воскресенье, 31 октября 2010 г.

Biology of the Cell

The smallest living entity of an organism is the cell. In contrast to single-celled organisms that are independent entities, the cells of higher organisms form functional units. In accordance with their function, the cells are differentiated by size, shape, and the degree of definition of certain characteristics.
For all cells of the body there are a certain basic structure and numerous basic properties. The basic properties include the ability to divide and to sense and respond to stimuli.
Basic Cell Structure
By and large, the cell consists of the cytoplasm containing the cell organelles, the nucleus, and the cell membrane surrounding the whole structure.
Cell Membrane
The cell membrane, also known as the elementary membrane, consists of a double lipid layer, in which the fat-soluble components face each other while the water-soluble parts form the inner and outer boundaries (a three-layered structure). The lipid molecules are infiltrated with proteins. The outer side of the membrane is covered by a glycocalyx. An elementary membrane also surrounds the cell organelles and the nucleus.
Cytoplasm and Cell Organelles
The cytoplasm consists of the intracellular fluid (cytosol), the cell organelles, and various cell inclusions (phakeroplasm). The cell organelles are responsible for the cell’s metabolism.
Endoplasmic Reticulum (ER)
Present in all cells except erythrocytes; serves intracellular material transport; protein synthesis (granular ER); lipid and hormone synthesis (smooth ER).
Ribosomes
No elementary membrane; multienzyme complexes made up of proteins and rRNA molecules that link amino acid chains for protein synthesis.
Free ribosomes: intracellular proteins (enzymes, etc.). Ribosomes in the ER (granular ER): exported proteins (glandular secretions, etc.).
Golgi Apparatus
Present in all cells except erythrocytes; uptake and discharge products of synthesis in the form of membrane-bounded transport vesicles that are flushed from the cell (secretory vesicles) and serve the renewal of the cell membrane or take part in intracellular digestion as primary lysosomes.
Lysosomes
“Digestive organs” of the cell; with the aid of enzymes they degrade cell-alien structures and the cell’s own decaying organelles.
Centrioles
Build the spindle fibers during cell division.
Mitochondria
“Power stations” of the cell; here nutrients (proteins, fats, carbohydrates) are metabolized essentially to CO2 and H2O, generating the energy necessary for metabolism (e. g., muscle contraction, synthesis of structural substances), which is then stored in the form of ATP.
Cell Nucleus
Present in all cells except erythrocytes; the nucleus contains the nucleolus (production of rRNA ⇒ protein biosynthesis) and the chromosomes, carriers of the hereditary factors (genes). Human nuclei contain 23 chromosome pairs (23 paternal, 23 maternal ⇒ diploid chromosome set); the 23rd pair determines sex.
The appearance of the nucleus and of the chromosomes changes with the individual phases of cell division.
During the interphase (working phase of the cell) between two cell divisions (mitoses) the genetic material is duplicated and chromosomes form, each with two chromatids joined by a constriction (centromere). Each chromatid consists of one molecule of DNA (deoxyribonucleic acid). The basic units contained in DNA, the nucleotides, are each composed of one base (adenine, cytosine, guanine, or thymine), a sugar (deoxyribose), and an acid phosphate radical. DNA contains the complete hereditary matter in the form of genes.
Each unit of information comprises three bases (triplet, codon) in varying combinations. Each triplet represents the information for one amino acid. One gene consists of about 300−3000 base triplets and provides the information for one protein. This genetic code is the same for all living things and contains the information for the biosynthesis of proteins, the most important structural and energizing  substances in all organisms.
Protein Biosynthesis
Single-stranded RNA synthesized in the nucleus copies the genetic code (transcription) and brings the message to the ribosomes, the site of protein biosynthesis. Each copied triplet represents one amino acid in the final protein. tRNA molecules, also synthesized in the nucleus, bind amino acids in accordance with the genetic code (according to the sequence of triplets) and transport them to ribosomes, where they are linked into proteins with the aid of enzymes. Each tRNA is specific for one amino acid.
Cell Division (Mitosis)
Chromosomes containing two chromatids are created by the duplication of genetic material during interphase. This process is necessary for the transmission of genetic information to the daughter cells. Mitotic division of cells makes possible growth and the renewal of cells.
Reduction or Maturation Division (Meiosis)
Two successive cell divisions lead to the creation of male or female sex cells with half the chromosome complement (haploid cells).
First maturation division: The (homologous) paternal and maternal chromosomes lying next to each other separate, which leads to the exchange of homologous fragments by “crossing-over.” This results in two daughter cells with haploid chromosome sets.
Second maturation division: Corresponds to a normal mitosis. The chromatids of the chromosomes separate again. The two daughter cells create four mature sex cells with a haploid set of chromosomes.
Fertilization creates a new diploid set of chromosomes. The actual reason for meiosis is the restructuring and recombination of the chromosomes, that is, the shuffling of genetic material.
Intracellular and Extracellular Fluid
The body of an adult person consists of 60% water, two-thirds of which is intracellular, one-third extracellular. Of the 14 liters of extracellular fluid, three-quarters occupy the interstitial spaces and onequarter the vascular system.
Membrane Potential
In the extracellular fluid, sodium is the predominant cation and chloride is the predominant anion; in the intracellular fluid, the predominant cation is potassium and proteins are the predominant anions.
By the differential distribution of ions in the intracellular and extracellular spaces, a potential difference is created across cell membranes (membrane or resting potential). This is caused by the active accumulation of potassium inside the cell (ATP-dependent Na+−K+ pump).
Solid and Fluid Transport
Transport processes between the cells and their environment play an important role in the maintenance of the “internal milieu” (homeostasis). A distinction is made between passive and active (energy-dependent) transport processes. Passive processes include free diffusion (e. g., of O2, CO2, H2O), facilitated diffusion (e. g., of glucose and amino acids in the cells of the intestinal mucosa), osmosis, and filtration (e. g., of glucose and amino acids in the capillaries of the tissue). Active processes include active transport (e. g., of ions) as well as endocytosis and exocytosis (e. g., of proteins).

