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Cell structure and Genetic control Chapter 3 Cell Cell – Cell-membrane, Cytoplasm and Nucleus Cytoplasm – Cytosol and Cell Organelles Nucleus – Nuclear Envelope, Nucleoplasm and Chromatin (DNA + Histones) Cell Membrane All cells are covered with a thin covering of a double layer of Phospholipids and associated Proteins present here and there. Each phospholipid has a polar (hydrophilic) head and non-polar (hydrophobic) tails. In the double layer the tails face each other forming a hydrophobic barrier which keeps water dissolved contents inside. Proteins may be Intrinsic – embedded in the lipid double layer and Extrinsic associated outside the lipid double layer. Glycocalyx = Glycoprotein + glycolipid; function – Cell-cell recognition Inter-Cellular Junctions 3 important inter-cellular junctions are present between cell membranes of neighboring cells: Desmosomes, Tight Junctions and Gap Junctions. Desmosomes: small specialized areas with interlocking Cadherin proteins between 2 membranes. On the cytoplasm side of cell membrane Dense Plaque Proteins accumulate and keratin filaments emerge from them. Desmosomes help to hold cells of tissue together. Desmosomes are disc like areas and act like rivets or spot welds. Tight and Gap Junctions Tight Junctions: are circular bands around epithelial cells where the membranes of adjacent cells fuse together. Tight junctions block extracellular pathway and are usually present near outer surface of tissue. Gap Junctions: are channels (1.5 nm) between adjacent membranes. The cytosol of 2 cells is continuous through them. Small molecules like water and ions like Na+ and K+ can move through them. Different kinds of cells have gap junctions. For example heart muscle cells have gap junctions that enable them to stimulate adjacent cells. Cytoplasm Cytoplasm is the living fluid part between cell membrane and nucleus. It has special structures called Cell Organelles in it. Cytosol is the matrix (formless) part of cytoplasm formed of water having dissolved or suspended substances in it. Cell Organelles are organ like each performing specific function/s but formed of molecules and membranes only (sub-cellular). Double Membrane bound Organelles: Mitochondria, Chloroplasts, Endoplasmic Reticulum, Golgi Body, and Nucleus. Single Membrane bound Organelles: Lysosomes, Peroxisomes, Vacuoles Organelles lacking any membrane: Ribosomes, Centrioles, Nucleolus Table 3.1 Nucleus and Ribosomes 1 Genetic Control of the Cell Nucleus: is the most distinct structure inside cell visible with light microscope. It has inside it DNA having all the information needed to form and run the cell. The segments of DNA are called Genes. 1 Nuclear Envelope: is formed of 2 membranes with a gap between them. It has a large number of Nuclear Pores usually bound by a nuclear complex. The pores are large enough to allow RNA and proteins to pass through. Nucleoplasm: is the matrix (liquid part) of nucleus and has a different composition than cytosol. Chromatin fibers: are very long molecules of DNA associated with Histone proteins. DNA wraps around octamer of histones to form Nucleosome. This thin chromatin forms loops to form thick chromatin. Thick chromatin packs further to form Chromatid. At the time of cell division, chromatids packs into Chromosomes. Nucleolus: is denser body in the nucleus when the cell is not dividing. No membrane bounds it. It assembles both units of Ribosomes. Ribosomes Each ribosome has 2 sub-units larger (60S) and smaller (40S). Prokaryotic cells (bacteria) have 50S and 30S subunits. S = Svedberg unit of sedimentation. Ribosomal RNA = r-RNA and ribosomal proteins form the ribosomal subunits. r-RNA acts as ribozymes. No membrane covers the ribosomal subunits. Ribosomal subunits join only around m-RNA for protein synthesis otherwise remain separate. The Endomembrane System 1 Manufacturing and Distributing Cellular Products Endoplasmic Reticulum, Golgi Apparatus, Lysosomes and Vacuoles collectively form Endomembrane System. Endoplasmic Reticulum: is a system of double