• Cells are the basic units of life. All cells of today are believed to have evolved from an ancestral cell that existed more than 3 billion years ago.

• All cells are surrounded by a plasma membrane, which separates the inside of the cell from its surroundings.

• All cells contain DNA / RNA as a genetic database and use it to direct the synthesis of RNA molecules and proteins.

• Cells in a multicellular organism, even though they all contain the same DNA , can be very different. They activate different sets of genes depending on their developmental history and the signals they receive from their environment.

microscopy – how to watch on cell?

• The diameter of animal and plant cells is usually 5-20 pm and can be seen with a light microscope, which also reveals some of their internal components, including the larger organelles.

• The electron microscope reveals even the smallest organelles, but specimens require detailed preparation and cannot be viewed while alive.

• Specific large molecules can be located in fixed or living cells with a fluorescence microscope.

• The simplest living cells today are prokaryotes : although they contain DNA , they lack a nucleus and other organelles and are probably most similar to the primitive cell.

how caracteris the living cells on earth? which categories there is?

• Different species of prokaryotes are diverse in their chemical capabilities and inhabit an incredibly wide variety of habitats. Two basic evolutionary subdivisions are recognized: bacteria and archaea .

• Eukaryotic cells have a nucleus and other organelles that are not found in prokaryotes . They probably evolved in a series of steps, including the acquisition of mitochondria by ingestion of aerobic bacteria and (for plant cells) the acquisition of chloroplasts by ingestion of photosynthetic bacteria .

• The nucleus contains the genetic information of the eukaryotic organism , which is stored in DNA molecules .

• The cytoplasm includes all the contents of the cell outside the nucleus and contains a variety of membrane-enclosed organelles with special functions: the mitochondria carry out the final oxidation of food molecules; In plant cells, chloroplasts carry out photosynthesis; The endoplasmic reticulum and the Golgi apparatus synthesize complex molecules for export from the cell and insertion into cell membranes; Lysosomes digest large molecules.

• Outside the membrane- enclosed organelles in the cytoplasm is the cytosol , a highly concentrated mixture of large and small molecules that carry out many vital biochemical processes.

• The cytoskeleton consists of protein threads that stretch along the cytoplasm and are responsible for the cell’s shape and movement and for transporting organelles and other large molecular complexes from one place to another.

eukaryotic

• Free-living unicellular eukaryotic microorganisms are complex cells that can swim, mate, hunt and devour other microorganisms.

• Animals, plants, and certain fungi are composed of diverse eukaryotic cell types , all derived from a single fertilized egg cell; The number of such cells cooperating to form a multicellular organism as large as a human reaches thousands of billions cells.

genome research

• Biologists have chosen a small number of model organisms to study closely, including the bacterium E. coli , brewer’s yeast, a nematode worm, a fly, a small plant, a fish, a mouse, and humans themselves.

• The simplest known cell is a bacterium with about 500 genes, but most cells contain significantly more. The human genome has about 25,000 genes, which is only twice that of a fly and six times that of E. coli .

Chapter 2 Biochemical basis

chemical bonds and atoms level

• Living cells obey the same chemical and physical laws as non-living things. Like all other forms of matter, they are made of atoms, which are the smallest unit of a chemical element that retain the unique chemical properties of that element.

• Cells consist of a limited number of elements, four of which – C, H, N, O – make up about 96% of the cell’s mass.

• Each atom has a positively charged nucleus, surrounded by a cloud of negatively charged electrons. The chemical properties of an atom are determined by the number and arrangement of its electrons: it is most stable when its outer electron shell is completely filled.

• A covalent bond is formed when a pair of electrons from the outer shell is shared between two adjacent atoms; If two pairs of electrons are shared, a double bond is formed. Clusters of two or more atoms held together by covalent bonds are known as molecules.

• When an electron jumps from one atom to another, two ions of opposite charge are formed; These ions are held together by mutual attraction forming a non- covalent ionic bond .

Organic chemistry

• Living organisms contain a unique and limited group of small molecules based on (organic) carbon, which are basically the same for every living species. The main categories are sugars, fatty acids, amino acids and nucleotides.

• Sugars are a primary source of chemical energy for cells and can also be linked together to form shorter polysaccharides or oligosaccharides .

Fatty acids

• Fatty acids are more richer source of energy than sugars.

but they yous mostly to create lipid molecules that assemble into cell membranes.

amino acids

• The most diverse and versatile class of macromolecules are proteins, which are formed from 20 types of amino acids covalently linked by peptide bonds to long polypeptide chains

majority of the dry mass of the DNA and RNA cell

• The vast majority of the dry mass of the cell consists of macromolecules -mainly polysaccharides ( , proteins and nucleic acids ( DNA and RNA ); These macromolecules are formed as polymers of sugars, amino acids or nucleotides, respectively.

• Nucleotides play a central role in energy transfer reactions within cells; They are also joined together to form information-containing RNA and DNA molecules , each of which is made up of only four types of nucleotides.

• Protein, RNA and DNA molecules are synthesized from subunits by repeated condensation reactions, and it is the specific sequence of the subunits that determines their unique functions.

Bonds between organic molecules

• Four types of weak noncovalent bonds — hydrogen bonds, electrostatic attraction, van der Waals attraction, and hydrophobic interactions—allow macromolecules to bind specifically to other macromolecules or to selected small molecules.

• The same four types of non- covalent bonds between different regions of a polypeptide chain or RNA allow these chains

chapter 3 Energy, Catalysis and biosynthesis

• Living organisms are able to exist because of a continuous supply of energy. Some of this energy is used to carry out essential reactions that support cell metabolism, growth, movement and reproduction; The rest is lost as heat.

Autotrophs and heterotrophs

• The ultimate source of energy for most living organisms is the sun. Plants, algae and photosynthetic bacteria use solar energy to make organic molecules from carbon dioxide. Animals obtain food by eating plants or by eating animals that feed on plants.

• Each of the many hundreds of chemical reactions occurring in a cell is specifically catalyzed by an enzyme. A large number of different enzymes work in sequence to create chains of reactions, called metabolic pathways , each performing a different role in the cell.

• Catabolic reactions release energy by breaking down organic molecules , including foods, through oxidation pathways. Anabolic reactions create the many complex organic molecules necessary for the cell, and they require energy input. In animal cells, both the building blocks and the energy required for anabolic reactions are obtained through catabolic reactions .

Enzymes

• Enzymes catalyze reactions by binding to certain substrate molecules in a way that lowers the activation energy required to form and break specific covalent bonds .

This topic described on the biochemistry page valu- Enzymes

• The rate at which an enzyme catalyzes a reaction depends on how quickly it finds its substrates and how quickly the product is formed and then diffuses away. These rates vary greatly from one enzyme to another.

• The only possible chemical reactions are those that increase the total amount of disorder in the universe. The change in the free energy for the reaction, ΔG , measures this disturbance, and it must be less than zero for the reaction to proceed spontaneously.

• The ΔG for a chemical reaction depends on the concentrations of the reacting molecules, and it can be calculated from these concentrations if the equilibrium constant ( K ) of the reaction (or the standard free energy change, ΔG °, for reactants) is known.

chemical equlibrium

• Equilibrium constants control all the associations (and dissociations) that occur between macromolecules and small molecules in the cell. The greater the binding energy between two molecules, the greater the equilibrium constant and the more likely these molecules will be found bound to each other.