среда, 27 октября 2010 г.

Endocytosis and Exocytosis

Large molecules, such as proteins, enter (endocytosis) or exit (exocytosis) through the cell membrane by so-called vesicular transport. During this process, substances are attached in part to the outside of the cell by membrane-bound receptors, enclosed by a part of the plasma membrane, and moved into the interior of the cell as a membranewrapped vesicle (receptor-mediated endocytosis). Depending on the size of the absorbed particle, this process may also be called pinocytosis or phagocytosis.
In exocytosis, products synthesized in the cell are enclosed in membranous vesicles and, by coalescence of these vesicles with the inside of the plasma membrane, reach the extracellular space. In this way, the transmitter substances in the endings of nerve cell processes are liberated at the synapses. The secretory products of most glandular cells leave the cell interior in similar fashion. Endocytosis and exocytosis are dependent on the action of ATP.


Exocytosis and endocytosis

понедельник, 25 октября 2010 г.

Active Transport

Active transport is the transport of substances through the cell membrane by means of an energy-consuming transport system (transport ATPase). Here, again, ATP serves as universal fuel. Such a transport process can move a substance through the membrane against a concentration gradient. Thus cells have the ability to maintain in their interior stable ion concentrations, for example, that are clearly different from their concentrations in the extracellular fluid. These active transport processes are served by specialized proteins in the cell membrane that can move several ions simultaneously. In this process, the coupled transport of substances can occur in the same direction (cotransport) or in opposite directions (countertransport). For instance, in the kidney the transport of amino acids is coupled with an active Na+ transport. Additionally, active ion transport through cell membranes is necessary for the formation of  membrane or resting potentials.

воскресенье, 24 октября 2010 г.

Filtration

Filtration occurs when water and any dissolved particles are pushed through cell membranes or pore systems by a hydrostatic pressure difference. Pores occur, for instance, when there are small spaces between endothelial cells (intercellular clefts) or holes (fenestrations) in the cell membranes. Such a process is found in the capillaries of the tissues. The term ultrafiltration is used when, in the course of filtration processes such as that in the capillaries of the renal corpuscles, larger blood components are retained or dissolved molecules are separated out because of their size or charge.

суббота, 23 октября 2010 г.

Osmosis and Osmotic Pressure

When two solutions containing different concentrations of the same solute are separated by a partly permeable membrane, a so-called semipermeable membrane, osmosis can take place. In osmosis the semipermeable membrane allows the solvent, but not the solute, to pass.Water diffuses through the membrane toward the solution of higher concentration, until equilibrium is attained. During this process the volume of the side that initially contained the higher concentration increases. The pressure that must be applied to this side to reverse the process of osmosis is called the osmotic pressure. It is expressed inmmHg or in the SI units of pascals (Pa) or kilopascals (kPa). When such a measurement is applied, it is found that the osmotic pressure depends only on the number of dissolved particles in a defined volume, and not on their size or charge.
The cell membranes are more or less semipermeable membranes, since the lipid layer is less permeable to charged molecules such as ions and proteins. The osmotic pressure of the extracellular fluid depends on its content of protein and salts and corresponds approximately to that of a 0.9% solution of NaCl. Such a physiological salt solution is isotonic (that is, it is in osmotic equilibrium with the cell). Consequently, cells bathed in hypertonic (more concentrated) solutions lose water and shrink, while in hypotonic (less concentrated) solutions they take up water and swell. The organism therefore endeavors by special regulatory mecha nisms to keep the osmotic pressure of the extracellular fluid as constant as possible. Because of the good permeability of cell membranes to water, these mechanisms lead to a more or less constant osmotic pressure in the cell interior.

Thetermcolloidosmoticpressureisusedwhen,for instance, proteins for which the capillary wall is impermeable are dissolved in the blood plasma and not in the interstitial fluid. They create an osmotic pressure difference of about 25mmHg (3.3 kPa) between the interstitial fluid and the capillary space. Thiswould lead to amovement of fluid into the vessels if the hydrostatic blood pressure active inside the blood vessels were not opposed to it. Since the blood pressure at the beginning of the capillaries (37 mmHg)is greaterthanthe colloidosmotic pressure, fluid is actuallyfiltered into the interstitial space.



Development of osmotic pressure in a semipermeable membrane.

вторник, 19 октября 2010 г.

Solid and Fluid Transport

The specific transport processes that take place in the microscopic realm, e. g., between the cells on the one hand and the blood capillaries and their surrounding cells on the other, can be divided into essentially passive (diffusion, osmosis, and filtration) and active (energy-dependent) transport processes (active transport, endocytosis, exocytosis).

понедельник, 18 октября 2010 г.

