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Biology in general and cell biology in particular depend heavily on both chemistry and physics. Simply, cells and organisms follow all the laws of the physical universe, and biology is really just the study of chemistry in systems that happen to be alive. In fact, everything cells are and do has a molecular and chemical basis. Therefore, we can truly understand and appreciate cellular structure and function only when we can describe that structure in molecular terms and express that function in terms of chemical reactions and events. 5 themes in the chemistry of the cell 1. Carbon: biology deals with carbon containing molecules Valence of four and covalent bond Carbon containing molecules are stable Carbon-containing molecules are diverse Carbon-containing molecules can form isomers 2. Water: Cellular world is an aqueous world Water molecules are polar Water molecules are cohesive Water is an excellent solvent Hydrophilic and hydrophobic molecules 3. Selectively permeable membrane: Separation of two water environments Amphipathic molecules Membrane bilayer Movement across the membrane 4. Polymerization: Addition of molecular building units Monomers and polymers Biological polymers: proteins, nucleic acids, polysaccharides and lipids(fat) Condensation reaction Directionality 5. Self-assembly: spontaneous assembly of the parts Characteristics Driving forces Protein assembly   Reading Assignments: Text pages 41-78. Questions:  1. Which of the following statements is false? The molecules of liquid water are extensively hydrogen-bonded to one another When exposed to an aqueous environment, amphipathic molecules undergo hydrophobic interactions The water molecule is polar because it has an asymmetric charge distribution The carbon-carbon double bonds are less stable than the single bonds and therefore result in a bend or kink in the unsaturated fatty acid None of above (all are true) 2. Hydrogen bond is a covalent bond. True___ False____ 3. Why are the carbon containing molecules are stable? 4. What is the currency of the biological energy? 5. Why is the polarity of water the most important chemcial property? 6. Hydrophobic interaction is _________________________ 7. Amphiphatic molecules are _________________________ 8. Condensation is __________________________________ 9. Self-assembly is _________________________________ Carbohydrates and Polysaccharides  Polysaccharides: they usually consist of a single kind of repeating unit, or sometime a strictly alternating pattern of two kinds. Monomers :Monosaccharides 1. Either consists of aldehyde or ketone functional group 2. 2 or more -OH' groups 3. Formula: CnH2nOn, where n= 3 to 7     Triose, n=3               glyceraldehyde               dihydroxyacetone     Pentose, n=5               ribose               deoxyribose     Hexose, n=6               glucose               fructose               galatose 4. Ring form and chair form 5. aš and bš configuration 6. Sugar derivatives  Oligosaccharides: consist of 2 to 20 monosaccharides covalently linked together 1. Glycosidic bond: covalent bond              aš and bš linkages 2. Disaccharides              maltose              lactose              sucrose 3. Complex oligosaccharides              glycoproteins              glycolipids Polysaccharides 1. Storage polysaccharides             starch: storage polysaccharides in the plant cells                        amylose                        amylopectin             glycogen : storage polysaccharides in animal cells 2. Structural polysaccharides             cellulose: structural polysaccharides found in the plant cells chitin Secondary structure of polysaccharides 1. Determining factors             linkage configuration             branching degree 2. Types             Loose helices             Rigid, liner rods Glycosaminoglycan chains and proeoglycans in the extracellular matrix of animals Glycosaminoglycan (GAG) Protroglycans  Lipids: any discussion of cellular structure and chemical components would be incomplete without reference to this important group of molecules. Especially, they are frequently associated with the macromolecules, i. e. proteins. 1. Hyprophobic nature 2. Amphipathic Triglycerides are storage lipids             1. Ester bonds             2. Fatty acids             3. Fats             4. Vegetable oils   Phospholipids are important in membrane structure             1. Phosphatidic acid             2. Phosphoester bonds   Sphingolipids are also found in membranes             1. In animal membranes             2. Sphingosine             3. Amide bonds   Steroids are lipids with a variety of functions             1. Ring structures             2. Steroids play in a variety of roles in the cells of higher organisms but not present in bacteria             3. Some mammalian hormones are steroids                        Adrenocortical hormones                        Sex hormones             4. Bile acids             5. Cholesterol Proteins and Polypeptides Monomers             amino acids     š š š š š š š š š š š š š š š šaš carbon                       Families of amino acids                              Hydrophilic amino acids                                       Non-polar amino acids                              Hydrophobic amino acids                                       Basic amino acids                                       Acidic amino acids                                       Non-charged polar amino acids Primary sequence Peptide bonds Primary sequences determine their higher organization Driving forces for the higher organization of proteins (polypeptides) Non-covalent bonds         Hydrogen bonding         Ionic interactions         Hydrophobic interaction         van der Waals interaction Covalent bonds         Disulfide bonds Secondary structure Driving force: hydrogen bonds aš helix bš pleated sheets Tertiary structure Driving forces         Non-covalent bonds              Hydrogen bonding              Ionic interactions              Hydrophobic interaction              van der Waals interaction         Covalent bonds              Disulfide bonds              The chemistry of amino acid side chain (R groups) is the                  determining factor       Quaternary structure           Driving forces                  Non-covalent bonds                       Hydrogen bonding                       Ionic interactions                       Hydrophobic interaction                       van der Waals interaction                  Covalent bonds                       Disulfide bonds           Multimeric protein structure Protein modification: post-translational modification Phosphorylation Tyrosination Acetylation Classifications of proteins Fibrous proteins versus globular proteins Membrane proteins versus cytosol proteins Structural proteins Glycoproteins Proteoglycans    Reading Assignments: Text pages 56-57; 111-128 Questions: 1. Which amino acid is always found on the outside of protien molecules? cluster together inside of protein molecule? within plasma membrane? 2. The shape of a protein molecule is determinedby its amino acid sequence. True____ False____ 3. What is a peptide bond? 4. What is a difulfide bond? Which amino acid is involved? 5. What is aš -carbon in an amino acid? 6. List 3 globular proteins and 3 fibrous proteins. 7. What is the tertiary of a protein? What is the quarternary structure of a protein? Nucleic Acids Nucleic acids play the roles in the storage, transmission and expression of genetic information.                  DNA                  RNA                        mRNA                        tRNA                        rRNA                  Monomers                        Nucleotides (4 different basic nucleotides for DNA and RNA, respectively)                             3 chemical groups                                  a pentose                                       DNA: bš -D-deoxyribose                                       RNA: bš -D-ribose                                     a phosphate group                                  a nitrogen containing base (purine and pyrimidine)                                       DNA: A, G, C, T                                       RNA: A, G, C, U                        Other functional roles of nucleotides                                       energy providers                                       enzyme cofactors                                       signaling molecules in intracellular signal transduction                  Polynucleotide formation: 3’, 5’-phosphodiester bonds                        Condensation reaction                        Sugar-phosphate is the backbone                        Intrinsic directionality (5’ 3’)                        Require energy and information                  Hydrogen bonding between bases and complementary base pairing                       A=T(U)                       G=C                   Double helix of nucleic acids                       DNA                              2 complementary chains of DNA twisted with each other                              They are in opposite direction                              Backbone: sugar and phosphate unit                              Bases are pairing inward                              Right handed double helix with ~ 10 nucleotide pair per turn                       RNA                              Only local region of short complementary base pairing                  What does the DNA helix tell us?                       