MEDICAL STUDIES BLOG

FERTILIZATION AND IMPLANTATION

2009-06-24T05:32:00.000-07:00

FERTILIZATION AND IMPLANTATION

IMPLANTATION

GAMETOGENESIS

2009-06-24T05:24:00.000-07:00

SPERMATOGENESIS

OOGENESIS

Glycosaminoglycans and glycoproteins

2009-06-08T08:46:00.001-07:00

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 β1 4-linked and β1 3-linked.

Due to the unusual β1 3 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 β1 4 linkage, but

also β1 2, α1 3, and α1 6 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

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Plant polysaccharides

Two glucose polymers of plant origin are of

special importance among the polysaccharides:

β1 4-linked polymer cellulose

and starch, which ismostly α1 4-linked.

A. Cellulose

Cellulose, a linear homoglycan of β1 4-

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 β1 4 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 α1 4-

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 α1 6 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

2009-06-08T08:38:00.000-07:00

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

α1 4-linked glucose residues. In glycogen,

on average every 8th to 10th residue carries

—via an α1 6 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 β1 4-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 α1 6-linked and α1 3-

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 β1 4-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

2009-06-08T08:33:00.000-07:00

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

2009-06-08T08:24:00.000-07:00

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

2009-06-08T08:10:00.000-07:00

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.

Anatomy of the Heart

2009-06-08T00:53:00.000-07:00

Basic anatomy of the heart

Cardiac Cycle 1

2009-06-08T00:35:00.001-07:00

cardiac cycle 1

Cardiac Cycle 2

2009-06-08T00:34:00.001-07:00

cardiac cycle 2

3d animation of a cardiac cycle + electrical activity

2009-06-08T00:31:00.000-07:00

short video on cardiac cycle and electrical activity

The Pacemaker of the Heart

2009-06-08T00:24:00.001-07:00

The pacemaker of the heart

Intro EKG Interpretation Part 1

2009-06-07T22:41:00.000-07:00

ecg interpretation part 1

Intro EKG Interpretation Part 2

2009-06-07T22:39:00.000-07:00

ecg interpretation part 2

Intro EKG Interpretation Part 3

2009-06-07T22:34:00.000-07:00

ecg interpretation part 3

CARDIAC ARRHYTHMIAS

2009-06-06T05:50:00.000-07:00

BASIC INFORMATION ON CARDIAC ARRHYTHMIAS

CARDIAC ARRHYTHMIAS

2009-06-06T05:47:00.000-07:00

TRACHYCARDIA

THIS VIDEO WILL HELP U IN UNDERSTANDING TRACHYCARDIA

CARDIAC ARRHYTHMIAS

2009-06-06T05:45:00.000-07:00

VENTRICULAR FIBRILLATION

THIS VIDEO WILL BE VERY HELPFUL IN UNDERSTANDING VENTRICULAR FIBRILLATION

CARDIAC ARRHYTHMIAS

2009-06-06T05:40:00.000-07:00

ATRIAL FIBRILLATION ( VIDEO )

THIS VIDEO WILL BE VERY HELPFUL IN UNDERSTANDING ATRIAL FIBRILLATION