Membrane or Resting Potential of a Cell

Because the ions are distributed unevenly between the intracellular and extracellular spaces, a potential difference, known as the membrane potential, is created at the cell membrane. This creates a negative charge in the interior of the cell relative to the extracellular space, the so-called resting potential. This potential difference can be measured with sensitive instruments and is about 60−80mV.
The reason for the negative potential inside the cell with respect to its surroundings lies in the differential distribution of ions between the intracellular and extracellular spaces. Thus, the intracellular potassium concentration is about 35 times greater than the extracellular concentration, while proteins are the preponderant anions inside the cell. Sodium ions dominate in the extracellular space, balanced on the negative side by chloride anions. The accumulation of potassium ions inside the cell is a specific activity of almost every cell and represents one of its most important active transport processes. This “ion pump” transports potassium ions into the cells and, to balance this, transports sodium ions out. It is therefore also called the sodium−potassium (Na+−K+) pump. It includes an ATP-splitting enzyme (sodium−potassium ATPase, Na+,K+-ATPase). This reaction liberates the energy required for ion transport. The cell membrane is impermeable to ions, so there are membrane pores (channels) forNa+, K+, and Cl−, but not for protein anions. During resting potential, the K+ channels are often open, but the Na+ and Cl− channels are mostly closed. Because of the concentration difference, the K+ ions have a tendency to diffuse outward. However, the diffusion of positively charged potassium ions out of the cell is limited by the negatively charged protein anions, which cannot cross the membrane because of their size. The diffusion of even a few potassium ions out of the cell leaves anions with the opposite (negative) charge (protein anions) on the inside of the cell membrane, so that the interior of the cell is negatively chargedwith respect to its surroundings. The resting potential is therefore also known as the diffusion potential. The diffusion of ions outwardthrough the membrane pores is independent of the Na+−K+ pump.
The energy-consuming ion pumps can be impeded or blocked by lack of oxygen (failure of ATP production) or by metabolic poisons (e. g., cyanide), leading to severe disturbances in the specific performance of a cell. The initiation and propagation of nerve or muscle cell excitation depends on brief membrane potential changes (action potentials) (see Chapter 3: Nerve Tissue).

суббота, 16 октября 2010 г.

Composition of the Intracellular Fluid

In contrast to the extracellular fluid, where sodium predominates, the quantitatively dominant intracellular cation is potassium (K+). The sodium concentration inside the cell is about 10 times smaller than that outside it. The major portion of the intracellular anions consists of proteins, while phosphates (HPO4
−/H2PO4 −) are present in lower concentrations.

пятница, 15 октября 2010 г.

Composition of the Extracellular Fluid

The substances dissolved in the extracellular fluid (e. g., salts) are present as electrically charged particles (ions) and the solutions are called electrolytes. Because of their electric charge, ions can migrate in electric fields. For this reason, positively charged ions are also called cations (they migrate to the negative pole, the cathode) and negatively charged ions are called anions (they migrate to the positive pole, the anode). The salt present in the largest amount is common table salt (NaCl), consisting of a positively charged sodium ion (Na+) and a negatively charged chloride ion (Cl−) dissolved in a concentration of about 9 g/l. Other cations and anions are also present, though in distinctly smaller quantities: e. g., potassium (K+), calcium (Ca2+) and magnesium (Mg2 +), as well as
bicarbonate (HCO3 −) and negatively charged proteins. The three compartments of the extracellular space—the interstitial fluid, the blood plasma, and the lymph—differ mainly in the amount of protein dissolved in each. For instance, the walls of the blood and lymph capillaries are permeable only to small ions and smaller organic particles, while large proteins are retained within the lumina of these vessels.

среда, 13 октября 2010 г.

Exchange of Materials between the Cell and Its Environment

Billions of years ago, life developed in the form of small, single-celled organisms in a large primal ocean. Their aqueous (watery) environment was marked by a milieu of constant composition. Nutrients were plentiful, and waste products were instantly diluted effectively to infinity. In a similar way, the cells of a multicellular organism live in an aqueous environment that contains all the salts and nutrients required for the sustenance of the cell. Compared to the primal ocean, however, this fluid has a much smaller volume, and there is a much greater danger of short-term changes in its composition.
Of all the chemical compounds in the organism, water (H2O) forms the largest percentage part. Thus the body of an adult contains about 60% water, which is distributed in two distinct compartments: the intracellular space (total volume enclosed in all the cells) and the extracellular space (total volume present outside the cells). About two-thirds of the total body fluids are located inside the cells (intracellular fluid) and the remaining third (about 14 liters in a person weighing 70 kg) bathes the exterior of the cells. Of the 14 liters of extracellular (interstitial) fluid, three-quarter are contained in the tiny spaces that separate the cells from each other, and one-quarter in the vascular systems (arteries, veins, capillaries, and lymphatic vessels), where it forms the aqueous part of the plasma and the lymphatic fluid.
The environment (milieu) in which the cell lives. (After Silbernagel)
a Unicellular organism: Interaction between the first cells and their environment—the primal ocean, a milieu distinguished by its constant composition
b Human: Cells in a multicellular organism are bathed in extracellular fluid, the volume of which is distinctly smaller than that of the fluid inside the cell. This “internal milieu” would change its composition very quickly if the space between the cells (interstitial space, intercellular space) were not connected to organs such as the lung, the kidney, or the digestive tract by the vascular bed, which take up fresh nutrients and eliminate metabolic waste products.

The water content of the body is kept constant with great precision. This is necessary in order not to endanger the equilibrium of the numerous substances dissolved in the body fluids. For instance, physiological water losses (e. g., the production of urine, the secretion of sweat, and loss by humidification of expired air) must be balanced by fluid intake.
Keeping the “internal milieu” constant (homeostasis) is a life-preserving precondition for the optimal functioning of every cell in the body. Since the most diverse substances reach the extracellular space as a result of respiration, the intake of nutrients, and the metabolic activity of cells, maintaining homeostasis is one of the most important tasks of the organism. Besides the activity of the lungs, the intestines, and the kidneys, certain specific transport processes are of importance; these processes (e. g., diffusion, osmosis, active transport) serve to exchange solids and fluids between the cell and its environment (see Solid and Fluid Transport below). Transport of substances over greater distances within the body (e. g., nutrients taken up in the intestines and oxygen taken up in the lungs) is accomplished in the blood vessels. Similarly, transport by the lymphatics, passage through the intestines, and the emptying of the gallbladder accomplish rapid distribution of solids and fluids.

воскресенье, 10 октября 2010 г.

Schematic representation of maturation division (meiosis).