Quantitative biochemistry                            [A]=[T] and [G]=[C]                       Explain heredity                             DNA replication process is semiconservative                   RNA serves as an informational carrier intermediate between DNA and protein                       Prokaryotes                       Eukaryotes Enzymes: Biological Catalysts The law of thermodynamic spontaneity      All reactions that occur spontaneously result in a decrease in the free energy content of the system In the cells:      1) Some reactions are thermodynamic feasible but do not occur at appreciable rates      2) The only reactions that occur at appreciable rates are those from which an enzyme is present      3) All reactions are mediated by the biological catalysts called enzymes Activation energy      How to overcome the activation energy barrier      1) Heat      2) Lower the activation energy: catalysts Properties of catalysts      1) Increase rates of reaction by lowering activation energy to allow more molecules to react without use of heat      2) Form transient complexes with substrates in a fashion that facilitates reaction      3) Only change rate at which reaction equilibrium is achieved, has no effect on the position of the equilibrium Enzyme Structure      Proteins           Tertiary or quaternary proteins           Active sites           Prosthelic groups      RNAs           Ribozyme Enzyme Specificity Enzyme mechanisms      1).Random collisions      2) Driving forces      3) Induced fit      4) Form temporary covalent bonds Enzyme sensitivity to environment      Temperature      pH Enzyme kinetics      Michaelis-Menten kinetics      Vmax and Km Enzyme Regulations      Allosteric regulation           Negative regulation                Feedback inhibition           Positive regulation                Subtract activation      Enzyme inhibitors           Reversible inhibitors           Irreversible inhibitors Definitions Allosteric effector Small molecule that cause a change in the conformation of an allosteric protein (or enzyme) by binding to a site other than the active site. Allosteric protein (allosteric enzyme) Regulatory protein that has two alternative conformations, each with a different biological property; interconversion of the two conformations is mediated by the reversible binding of a specific small molecule to the effector site. Allosteric regulation Control of a reaction pathway by the effector-mediated reversible interconversion of the two conformations of an allosteric enzymes in the pathway. How Cells are Studied I Optic techniques for cellular and subcellular architecture The Light Microscopy      Limit of resolution      Scale of cell biology     š š š š š šmš m, nm, and A      Compound microscopy Types of light microscopy      Brightfield microscopy           basic form           inexpensive and easy           for color and fixed specimen and not for living species      Phase-contrast microscopy           phase plate           good for living, unstained specimen      Dark field microscopy      Fluorescence microscopy           fluorescent compounds           exciter filter           barrier filter      Differential -interference -contrast microscopy (DIC)      (Nomarski)           polarizer           analyzer           Wollaston prism           to produce 3-D image      Confocal microscopy           to produce 3-D image from a collection of optic sections Sample preparation techniques in light microscopy           Fixation           Cryoprotection           Embedding and sectioning           Staining           Labeling                radioisotope                immunolabeling The Electron Microscopy      Use a beam of electron to produce an image Two major types of electron microscopy      Transmission electron microscopy (TEM)            Vacuum system            Electron gun            Electromagnetic lenses and image formation            Photographic system      Sample preparation techniques in TEM microscopy            Fixation            Embedding, Sectioning, and poststaining            Electron microscopic autoradiography            Negative staining            Shadowing            Freeze-fracturing            Freeze-etching      Scanning electron microscopy (SEM): 3 D images            Second electrons      Sample preparation techniques in SEM microscopy            Fixation            Postfixation            Dehydration            Poststaining            Mounting            Coating                  with a layer gold or a mixture of gold and palladium. How Cells are Studied II Biochemical Techniques for Cellular and Subcelllular Functions Isolation of cells             Source for the best yield                     fetal or neonatal tissue             Disrupting the extracellular matrix and intercellular junctions                     Proteolytic enzymes                     Chelating agents             Approaches to separate cell types                     Centrifugation                     Cell sorter: fluorescence-activated cell sorter             What to do with a uniform population of cells                     For biochemical analysis                     For cell culture Fractionation of organelles and macromolecules              Cell disruption: homogenate              Centrifugation                       Separation by size                     Separation by size and shape                     Separation by buoyant density              Cell-free system                     Isolation                     Reconstitution              Chromatography                     Partition chromatography                     Column chromatography                             Ion-exchange chromatography                             Gel-filtration chromatography                             Affinity chromatography                             HPLC               Electrophoresis                             Proteins usually have a net positive or negative charge that reflects the                             mixture of charged amino acids they contain. If an electric field is                             applied to a solution containing a protein molecules, the protein will                             migrate at a rate that depends onits net charge and on its size and shape                             SDS-PAGE                                    SDS                                    bš -mercaptoethanol                                    Coomassie blue                                    Silver stain                                    Western blotting                2-D gel electrophoresis                             First dimension: isoelectrical focusing                             Second dimension: SDS-PAGE Analysis of polypeptides                Peptide mapping                Amino acid sequena Membranes: Their Structure and Function           Generalization of membranes                         They are assembly of lipids and proteins held together by noncovalent                          interactions. They are dynamic fluid structure. Depending on the source,                          membranes vary in thickness, in lipid composition and in their ratio of                          lipid and protein.           Functional roles of membranes                          Define and compartmentalize the cell                          Serve as the locus of specific functions                          Control movement of substances into and out of the                               cell and its compartments                          Play a role in cell-to-cell communication and detection                               of external signals           Biochemical models of membranes                          Fluid mosaic model                          Transmembrane protein structure           Three main constituents of membranes                          Membrane lipids                                  Approximately 50% of mass                                  Lipid bilayers: amphipathic molecules                                  Typical membrane lipids                                           phospholipids                                           glycolipids                                           sphingolipids                                           cholesterol                                  Analysis of membrane lipids                          Membrane proteins                                  Association with lipids                                  Peripheral membrane proteins and integral membrane proteins                                  Classification of membrane proteins by function                                  Studies of membrane proteins                                           Solubilization, isolation and reconstitution                                           Studies of red blood cell ghosts*                          Membrane carbohydrates                                  Approximately 2-10 % of mass                                  Confined mainly to the non-cytosolic surface                                           On the extracellular surface of the cells                                            