• By creating a reaction pathway that connects an energetically favorable reaction to an energetically unfavorable reaction, enzymes can cause otherwise impossible chemical changes.

• A small group of activated carriers, especially ATP, NADH and NADPH , play a central role in these integrated reactions in cells. ATP carries high-energy phosphate groups, while NADH and NADPH carry high-energy electrons.

• Food molecules provide the carbon skeletons for the formation of macromolecules. The covalent bonds of these larger molecules are produced by condensation reactions linked to energetically positive bond changes in activated carriers such as ATP and NADPH

chapter 4 protein structure and function

this topic describe more detail in the page biochemistry in the value about amino acids and proteins

• Living cells contain an enormously diverse group of protein molecules, each of which is made up of a linear chain of amino acids linked together by Cuban peptide bonds .

• Each type of protein has a unique amino acid sequence, which determines both its three- dimensional shape and its biological activity.

• The folded structure of a protein is stabilized by multiple non- covalent interactions between different parts of the polypeptide chain .

• Hydrogen bonds between adjacent regions often result in regular folding patterns.

• The structure of many proteins can be divided into smaller spherical regions with a compact three- dimensional structure , known as protein domains.

• The biological function of a protein depends on the detailed chemical properties of its surface and the way it binds to other molecules, called ligands .

• When a protein catalyzes the formation or breaking of a specific covalent bond in a ligand , the protein is called an enzyme and the ligand is called a substrate.

• In the active site of an enzyme, the amino acid side chains of the folded protein are precisely positioned to favor the pairing of the high-energy transition states that the substrates must pass through to become the product.

• The three- dimensional structure of many proteins has evolved so that the binding of a small ligand can cause a significant change in the shape of the protein.

• Most enzymes are allosteric proteins that can exist in two different conformations in catalytic activity, and the enzyme can be activated or deactivated by ligands that bind to a distinct regulatory site to stabilize the active or inactive structure.

• The activity of most enzymes inside the cell is strictly regulated. One of the most common forms of regulation is feedback inhibition, where an enzyme early in a metabolic pathway is inhibited by binding one of the end products of the pathway.

• Many thousands of proteins in a typical eukaryotic cell are regulated by cycles of phosphorylation and dephosphorylation .

• GTP- binding proteins also regulate protein function in eukaryotes ; They act as molecular switches that are active when GTP is bound and inactive when GDP is bound; turn themselves off by hydrolyzing their GTP- bound product.

• Motor proteins produce directed movement in eukaryotic cells through conformational changes related to the hydrolysis of ATP to ADP .

• Highly efficient protein machines are created by assemblies of allosteric proteins in which the various conformational changes are coordinated to perform complex functions.

• Covalent modifications added to the amino acid side chains of a protein can control the location and function of the protein and can serve as docking sites for other proteins.

• Starting with the homogenization of crude cells or tissues, individual proteins can be obtained in pure form through a series of chromatography steps.

• The function of a purified protein can be discovered by biochemical analyses, and its exact three-dimensional structure can be determined using X-ray crystallography or NMR spectroscopy .

Chapter 5 DNA abd Chromosomes

• Life depends on the stable storage and inheritance of genetic information.

• Genetic information is carried by very long DNA molecules and encoded in the linear sequence of four nucleotides: A, T, G and C.

• Each DNA molecule is a double helix consisting of a pair of antiparallel and complementary DNA strands, held together by hydrogen bonds between base pairs GC and AT .

DNA replication

DNA replication in both prokaryotes and eukaryotes follows similar stages, including initiation, elongation, and termination. Here’s an overview of these stages along with the enzymes involved:

Initiation:
- Prokaryotes: The initiation of DNA replication in prokaryotes begins at the origin of replication, where the DNA helicase enzyme unwinds the double-stranded DNA to form a replication bubble. DNA gyrase helps relieve the torsional stress ahead of the replication fork. Single-stranded binding proteins (SSBs) stabilize the unwound DNA strands.
- Eukaryotes: Eukaryotic DNA replication also starts at origins of replication. Origin recognition complex (ORC) proteins bind to specific sequences at the origin, initiating the assembly of the pre-replication complex (pre-RC). Helicase enzymes, such as MCM2-7, unwind the DNA, and single-stranded binding proteins (SSBs) stabilize the exposed single strands.
Elongation:
- Prokaryotes: In prokaryotes, the leading strand is synthesized continuously by DNA polymerase III in the 5′ to 3′ direction, following the helicase as it unwinds the DNA. The lagging strand is synthesized discontinuously in short fragments called Okazaki fragments. RNA primase synthesizes RNA primers on the lagging strand, and DNA polymerase III adds DNA nucleotides to extend these primers. DNA polymerase I then removes the RNA primers and fills the gaps with DNA nucleotides, and DNA ligase joins the Okazaki fragments together.
- Eukaryotes: Eukaryotic DNA replication also involves leading and lagging strands. The leading strand is synthesized continuously by DNA polymerase ε, which moves along with the replication fork in the 5′ to 3′ direction. The lagging strand is synthesized discontinuously by DNA polymerase α and δ. RNA primase synthesizes RNA primers on the lagging strand, and DNA polymerase α adds DNA nucleotides to extend these primers. DNA polymerase δ then replaces RNA with DNA and elongates the Okazaki fragments. DNA ligase joins the fragments together.
Termination:
- Prokaryotes: Termination of DNA replication in prokaryotes occurs when the replication forks from opposite directions meet and the entire circular DNA molecule is replicated. Tus proteins bind to termination sites (ter sites) to halt the progress of the replication forks.
- Eukaryotes: Termination of DNA replication in eukaryotes is more complex and involves multiple mechanisms to ensure complete and accurate replication of all chromosomes. Telomeres, repetitive DNA sequences at the ends of linear chromosomes, also play a role in replication termination by preventing the loss of genetic material during successive rounds of replication.
Replication Fork:
- The replication fork is a structure that forms during DNA replication where the double-stranded DNA is unwound and separated into two single strands. It’s the site where DNA synthesis occurs. The leading strand is synthesized continuously toward the replication fork, while the lagging strand is synthesized discontinuously away from the fork.
Leading Strand vs. Lagging Strand:
- The leading strand is synthesized continuously in the 5′ to 3′ direction because its orientation allows DNA polymerase to add nucleotides without interruption as the replication fork opens up.
- The lagging strand is synthesized discontinuously in the 5′ to 3′ direction away from the replication fork. It’s synthesized in short fragments called Okazaki fragments, which are later joined together by DNA ligase.

These stages and processes ensure accurate and complete duplication of the genetic material during DNA replication in both prokaryotes and eukaryotes.

DNA replication in Prokaryotes compere to Eukaryotes

DNA replication is a fundamental process in both prokaryotes and eukaryotes, but there are some key differences between the two.