In order to provide a better overview, the course of the two maturation divisions is exemplified in a germ cell with three pairs of chromosomes (red chromosomes = paternal, blue chromosomes = maternal). During the pachytene of the prophase of the first maturation division, the chromatids become visible. The maternal and paternal chromosomes arrange themselves next to each other and form a tetrad (two chromosomes each with two chromatids). During this process the paternal and maternal chromatids partly overlap and when they separate there is an interchange of fragments (“crossing-over”). During themetaphase of the first maturation division, the homologous (paternal and maternal) chromosomes separate, and are randomly distributed to the two daughter cells. This process creates two haploid daughter cells each with a single set of chromosomes. During the second maturation division, the two daughter chromatids separate by mitotic cell division, so that the first and second maturation divisions result in the creation of four haploid sex cells. (After Beske)

пятница, 8 октября 2010 г.

Reduction or Maturation Division (Meiosis)

Reduction or maturation division (meiosis) is a special form of cell division. In preparation for later fertilization, the male and female germ cells must halve their set of chromosomes (to form a haploid set), so that when ovum and sperm join, a normal double (diploid) set of chromosomes is formed. This process is known as meiosis, a cell division that comprises two steps: first and second maturation divisions.
Shortly before the first maturation division, the male and female sex cells duplicate their DNA as in mitosis, with each chromosome containing two identical chromatids. In meiosis, the prophase of the first maturation division lasts a good deal longer than the prophase of mitosis. As a rule it takes 24 days in male germ cells, while in the female it may at times take decades, because of an interpolated resting phase (dictyotene) (see Chapter 11: Development of the Ovum (Oogenesis) and Follicle Maturation). Prophase is divided into five phases: leptotene, zygotene, pachytene, diplotene, and diakinesis.


First maturation division. During the leptotene of the prophase, the chromosomes become visible as fine threads; in the ensuing zygotene, they arrange themselves side by side in pairs (chromosome pairing). During this process, the corresponding (homologous) paternal and maternal chromosomes are always arranged next to each other. Since each single chromosome contains two chromatids (sister chromatids), the chromosome pairs contain four chromatids, two maternal and two paternal, the so-called tetrad, which is especially conspicuous during the diplotene of prophase. At this point the homologous chromosomes begin to separate. During this process, homologous paternal and maternal chromatids lying in parallel next to each other can interchange homologous fragments by so-called crossing-over (forming a chiasma) and reattachment of the fragments.
In the metaphase which follows, the chromosomes arrange themselves in the equatorial plane, similarly to a mitosis. During anaphase, the separation of the homologous chromosomes by a spindle is completed. Telophase completes the first maturation division. The two daughter cells each now have only half the number of chromosomes of the initial cell, though each chromosome still consists of two chromatids.
Second maturation division. After a brief phase (interkinesis) during which the DNA is not duplicated, the second maturation division begins. This maturation division proceeds entirely like a normal mitosis, that is, during anaphase the two chromatids of each chromosome divide and are distributed to two daughter cells. Consequently, the haploid daughter cells that originated when the double set of chromosomes was halved during the first maturation division, once again halve their DNA content during the second maturation division.
The result of the two maturation divisions = mature sex cells. Thus four daughter cells (mature sex cells) result from the two-step division of meiosis. In each of these, the number of chromosomes and the DNA content have been reduced to half the original. In addition, the chromosomes have been restructured as a result of the crossing-over, and recombined as a result of the random distribution of the two homologous chromosomes into the daughter cells. The real biological significance of meiosis lies in this shuffling of genetic material.

вторник, 5 октября 2010 г.

Course of a Mitosis

At the beginning of prophase the cell becomes round and the chromosomes appear in the nucleus as convoluted threadlike structures. Simultaneously, the nuclear membrane disappears and the two centrioles move apart. They migrate toward the poles of the cell and form the socalled central spindle. In metaphase, which follows, the chromosomes become shorter and thicker, the two chromatids become visible and can be distinguished clearly by their size and shape. As the process continues, the chromosomes arrange themselves in the so-called equatorial plane between the two poles.

Schematic representation of cell division (mitosis) (After Hadorn and Wehner)
a Prophase: Chromosomes in the nucleus become visible by coiling and the nuclear spindle apparatus develops the central spindle;
b Early metaphase: the central spindle stretches and the chromosomes migrate toward the equatorial plane;
c Late metaphase: The division of each chromosome into two chromatids is clearly visible and arrangement along the spindle’s equator is complete;
d, e Anaphase: the daughter chromosomes are moving away from each other in the direction of the spindle’s pole;
f Telophase: the chromosomes have uncoiled, a nuclear membrane has formed and the cell body is constricted.

At the end of metaphase the chromosomes have arranged themselves in the equatorial plane in such a way that each of their constrictions (centromere) is oriented toward the central axis. Because the arrangement looks star-shaped when viewed from the two poles, it is called a “monaster” (Greek for single star). As anaphase begins, the chromatids (chromosome halves) of each chromosome separate, forming two starshaped figures called “diasters” (double star). Since each of the halves of a chromosome (daughter chromatids) migrates to one or other of the two opposite poles, all of the genetic material is divided equally between the two daughter cells.
In the ensuing telophase the chromatids, which now form the chromosomes of the two daughter cells, collect near the centrioles, uncoil, and again become invisible. As a newnuclear membrane forms, two new interphase nuclei have been created. There follows a complete division of the cell body, resulting essentially in two equal, independent daughter cells.
On average one mitosis takes about 60 minutes to complete. Anaphase is the shortest phase, lasting about 3 minutes.

суббота, 2 октября 2010 г.