Inward toward the lumen of the compartment                                  Covalent linkage to proteins and lipids                                           Glycoproteins and proteoglycans                                           Glycolipids                                  Analysis of carbohydrate moiety of membranes                                            Lectins                                  Functions of membrane carbohydrates                     Membrane asymmetry                                  Asymmetric distribution of lipids, proteins and carbohydrates                                  Diffusion in the membranes                                           Transverse diffusion                                            Lateral diffusion                     Membrane fluidity                                  Lipid bilayer is a two-dimensional fluid                                  Membrane fluidity depends upon its composition                                            Length of hydrocarbon chain and saturation                                            Cholesterol                                            Regulation of membrane fluidity                                  Mobility of membrane proteins                                  Cell fusion experiment Transport Across Membranes         Categories of membrane transport                  Cellular transport                             It concerns the exchange of materials between the cells and its                             environment Intracellular transport It evolves movement of substances                             across membranes of organelles inside the cell                       Transcellular transport                             It involves the movement of a substance in on one side and out on the                             other side            Mechanisms of membrane transport for small molecules                   Passive Transport:                              It does not require energy; it occurs because of the tendency for                             dissolved molecules to move from higher to lower concentrations.                        1.) Simple diffusion                                  Factors governing diffusion across lipid bilayers                                            size                                            polarity                                            ionization                                   Kinetics for simple diffusion                                            V=kD [X] outside-[X] inside                          2.) Facilitated transport                                   Involvement of a membrane transport protein                                            carrier protein                                            channel protein                                   Kinetics for facilitated transport                                             follow Michaelis-Menten kinetics                                   Specificity of transport proteins                                   Examples                         3.) Ionophores:                                    They are small hydrophobic molecules that dissolve in lipid                             bilayers and increase their ion permeability                                    Classes of ionophores                                             mobile ion carriers                                             channel formers                          Active Transport                                          It requires energy; it takes place against the electrochemical                              gradient                                     1.) 3 major functions                                            -  uptakes of fuel molecules and nutrients                                           -   removal of waste materials, secretory products and sodium                                             ions                                           -   maintenance of a constant, optimal internal environment of                                             inorganic ions                                     2.) Directionality                                     3.) Kinetics                                              for uncharged molecules                                              for charged molecules                                     4.) Involvement of membrane potential                                     5.) Simple versed coupled transport                                     6.) Energy source                                     7.) Examples         Cellular transports: exocytosis and endocytosis                       Both involve the sequential formation and fusion of membrane-                       bounded vesicles         Exocytosis:                       1.) Steps                                     Packing secretory vesicles                                     Response to extracellular signals                                     Fusion with membrane: recognition sites and Ca++                                                 Discharge the contents                       2.) Membranes asymmetry is maintained through secretion                       3.) Two pathways of exocytosis                                     Constitutive exocytosis                                                continuous secretion in all eukaryotic cells                                     Regulated exocytosis                                                extracellular triggers control the secretion in secretory cells:                                                      hormones, neurotransmitters or digestive enzymes          Endocytosis:                      1.) Steps: a complementary process of exocytosis                      2.) Two types of endocytosis                                     Pinocytosis: cellular drinking                                               ingestion of fluid and solutes via small vesicles in many cell                                               types                                     Phagocytosis: cellular eating                                               ingestion of macromolecules in specified phagocytic cells                      3.) Steps with pinocytosis:                                     Begins at clathrin coated pits                                     Form coated vesicles                                     Shed the coats                                     Fused with endosome                                     Lysosome                      4.) Receptor-mediated endocytosis                                     Ligands and cell-surface receptors are involved                                     Example: uptake of cholesterol                      5.) Transcytosis Intracellular Transport and Compartments        Road maps of biosynthetic protein traffic (Figure 12-7)        Three fundamental mechanisms                    via gated transporters                               i.e. transport from cytosol to nucleus                    via translocators (membrane bound translocators)                               i.e. transport from cytosol to mitochondria (plastids), ER and                                peroxisome                    via transport vesicles                               i.e. transport from ER to Golgi etc         Sorting signals                    Types of sorting signals (Figure 12-8)                              signal peptides (Table 12-3)                              signal patches         Ubiquitin- and ATP-dependent protease (Figure 5-39)                    The fate of protein without sorting signals                    Ubiquitin-enzyme complex                    Chain of ubiquitins                    Proteosome (large protein complex) as a trash can in the cell         Transport between cytosol and nucleus                    Nuclear pore complex                              mechanism of transport                                      simple diffusion and active transport                              more active in transcription, more number of nuclear pore                    Nuclear localization signals                              rich in positive charge amino acids and have proline                              signals are not cut off after the transport                    Export of RNA via specific receptor proteins         Transport into mitochondria                    Matrix target signals                              20-80 amino acid residues                              at amino end                              signals are removed after transport by protease                    2 stages transport                    Chaperonins in the cytosol and mitochondria hsp70 and hsp60          Transport into ER                    Types of protein into ER                              Transmembrane proteins                              Water soluble proteins                    Cotranslational mechanism                    Signal hypothesis                               ER signal peptide                               Signal recognition particle (SRP)                               Specific receptors on ER                               Translocator protein (hydrophilic pore)                    Start transfer signal and stop transfer signal. Cytoskeleton I A complex network of interconnected filaments and tubules called cytoskeleton extends throughout the cytoplasm, from the nucleus to the inner surface of the plasma membrane. This elaborate array of filaments and tubules forms a highly structured yet very dynamic matrix that helps to establish the shape of the cell and plays important roles in cell movement and cell division.                  