidal form when the mixture
is subjected to prolonged boiling. This
proportion is called amylose (“soluble
starch”).
Amylose consists of unbranched α14-
linked chains of 200–300 glucose residues.
Due the α configuration at C-1, these chains
form a helix with 6–8 residues per turn (1).
The blue coloring that soluble starch takes on
when iodine is added (the “iodine–starch reaction”)
is caused by the presence of these
helices—the iodine atoms form chains inside
the amylose helix, and in this largely nonaqueous
environment take on a deep blue
color. Highly branched polysaccharides turn
brown or reddishbrown in the presence of
iodine.
Unlike amylose, amylopectin, which is
practically insoluble, is branched. On average,
one in 20–25 glucose residues is linked to
another chain via an α16 bond. This leads
to an extended tree-like structure, which—
like amylose—contains only one anomeric
OH group (a “reducing end”). Amylopectin
molecules can contain hundreds of thousands
of glucose residues; their mass can be more
than 108 Da.

Polysaccharides: overview


Polysaccharides: overview


Polysaccharides are ubiquitous in nature.
They can be classified into three separate
groups, based on their different functions.
Structural polysaccharides provide mechanical
stability to cells, organs, and organisms.
Waterbinding polysaccharides are strongly
hydrated and prevent cells and tissues from
drying out. Finally, reserve polysaccharides
serve as carbohydrate stores that release
monosaccharides as required. Due to their
polymeric nature, reserve carbohydrates are
osmotically less active, and they can therefore
be stored in large quantities within the cell.


A. Polysaccharides: structure 


Polysaccharides that are formed from only
one type of monosaccharide are called homoglycans,
while those formed from different
sugar constituents are called heteroglycans.
Both forms can exist as either linear or
branched chains.
A section of a glycogen molecule is shown
here as an example of a branched homoglycan.
Amylopectin, the branched component of
vegetable starch, has a very similar
structure. Both molecules mainly consist of
α14-linked glucose residues. In glycogen,
on average every 8th to 10th residue carries
—via an α16 bond—another 1,4-linked
chain of glucose residues. This gives rise to
branched, tree-like structures, which in animal
glycogen are covalently bound to a
protein, glycogenin .
The linear heteroglycan murein, a structural
polysaccharide that stabilizes the cell
walls of bacteria, has a more complex structure.
Only a short segment of this thread-like
molecule is shown here. Inmurein, two different
components, both β14-linked, alternate:
N-acetylglucosamine (GlcNAc) and
N-acetylmuraminic acid (MurNAc), a lactic
acid ether of N-acetylglucosamine. Peptides
are bound to the carboxyl group of the lactyl
groups, and attach the individual strands of
murein to each other to form a three-dimensional
network . Synthesis of the
network-forming peptides in murein is inhibited
by penicillin .

B. Important polysaccharides 


The table gives an overview of the composition
and make-up both of the glycans mentioned
above and of several more.
In addition to murein, bacterial polysaccharides
include dextrans—glucose polymers
that are mostly α16-linked and α13-
branched. In water, dextrans form viscous
slimes or gels that are used for chromatographic
separation of macromolecules after
chemical treatment . Dextrans are
also used as components of blood plasma
substitutes (plasma expanders) and foodstuffs.
Carbohydrates from algae (e. g., agarose
and carrageenan) can also be used to produce
gels. Agarose has been used in microbiology
for more than 100 years to reinforce culture
media (“agar-agar”). Algal polysaccharides are
also added to cosmetics and ready-made
foods tomodify the consistency of these products.
The starches, themost important vegetable
reserve carbohydrate and polysaccharides
from plant cell walls, are discussed in greater
detail on the following page. Inulin, a fructose
polymer, is used as a starch substitute in diabetics’
dietary products. In addition,
it serves as a test substance for measuring
renal clearance .
Chitin, a homopolymer from β14-linked
N-acetylglucosamine, is the most important
structural substance in insect and crustacean
shells, and is thus the most common animal
polysaccharide. It also occurs in the cell wall
of fungi.
Glycogen, the reserve carbohydrate of
higher animals, is stored in the liver andmusculature
in particular . The
formation and breakdown of glycogen are
subject to complex regulation by hormones
and other factors .