Cell Division (Mitosis)

Duplication (replication) of DNA and the transmission of genetic information to the two daughter cells connected with it precede every cell division and take place during the so-called interphase. The interphase is the stage between mitoses and is the working phase of the cell. Chromosomes with two chromatids are formed by duplication of the genetic material during interphase. This establishes the precondition for mitotic cell division. Chromosomes demonstrate evidence of their duplication by a longitudinal split visible in the microscopic image. The chromosomes become shorter and thicker through increased coiling. After cell division is complete, the chromosomes uncoil and, during the ensuing interphase, replicate again.
Mitotic cell divisions permit a fertilized ovum to develop into an organism. They are the preconditions for physiological renewal of cells and lead to regeneration of tissues after injury. With the exception of a fewcells (nerve cells, and cardiac and skeletal muscle cells), the ability to divide is maintained throughout the life cycle, though it varies among cells. As a rule, mitoses are less common in highly differentiated tissues.
Double helix of DNA and its duplication (replication). The double strand of DNA splits like a zipper and forms two new, completely identical DNA molecules. The original strands are shown in blue, the new ones in pink (the sugar−acid phosphate chain is shown as a band; A = adenine, C = cytosine, G = guanine, T = thymine; free nucleotide groups are marked by arrows) (After Hadorn and Wehner)

вторник, 28 сентября 2010 г.

Duplication of Genetic Material (Replication)

Because of the structure of the individual strands of DNA, they can make identical copies of themselves. During this process the base pairs of the double helix separate in the middle like a zipper and for each single strand an exact complementary strand is synthesized. In this way, the two single strands of the original molecule are copied. Through the making of these identical copies of DNA, called replication, hereditary information is passed to offspring.
Simplified representation of protein synthesis in a cell. Transfer of the instructions for the manufacture of a proteinby copying (transcription) of a single strand ofDNAby means of mRNA (in mRNA the base thymine is replaced by the base uracil). This is ollowed by the manufacture of the protein molecule (translation) on the surface of the ribosome with the help of tRNA molecules. These bind in the cytoplasm specifically to the individual amino acids, e. g. leucine, glycine, ormethionine, that correspond to their base triplets and transport them to the ribosomes. With the aid of enzymes and ATP, the individual amino acids are combined into a protein molecule (polypeptide chain) (After Nultsch)

суббота, 25 сентября 2010 г.

Protein Synthesis

Proteins accomplish tasks necessary for life in all organisms. They are some of the most important structural and energizing components of a cell. Some of them, for instance collagen in connective and supporting tissue, take on important structural tasks and provide the organism’s architecture. Others, such as the myosin and actin of muscle cells, enable the shortening (contraction) of muscles, and hence movement. Yet other proteins transport oxygen (the hemoglobin of the red blood cells) or serve as protective and defensive agents in the immune system (antibodies). Of special importance are the proteins that are the catalysts for the metabolism of the organism (enzymes). Enzyme proteins synthesize everything the cell needs to survive (proteins, fats, and carbohydrates).
If genetic information is seen as biological data storage, then that information must be available at any time. When needed, it must be transported within the cell from the nucleus to the site of protein synthesis (the ribosomes) by a biochemical mechanism. For this purpose, the genetic code is copied within the nucleus to ribonucleic acid (RNA), which has a structure similar to that of DNA but contains only a single strand. This process is known as transcription. Protein synthesis takes place during the interphase of cell division. Chromatin must be uncoiled to allowtranscription to take place. Hence only euchromatin is active in transcription. RNA is synthesized from free elements in the nucleus and is linked together into an RNA chain with the help of the enzyme RNA polymerase. RNA brings this message to the ribosomes of the endoplasmic reticulum, and is therefore also known as messenger RNA or mRNA. Like DNA it is composed of nucleotides, but instead of the base thymine it contains the base uracil, and contains the sugar ribose instead of the sugar deoxyribose. The mRNA bonds to the ribosome by base coupling with transfer RNA molecules.
a Inside the largely uncoiled chromosomes, amorphous DNA segments (euchromatin) undergoing transcription alternate with genetically inactive, not uncoiled DNA segments (heterochromatin)
b Section from a: DNA loop undergoing transcription

Other relatively short RNA molecules, similarly synthesized fromfree elements in the nucleus, bond to the amino acids present in the cytoplasm one-on-one and transport them to the ribosomes, where the mRNA is attached with its copies of the base triplets. These short RNA molecules are therefore also known as tRNA (transport or transfer RNA). Each tRNA is specific for one amino acid and the corresponding triplet on the mRNA. In this way, with the aid of ribosomal enzymes, the various amino acids are linked into a protein chain, corresponding to the sequence of triplets on the mRNA. The rRNA produced in the nucleus provides the information needed to manufacture these enzymes. The tRNA molecules liberated in this reaction can then be recharged with the same amino acid in the cytoplasm. This process of protein building, also known as translation, continues until the complete protein molecule has been synthesized. The protein chain varies in length according to the type of protein (from a few up to several hundred amino acids), and by chemical reactions it can be folded into a three-dimensional functional protein molecule.

среда, 22 сентября 2010 г.

The Genetic Code

The genetic information required for the construction of proteins follows from the type and arrangement of amino acids in the protein. The encoding of this information in DNA, the genetic code, is determined by the arrangement of the four bases (contituting the four different nucleotides)within the DNA and is the same in all living things. The variable sequence of the various bases determines the specific informational content of the genes that forms the blueprint for millions of different protein molecules, just as the placing of the letters of the alphabet in an intelligent sequence determines the informational content of a book.
The double helix consists of the bases adenine (A), cytosine (C), guanine (G), and thymine (T), and the sugar deoxyribose (Z), and phosphate bridges formed by acid phosphate radicals. Each base combines with a sugar and a phosphate radical to form a nucleotide. Using the analogy of a rope ladder, the sugar and phosphate units form the sides (ropes), and the bases the rungs of the ladder. By chemical affinity adenine always forms a base pair with thymine, and guanine with cytosine, connected to each other by bridges of hydrogen bonds (H). The distances between rungs and the radius of the double helix are given in nanometers (1 nm = 10−9m = one billionth of a meter). (After Beske)