Organization of Genetic Material:
- Prokaryotes: Prokaryotic cells, such as bacteria, have a single circular chromosome located in the nucleoid region of the cell. They also have plasmids, which are small, circular DNA molecules.
- Eukaryotes: Eukaryotic cells, found in plants, animals, fungi, and protists, have linear chromosomes located within a membrane-bound nucleus. They also have additional organelles such as mitochondria and chloroplasts, which have their own circular DNA.
Initiation of Replication:
- Prokaryotes: DNA replication in prokaryotes starts at a single origin of replication on the circular chromosome. The replication process is bidirectional, proceeding in both directions from the origin.
- Eukaryotes: Eukaryotic DNA replication involves multiple origins of replication distributed along each linear chromosome. Origins are typically located in regions called replication origins or replication foci.
Replication Machinery:
- Prokaryotes: Prokaryotic DNA replication involves three main enzymes: DNA helicase, DNA polymerase, and DNA ligase. DNA polymerase III is the primary enzyme responsible for synthesizing new DNA strands, while DNA polymerase I helps in removing RNA primers and filling the gaps.
- Eukaryotes: Eukaryotic DNA replication is more complex and involves several DNA polymerases, such as DNA polymerase α, δ, and ε. Additionally, eukaryotic replication requires the assembly of a larger replication complex involving many proteins, including helicases, primases, and various DNA-binding proteins.
Handling of Telomeres:
- Prokaryotes: Prokaryotic chromosomes do not have telomeres, which are protective caps found at the ends of eukaryotic chromosomes.
- Eukaryotes: Eukaryotic DNA replication involves specialized mechanisms for dealing with telomeres. Telomerase is an enzyme that adds repetitive nucleotide sequences to the ends of chromosomes to prevent loss of genetic material during replication.
Proofreading and Repair:
- Both prokaryotes and eukaryotes have proofreading mechanisms during DNA replication to ensure accuracy. DNA polymerases have exonuclease activity that allows them to remove mismatched nucleotides and replace them with the correct ones.
- Eukaryotes generally have more sophisticated DNA repair mechanisms compared to prokaryotes, including base excision repair, nucleotide excision repair, and mismatch repair systems.
Speed of Replication:
- Prokaryotes: Prokaryotic DNA replication is typically faster than eukaryotic replication because prokaryotic genomes are smaller and have fewer regulatory complexities.
- Eukaryotes: Eukaryotic DNA replication is slower due to the larger genome size, presence of multiple chromosomes, and the need for more complex regulatory mechanisms.

These are some of the major differences between DNA replication in prokaryotes and eukaryotes. Each system has evolved to suit the specific needs and complexities of the respective organisms’ genetic material and cellular structures.

Prokaryotes

• The genetic material of a eukaryotic cell is contained in a group of chromosomes , each of which is formed from a single and incredibly long DNA molecule containing many genes.

• When a gene is expressed, part of its nucleotide sequence is transcribed into RNA molecules , many of which are translated into protein.

• The DNA that makes up each eukaryotic chromosome contains, in addition to genes, many sources of replication, one centromere and two telomeres . These special DNA sequences ensure that before the cell divides, each chromosome can be replicated efficiently, and that the resulting daughter chromosomes are divided equally between the two daughter cells.

• In eukaryotic chromosomes , the DNA is tightly folded by binding to a group of histone and non- histone proteins . This complex of DNA and protein is called chromatin.

• Histones package the DNA into a repeating array of DNA protein particles called nucleosomes , which fold further into even more compact chromatin structures.

• A cell can regulate its chromatin structure – decondensing or temporarily condensing certain regions of its chromosomes – using complexes and enzymes that covalently change the histone tails in different ways.

• The loosening of the chromatin to a more compact state allows the proteins involved in gene expression, DNA replication and DNA repair to gain access to the necessary DNA sequences .

• Some forms of chromatin have a pattern of histone tail modification that causes the DNA to condense so much that its genes cannot be expressed to produce RNA ; Such condensation occurs on all chromosomes during mitosis and in the heterochromatin of interphase chromosomes.

DNA Transcription Initiation:

In both prokaryotes and eukaryotes, transcription is the process of synthesizing RNA from a DNA template. However, the mechanisms of transcription initiation differ between these two types of organisms.

Prokaryotic Transcription Initiation:

Promoter Recognition: In prokaryotes, transcription initiation begins with the recognition of specific DNA sequences called promoters by the RNA polymerase enzyme. The promoter region typically contains two key sequences: the -10 box (TATAAT) and the -35 box (TTGACA). These sequences are recognized by the sigma factor of RNA polymerase, forming a holoenzyme complex.

Formation of the Transcription Bubble: The RNA polymerase holoenzyme binds to the promoter region and unwinds a short segment of the DNA double helix, forming a transcription bubble. This region of unwound DNA serves as the template for RNA synthesis.

Initiation of RNA Synthesis: Once the transcription bubble is formed, RNA polymerase starts synthesizing RNA in the 5′ to 3′ direction, using one of the DNA strands (the template strand) as a template. The growing RNA molecule elongates as RNA polymerase moves along the DNA template.

Eukaryotic Transcription Initiation:

Promoter Recognition: Eukaryotic transcription initiation is more complex than prokaryotic initiation. It involves the recognition of specific DNA sequences within the promoter region by a multi-subunit complex called RNA polymerase II and several transcription factors. The core promoter region includes the TATA box (TATAAAA) and other regulatory elements such as the initiator element (Inr) and the downstream promoter element (DPE).

Assembly of the Pre-Initiation Complex (PIC): Transcription factors bind to the promoter sequences, recruiting RNA polymerase II and other accessory proteins to form the pre-initiation complex (PIC). This complex helps position RNA polymerase II at the transcription start site (TSS).

Formation of the Transcription Bubble: The PIC and RNA polymerase II bind to the promoter region, leading to the unwinding of the DNA double helix and the formation of a transcription bubble. The template strand of DNA serves as a template for RNA synthesis, while the non-template strand (coding strand) remains uninvolved.

Initiation of RNA Synthesis: RNA polymerase II begins synthesizing RNA in the 5′ to 3′ direction, using the template strand of DNA within the transcription bubble. Transcription factors and other regulatory proteins help facilitate the process and regulate gene expression.

In summary, prokaryotic transcription initiation involves the recognition of specific promoter sequences by RNA polymerase with the assistance of sigma factors, while eukaryotic transcription initiation is more complex and involves the assembly of a pre-initiation complex (PIC) and the recognition of multiple promoter elements by RNA polymerase II and transcription factors.

chapter 6 DNA replication and repair

• Because the two strands of a DNA double helix are complementary, each strand can serve as a template for the synthesis of the other. Thus, DNA replication produces two identical double-helical DNA mother poles , which allow genetic information to be copied and transferred from a cell to its daughter cells and a parent to its offspring.

• During replication, the two strands of a DNA double helix pull apart at the origin of replication to form two Y- shaped replication forks . polymerases DNA at each fork produces a new complementary DNA strand on each parent strand.

• DNA Polymerase replicates a DNA template with extraordinary fidelity, making only one error in every 10 7 nucleotides copied. This precision is made possible, in part, by a proofreading process in which the enzyme corrects its mistakes as it moves along the DNA .

• Because DNA Polymerase synthesizes new DNA in one direction only, only the leading strand at the replication fork can be synthesized continuously. On the forward strand, the DNA is synthesized by a discontinuous backstitching process, producing short stretches of DNA that are later joined by ligase DNA .