Major structural elements                         Microtubules: Mts                         Microfilaments: Mf                         Intermediate filaments: IF               Unique to Eukaryotic cells               Microtubules                        Two groups of Mts                                Axonemal Mts                                        The highly organized, stable Mts found in specific subcellular                                        structures associated with cellular movement, including cilia,                                        flagella and the basal bodiesto which these appendages are                                        attached .                               Cytoplasmic Mts                                        Mts radiate out as lacelike threads toward the periphery of the                                        cell from a Microtubule-organizing center (MTOC) near the                                        nucleus, i.e. centrosome (cell center)                               Monomers                                        aš -tubulin and bš -tubulin                                         Heterogeneity                                               genetic aspects                                               post-translational modification                               Assembly of Mts                                         Nucleation                                         Tubulin monomers                                         Tubulin dimers                                         Rings                                         Sheet of protofilaments                                         Closed Mts                                         Elongation                               Structure:                                         Hollow tube with a wall consisting of 13 protofilaments                                               Diameter:                                                    outer: 25 nm; inner: 15 nm                                         Polarity: plus end and minus end                                                       Microtubule motor proteins                                         Cell motility                                         Disposition and movement of orgenelles                                         Determination of cell shape                                         Maintenance of cell shape Cytoskeleton II Microfilaments (Mfs)                        Monomers: G-actin                                   actin is single most abundant protein in most cells                                   muscle cell: aš -actin                                   nonmuscle cells: bš -actin and gš -actin                                   actin gene is highly conserved                        Diameter: 8 nm                        Assembly of Mfs                                    spontaneous assembly of G-actin monomers into F-actins                                    possible addition of actin monomers to bith ends of the growing                                    filament                                    accompanied with hydrolysis of ATP but not ATP energy required                        Structure                                    Two intertwined chains of F-actins                                    Treadmilling model                        Actin-binding proteins                                    length-regulating proteins                                    depolymerizing proteins                                    cross-linking and bounding proteins                                              Spectrin-ankyrin-actin network                        Myosin and actin                                   muscle striation                                   muscle contraction                        Functions                                   muscle contraction                                   amoeboid movement                                   cell locomotion                                   cytoplasmic streaming                                   cell division                                   cell shape Intermediate filaments (Ifs)                        Monomers                                   Three distinctive domains                                   tissue specific IFs proteins                                               epithelial cells: keratins                                               mesenchymal: vimentin                                               muscle: desmin                                               glial: glial fibrillary acidic protein                                               neurons: neurofilamanet protein                                   nuclear lamina of all cells: nuclear lamains A, B, and C                                               located on the inside surface of the nuclear envelop                                               common to most animal cells                                   They are coded by a single family of related genes                                              Type I                                              Type II                                              Type III                                              Type IV                                              Type V                                   Intermediate filament typing                                               to identify the origin of tissues                                   Assembly of Ifs: Ifs are fibrous proteins                                               two IF polypeptides                                               a coiled coil dimer of two intertwined polypeptides                                               a tetrameric protofilament consisting of two aligned coile-                                               coil dimers                                               staggered association of protofilaments into a long rope-like                                                filament                                               final structure of intermediate filament with width of 8                                                protofilaments (16coiled-coil dimers; 32 monomers) in                                                staggered overlaps                                               Regulation                                                        phosphorylation of serine residue and mitosis                                    Functions                                               structure support                                               maintenance of cell shape                                               formation of nuclear lamin and scaffolding                                               strengthening of nerve axon Energy Conversion I Mitochondria structure           Size           Shape           Matrix           Outer membrane           Inner membrane           Intermembrane space 5 Stages of respiratory metabolism           1) Glycolysis           2) TCA cycle           3) Electron transport chain           4) Pumping of proton           5) Oxidative phosphorylation The Tricarboxylic Acid Cycle: TCA cycle           It occurs in mitochondria matrix           Substrate: acetyl CoA           Products: carbon dioxide and reduced coenzymes, NADH and FADH           Reaction involved with TCA cycle                    Conversion of pyruvate to acetyl coenzyme A                            decarboxylation and oxidative reaction coenzyme A                     Entry of acetate into the TCA cycle                     The oxidative decarboxylation steps of the cycle                     The ATP generating step of the cycle via the formation of GTP                     Regeneration of oxaloacetate           Regulation of TCA cycle activity                     1. NAD+/ NADH ratio                     2. ATP/ADP ratio                     3. Pyruvate dehydrogenase                     4. Phosphofructokinase           Summary of TCA cycle                     1. Acetate to citrate                     2. Decarboxylation                     3. Oxidation                     4. ATP generation                     5. Regeneration of oxaloacetate Electron Transport Chain            Outcome of TCA cycle: reduction of coenzymes                     electrons are transferred to NAD+ an FAD             Definition of electron transport                      the process of coenzymes reoxidation by transfer of electron to                         oxygen                      this process is NOT directly                      it is through a multiple process and involves a series of reversibly                            oxidizable electron acceptors: electron transport chain             Reduction Potentials                            Standard reduction potential E: a convention used to                            quantify the electron transfer potential of oxidation-reduction                            chain             Electron Carriers of the Transport Chain                     