Three bases at a time in varying combinations define one informational unit, a “word”—also called a triplet or a codon—that must be translated into one of the 20 amino acids present in proteins. For instance, the combination of the bases guanine (G), adenine (A), and thymine (T)—GAT in abbreviated form—contains the information for the amino acid asparagine; and the triplet AAG is the code for lysine. The amino acids present in the cytoplasm are combined according to the sequence of the base triplets, to form the corresponding protein molecules (see below). Consequently, the four building blocks provide a total of 43 (4 × 4 × 4 = 64) possible combinations (informational units = “words”). Of these, 61 are used in the instructions to build proteins. The remaining triplets indicate the beginning and end of a protein molecule or a gene. The program for the construction of a protein consisting of, say, 340 amino acids therefore includes 340 such base triplets (or codons). The complete set of these triplets is called a gene (factor).
Thus, a gene determines how many amino acids constitute a protein, and in what sequence these must be arranged. One gene contains on average 300−3000 base triplets. Itmay take several genes to determine a single characteristic.

понедельник, 20 сентября 2010 г.

Structure of a Chromosome

Two chromosome arms, connected by a constriction (centromere) can be distinguished on each chromosome. During cell division, two spirally coiled chromatids can be seen in the chromosome arms. These uncoil between cell divisions (interphase) and so cannot be seen. Each chromatid consists of a single giant molecule, folded and wound in a complicated double strand in the shape of a double helix of deoxyribonucleic acid (DNA). It consists of two threads, only about two one-millionths of a millimeter (2 nm) thick, the length of which is determined by the amount of information stored in it. If, for instance, one were to place all the chromosomes of one cell end to end, they would extend 1 millimeter in a bacterium but more than 2 meters in a human. The two threads run in parallel but counter to each other (in opposite directions) and correspond to each other like a photographic negative to its print. They wind around an imaginary axis and can be compared to a twisted rope ladder (a double helix). The DNA forms complexes with basic proteins (histones) to form chromatin. Chromatin is coiled (condensed) into chromosomes, which are visible in optical microscopes only during cell division. During the interphase, it mostly becomes amorphous (euchromatin) apart from a few regions that do not uncoil (heterochromatin). Euchromatin is the genetically active chromatin (see Protein Synthesis), while heterochromatin is genetically inactive.

a, b Schematic representation of a chromosome in metaphase. (After Koolman and Röhm)
a The centromere (primary constriction) is located between the two arms of the chromosome, which are uneven in length and each of which consist of two chromatids 
b Section from a: DNA, together with basic histone proteins, forms tightly coiled complexes arranged like strings of pearls—the nucleosomes

Those histones that are intimately associated with DNA form about one half of the chromatin. The DNA is curled around the histone particles, so that a chromatin fiber is structured like a string of pearls. A histone particle with a DNA segment curled around it (~180 base pairs, see below) is called a nucleosome. Each histone particle consists of eight histone molecules (an octamere).
At the ends of the chromosome arms there are heterochromatin segments (telomeres, satellites) that determine the lifespan of the cell. During each cell division a small segment of chromatin separates until the satellite is used up. At that point the cell dies.
The building blocks of DNA are the nucleotides. They each consist of a base (adenine, cytosine, guanine, or thymine), a sugar (deoxyribose), and an acid phosphate radical. The phosphate radicals of two successive nucleotides form phosphate bridges that connect the nucleotides. Two opposing nucleotides are connected by hydrogen bonds between their bases. When viewed as a rope ladder, the sugar and phosphate units form the sides (the ropes) and the base pairs the rungs of the ladder. The opposing bases are joined in a tongue-and-groove fashion. Because of chemical affinity, adenine always forms a base pair with thymine, and guanine forms a base pair with cytosine.
The total human hereditary material is contained in 23 chromosome pairs in the form of deoxyribonucleic acid. The DNA can be subdivided into three separate segments, genes or hereditary factors, and has three important functions:
The storing of genetic information (the genetic code)
The transmission of information for protein biosynthesis
The identical duplication (replication) of genetic information during cell division

пятница, 17 сентября 2010 г.

The Cell Nucleus

Every cell with the exception of red blood cells has a nucleus. However, there are cells with two nuclei (some liver cells) or greater numbers of nuclei, e. g., osteoclasts in bony tissue (5−20 nuclei) or skeletal muscle cells (more than 1000 nuclei). Cells without nuclei can no longer divide. The nuclei are separated from the surrounding cytoplasm by two elementary membranes (nuclear membranes, nuclear envelope) but are connected to the endoplasmic reticulum by so-called nuclear pores. The nucleus usually contains a clearly defined round structure, the nucleolus. Its task is the production of ribosomal RNA (rRNA). It is therefore inconspicuous in inactive cells, but is welldefined in metabolically active cells with increased protein synthesis. Multiple nucleoli may occur in such cells. The size and shape of the nucleus vary from cell to cell: its form may be round, lobulated, or extended. Its shape and structure also depend at any one time on the current phase of the cell’s cycle. For instance, in the phase of cell division, filiform structures—the chromosomes—become apparent, while these are invisible in the phase between divisions, the so-called interphase.
Chromosomes and Genes
Chromosomes are the carriers of hereditary characteristics called genes. The human cell nucleus contains 46 chromosomes (diploidy) in the form of 23 chromosome pairs (23 male, 23 female chromosomes). The individual chromosomes can be distinguished by their total length, the lengths of their arms, and the position of their segmentations. By these means, individual chromosomal pairs can be assigned to specific groups (karyotyping)and numbered in decreasing size from 1 to 22, with the 23rd pair determining sex. With the exception of the sex chromosomes (heterochromosomes = allosomes), male and female chromosomes (homologous chromosomes = autosomes) correspond to each other in their hereditary characteristics. Whereas the female human has two sex chromosomes of equal size, the male human has one large and one small sex chromosome.
In humans the 23 chromosome pairs contain about twice 30000−40000 hereditary markers or genes. Each of their genes occurs twice in each cell of the body, namely one male and one female (diploidy). In contrast, the germ cells (egg and sperm cells) each have only a single set of chromosomes (haploidy). With 23 chromosomes and a total complement of 30000−40000, each chromosome therefore contains about 1300−1700 genes.