• DNA Polymerase is unable to start a new DNA chain from scratch. Instead, DNA synthesis is advanced by an RNA polymerase called Primes , which creates short lengths of RNA primers that are then extended by DNA polymerase . These primers are then deleted and replaced with DNA .

• DNA replication requires the cooperation of many proteins that create a multi-enzyme replication machine that copies the two strands of DNA while moving along the double helix.

• In eukaryotes , a special enzyme called telomerase replicates the DNA at the ends of the chromosomes.

• The rare copying errors that escape proofreading are handled by mismatch repair proteins, which increase the accuracy of DNA replication to one error per 10 9 nucleotides copied.

a way to protect DNA :

Dam, dcm, CpG Methylase The Effect of DNA Methylation on Restriction Digests

• Damage to one of the two DNA strands , caused by inevitable chemical reactions, is repaired by a variety of DNA repair enzymes that identify damaged DNA and cut a short stretch of the outdated strand. The missing DNA is then resynthesized by polymerase DNA for repair, using the undamaged strand as a template.

• If both DNA strands break, the double strand break can be quickly repaired by non-homologous end joining. Nucleotides are lost in the process, changing the DNA sequence at the repair site.

non homologous dna repair

• Homologous recombination can flawlessly repair double-strand breaks using an undamaged homologous double helix as a template.

Homologous Recombination

DNA Double Strand Breaks And Repair Systems Part 2 (youtube.com)

• Highly precise DNA replication and repair processes play a key role in protecting us from the uncontrolled growth of somatic cells known as cancer.

Chapter 7

• The flow of genetic information in all living cells is DNA ^ RNA ^ protein. The conversion of the genetic instructions in DNA to RNA and proteins is called gene expression.

• To express the genetic information carried in DNA , the nucleotide sequence of a gene is first transferred to RNA . The transcription is catalyzed by the enzyme RNA Polymerase , which uses nucleotide sequences in the DNA molecule to determine which strand to use as a template, and where to start and stop transcription .

• RNA differs from DNA in several aspects . It contains the sugar ribose instead of deoxyribose and the base uracil (U) instead of thymine (T). RNA in cells is synthesized as single- stranded molecules , which often fold into complex three- dimensional shapes .

• Cells produce several functional types of RNA , including messenger RNA ( mRNA ), which carry the instructions for protein production; RNAs Ribosomes ( rRNAs ), which are the essential components of

ribosomes ; and transfer RNAs (tRNAs) , which act as co -ordinators in protein synthesis.

• To begin transcription , RNA Polymerase binds to specific DNA sites called promoters that are immediately upstream of genes. To initiate transcription, polymerases RNA Eukaryotes require the assembly of a complex of general transcription factors at the promoter , while polymerase Bacterial RNA requires only one additional subunit, called the sigma factor.

• Most protein-coding genes in eukaryotic cells consist of several coding regions, called exons, embedded in larger non-coding regions, called introns . When a eukaryotic gene is transcribed from DNA to RNA , both the exons and introns are transcribed.

• Introns are removed from the RNA transcripts in the nucleus by RNA splicing , a reaction catalyzed by small ribonucleoprotein complexes known as snRNPs . Splicing removes the introns from the RNA and joins the exons – often in a variety of combinations, making it possible to produce multiple proteins from the same gene.

• Pre- mRNA Eukaryotes go through several additional RNA processing steps before they leave the nucleus as mRNA , including RNA 5 ‘ capping and 3’ polyadenylation . These reactions, along with splicing, occur during transcription of the pre- mRNA .

• Translation of the nucleotide sequence of mRNA into protein occurs in the cytoplasm on large ribonucleoprotein assemblies called ribosomes . When the mRNA passes through the ribosome , its message is translated into a protein.

• The sequence of nucleotides in mRNA is read in groups of three nucleotides called codons ; Each codon corresponds to one amino acid.

• The correspondence between amino acids and codons is defined by the genetic code. The possible combinations of the 4 different nucleotides in RNA give 64 different codons in the genetic code. Most amino acids are defined by more than one codon .

• tRNAs act as adapter molecules in protein synthesis. Enzymes called aminoacyl-tRNA synthetases covalently link amino acids to their corresponding tRNA . Each tRNA contains a sequence of three nuclear nucleotides , the anticodon , which identifies a codon in mRNA through complementary base pairing.

• Protein synthesis begins when a ribosome assembles at the start codon ( AUG ) in an mRNA molecule , a process that depends on proteins called translation initiation factors. The complete protein chain is released from the ribosome when a stop codon ( UAA, UAG or UGA ) is reached in the mRNA .

• The gradual linking of amino acids to a polypeptide chain is fought by the rRNA molecule in the large ribosomal subunit , which thus acts as a ribozyme .

• The concentration of the protein in the cell depends on the rate of degradation and degradation of the mRNA and the protein. Protein degradation in the cytosol and nucleus takes place within large protein complexes called proteasomes .

• From our knowledge of present-day organisms and the molecules they contain, it seems likely that life on Earth began with the development of RNA molecules that could speed up their replication.

• It has been suggested that RNA served as both the genome and catalysts in the first cells, before DNA replaced RNA as a more stable molecule for storing genetic information, and proteins replaced RNA as major catalytic and structural components. RNA catalysts in modern cells are thought to provide a glimpse into an ancient, RNA- based world .

Chapter 8

• A typical eukaryotic cell expresses only a small fraction of its genes, and the distinct cell types in multicellular organisms arise because different sets of genes are expressed as the cells differentiate.

• In principle, gene expression can be controlled at any of the stages between the gene and its final functional product. However, for most genes, transcription initiation is the most important control point.

• The transcription of individual genes is turned on and off in cells by transcription regulatory proteins, which bind to short segments of DNA called regulatory DNA sequences .

• In bacteria, transcriptional regulators usually bind to regulatory DNA sequences close to where RNA polymerase binds. This link can activate or repress transcription of the gene. In eukaryotes , regulatory DNA sequences are often separated from the promoter by many thousands of nucleotide pairs.

Eukaryotic transcriptional regulators act in two main ways: (1) they can directly affect the assembly process that requires RNA polymerase and the general transcription factors in the promoter , and (2) they can locally

• Change the chromatin structure of promoter regions .

• In eukaryotes , the expression of a gene is usually controlled by a combination of different transcription regulatory proteins.

• In multicellular plants and animals, production of different transcriptional regulators in different cell types ensures expression of only those genes appropriate for the particular cell type.

• One differentiated cell type can be converted to another by artificially expressing an appropriate set of transcriptional regulators. A differentiated cell can be reprogrammed into a stem cell by artificially expressing a particular set of such regulators.

• Cells in multicellular organisms have mechanisms that allow their offspring to “remember” what type of cell they should be. A prominent mechanism for propagating cell memory relies on transcriptional regulators that perpetuate transcription of their gene—a form of positive feedback.

• A master transcriptional regulator, if expressed in the appropriate precursor cell, can trigger the formation of a specialized cell type or even an entire organ.

• The DNA methylation pattern can be passed from one cell generation to another, creating a form of epigenetic inheritance that helps the cell remember the state of gene expression in its parent cell. There is also evidence for a form of epigenetic inheritance based on transmitted chromatin structures.