Monosaccharides and disaccharides


Monosaccharides and disaccharides

A. Important monosaccharides 

Only the most important of the large number
of naturally occurring monosaccharides are
mentioned here. They are classified according
to the number of C atoms (into pentoses,
hexoses, etc.) and according to the chemical
nature of the carbonyl function into aldoses
and ketoses.
The best-known aldopentose (1), D-ribose,
is a component of RNA and of nucleotide
coenzymes and is widely distributed. In these
compounds, ribose always exists in the furanose
form (see p. 34). Like ribose, D-xylose and
L-arabinose are rarely found in free form.
However, large amounts of both sugars are
found as constituents of polysaccharides in
the walls of plant cells (see p. 42).
The most important of the aldohexoses (1)
is D-glucose. A substantial proportion of the
biomass is accounted for by glucose polymers,
above all cellulose and starch. Free D-glucose
is found in plant juices (“grape sugar”) and as
“blood sugar” in the blood of higher animals.
As a constituent of lactose (milk sugar), Dgalactose
is part of the human diet. Together
with D-mannose, galactose is also found in
glycolipids and glycoproteins .
Phosphoric acid esters of the ketopentose
D-ribulose (2) are intermediates in the pentose
phosphate pathway and in
photosynthesis . The most widely
distributed of the ketohexoses is D-fructose. In
free form, it is present in fruit juices and in
honey. Bound fructose is found in sucrose (B)
and plant polysaccharides (e. g., inulin).
In the deoxyaldoses (3), an OH group is
replaced by a hydrogen atom. In addition to
2-deoxy-D-ribose, a component of DNA
that is reduced at C-2, L-fucose is shown
as another example of these. Fucose, a sugar
in the λ series is reduced at C-6.
The acetylated amino sugars N-acetyl-Dglucosamine
and N-acetyl-D-Galactosamine
(4) are often encountered as components of
glycoproteins.
N-acetylneuraminic acid (sialic acid, 5), is a
characteristic component of glycoproteins.
Other acidic monosaccharides such as D-glucuronic
acid, D-galacturonic acid, and liduronic
acid, are typical constituents of the glycosaminoglycans
found in connective tissue.
Sugar alcohols (6) such as sorbitol and
mannitol do not play an important role in
animal metabolism.

B. Disaccharides 


When the anomeric hydroxyl group of one
monosaccharide is bound glycosidically with
one of the OH groups of another, a disaccharide
is formed. As in all glycosides, the glycosidic
bond does not allow mutarotation. Since
this type of bond is formed stereospecifically
by enzymes in natural disaccharides, they are
only found in one of the possible configurations
(α or β).
Maltose (1) occurs as a breakdown product
of the starches contained in malt (“malt
sugar”; and as an intermediate in
intestinal digestion. In maltose, the anomeric
OH group of one glucose molecule has an α-
glycosidic bond with C-4 in a second glucose
residue.
Lactose (“milk sugar,” 2) is themost important
carbohydrate in the milk of mammals.
Cow’s milk contains 4.5% lactose, while human
milk contains up to 7.5%. In lactose, the
anomeric OH group of galactose forms a β-
glycosidic bond with C-4 of a glucose. The
lactose molecule is consequently elongated,
and both of its pyran rings lie in the same
plane.
Sucrose (3) serves in plants as the formin
which carbohydrates are transported, and as a
soluble carbohydrate reserve. Humans value
it because of its intensely sweet taste. Sources
used for sucrose are plants that contain particularly
high amounts of it, such as sugar
cane and sugar beet (cane sugar, beet sugar).
Enzymatic hydrolysis of sucrose-containing
flower nectar in the digestive tract of bees—
catalyzed by the enzyme invertase—produces
honey, a mixture of glucose and fructose. In
sucrose, the two anomeric OH groups of glucose
and fructose have a glycosidic bond; sucrose
is therefore one of the non-reducing
sugars.

Chemistry of sugars


Chemistry of sugars

A. Reactions of the monosaccharides 

The sugars (monosaccharides) occur in the
metabolism in many forms (derivatives).
Only a few important conversion reactions
are discussed here, using D-glucose as an example.

1. Mutarotation.

In the cyclic form, as opposed
to the open-chain form, aldoses have a
chiral center at C-1 . The corresponding
isomeric forms are called anomers.
In the β-anomer (center left), the OH group at
C-1 (the anomeric OH group) and the CH2OH
group lie on the same side of the ring. In the α-
anomer (right), they are on different sides.
The reaction that interconverts anomers into
each other is known as mutarotation (B).

2. Glycoside formation.

When the anomeric
OH group of a sugar reacts with an alcohol,
with elimination of water, it yields an
O–glycoside (in the case shown, α –methylglucoside).
The glycosidic bond is not a normal
ether bond, because the OH group at C-1 has a
hemiacetal quality. Oligosaccharides and polysaccharides
also contain O-glycosidic bonds.
Reaction of the anomeric OH group with an
NH2 or NH group yields an N-glycoside (not
shown). N-glycosidic bonds occur in nucleotides
and in glycoprotein, for example.

3. Reduction and oxidation.

Reduction of
the anomeric center at C-1 of glucose (2) produces
the sugar alcohol sorbitol. Oxidation of
the aldehyde group at C-1 gives the intramolecular
ester (lactone) of gluconic acid (a glyconic
acid). Phosphorylated gluconolactone is
an intermediate of the pentose phosphate
pathway . When glucose is oxidized
at C-6, glucuronic acid (a glycuronic
acid) is formed. The strongly polar glucuronic
acid plays an important role in biotransformations
in the liver .

4. Epimerization.

In weakly alkaline solutions,
glucose is in equilibrium with the
ketohexose D-fructose and the aldohexose Dmannose,
via an enediol intermediate (not
shown). The only difference between glucose
andmannose is the configuration at C-2. Pairs
of sugars of this type are referred to as epimers,
and their interconversion is called epimerization.