Flavoproteins                            NADH dehydrogenase                     Coenzyme A                     Iron-sulfur proteins                            NADH dehydrogenase                     Cytochromes                            heme and heme A                            cytochrome b, c, c1, a1, and a3                     Organization of Electron Transport Chain                            NADH dehydrogenase                            Coenzyme Q-cytochrome c reductase                            Cytochrome c oxidase Oxidative Phosphorylation                    ATP production depends upon phosphorylation events that are                    coupled to oxygen-dependent electron transport                            Coupling of ATP synthesis to electron transport                                  2 points:                                  1) ATP generation depend on electron flow                                  2) electron flow is possible only when ATP is synthesized                    Uncoupler: 2,4-dinitrophenol (DNP)                    ADP is the respiratory control                    Sites of synthesis                                  1) between NADH and coenzyme Q                                  2) between coenzyme Q and cytochrome c                                  3) between cytochrome c and oxygen Chemiosmotic coupling model                             Each of three sites of coupling along the transport chain                             involves electron transfer event that is accomplanied by the                             unidirectional                             pumping of protons across the membrane where the transport                             chain is localized                         Electrochemical proton Gradient                             Proton motive force (pmf)                         ATP synthetase and the proton translocator                             F1                             F°                         Summary of respiratory metabolism                             ATP yield of respiratory metabolism Energy Conversion II Review of chloroplast structure            size            shape            inner membrane            outer membrane            stroma            thylakoids, grana and stroma lamellae            intermembrane space Phototrophs          photoheterotrophs            photoautotrophs Photosynthesis: 2 unique reactions          Light dependent reactions                        photosynthetic electron transfer reactions                        light reactions                        light driven production of ATP and NADPH            Light independent reactions                        carbon fixation reactions                        dark reactions                        conversion of carbon dioxide to carbohydrate            Oxygenic phototrophs: use water as an electron donor                        It needs energy and it comes from sunlight (photon)            Light dependent reactions to produce ATP and NADPH                       Chlorophyll                       It is the only pigment (light-absorbing compound) that can                          donate photoenergized electrons to organic compounds                       Chlorophyll a: common to all oxygenic phototrophs                       Chlorophyll b, c and d: a second kind of chlorophyll               Accessory pigments                       Carotenoids and phycobilins                       2 functional roles:                                  1.) broad absorption spectrum                                  2) good agreement between absorption spectrum and                                            action spectrum            Reaction centers                       P680                       P700            Photosystem I and generation of NADPH                       Photosystem I: the cluster responsible for the reduction of NADPH                       Photoreduction                       Chlorophyll and Chlorophyll*            Photosystem II and the oxidation of water                       Water is not a good electron donor (E° = + 0.86)            Photosystem I: to reach ferredoxin            Photosystem II: to reach water            Summary of the transfer of electron from water to NADP+                                1.) Photosystem II: receive electron from water                                2.)  Photosystem II: accept electrons from plastocyanin                                3.) Electron carriers link electron acceptor for photosystem                                 II and electron donor for photosystem I                                       4.) Electron carriers link the electron acceptor for photosystem                                 I with the ultimate acceptor NADP+            ATP synthesis                        Electron flow downhill results in the proton pumpled across the                              membrane from the stroma into the intrathylakoid space.                              Therefore, an electrochemical proton gradient is generated.                        CF1                                CF°            PMF in the chloroplast is due to the pH gradient             Photosynthetic carbon metabolism: The Calvin Cycle                        Carbon fixation                        Ribulose bisphosphate carboxylase                        Reduction of 3-phosphoglycerate                        Carbohydrate synthesis                               glucose                               sucrose                               starch                               Regeneration of ribulose-1,5-bisphophate                               Summary: 3 ATP and 2 NADPH are used to fix 1 CO2               The C4 plants                               Mesophyll cells                               Bundle sheath cells                               The Hatch-slack cycle: feeder system Flow of Information I               The flow of genetic information between generations              The expression of genetic information Expression of Genetic Information              Protein synthesis: translation              RNA synthesis: transcription              DNA synthesis: replication DNA replication             Chemistry and structure of DNA                      Hydrogen bonds between G-C and A-T                      Double-helix                             B-DNA (Watson-Crick Model)                                            right-handed helix                             Z-DNA                                            left-handed configuration                             A-DNA                                           A right-handed helix induced by                                              dehydration of B-DNA                     Major and minor grooves                     Polarity                     Supercoiled DNA                            Topological isomers                                           The molecules that differ only in their                                              state of supercoiling                            Enzymes: Topoisomerases                                           Type I                                           Type II : DNA gyrase is a Type II                                                           topoisomerase                            Model of replication of circular DNA                                           Origin of replication                                           Replication is bidirection                                           Theta replication                                           Multiple origins of replication for                                                Eukaryotic DNA                            DNA polymerase                                           Multiple DNA polymerizes                                                In E Coli: 3 polymerases                                                      DNA polemerase I                                                      DNA polymerase III                                                In Eucayrotes                                                      Polymerase a                                                      Polymerase ß                                                      Polymerase ?                    