membranes in the form of tubes and sacs throughout cytoplasm (in between cell membrane and nuclear envelope). Main manufacturing facility. Functions include synthesis of proteins and lipids including steroids, detoxification, and cellular transportation. It transports materials inside the cell by transport vesicles. RER SER 1. Rough ER, Ribosomes fixed 1. Smooth ER, no Ribosomes 2. Flat sacs – cisternae 2. Tubular sacs 3. Synthesis of membrane proteins 3. Synthesis of Lipids, steroids 4. Synthesis of secretary proteins 4. Detoxification of drugs The Endomembrane System 2 Golgi Apparatus: is a stacks of flattened sacs called cisternae. A cell may have from a few to a few hundred of Golgi stacks. Golgi Apparatus receives transport vesicles from ER on one side, modifies received chemicals, can store them and packs them in secretory vesicles and releases them on shipping side. Lysosomes: are single membrane bound organelles rich in 40 digestive enzymes, help in breakdown of large molecules like proteins, polysaccharides, lipids and nucleic acids. Lysosomes provide a safe place for digestion of large molecules without damaging molecules of the cell. A Lysosome joins a food vacuole to digest the materials inside vacuole. Lysosomes are absent in most plant cells. Mutations in genes forming digestive enzymes result in defective enzymes causing accumulation of lipids or glycogen. Tay-Sachs disease and Gaucher disease. Vacuoles: are membrane bound sacs and pinch off from ER, Golgi Apparatus and cell membrane. Functions include endocytosis, exocytosis, and trasnportation. Mitochondria Energy Conversion Mitochondria (sing. Mitochondrion): are the powerhouses of cells and the site for cellular respiration. 2 Respiration is oxidation of food and chief source of energy for the cell. These are bound with double membrane, outer smooth and inner folded into cristae. Mitochondria have enzymes for breakdown glucose derivatives, fatty acids and amino acids. Mitochondria have Electron-Transport-System that generates ATP molecules by using the energy contained in H’s produced during breakdown of glucose. Only organelle to have DNA outside nucleus. It is a circular DNA and always comes from mother through cytoplasm of egg. Single Membrane Bound Organelles Lysosomes are rich in hydrolytic = digestive enzymes (40-60) Lysosomes are produced by Golgi Apparatus Help in digesting large molecules of lipids, proteins, and glycogen. Act as ‘cellular stomachs’. Usually a cell has hundreds of Lysosomes in it. Cells involved in body defense have a large # of Lysosomes Peroxisomes: All cells produce hydrogen peroxide as a metabolic bye product. It is highly reactive and can easily damage the proteins and nucleic acids in cells. Cells have single membrane bound dense oval bodies – Peroxisomes. Peroxisomes are rich in Catalase enzyme which converts hydrogen peroxide into water and oxygen gas. 2H2O2 2H2O + O2 The Cytoskeleton Cell Shape and Movement Maintaining Cell Shape: The shape of the cell is maintained by Intermediate Filaments, the thick ropes of twisted protein fibers (Keratin), Microtubules, the hollow organelles and Microfilaments, the solid thinner organelles. These maintain the shape of cells and keep the nucleus in position. The framework of support is highly dynamic that can organize and dismantle really fast. Transport of organelles and molecules: Microtubules are the freeways used by organelles like Lysosomes to move from one part of cell to another. Microfilaments are the roads/streets used by smaller things. Recap 1 1. The liquid part of cytoplasm is --------------2. Structures formed of membranes and molecules, present in cytoplasm, doing a special function, are ------------------------3. 