5. Esterification.

The hydroxyl groups of
monosaccharides can form esters with acids.
In metabolism, phosphoric acid esters such as
glucose 6-phosphate and glucose 1-phosphate
(6) are particularly important.


B. Polarimetry, mutarotation 


Sugar solutions can be analyzed by polarimetry,
a method based on the interaction between
chiral centers and linearly polarized
light—i. e., light that oscillates in only one
plane. It can be produced by passing normal
light through a special filter (a polarizer). A
second polarizing filter of the same type (the
analyzer), placed behind the first, only lets the
polarized light pass through when the polarizer
and the analyzer are in alignment. In this
case, the field of view appears bright when
one looks through the analyzer (1). Solutions
of chiral substances rotate the plane of polarized
light by an angle α either to the left or to
the right. When a solution of this type is
placed between the polarizer and the analyzer,
the field of view appears darker (2).
The angle of rotation, α, is determined by
turning the analyzer until the field of view
becomes bright again (3). A solution’s optical
rotation depends on the type of chiral compound,
its concentration, and the thickness of
the layer of the solution. Thismethodmakes it
possible to determine the sugar content of
wines, for example.
Certain procedures make it possible to obtain
the α and β anomers of glucose in pure
form. A 1-molar solution of α-D-glucose has a
rotation value [α]D of +112°, while a corresponding
solution of β-D-glucose has a value
of +19°. These values change spontaneously,
however, and after a certain time reach the
same end point of +52°. The reason for this is
that, in solution, mutarotation leads to an
equilibrium between the α and β forms in
which, independently of the starting conditions,
62% of the molecules are present in the
β form and 38% in the α form.

Overview of carbohydrates


Overview of carbohydrates



The carbohydrates are a group of naturally
occurring carbonyl compounds (aldehydes
or ketones) that also contain several hydroxyl
groups. The carbohydrates include single sugars
(monosaccharides) and their polymers,
the oligosaccharides and polysaccharides.

A. Carbohydrates: overview 


Polymeric carbohydrates–above all starch, as
well as some disaccharides–are important
(but not essential) components of food .
In the gut, they are broken down into
monosaccharides and resorbed in this form
. The form in which carbohydrates
are distributed by the blood of vertebrates is
glucose (“blood sugar”). This is taken up by the
cells and either broken down to obtain energy
(glycolysis) or converted into other metabolites
. Several organs (particularly
the liver and muscles) store glycogen as
a polymeric reserve carbohydrate .
The glycogenmolecules are covalently
bound to a protein, glycogenin. Polysaccharides
are used by many organisms as building
materials. For example, the cell walls of bacteria
contain murein as a stabilizing component
, while in plants cellulose and
other polysaccharides fulfill this role .
Oligomeric or polymeric carbohydrates
are often covalently bound to lipids or proteins.
The glycolipids and glycoproteins
formed in this way are found, for example,
in cell membranes (center). Glycoproteins
also occur in the blood in solute form(plasma
proteins; and, as components of
proteoglycans, form important constituents of
the intercellular substance .

B. Monosaccharides: structure 


The most important natural monosaccharide,
D-glucose, is an aliphatic aldehyde with six C
atoms, five of which carry a hydroxyl group
(1). Since C atoms 2 to 5 represent chiral
centers , there are 15 further
isomeric aldohexoses in addition to D-glucose,
although only a few of these are important in
nature. Most natural monosaccharides
have the same configuration at C-5 as
D-glyceraldehyde–they belong to the D series.
The open-chained form of glucose shown
in (1) is found in neutral solution in less than
0.1% of themolecules. The reason for this is an
intramolecular reaction in which one of the
OH groups of the sugar is added to the aldehyde
group of the same molecule (2). This
gives rise to a cyclic hemiacetal . In
aldohexoses, the hydroxy group at C-5 reacts
preferentially, and a six-membered pyran
ring is formed. Sugars that contain this ring
are called pyranoses. By contrast, if the OH
group at C-4 reacts, a five-part furan ring is
formed. In solution, pyranose forms and
furanose forms are present in equilibrium
with each other and with the open-chained
form, while in glucose polymers only the
pyranose form occurs.

The Haworth projection (2) is usually used
to depict sugars in the cyclic form, with the
ring being shown in perspective as viewed
from above. Depending on the configuration,
the substituents of the chiral C atoms are then
found above or below the ring. OH groups
that lie on the right in the Fischer projection
(1) appear under the ring level in the Haworth
projection, while those on the left appear
above it.

As a result of hemiacetal formation, an additional
chiral center arises at C-1, which can
be present in both possible configurations
(anomers) . To emphasize this, the
corresponding bonds are shown here using
wavy lines.

The Haworth formula does not take account
of the fact that the pyran ring is not
plain, but usually has a chair conformation. In
B3, two frequent conformations of D-glucopyranose
are shown as ball-and-stick models. In
the 1C4 conformation (bottom), most of the
OH groups appear vertical to the ring level, as
in the Haworth projection (axial or a position).
In the slightly more stable 4C1 conformation
(top), the OH groups take the equatorial
or e position. At room temperature, each
formcan change into the other, as well as into
other conformations.