Leading and lagging strands                                                      Okazaki fragments                                                 DNA ligase                                                 RNA primer                                                      Primase                                                      Primosome                                                 Replication forks                                                 Unwinding the DNA                                                      Helicase (unwinding protein)                                                      Gyrase                                                      Single strand binding protein                                                         (Helix destabilizing protein)                                          Summary DNA repair RNA synthesis and processing                RNA polymerases                             E coli: a single kind of polymerase consisting of a                             core enzyme complex as a2ßߑ                             and a dissociate factor s (sigma)                             Eukaryotes: 5 polymerases different in                             location, products and sensitivity to a-amanotin                                           RNA polymerase I                                           RNA polymerase II                                           RNA polymerase III                                           Mitochondrial polymerase                                           Chloroplast polymerase                    The Steps of transcription                              Binding: binding of polymerase to a promoter                                    Promoters                                         E coli:                                              recognition of promotors                                              about 40 nucleotide pairs                                              start site, 6-8 hexanucleotide sequence                                          Eukaryotes:                                              each of the polymerases has its                                              own promotors i.e. TATA box in the                                               promotors for polymerase II                              Initiation                                     Unwinding of one turn of the DNA                                         doulbe helix                                      As soon as the first two rNTP                                      (N=a, U, G, C) in place, polymerase                                       joint the phosphodiester bond                              Elongation                                      Polymerase moves up in 3’ to 5’ direction                                      RNA strand grows in 5’ to 3’ direction                                      A short DNA-RNA hybrid form                                      DNA return to its double helix form                                       (thermodynamic stability)                             Termination                                      Termination signal (stop signal)                                          E coli: it is a sequence that fige rise in the RNA                                          product to a hairpin helix followed by                                          a string of U’s (the hairpin structure is the factor)                                      ? factor in other region Processing of RNA                             Ribosomal RNA                                     rRNA is the most abundant and most stable form                                      of RNA                                     In eukaryotes                                          Processing of 45S to 18S, 28S and 5.8S                                          5S is a separate product                            Transfer RNA                                     At 5’ end, a short leader sequence is removed                                     At 3’ end, the two terminal nucleotide (UU) is                                            replaced with CCA which is a distinguishing                                             characteristic of functional tRNA                                     Methylation                                     Splicing                             Messenger RNA                                      E coli: transcription and translation are coupled                                         processes                                      Eukaryotes: the compartmentization is associated                                          with the need of mRNA processing (splicing)                                      Transcription unit for mRNA is monocistronic                                          hnRNA (heterogeneous RNA): precusor of mRNA                                      Introns and Exons                                      Splicing                                      Caps and Tails Protein Synthesis Reading Assignments:            Text pages: 223-273 Questions: 1. Z-DNA co-exists with B-DNA in the same DNA               True________False_________ 2. DNA ligase is a Type II topoisomerase.               True________False_________ 3. Primase is accompanied by a large complex of protein called      primosome.                  True________False_________ 4. In most vertebrate cells, the clusters of genes encoding 28 s     rRNA are transcribed independently              True________False_________ 5. Transcription unit is a segment of DNA that is transcribed as a     single, continues RNA with a promoter on one end and a termination     signal on the other end              True________False_________ 6. Which of the following is false about hnRNA (heteronuclear RNA)? A. Contains introns B. Lacks cap and tail C. Can be polycistronic D. Contains exons E. None of the above Recombinant DNA Technology        Restriction Enzymes               Endonucleases, are present in most bacterial cells                         Protect the bacterial cell from foreign DNA molecule,                           particularly those of bacteriophages                         Part of a restriction/methylation system                             Foreign DNA is degraded by restriction enzymes, and                             the bacterial genome is protected by methylation                         i. e. Ecor RI from E. coli strain R                        HaeIII from Hemophilus aegyptius                  Recognition sequences                        Specificity                        4 or 6 nucleotide pairs                        Palindromes; twofold rotational symmetry of the sequence                        The recognition sequence has the same order of nucleotides                            on both strands but is read in opposite directions on the                            strands because of their antiparallel orientation                  Restriction fragments                        With blunt ends                        With cohesive (sticky) ends                  Gel electrophoresis of DNA                         Polyacryamide                         Agarose                         Because of the negative charge of their phosphate groups,                         DNA fragments migrate down the gel toward the anode; the                         technique separate DNA based on their size                         Detection of DNA                             Ethidium bromide                             Autoradiography                  Restriction Maps                         Restriction maps indicate the location of restriction enzyme                         cleave sites in relation to one another                  Recombinant DNA molecules                         DNA cloning                               1) Insertion of DNA into a cloning vector                                        bacteriaphage                                        plasmid                                        antibiotic resistance genes: selectable markers                                        DNA ligase                               2) Amplification of recombinant vector molecules in                                    bacterial cells                                        Transduction or transfection                               3) Selection of bacterial cells containing recombinant                                   DNA                               4) Identification of bacterial colonies containing the DNA                                   of interest                                        Screening                                              Colony hybridization                                                  nucleic acid probe                                             Antibody approach                                                expression vectors                   Genomic and cDNA libraries                                Genomic library                                 cDNA library                                         reverse transcription of mRNA                                        a cDNA library will contain only those DNA                                        sequences that are transcribed into RNA, presumably                                        the active genes in the tissue from which the mRNA                                        was prepared.                  