• Cells can regulate gene expression by controlling events that occur after transcription begins. Many of these post-transcriptional mechanisms rely on RNA molecules that can affect their stability or translation.

• MicroRNAs (miRNAs) control gene expression by base pairing with specific mRNAs and inhibiting their stability and translation.

• Cells have a defense mechanism to destroy “foreign” double-stranded RNA , many of which are produced by viruses. It uses small interfering RNAs ( siRNAs ) produced from the foreign RNA in a process called RNA interference (RNAi) .

• Scientists can utilize RNAi to inactivate specific genes of interest.

• The recent discovery of thousands of long non-coding RNAs in mammals has opened a new window into the roles of RNA in gene regulation.

Chapter 9

• By comparing the DNA and protein sequences of contemporary organs, we begin to reconstruct how the genome developed in the billions of years that have passed since the appearance of the first cells.

• Genetic variation – the raw material for evolutionary change – is created through a variety of mechanisms that change the nucleotide sequence of genomes . These sequence changes range from simple point mutations to larger scale deletions, duplications and rearrangements.

• Genetic changes that give the organism a selective advantage are the most likely to be retained . Changes that harm an organ’s fitness or ability to reproduce are eliminated through natural selection.

• Gene duplication is one of the most important sources of genetic diversity. After duplication, the two genes can accumulate different mutations and thus diversify to perform different functions.

• Repeated rounds of gene duplication and divergence during evolution have created many large gene families.

• It is believed that the evolution of new proteins was greatly facilitated by the exchange of exons between genes to create hybrid proteins with new functions.

• The human genome contains 3.2 x 10 9 pairs of nucleotides spread between 23 pairs of chromosomes – 22 autosomes and a pair of sex chromosomes. Less than a tenth of this DNA is transcribed to form protein-coding RNAs or other functional RNAs .

• Individual humans differ from each other in an average of one pair of nuclear otides per 1000; This and other genetic variation underlies most of our individuality and provides the basis for identifying individuals by DNA analysis .

• Almost half of the human genome consists of mobile genetic elements that can move from one site to another within a genome. Two classes of these elements have multiplied to extremely high copy numbers.

• Viruses are genes packaged in protective coats that can pass from cell to cell and organism to organism, but they require host cells to reproduce.

• Some viruses have RNA instead of DNA as their genetic material. Retroviruses copy their RNA genome into DNA before integrating into the host cell genome .

• Comparing genome sequences of different species provides a powerful way to identify conserved and functionally important DNA sequences.

• Related species, such as man and mouse, have many genes in common; Evolutionary changes in the regulatory DNA sequences that affect how these genes are expressed are particularly important in determining differences between species.

Chapter 10

• DNA technology Recombinant revolutionized the study of cells, and made it possible to select any gene at will from among the thousands of genes in the cell and to determine its nucleotide sequence.

• A crucial element of this technology is the ability to cut a large DNA molecule into a specific and reproducible set of DNA fragments using restriction nucleases , each of which cuts the DNA double helix only at a specific nucleotide sequence.

• DNA fragments can be separated from each other on the basis of size by gel electrophoresis .

• Nucleic acid hybridization can detect any given DNA or RNA sequence in a mixture of nucleic acid fragments. This technique depends on very specific base pairing between a labeled, single- stranded DNA or RNA probe and another nucleic acid with a complementary sequence.

• DNA cloning techniques make it possible to select any DNA sequence from millions of other sequences and produce it in unlimited quantities in a pure form.

• DNA fragments can be joined in vitro by using DNA ligase to create DNA molecules Recombinants that are not found in nature.

• DNA fragments can be saved and amplified by inserting them into a larger DNA molecule capable of replication, such as a plasmid . Next, a DNA molecule This recombinant is inserted into a rapidly dividing host cell, usually a bacterium, so that the DNA is replicated with each cell division.

• A collection of cloned segments of chromosomal DNA that represents the complete genome of an organism is known as a genomic library . The library is often maintained as millions of bacterial clones, each different clone carrying a different fragment of the organism’s genome.

• cDNA libraries contain cloned DNA copies of the total mRNA of a certain type of cell or tissue. Unlike DNA clones Genomic , cDNA clones mainly contain protein-coding sequences; They lack introns , regulatory and promoter DNA sequences. Thus they are useful when the cloned gene is needed for protein production.

• The polymerase chain reaction ( PCR ) is a powerful form of DNA amplification that is carried out in vitro using a purified DNA polymer . PCR requires prior knowledge of the sequence to be amplified, as two synthetic oligonucleotide primers must be synthesized that refer to the DNA segment to be replicated.

• Historically, genes were cloned using hybridization techniques to identify the bacteria carrying the desired sequence in the DNA library . Today, a gene is usually cloned using PCR to specifically amplify it from a sample of DNA or mRNA .

• That today the entire genome of thousands of different organs is known, including thousands of individual humans.

• Using DNA techniques Recombinant , a protein can be attached to a molecular tag, such as green fluorescent protein ( GFP ), which allows its movement to be followed within a cell and, in some cases, within a living organism.

• In situ to identify the exact location of genes in chromosomes and of RNA in cells and tissues.

• DNA microarrays and RNA-Seq can be used to monitor the expression of tens of thousands of genes at once.

• Cloned genes can be modified in vitro and stably inserted into the genome of a cell or organism to study their function. Such mutants are called transgenic organisms.

• The expression of certain genes in cells or organs can be inhibited by the RNAi interference technique (RNAi) , which prevents the translation of mRNA into protein.

• Bacteria, yeast and mammalian cells can be engineered to synthesize large amounts of any protein whose gene has been cloned, making it possible to study proteins that are normally rare or difficult to isolate.

Chapter 11

• Cell membranes allow cells to create barriers that restrict certain molecules to specific cells. They consist of a continuous double layer – bilayer – of lipid molecules in which proteins are embedded.

• The lipid bilayer provides the basic structure and barrier function of all cell membranes.

• The lipid molecules of the membrane are amphipathic , having both hydrophobic and hydrophilic areas. This property promotes their spontaneous assembly into bilayers when placed in water, forming closed cells that reseal if ruptured.

• There are three main classes of lipid molecules in the membrane: phospholipids , sterols and glycolipids .

• The lipid bilayer is liquid, and individual lipid molecules are able to disperse within their monolayer; However, they do not spontaneously flip from one layer to another.

• The two lipid monolayers of the cell membrane have different lipid compositions, reflecting the different functions of the two faces of the membrane.

• Cells that live at different temperatures maintain their membrane effect by changing the lipid composition of their membranes.

• Membrane proteins are responsible for most of the functions of cell membranes, including the transport of small, water-soluble molecules across the lipid bilayer.

• Transmembrane proteins extend across the lipid bilayer, usually as one or more coils, but sometimes as a 0-sheet rolled into a barrel shape.

• Other membrane proteins do not extend across the lipid bilayer, but are attached to one side or the other of the membrane, either by non- covalent association with other membrane proteins, by covalent attachment of lipids, or by association of an exposed amphipathic helix with a helix Single. monolayer of lipids.

• Most cell membranes are supported by a cross-linked framework of proteins. A particularly important example is the network of fibrous proteins that form the cell cortex beneath the plasma membrane.

