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)

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.

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.

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

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)

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).

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.

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).

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.