PCR (Polymerase Chain Reaction)                                 Amplification of selected DNA sequences                                 In the test tube                                 Need DNA oligonucleotide primers                                 Heat stable enzyme:The DNA polymerase was first isolated                                 from bacteria able to grow in thermal hot springs                                    (70- 80oC)                                 Procedures                                         1) reverse transcriptase synthesizes cDNA from                                             mRNA                                         2) Alkali digestion of mRNA                                         3) DNA polymerase synthesize double strain DNA                                         4) Terminal transferase                                         5) Mix with a cloning vector with a                                              complementary fragment                  Genetic Engineering                                Application of recombinant DNA technology to the practical                                 problems                                     In medicine                                     insulin                                     human growth hormone and hypopituitarism                                     human gene therapy                                     Transgenic animals and plants Regulation of Gene Expression in Eukaryotes Differences between Prokaryotes and Eukaryotes      Genome Size and Complexity            Large genome for eukaryotes            Uncoding sequence in eukaryotic genome        Genomic Compartmentalization            Nuclear envelope serves to screen antibody            Transcripts       Structural Organization of Genome            Highly ordered in packing in eukaryotes            Binding of regulatory protein to desired region            Regulatory elements       Stability of mRNA            Greater longevity for eukaryotic mRNA            Environmental constancy is not assured for prokaryotes       Protein Turnover: What to do with defective and unwanted proteins            Proteolytic enzymes            Cease cell division            Cease synthesis Multiple Levels of Gene Control in Eukaryotes      Genomic Control            Totipotency of differentiated cells                 1) nuclear transplantation in animals                 2) tissue culture study in plants       Gene amplification            Some interesting examples take place, but it does not seem               to be a critical control mechanism for most genes.       Transcriptional Control            Evidence                 1) differential transcription of genes                 2) nuclear run-on transcription assays       Two-Stage Process                 1) decondensation of coiled chromatin                 2) regulated transcription of uncoiled region       Binding of Transcriptional Factors Regulates Transcription                 Regulatory proteins                 Consensus binding sites                 Combinatorial model for gene regulation       Cis-Acting Elements: Eukaryotic Promoters and Enhancers                 Promoters                 Upstream promoter region                 Enhancers                 Deletion mutant technique        Trans-Acting Factors: Regulatory Proteins Bind to Promoters and       Enhancers                 2 Structural Domains                      1) DNA binding domain                      2) transcription activation domain                 3 Common Structural Motifs                      1) Helix-turn-helix                      2) Zinc finger                      3) Leucine zipper      Mechanisms of Action of Enhancers and Transcriptional Factors                 Long range chromatin effect                 Gateway for liner diffusion                 Looping/interaction      Possible Role of DNA Methylation in Regulating DNA Availability                 Methylation of cytosine                 DNA of inactive gene tends to have more methylation.                 Methylation      Posttranscriptional Control                 RNA Processing and Translocation                       Alternative splicing                       Translational control                            1) Selective utilization of specific mRNA                            2) Variation in rates of mRNA degradation                            3) Availability of tRNA and tRNA synthetase                            4) Prosthetic group availability                                example: regulation of transcription by Hemin                                               in red blood cells      Posttranslational Control                 Permanent Modification                       Glycosylation                        Proteolytic actions                        Reversible structural modification                             phosphorylation      Responses to Intracellular Elements                Ca++, cAMP, IP3 Cell Signaling Cell-cell communication in animal cells      Via secreted molecules             paracrine signaling              endocrine signaling             synaptic signaling       Via plasma-membrane-bound-molecules             Cell adhesion, cell junction and extracellular matrix Receptors and hydrophobicity of signaling molecules      Cell surface receptors and hydrophilic signaling molecules        Intracellular receptors and hydrophophobic molecules Intracellular receptors       Diffusion into the cells         Binding to the intracellular receptors         Inducing the conformational change of receptor         The activated receptor comples enters into the nucleus         Binding to the response element (i.e. hormone response element) Cell surface receptors       Types of cell surface receptors         First messenger         Second messenger              Cyclic AMP (cAMP) as a second messenger                    G proteins and cAMP synthesis                    Regulation of G proteins                    cAMP and glycogen degradation              Ca++ as a second messenger                    Calcium binding protein                       Calmodulin               Inositol Triphosphate (IP3) and Diacylglycerol (DAG) as                 second messengers               Third messengers                     Protein and protein phosphatase               Fourth messengers                     Transcriptional factors (messengers in nucleus) Signaling amplification            Cascade of intracellular events and amplification of                  extracellular signals                     Rapid turnover of intracellular mediators                     "All or none" effect of chemical signals                             Cooperativity                             Activation of one enzyme and inhibition of another                             one with opposite reaction Target cell adaptation            Mechanisms                     Down-regulation of receptors                             Receptor sequestration                             Receptor degradation                                 Receptor mediated endocytosis               Inaction of receptors               Inaction of none-receptor prot Cell Junction, Cell Adhesion and Extracellular Matrix Cell Junctions       Three functional types             Occluding junctions             Anchoring junctions             Comunicating junctions        Tight junctions: occluding function             Function             Features             Intermembrane space             Associated structures             Molecular structure         Anchoring junctions             Function             Forms                 Adherens junction                 Desmosomes                 Hemidesmosomes             Associated structures             Intermembrane space             Features         Gap junctions             Function             Features          Intermembrane spaces          Associated structure Cell Adhesion        Mechanisms              Homophilic binding              Heterophilic binding          Through an extracellular linker molecule              Neural Cell Adhesion Molecules (N-CAM)              Cardherins Extracellular Matrix (ECM)        Connective tissues          Fibroblasts              Chondroblasts              Osteoblasts          Components of ECM              Glycosaminoglycans (GAGs)              Fibrous proteins                  Collagen                       It is the major protein of ECM                            It is also the most abundant protein                             in the animal cells                            At least 10 types of collagen have been                            determined, 4 will be studied                                   Type I                                   Type II                                   Type III                                   Type IV                  Elastin                        It is a hydrophobic protein                        It is not a glycoprotein                        Forms a network of elastic fibers in ECM                  Adhesive components                        Fibronectin                              It is a glycoprotein                              It helps to mediate cell-matrix adhesion                              Alternative RNA splicing produces the multiple                              forms of fibronectin                        Laminin                              One of the components of basal lamina                               Basal laminae are continuous thin mats of specialized                               ECM that underlie all epithelial cell sheets and tubes and                               also surround the other cells                  ECM receptors Matrix receptors                         Low affinity binding and high concentration presence                         Fibronectin receptor                               Integrins The Nervous System CNS and PNS The Cells           Neurons                 Cellular structures                      Cell body                      Axon                      Dendrite                 Different types of neurons          Glial cells                 Central nervous system                     Oligodendrocyte                     Microglia                     Ependymal cells                     Astrocytes          Peripheral nervous system                     