• Although many membrane proteins can diffuse rapidly in the plane of the membrane, cells have ways of confining proteins to specific membrane domains. They can also immobilize certain membrane proteins by attaching them to intracellular or extracellular macromolecules.

• Sugar chains are attached to many of the proteins and some of the lipids exposed on the cell surface, which form a carbohydrate layer that helps protect and lubricate the cell surface, while also being involved in identifying specific cells.

Chapter 12

• The lipid bilayer of cell membranes is very permeable to small non-polar molecules such as oxygen and carbon dioxide, and to a lesser extent, to very small polar molecules such as water. It is highly impermeable to most large water-soluble molecules and all ions.

• The transfer of nutrients, metabolites and inorganic ions across cell membranes depends on membrane transport proteins.

• Cell membranes contain a variety of transport proteins that function as transporters or channels, each responsible for moving a specific type of solute.

• The channel proteins form pores on the surface of the lipid bilayer through which solutes can passively diffuse.

• Both transporters and channels can mediate passive transport, in which an uncharged solute moves spontaneously down its concentration gradient.

• For passive transport of a charged solute, its electrochemical gradient determines its direction of movement, not its concentration alone.

• Transporters can act as pumps to mediate active transport, where solutes are transported uphill against their concentration or electrochemical gradients; This process requires energy provided by hydrolysis of ATP , downstream flow of Na + or H + ions, or sunlight.

• Transporters move specific solutes across the membrane by making conformational changes that expose the solute binding site first on one side of the membrane and then on the other.

• The Na + pump in the plasma membrane of animal cells is ATPase ; It actively transports Na + out of the cell and K + in, maintaining a steep Na + gradient across the plasma membrane that is used to drive other active transport processes and transmit electrical signals.

• Ion channels allow inorganic ions of appropriate size and charge to cross the membrane. Most of them are closed and open transiently in response to a specific stimulus.

• Even when activated by a specific stimulus, ion channels do not remain open continuously: they flicker randomly between open and closed conformations . An activating stimulus increases the fraction of time the channel spends in the open state.

• The membrane potential is determined by the unequal distribution of charged ions on both sides of the cell membrane; This changes when these ions flow through open ion channels in the membrane.

• In most animal cells, the negative value of the resting membrane potential across the plasma membrane depends mainly on the K + gradient and the action of selective K + leak channels ; At this resting potential, the driving force for the movement of K + across the membrane is almost zero.

• Neurons propagate electrical impulses in the form of an action potential, which can travel long distances along the axon without weakening. The action potential is mediated by voltage-gated Na + channels that open in response to depolarization of the plasma membrane.

• 2+ voltage gated channels in a nerve terminal couple the arrival of an action potential to the release of a neurotransmitter at the synapse. Ion channels with a transmitter convert this chemical signal back into an electrical signal in the postsynaptic target cell.

• Excitatory neurotransmitters open transmitter- gated cation channels that allow an influx of Na + , which loosens the plasma membrane of the postsynaptic cell and encourages the cell to fire an action potential. Inhibitory neurotransmitters open transmissible Cl − channels in the plasma membrane of the postsynaptic cell, making it difficult for the membrane to depolarize and fire an action potential.

• Complex groups of neurons in the human brain utilize all of the above mechanisms to enable human behaviors.

Chapter 13

• Food molecules are broken down in successive stages, where energy is absorbed in the form of activated carriers such as ATP and NADH .

• In plants and animals, these catabolic reactions occur in different cell compartments: glycolysis In the cytosol , citric acid cycle in the mitochondrial matrix and oxidative phosphorylation in the inner mitochondrial membrane .

• During glycolysis , the six-carbon sugar glucose is split to form two molecules of the three- carbon sugar pyruvate , which produce small amounts of ATP and NADH .

• In the presence of oxygen, eukaryotic cells convert pyruvate to acetyl CoA plus CO 2 in the mitochondrial matrix . The citric acid cycle then reverses the acetyl group in acetyl CoA to CO 2 and H 2 O , and captures a large part of the energy released as high-energy electrons in carriers activated by NADH and FADH 2 .

• Fatty acids produced from fat digestion are also imported into the mitochondria and become acetyl molecules CoA , which are then further oxidized through the citric acid cycle.

• In the mitochondrial matrix , NADH and FADH 2 transfer their high-energy electrons to the electron transport chain in the inner mitochondrial membrane , where a series of electron transfers is used to drive the formation of ATP . Most of the energy captured during the breakdown of food molecules is harvested during this process of dephosphorylation (described in detail in Chapter 14).

• Many intermediates of glycolysis and the citric acid cycle are starting points for the anabolic pathways that lead to the synthesis of proteins, nucleic acids and many other organic molecules of the cell.

• The thousands of different reactions carried out simultaneously by a cell are regulated and coordinated by positive and negative feedback, which allows the cell to adapt to changing conditions; For example, such feedback allows the cell to switch from glucose breakdown to glucose synthesis when food is scarce.

• Cells store food molecules in special reservoirs. Glucose subunits are stored as glycogen in animal cells and as starch in plant cells; Both animal and plant cells store fatty acids as lipids. The food reserves stored by plants are major sources of food for animals, including humans.

Chapter 14

• Mitochondria, chloroplasts And many prokaryotes generate energy by a membrane-based mechanism known as chemiosmotic coupling , which involves using an electrochemical proton gradient to drive the synthesis of ATP .

• The mitochondria produce most of the ATP of the living cell, using the energy produced from the oxidation of sugars and fatty acids.

• Mitochondria have an inner and outer membrane. The inner membrane surrounds the mitochondrial matrix , where the citric acid cycle produces large amounts of NADH and FADH 2 from the oxidation of acetyl COA .

• In the inner mitochondrial membrane , high-energy electrons donated by NADH and FADH 2 pass along an electron transport chain and eventually combine with molecular oxygen ( O 2 ) to form water.

• A large part of the energy released by transferring electrons along the electron transport chain is harnessed to pump protons ( H + ) out of the matrix, creating an electrochemical proton gradient. The pumping of the protons is carried out by three large respiratory enzyme complexes embedded in the inner membrane.

• The electrochemical proton gradient across the inner membrane of the mitochondria is harnessed to generate ATP when protons move back into the matrix via synthase ATP located in the inner membrane.

• The electrochemical proton gradient also drives the active transport of selected metabolites into and out of the mitochondrial matrix.

• In photosynthesis in chloroplasts and photosynthetic bacteria , sunlight energy is absorbed by chlorophyll molecules embedded in large protein complexes called photosystems; In plants, these photosystems are located in the thylakoid membranes of chloroplasts in leaf cells.

• Electron transport chains associated with photosystems transfer high-energy electrons from water to NADP + to form NADPH , which produces O 2 as a byproduct.

• Photosynthetic electron transport chains In chloroplasts, a proton gradient is also produced across the thylakoid membrane , which serves as a synthase ATP embedded in the membrane to form ATP .

• The ATP and NADPH created by photosynthesis are used within the chloroplast stroma to drive the carbon fixation cycle, which produces carbohydrates from CO2 and water.

• Carbohydrate is exported from the stroma to the cytosol of the cell, where it provides the starting material for the synthesis of other organic molecules.