a, b Chromosome set of a normal human cell. (After Langman)
a The chromosomes are prepared and viewed by cultivating the cells in an artificial medium. This is followed by treatment with a colchicine solution, which blocks the mitoses in metaphase. The cells are then fixed, spread on a slide, and stained
b The chromosomes shown in a are arranged in a karyotype by total length and position of the centrosome. The two sex chromosomes (XY) determine the sex (male in this case)

вторник, 14 сентября 2010 г.

Number, Size, Shape, and Properties of Cells. part3

Golgi Apparatus
The Golgi apparatus is composed of several Golgi bodies and also represents a system of internal channels taking part in the ingestion and excretion of substances in the form of membrane-bounded secretory vesicles. Lysosomes are also formed by this mechanism. The Golgi bodies have one side for uptake and one for discharge. Precursors of protein secretions migrate from the granular endoplasmic reticulum to the intake side of the Golgi body, where they are loaded into transport vesicles and flushed out of the cell through the discharge side. During this process, the membrane of the vesicle fuses with the cell membrane. Hence the renewal of the cell membrane is an important task of the Golgi apparatus.

Lysosomes
The more or less spherical lysosomes are the digestive organs of the cell. They contain large quantities of enzymes, especially acid hydrolases and phosphatases, with the aid of which they can degrade ingested foreign material or the cell’s own decaying organelles and return them in the form of metabolites for cellular metabolism (recycling). The lysosome’s membrane protects intact cells from uncontrolled activity of the lysosomal enzymes. In damaged cells, the liberated enzymes can contribute to tissue autolysis (e. g., in purulent abscesses).

Centrioles
Centrioles are hollow, open-ended cylinders. Their walls are composed of microtubules, which are rigid, filamentous proteins. Centrioles play a major role in cell division, when they build threadlike spindle structures that are connected with the movement of the chromosomes. Evidently this process determines the polarity of the cell for the direction of a cell division.

Mitochondria
Mitochondria are small filiform structures, 2−6 μm long that are present in varying numbers (a few to more than a thousand) in all cells with the exception of red blood corpuscles. Their walls consist of an inner and an outer elementary membrane. The inner has multiple folds, and so possesses a large surface area. Mitochondria are the “power plants” of the cell, as they provide the energy necessary for all metabolic processes in the form of a universal biological fuel, adenosine triphosphate (ATP). The manufacture of ATP from the three basic materials—proteins, fats, and carbohydrates—takes place almost exclusively in the mitochondria, where the energy liberated as part of a process of oxidative combustion (mitochondrial respiratory sequence) is not dissipated as heat but is stored in the form of high-energy compounds (ATP).


ATP consists of three chemical substances linked to each other by high-energy bonds: a nitrogen-containing adenine, the sugar ribose, and three phosphate molecules (adenosine triphosphate). When one phosphate molecule is split off, energy is liberated and ATP becomes ADP (adenosine diphosphate), which, with added energy, can revert to adenosine triphosphate in the mitochondria.
From the mitochondria, ATP reaches the sites in the cell where energy is utilized. It is needed among other uses for the transport of materials through the cell membrane, for the synthesis of proteins and other cell components, and for muscle movement (contraction).

суббота, 11 сентября 2010 г.

Number, Size, Shape, and Properties of Cells. part2

Structure of the Cell and Cell Organelles

Basic Structure
Examination of a cell by light microscopy shows a fluid cell body (cytoplasm), a cell nucleus and the surrounding cell membrane (plasmalemma). The cytoplasm contains a number of highly organized small bodies, called cell organelles, that can often only be seen by electron microscopy. It also contains certain supportive structures (parts of the cytoskeleton) and numerous cell inclusions (e. g., metabolic substrates and end products).

Cell Membrane
The surrounding cell membrane (plasmalemma) contains the fluid cell body (protoplasm). An electron-microscopic section demonstrates a three-layered structure: this includes a double layer of lipids in which two layers of lipid molecules (phospholipids, cholesterol), are arranged so that their lipid-soluble parts (fatty acids) oppose each other (light middle line) while the water-soluble ends form the outer and inner boundaries of the cell membrane (dark outer and inner lines). The double lipid layer is infiltrated with proteins in a more or less mosaiclike fashion. These protein molecules have multiple functions. They may form pores that serve the transmission of water and salts, or they may take part in regulatory functions as receptor proteins. The membrane proteins abutting on the outer side of the cell, and in part the watersoluble ends of the phospholipids, are covered with a thin film of sugar molecules (carbohydrates). This film is called the glycocalyx. The chemical structure of the glycocalyx is laid down genetically and it is specific for each cell. By this structure cells can “recognize” each other as self and non-self (see Chapter 6: The Immune System, Specific Immunity). This so-called elementary membrane has a thickness of 7.5 nm (1 μm = 1000 nm) and forms a barrier between the cell interior and the extracellular space. The cell organelles are also surrounded by elementary membranes.