Schwann cells          Blood-brain barrier Transport Mechanisms        Fast transport and slow transport          Anterograde transport and retrograde transport Synaptic Transmission        Synapses                 Electrical synapses                 Chemical synapses          Chemical Synapse                 Neurotransmitters                      Criteria to be a neurotransmitter                           It must elicit the appropriate response upon                                microinjection into the synaptic cleft                           It must be found to occur naturally in the                                presynaptic axon                           It must be released at the right time when the                                presynaptic membrane is stimulated                      Neurotransmitters are released by exocytosis                      Neurotransmitter release is quantal and probabilistic                      Excitatory effects and inhibitory effects                           Excitation                           Inhibition                      Structure of chemical synapse                           Synaptic cleft                           presynaptic membrane                                 Synaptic vesicles                           Postsynaptic membrane                      Mode of action of acetylcholine                           Acetylcholine is an excitatory neurotransmitter                           Structure synthesis and hydrolysis of acetylcholine                           The acetylcholine receptor                      Other neurotransmitters                           GABA and glycine are inhibitory neurotransmitter                                  GABA: gš -aminobutyric acid                                  GABA receptors                                        Tranquilizers act on GABA receptors                                                 Benzodiazepines                           Catecholamines and aderenergic synapses                                  Catecholamines are derivatives of tyrosine                                        Dopamine                                        Norepinephrine                                        Epinephrine                                  Monoamine oxidase inactivates catecholamine                             Neurotoxins                                  Strychnine                                  Curare Cellular Aspects of the Immune Response Innate immunity and adaptive immune system The immune response        Antigen and antigenic determinants          Characteristics of the immune response          Types of immune responses                 Cell-mediated immune responses                 Humoral immune responses Cellular basis of the immune response         Lymphocytes                 T cells and B cells           Development of lymphocytes           Clonal selection                 Antigen receptors                 Formation of clones and their selection by antibodies                       Antigen-independent differentiation                       Antigen-dependent differentiation           Immunological memory                 Primary and secondary responses                 Effector cells and memory cells                       Production of memory cells           Differentiation markers                 B cells: immunoglobulins                 T cells: CD3 complex 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hŸĆ5\;ėińi5jUj!kUkVkzk{k˜kĻkŚkökl¾mæm?pVprp{pTqiqkq~qr ryr{rĪrŠrgsisˆw»wzzR~T~|~}~~~€€††:ˆ>ˆLˆMˆŽˆšˆ£ˆ»ˆ/‰Z‰Ų‰ņ‰zŠ½Š ŽüõüõģāģāģõüõüõŚõüõüõģŌģõüõüõüõüõĢõüõüĮ¹Įõüõüõü«Įü¤ü¤ü¤ü™ü™ühŸĆ5CJ\aJ hŸĆ5\hŸĆhŸĆ5CJ \aJ hŸĆCJ aJ hŸĆhŸĆCJ aJ hŸĆhŸĆH* hŸĆ0JhŸĆhŸĆH*hŸĆhŸĆ5\hŸĆhŸĆ0J hŸĆhŸĆhŸĆ; ŽŽ*Ž,Žö’“;”=”L”M”b”––x–z–’–”–ćœåœ…£‡£-¤/¤’¤Ÿ¤Ķ¤ā¤4„7„?§A§T§U§l§ģ§ØŖØŅØb«c«Ł¬Ū¬ō¬`­a­1²^²TµVµ¢·¤·>ø@øTøUøuø,¹A¹n¹Ė¹hŗ›ŗ*»v»µ»ž»J½ųōųōšōšā×ĶʻʻʻʚĶʚʚʚʚʚʚā×ĶĘĶĘĶĘ³ĘšĶĘ³ĘĶʚʫʚā×ĶĘĶĘĶĘĶĘĶĘĶĘhFnhFnH*hFnhFnH*hFnhFnOJQJ hFnhFnhFnhFn5\hFnhFnCJ aJ hFnhFn5CJ \aJ hFnhŸĆhŸĆOJQJC?øUø,¹n¹åĆ+ĒCĒ·ĒŁĒWČ3ĪŖÖ9Ž>äSärä~äÕä(å£å3ęēEē®ēÜīcł&ūSūNžśśĄ!¬śĄ!¬ś-Ą!¬õĄ!¬śśĄ!¬śĄ!¬śĄ!¬śĄ!¬śśśśĄ!¬śĄ!¬śśĄ!¬śĄ!¬śĄ!¬śĄ!¬śĄ!¬śĄ!¬õĄ!¬õõõššĄ!¬gd .tgdŸĆgdFnJ½s½’¾¹¾ä¾ æÅæšæšĄŠĄŅĄĘĀöĀžĆÄ/Ä·ÄjĘyĘʀʦĘ*Ē,ĒBĒCĒ·ĒŲĒWČgČ2Ī4ĪŠÓ!ŌœŌŌ©Ö«Ö¾ÖöÖ8Ž:ŽšŽÕßą§įŪį,ä=ä>äRäräsä}äē#ēŽēÆēŹēöļöļöļöļöäļöļÜļöļÜöŃöļĶæ“ļöļöļĶļöļÜļĶļöļĶöļöļöļöļöļ­öļöļ©›h .th .t5CJ \aJ h .t h .t5\hFnhFnCJ aJ hFnhFn5CJ \aJ hFnhFnhFn5H*\hFnhFnH*hFnhFn5H*\ hFnhFnhFnhFn5\:Źēóē°é·é½éĆéĢéėéńéņéüéžéźEź×ėģXģ‹ģ4ī]īŪīŻīīī ļgó³ó…õÅõbłdłlłŸł%ū'ūRūSū‡ūNžž‚„     " # P 3 l ä   % H J Ō Õ Ķšy{ĖĶ™ÉRrHböļöļöļöļöļöļöļöļöļöļėļöļöļöļėļöļėŻŅöļöļėļŹļĀ½ŻŅöļöļöļöļŹļĀļöļėöļėŻŅöļöļöļö h .tH*h .th .tH*h .th .tH*h .th .tCJ aJ h .th .t5CJ \aJ h .t h .th .th .th .t5\JNžƒ # zĢ¼œzŽõĄ)é)ņ/õ…†vuśĄ!¬śõõ*Ą!¬śõõĄ!¬õĄ!¬śššĄ!¬šĄ!¬śšš&Ą!¬śšś%Ą!¬śgda|xgd .tgdŸĆb¼Ńœæy{ŽĘe”ōõ+j‹&&æ)Į)č)é)/*ž*,+­-®-Ģ-Ķ-0.1.6.7.I.J.Ž//·/ø/ń/ó/ž/„8„į…ō…ö…††ʆuw«łļłčļłäÖĖĮŗĮŗĮ²ŗĮŗĮŗ§ŗ£ÖĖĮŗĮŗ›ŗ›ŗŗŗŗ›ŗ›ŗ£ŗŽĮŗĮ£ÖĖĮŗ£ĮUha|xha|x5>*\ha|xha|xH*ha|xha|xha|xOJQJha|xha|x\ ha|xha|xha|xha|x5\ha|xha|xCJ aJ ha|xha|x5CJ \aJ h .t h .t5\h .th .t5\ h .th .t8The structure and function and antibodies               The antibody molecule                       Variable domains and constant domains                       Antigen binding sites and effector sites                  Classes of immunoglobulins in mammals                                 IgG                                 IgM                                 IgA                                 IgD                                 IgE                  Antibody valence            Monoclonal antibody Cellular Aspects of Cancer Cancer: lost of normal growth and positional regulation         Neoplastic transformation           Classification of neoplasm (tumor)           Causes of neoplastic transformation                 Chromosomal alteration                         Chronic myelogenous leukemia (CML) and Philadelphia                           chromosome                 Oncogenic Viruses:                         RNA tumor viruses in the retrovirus family                           replication cycle of retrovirus                         How to demonstrate a viral etiology for a specific tumor                         Patterns of infection                              Horizontal transmission                              Vertical transmission                 Environmental carcinogens                        Physical factors                        Chemical carcinogens                         Metabolic conversion of the procarcinogen to                             ultimate carcinogen                                   Mixed-function oxidase or aryl hydroxylase                        Chemical carcinogens act by producing genetic                        mutations                                   Ames test is a mutagenesis assay                 The genetic basis of neoplasia                       Oncogene                            Definition                            Proto-oncogene                            Alternation of proto-oncogene to oncogene                                   Dosage effects                                   Gene mutation                 Tumor-suppresser genes                       Dominant character of the oncogene                       Recessive character of spontaneous tumors                       rbl human gene:                                   Inactivation of rbl gene is associated with the inherited                                   tumor bilateral retinoblastoma           Tumor Dissemination                       Tumor invasion                            Dissemination to nearby tissue                            Process contribute to tumor invasion                                  release of degradative enzymes                                  loss of contact paralysis                      Metastasis                            Dissemination to distant organs                            It can occur in 4 systems                                  peritoneal cavity                                  neural canal                                  lymphatic system                                  vascular system                           Vascular metastasis                                  Establishment of a vascular supply «tułņ ha|xhŸĆ ha|xha|x 1h°Š/ °ą=!°"°# $ %°}DŠÉźyłŗĪŒ‚ŖK© chemofthecell}DŠÉźyłŗĪŒ‚ŖK© carbs_polysacDŠÉźyłŗĪŒ‚ŖK© proteins_polypeptidessDŠÉźyłŗĪŒ‚ŖK©  nucacidsqDŠÉźyłŗĪŒ‚ŖK© enzymeswDŠÉźyłŗĪŒ‚ŖK©  cellstudyIyDŠÉźyłŗĪŒ‚ŖK©  cellstudyII›DŠÉźyłŗĪŒ‚ŖK© membranes_structure_functionDŠÉźyłŗĪŒ‚ŖK© trans_membranes‘DŠÉźyłŗĪŒ‚ŖK© intratrans_compartments‘DŠÉźyłŗĪŒ‚ŖK© intratrans_compartments}DŠÉźyłŗĪŒ‚ŖK© cytoskeletonIDŠÉźyłŗĪŒ‚ŖK© cytoskeletonII…DŠÉźyłŗĪŒ‚ŖK© energyconversionI‡DŠÉźyłŗĪŒ‚ŖK© energyconversionII‡DŠÉźyłŗĪŒ‚ŖK© energyconversionIIuDŠÉźyłŗĪŒ‚ŖK©  flowinfoIuDŠÉźyłŗĪŒ‚ŖK©  flowinfoIuDŠÉźyłŗĪŒ‚ŖK©  flowinfoIuDŠÉźyłŗĪŒ‚ŖK©  recombDNA™DŠÉźyłŗĪŒ‚ŖK© regulation_genes_eukaryotes™DŠÉźyłŗĪŒ‚ŖK© regulation_genes_eukaryotes™DŠÉźyłŗĪŒ‚ŖK© regulation_genes_eukaryotes™DŠÉźyłŗĪŒ‚ŖK© regulation_genes_eukaryotes}DŠÉźyłŗĪŒ‚ŖK© cellsignaling}DŠÉźyłŗĪŒ‚ŖK© cellsignaling{DŠÉźyłŗĪŒ‚ŖK©  celljunction{DŠÉźyłŗĪŒ‚ŖK©  celljunctionsDŠÉźyłŗĪŒ‚ŖK©  nervesyssDŠÉźyłŗĪŒ‚ŖK©  nervesysDŠÉźyłŗĪŒ‚ŖK© immuneresponseDŠÉźyłŗĪŒ‚ŖK© immuneresponseoDŠÉźyłŗĪŒ‚ŖK© canceroDŠÉźyłŗĪŒ‚ŖK© cancerœ@@ń’@ NormalCJ_HaJmH sH tH DA@ņ’”D Default 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