• Both mitochondria and chloroplasts are thought to have evolved from bacteria that were endocytosed by other cells. Each maintains its own genome and divides in processes similar to bacterial cell division.

• Chemiosmotic coupling mechanisms are of ancient origin. Modern microorganisms that live in environments similar to those thought to have existed on early Earth also use chemocytic coupling to produce ATP .

Chapter 15

• Eukaryotic cells contain many membrane- enclosed organelles , including nucleus, reticulum Endoplasmic ( ER ), Golgi stone , lysosomes , endosomes , mitochondria, chloroplasts (in plant cells) and peroxisomes . The ER , the Golgi apparatus , the peroxisomes , the endosomes And the lysosomes are all part of the endomembrane system .

• Most organelle proteins are produced in the cytosol and transported to the organelle where they function. Sorting signals in the amino acid sequence guide the proteins to the correct organelle; Proteins that function in the cytosol have no such signals and remain where they are made.

• Nuclear proteins contain nuclear localization signals that help direct their active transport from the cytosol to the nucleus through nuclear pores, which penetrate the double nuclear envelope. The proteins are transported in the fully folded structure.

• Most mitochondrial and chloroplast proteins are produced in the cytosol and then transported to the organelles by membrane proteins. The proteins unfold during the transport process.

• The ER produces most of the cell’s lipids and many of its proteins. The proteins are produced by ribosomes directed to the ER by a signal recognition particle ( SRP ) in the cytosol that recognizes an ER signal sequence on the growing polypeptide chain . The ribosome – SRP complex binds to a receptor on the ER membrane , which passes through the

ribosome A proteinaceous translocator that threads the growing polyp tide across the ER membrane through a translocation channel .

• Butter -soluble proteins destined for secretion or for the lumen of an organelle of the endomembrane system pass completely into the lumen of the ER , while transmembrane proteins destined for the membrane of these organelles or the plasma membrane remain anchored in the lipid bilayer in one or more membrane folds of helices.

• In the lumen of the ER , proteins fold, assemble with their protein partners, form disulfide bonds and decorated with necklaces Oligosque .

• Leaving the emergency room is an important step in quality control; Proteins that fail to fold properly or fail to assemble with their normal partners are kept sorted by chaperone proteins, which prevent their accumulation and help them to fold; Proteins that still fail to fold or assemble are transferred to the cytosol , where they are degraded.

• Excessive accumulation of unfolded proteins triggers an unfolded protein response that expands the ER , increases its ability to fold new proteins properly, and reduces protein synthesis.

• Protein transport from the ER to the Golgi apparatus and from the Golgi apparatus to other destinations is mediated by transport vesicles that continuously exit one membrane and fuse with another membrane, a process called vesicular transport.

• Bud transport vesicles have unique coat proteins on their cytosolic surface ; The assembly of the coat helps drive both the budding process and the incorporation of the cargo receptors, with their bound cargo molecules, into the forming vesicle.

• Coated vesicles quickly lose their protein coat, which allows them to anchor and then fuse with a specific target membrane; Docking and fusion are mediated by proteins on the surface of the vesicle and the target membrane, including Rab and SNARE proteins .

• Golgi apparatus receives new proteins made from sorting; It changes their oligosaccharides , sorts the proteins and launches them from the Trans Golgi network to the plasma membrane, lysosome (via endosomes ), or secretory vesicles.

• In all eukaryotic cells , transport vesicles continuously emerge from the trans- Golgi network and fuse with the plasma membrane; This process of constitutive exocytosis delivers proteins to the cell surface for secretion and incorporates lipids and proteins into the plasma membrane.

• Specialized secretory cells also have a regulated exocytosis pathway , where molecules concentrated and stored in secretory vesicles are released from the cell by exocytosis when the cell is signaled to secrete.

• Cells ingest liquids, molecules and sometimes even particles by endocytosis , in which areas of the plasma membrane penetrate and pinch to form endocytic vesicles .

• A large part of the material that undergoes endocytosis is transferred to endosomes , which mature into lysosomes , where the material is broken down by hydrolytic enzymes ; Most of the components of the endocytic vesicle membrane , however, are recycled in transport vesicles back to the plasma membrane for reuse.

Chapter 16

• Cells in multicellular organisms communicate using a large variety of extracellular chemical signals.

• In animals, hormones are carried in the blood to distant target cells, but most other extracellular signal molecules act only a short distance away. Neighboring cells often communicate through direct cell contact.

• For an extracellular signal molecule to affect a target cell it must interact with a receptor protein on or within a target cell. Each receptor protein recognizes a specific signal molecule.

• Small, hydrophobic, extracellular signal molecules, such as steroid hormones and nitric oxide, can cross the plasma membrane and activate intracellular proteins, which are usually transcription regulators or enzymes.

• Most of the extracellular signal molecules cannot pass through the plasma membrane; They bind to receptor proteins on the cell surface that convert (transmit) the extracellular signal into various intracellular signals, usually organized into signaling pathways.

• There are three main classes of cell surface receptors: (1) ion-coupled receptors, (2) G protein-coupled receptors (GPCRs) , and (3) enzyme-coupled receptors.

• GPCRs and enzyme-coupled receptors respond to cellular signals by activating one or more intracellular signaling pathways, which in turn activate effector proteins that alter cell behavior.

• Turning off signaling pathways is as important as turning them on. Any activated component in a signaling pathway must then be -disabled or removed for the pathway to function again.

• GPCRs activate GTP binding proteins trimers called G proteins ; These act as molecular switches, passing the signal on for a short period before turning themselves off by hydrolyzing their bound GTP to GDP .

• G proteins directly regulate ion channels or enzymes in the plasma membrane. Some of them activate (or deactivate) the enzyme adenylyl cyclase , which increases (or decreases) the intracellular concentration of the small messenger molecule cyclic AMP ; Others directly activate the phospholipase enzyme C , which produces the small messenger molecules inositol triphosphate ( IP 3 ) and diacylglycerol .

• IP 3 opens the Ca 2 + channels in the membrane of the endoplasmic reticu lum , which release a flood of free Ca 2 + ions into the cytosol . Ca 2 + itself acts as a second messenger, changing the activity of a wide variety of proteins that react to Ca 2 + . These include calmodulin , which activates various target proteins such as Ca 2+ / CaM – dependent protein kinases.

• An increase in cyclic AMP activates protein kinase A (PKA) , while Ca 2 + and diacylglycerol in combination activate protein kinase C (PKC) .

• PKA, PKC and CaM -kinases Phosphorylates selected signaling and effector proteins on serines and threonins , thus changing their activity. Different cell types contain different sets of signaling proteins and effector proteins and are therefore affected in different ways.

• Enzyme-binding receptors have intracellular protein domains that function as enzymes or bind to intracellular enzymes. Many enzyme-linked receptors are receptor tyrosine Kinase ( RTKs ), which phosphorylate themselves and select intracellular signaling proteins on tyrosines . The phosphotyrosines in the RTK then serve as docking sites for various intracellular signaling proteins.

• Most RTKs activate the GTPase Ras The monomer , in turn, activates a three-protein MAP-kinase signaling module that helps transmit the signal from the plasma membrane to the nucleus.

• Ras mutations stimulate cell proliferation by keeping Ras (and consequently, the Ras-MAP kinase signaling pathway ) constantly active and are a common feature of many human cancers.