2 halves of cell membrane are held together by -------------bonds 4. Cell membrane is fluid due to --------------- molecules 5. ---------- are branched chains sugars attached on outer surface of cell 6. Movement of solute from high to low concentration is ------------7. Net Movement of water across cell membrane from low concentration solution to high concentration solution is ---------8. This process can operate against concentration gradient and needs both a carrier protein and ATP. It is -------------------------9. This process moves along the concentration gradient and needs a carrier protein but no ATP. 10. Vesicular movement of solids into the cell in vesicle is --------- and of liquids is ------------------. Recap 2 1. Smooth E.R. synthesizes ---------------2. Rough E.R. synthesizes ----------------3. Golgi Apparatus is the --------- ------------ of the cell and produces secretory vesicles. 3 4. 5. 6. 7. 8. 9. 10. 11. ATP’s are synthesized in the --------- chamber of --------------. Synthesis of DNA takes place during ----------- of cell cycle. When cell is not dividing DNA occurs in the form of -----------When the cell is dividing the DNA occurs in the form of ------------During ------------ chromosomes arrange on mid-plate in mitosis Division of cytoplasm after mitosis is called ---------------Divided chromosomes move to opposite poles during ------------Spindle is formed, chromosomes appear randomly arranged and nuclear envelope breaks during ------------12. Nuclear envelope appears, chromosomes unpack during -----------Genetic Control Genes control metabolism and growth through Transcription, Translation, DNA replication and Gene splicing. A gene (DNA) produces m-RNA by transcription. The m-RNA comes out of nuclear pores into the cytoplasm. Here ribosomes attach one by one to m-RNA and synthesize a protein. t-RNA’s bring amino acids from cytosol to m-RNA – ribosome complex. At the time of cell division one DNA divides and produces 2 DNA molecules by replication. DNA replication allows cell to divide into 2 daughter cells. m-RNA = messenger RNA t-RNA = transfer RNA r-RNA = ribosomal RNA Replication DNA ----------------DNA + DNA (DNA polymerase) Protein Synthesis 2 main processes occur during protein synthesis. Transcription Translation DNA -------------------m-RNA -----------------------Protein Transcription: Cell uses information in DNA to form m-RNA in presence of enzyme RNA polymerase and special proteins. Human genes have exons = coding parts and introns = noncoding parts. DNA pre-mRNA m-RNA Precursor – mRNA has parts copied from both exons and introns. Parts corresponding to introns are removed in nucleus to form m-RNA. m-RNA leaves through nuclear pores to enter cytoplasm. Translation Translation: 2 sub-units of ribosome attach at one end of m-RNA. Then, t-RNA molecules bring required amino acids to ribosome/m-RNA complex. Codon of m-RNA and anticodon of t-RNA must be complementary to get incorporated in polypeptide chain. As ribosome moves over m-RNA, a new amino acid is added to the chain at each step. Polypeptide chain undergoes coiling to get specific 3-D shape of protein. RNA interference and Protein degradation RNA interference: 2 short RNA’s regulate translation. siRNA = short interfering RNA is double stranded and binds to m-RNA and destroys it. miRNA = microRNA has hair pin loop structure but forms a double stranded RNA which binds to m-RNA and prevents its translation into protein. Scientists have discovered 100s of miRNA. Clinical applications are under trials for macular degeneration and other genetic diseases. 4 Protein Degradation: Regulator proteins are regulated in Lysosomes by digesting proteins Proteasomes: Ubiquitin attaches to lysine amino acid in target protein and protease enzyme in a large complex, Proteasome, degrades the protein. Interphase – Mitosis – Cell Cycle Interphase – cell grows and prepares for cell division, DNA replication, DNA is in form of a diffuse network, Chromatin. Cell division = mitosis + cytokinesis Mitosis is division of nucleus. Chromatin packs into Chromosomes. Cytokinesis is division of cytoplasm. A cell cycle has one interphase and one cell division. Cell Cycle A cell is either dividing, M-phase or preparing to divide, I-phase. Interphase: is a phase between 2 successive cell divisions. Cell grows in size and DNA is replicated. Cell is now ready to divide. I-phase has 3 sub-phases. G1 and G2 are growth phases. DNA replication takes place in