Simplified image of a cell representing electron-microscopic findings

Schematic cross-section of a cell membrane. The three-layered structure seen
in the electron-microscopic image is produced by the two water-soluble inner and outer
components of the double lipid layer, and the fat soluble components between them.
(After Leonhardt)

Cytoplasm and Cell Organelles
The cytoplasm surrounds the cell nucleus. It is composed of the hyaloplasm or cytosol (intracellular fluid), the cell organelles that perform certain cellular functions, and various cell inclusions, the metaplasm (metabolic products of the cell). The intracellular fluid consists of an aqueous saline solution and proteins (microtubules, microfilaments, intermediate filaments) that determine the shape and mechanical solidity of the cell (the so-called cytoskeleton). The organelles vary in number according to the type and function of the cell containing them. The following essential cell organelles may be differentiated:
Endoplasmic reticulum
Ribosomes
Golgi apparatus
Lysosomes
Centrioles
Mitochondria

Endoplasmic Reticulum (ER)
The endoplasmic reticulum criss-crosses the cytoplasm in the form of tubular and vesicular structures surrounded by elementary membranes. It subdivides the interior of the cell into compartments and facilitates the intracellular transport of substances along its channels. Its large surface makes possible the rapid completion of specific metabolic processes (e. g., the synthesis of proteins and lipids) and serves as a depot for membranes, i.e., it originates other membranes. In many places the endoplasmic reticulum is dotted with small granular structures, the ribosomes (granular ER), that serve especially for the synthesis of proteins (see below). Granular endoplasmic reticulum is especially prominent in cells such as those of the pancreas. The endoplasmic reticulum is called smooth ER when ribosomes are absent, predominating especially in hormone-secreting cells. All cells except red blood cells contain endoplasmic reticulum.

Ribosomes
Ribosomes serve protein synthesis (see also The Cell Nucleus, Protein Synthesis below) and occur either separately in the form of free ribosomes or in combination with endoplasmic reticulum (granular ER). They are not surrounded by elementary membrane. In the granular ER they are responsible for the production of exported proteins (e. g., glandular secretions), whereas free ribosomes produce intracellular proteins (e. g., enzymes, structural proteins). Ribosomes contain complexes made up of several enzymes consisting of proteins and RNA molecules (ribosomal RNA, rRNA). These create the amino acid chains for protein synthesis. rRNA is also a structural element of ribosomes.

среда, 8 сентября 2010 г.

Number, Size, Shape, and Properties of Cells. part1

The human body is composed of roughly 75 × 1012 cells (= 75000 billion cells), of which as many as 25 × 1012 (25000 billion) occur as erythrocytes in the blood and which therefore constitute the commonest type of cell. Of the remaining cells, 100 × 109 (= 100 billion) are part of the nervous system. Since the number of cells is so great, each individual building block must be microscopically small. The size of each cell varies in the human body between 5 μm (e. g., single connective tissue cells) and 150 μm (the ovum of the female). When cell processes are included, however, some cells can reach considerable lengths; for example, nerve cells that run from the brain to the spinal cord attain lengths of up to 1m. The shapes of the various cells also vary considerably. Ova are round, connective tissue cells form processes, and other cells are spindleshaped (muscle cells), flat, cuboid, or highly prismatic (epithelial cells). Size and shape are often closely linked to a cell’s specific properties.

Properties
All cells have a number of basic properties in common, even if they are differentiated to carry out specific tasks.
Metabolism and the Generation of Energy
Every cell possesses a metabolism, by which absorbed substances are changed into compounds that serve the organization of the cell and are discharged in the form of end products. Therefore, in order to maintain the normal functions necessary for life, cells require nutrients fromwhich they acquire the energy for their tasks. The chemical processes that take place during the transformation of nutrients (fats, proteins, and carbohydrates) to generate energy are basically the same in all cells, as also is the release of end products into the fluids surrounding the cells.
Reproduction and Life Expectancy.
With few exceptions, almost all cells have the capacity to reproduce themselves by dividing. This property is often retained throughout life and is the prerequisite for the replacement of dead cells and the regeneration (restoration) of tissues and organs after injury. The human bone marrow, for instance, creates about 160 million red blood cells per minute, and in the male the testes create about 85 million sperm cells daily. Another instance of a high rate of cell division is given by the cells of the mucous membrane of the small intestine, which have an average life expectancy of only a few days (30− 100 hours). Yet other cells divide only in certain phases of development and subsequently survive for life, e. g., nerve and muscle cells.
Sensitivity to Stimulation and Response to Stimulation.
Almost all cells are connected to their immediate environment by specific structures on their surfaces (e. g., receptors) and can sense, evaluate, and respond to distinct stimuli.

Besides these basic properties, certain cells possess specific properties. These may include mobility (e. g., histiocytes in connective tissue; male sperm in the female genital tract), the assimilation and elimination of substances (e. g., assimilation of cell debris by defense cells; secretion by glandular cells), or the development of specific surface differentiations (e. g., cilia on the mucous membrane cells of the respiratory tract; brush border of the mucous membrane cells of the small intestine).

воскресенье, 5 сентября 2010 г.

Introduction

The basic building block of the human body as well as of all animals and plants is the cell. It is the smallest independent living entity and can live independently as a single-celled (unicellular) organism (e. g., flagellates, amebas). In multicellular organisms (metazoa) the cells organize in large units and become functional entities within an overarching framework. In unicellular organisms, such as bacteria and fungi, all the cells exhibit an identical basic structure. Multicellular organisms, such as plants, animals, and humans, also exhibit a fundamentally uniform organization. Here, however, there are great differences in the variety of tasks, and each type of cell specializes in the execution of a specific task within the organism. For instance, red blood cells (erythrocytes) transport oxygen, while other cells serve as conduits for stimuli (nerve cells) or serve reproduction (germ cells).
The actions of each individual cell in an organism depend on specific genetic information. In the cell this information is stored in certain sections of the substance termed deoxyribonucleic acid (DNA) in the genes. It consists of programs to direct cell reproduction as well as the synthesis of proteins. Both functions are essential to ensure that a fertilized ovum can develop into a multicellular organism and that cells differentiated in various ways, such as brain, lung, muscle, or liver cells, can develop from common precursor cells.