• Some RTKs stimulate cell growth and cell survival by activating PI 3-kinase , which phosphorylates specific inositol phospholipids in the cytosolic leaflet of the lipid bilayer of the plasma membrane. This inositol phosphorylation creates lipid docking sites that attract specific signal proteins from the cytosol , including protein kinase Akt , which becomes active and passes the signal on.

• Other receptors, such as Notch , have a direct route to the nucleus. When activated, part of the receptor migrates from the plasma membrane to the nucleus, where it regulates the transcription of specific genes.

• Plants, similar to animals, use cell surface receptors attached to the enzyme to recognize the extracellular signal molecules that control their growth and development; These receptors often act by facilitating the transcriptional repression of specific genes.

• Various intracellular signaling pathways interact, allowing each type of cell to produce the appropriate response to the combination of additional cellular signals. In the absence of such signals, most animal cells are programmed to kill themselves by performing apoptosis .

• We are far from understanding how a cell integrates all the many extracellular signals bombarding it to form an appropriate response.

Chapter 17

• The cytoplasm of a eukaryotic cell is supported and organized by a cytoplasmic skeleton of intermediate filaments, microtubules and actin filaments.

• Intermediate filaments are stable rope-like polymers – built from fibrous protein subunits – that give cells mechanical strength. Several intermediate filaments form the nuclear lamina that supports and strengthens the nuclear envelope; Others are scattered throughout the cytoplasm.

• Microtubules are rigid, hollow tubes formed by dimming globular tubulin. They are polarized structures, with a minus end that grows slowly and a plus end that grows quickly.

• Microtubules grow from organizing centers such as the centrosome , where the minus ends remain embedded.

• Many microtubules exhibit dynamic instability, alternating between growth and contraction. Shrinkage is promoted by the hydrolysis of the GTP that is tightly bound to tubulin dimers , reducing the affinity of the dimers to their neighbors and thus promoting the disintegration of the microtubulin .

• The microtubules can be stabilized by local proteins that capture the plus ends, thus helping to position the microtubules and harness them for specific functions.

• Kinesins And dyneins are microtubule-associated motor proteins that use the energy of ATP hydrolysis to move unidirectionally along microtubules . They carry specific organelles, vesicles and other types of cargo to specific locations in the cell.

• Eukaryotic cilia and flagella contain a bundle of stable microtubules. Their rhythmic beating is caused by the bending of the microtubules , driven by the dynein motor protein the eyelashes

• Actin filaments are helical polymers of globular actin monomers . They are more flexible than microtubules and are usually found in bundles or networks.

• Similar to microtubules , the actin filaments are polarized, with a plus end that grows rapidly and a minus end that grows slowly. Their assembly and disassembly are controlled by the hydrolysis of ATP tightly bound to each actin monomer and by various proteins associated with actin .

• The diverse arrangements and functions of actin filaments in cells result from the variety of actin binding proteins, which can control actin polymerization , cross actin filaments into loose networks or rigid bundles, connect actin filaments to membranes, or move two relatively adjacent filaments. to each other.

• A concentrated network of actin filaments beneath the plasma membrane forms the bulk of the cell cortex, which is responsible for the shape and movement of the cell surface, including the movements involved when a cell crawls along a surface.

• Myosins are motor proteins that use the energy of ATP hydrolysis to move along actin filaments. In non-muscle cells, myosin – I can carry organelles or vesicles along actin-filament pathways, and myosin – II can cause adjacent actin filaments to slide past each other in contractile bundles.

• In skeletal muscle cells, repeated arrays of overlapping filaments of actin and myosin – II form highly ordered myofibrils , which contract as these filaments slide past each other.

• Muscle contraction begins by a sudden increase in cytosolic Ca 2 + , which provides a signal to the myofibrils through Ca 2 + binding proteins associated with the actin filaments.

Chapter 18

• The eukaryotic cell cycle consists of several distinct phases. In the interphase phase, the cell grows and the nuclear DNA is replicated; In phase M , the nucleus divides ( mitosis ) followed by the cytoplasm ( cytokinesis ).

• In most cells, interphase consists of an S phase when the DNA is replicated, plus two gap phases – G 1 and G 2 . These gap phases give the proliferating cells more time to grow and prepare for S phase and M phase .

• The cell cycle control system coordinates cell cycle events by continuously and cyclically turning on and off the appropriate parts of the cell cycle machinery.

• The cell cycle control system depends on cyclin-dependent protein kinases ( Cdks ) , which are activated cyclically by binding cyclin proteins and by phosphorylation and dephosphorylation ; When activated, Cdks phosphorylate key proteins in the cell.

• Different cyclin- Cdk complexes activate different phases of the cell cycle: M- Cdk drives the cell into mitosis; G 1 – Cdk drives it through G 1; G 1 /S- Cdk and S- Cdk transfer it to S phase .

• The control system also uses protein complexes, such as APC , to activate the destruction of specific regulators of the cell cycle at certain stages of the cycle.

• The cell cycle control system can stop the cycle at specific transition points to ensure that intracellular and extracellular conditions are favorable and that each phase is completed before the next phase begins. Some of these control mechanisms rely on Cdk inhibitors that block the activity of one or more cyclin- Cdk complexes.

• S- Cdk initiates DNA replication during S phase and helps ensure that the genome is copied only once. The cell cycle control system can inhibit cell cycle progression during G 1 or S phase to prevent cells from replicating damaged DNA . It can also delay the onset of M phase to ensure that DNA replication is complete.

• Centrosomes duplicate during S phase and separate during G 2 . Some of the microtubules that grow from the replicated centrosomes interact and form the mitotic spindle .

• When the nuclear envelope breaks down, the microtubules of the spindle capture the replicated chromosomes and pull them in opposite directions, placing the chromosomes on the equator of the metaphase axis .

• The sudden separation of sister chromatids in anaphase allows the chromosomes to be pulled to opposite poles; This movement is driven by the depolymerization of spindle microtubules and by motor proteins associated with microtubules .

• A nuclear envelope is re-formed around two sets of separated chromosomes to form two new nuclei, thus completing mitosis.

• In animal cells, cytokinesis is mediated by a contractile ring of actin filaments and myosin filaments , which converges halfway between the spindle poles; In plant cells, however, a new cell wall forms within the parent cell to divide the cytoplasm into two.

• In animals, extracellular signals regulate cell number by controlling cell survival, cell growth, and cell proliferation.

• Most animal cells require survival signals from other cells to avoid apoptosis – a form of cell suicide mediated by a caspase cascade proteolytic ; This strategy helps ensure that cells survive only when and where they are needed.

• Animal cells reproduce only if stimulated by cellular mitogens produced by other cells; Mitogens release the normal intracellular brakes that block the progression from G 1 or G 0 to the S phase .

• For an organism or organ to grow, cells must grow as well as divide; Animal cell growth depends on extracellular growth factors that stimulate protein synthesis and inhibit protein degradation.

• Some of the extracellular signal molecules inhibit rather than promote cell survival, cell growth or cell division.

• Cancer cells fail to obey these normal “social” controls on cell behavior and therefore grow, divide and survive outside their normal neighbors.

Chapter 19