S-phase. Mitosis is division of nucleus followed by Cytokinesis the division of cytoplasm. Mitosis is the division of growth and replacement of lost or damaged cells. Mitosis has 4 distinct phases Prophase, Metaphase, Anaphase and Telophase. Memory aid: P-MAT Mitosis – Prophase pro = first Prophase: is the phase that prepares the cell for mitosis. Mitotic spindle formed Chromatin packs into chromosomes. Nuclear envelope degenerates and chromosomes are released in cytoplasm. Spindle fibers join to chromosomes. Mitosis – Metaphase meta = after Metaphase: Chromosomes align at equator. The centromeres of chromosomes lie at the plate. Mitosis – Anaphase ana = apart Anaphase: It starts suddenly when the centromeres divide. Chromosomes , now only with 1 chromatid move towards poles. Telophase telo = end Telophase: This phase is the reverse of prophase. Chromosomes unpack to diffuse chromatin. Nuclear envelope is reorganized. Spindle fibers disappear. One nucleus is completely divided into 2 genetically similar daughter nuclei. 5 Cytokinesis kinesis = motion Cytokinesis takes place along Telophase. A cleavage furrow appears at the middle and divides the cytoplasm into 2 equal halves, each with a nucleus. Cleavage furrow always where the metaphase plate was formed. Actin filaments join the cell membrane and pull it in like the strings of a purse. Meiosis Meiosis has 2 successive divisions and forms 4 daughter cells. Meiosis -1 is reduction division and reduces # of chromosomes from 46 to 23 in 2 daughter nuclei. Meiosis-2 is equation division and maintains # of chromosomes at 23. Prophase-1: Synapse is pairing of homologous chromosomes and Crossing over is exchange of genes between non-sister chromatids. It leads to recombination of genes. Metaphase-1: homologous chromosomes arrange in 2 plates at equator. Anaphase-1: chromosome pairs separate without division of centromeres. Centromeres divide in Anaphase-2. Spermatogenesis and Oogenesis are examples of meiosis. Mitosis & Meiosis Mitosis 1. It consists of 1 cell division. 1. 2. 2 haploid or diploid daughter cells produced. 3. 2 daughter cells are similar to each other and parent cell. 4. It is 2n 2n or n n. 2. 3. 4. Meiosis It consists of 2 divisions, Meiosis-1 and Meiosis-2. 4 haploid daughter cells produced. 4 daughter cells are different from each other and parent cell. (Why?) It is always 2n n. Unique Features of Meiosis It is a reductional division. 2n n It makes sexual reproduction possible. It is opposite to Fertilization. n 2n It consist of 2 cell divisions and produces 4 daughter cells. Crossing over in Prophase-1 leads to Recombination of genes. Recombination is the largest source of Variations. It operates only in diploid cells. Recap 1 Meiosis 1. 2 important events of Prophase-1 are ----- and ----- -------. 2. Meiosis divides a single -----cell into 4 --------. 3. --------- is Single largest source of variations 4. ---------arrange on mid-plate during Metaphase-1 5. Full Chromosomes move from mid-plate to poles during ---------- . 6. ---------- is failure of homologues to separate during Anaphase-1 7. Packing of chromatin into chromosomes facilitates --------; unpacking of chromosomes into chromatin facilitates -----. 8. Failure to control mitosis leads to -------------. 6 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. Recap 2 Meiosis Humans have --------- pairs of chromosomes in cells ----------- are 22 similar pairs in males and females. Sex chromosomes in males are --------- and in females are ----At metaphase a chromosome has ------ chromatids At anaphase a chromosome has ----- chromatids Chromatin is formed of ------- and --------- proteins In ------ ----------- DNA divides into 2 DNA molecules ------------ is synthesis of m-RNA from DNA ------------ is synthesis of polypeptide from m-RNA A -------- is a triplet of N-bases of m-RNA having information for 1 amino acid A ------- is a triplet of N-bases of t-RNA reading information about 1 amino acid ------- site carries the t-RNA with peptide chain already synthesized and ------ site carries the t-RNA to be added to the chain 7