3000 Exam 1 Book Notes - Summary Becker\'s World of the Cell PDF

Preview

Summary

Kozminski Book notes for Exam 1, chapters 1-7...

Description

Lecture 2 Material Chapter 4 Properties and Strategies of Cells 







All organisms are bacteria, archaea, or eukaryotes o Organisms have traditionally been divided into two broad groups  Prokaryotes  Bacteria  Archaea: include many species that live in extreme habitats on Earth and have very diverse metabolic strategies o Methanogens, halophiles, thermacidophiles o Descended from the common ancestor that also gave rise to the eukaryotes long after diverging from the bacteria  Eukaryotes: true, membrane bounded nucleus Limitations on cell size o Main limitation is set by the need to maintain an adequate surface area/ volume ratio  Cell’s internal volume determines amount of nutrients that must be imported and the quantity of waste products that must be excreted  Surface area represents amount of cell membrane available for such uptake and excretion  As cell increases in size, its surface area does not keep pace with its volume  Can only increase as long as the membrane surface area is still adequate  Effective surface area is most commonly increased by the inward folding or outward protrusion of the cell membrane o Many molecules move through the cell by diffusion  Rate of diffusion decreases as the size of the molecule increases  Many eukaryotic cells bypass this limitation by actively transporting ions, macromolecules and other materials o There is the need to maintain adequate concentrations of the essential compounds and enzymes  Number of molecules must increase proportionally with cell volume to maintain concentration Eukaryotic cells use organelles to compartmentalize cellular function o If the enzymes and compounds necessary are localized within a specific region, high concentrations are needed only in that region rather than through the whole cell o Organelles are membrane bound compartments that are specialized for specific functions Bacteria, archaea, and eukaryotes differ from each other in many ways o Presence of a membrane bound nucleus  Genetic information of a bacterial or archaeal cell is folded into a compact structure called the nucleoid o Use of internal membranes to segregate function

 Exception is cyanobacteria o The cytoskeleton  Imparts structure and elasticity to eukaryotic cells o Endocytosis and exocytosis  Eukaryotic cells have the ability to exchange materials between the membrane bound compartments within the cell and the exterior of the cell o Organization of DNA  Bacterial DNA is usually present in the cell as a circular molecule associated with relatively few proteins  In eukaryotic cells, DNA is packaged and segregated in chromosomes The Eukaryotic Cell in Overview The plasma membrane defines cell boundaries and retains contents The nucleus is the information center of the eukaryotic cell Intracellular membranes and organelles define compartments The endosymbiont theory o Did mitochondria and chloroplasts evolve from ancient bacteria?  Both contain their own DNA and ribosomes  Comparable processes with bacterial cells o Proposes that both of these organelles originated from prokaryotes that gained entry to, and established a symbiotic relationship within, the cytoplasm of ancient single celled organisms

   

Viruses   

Noncellular, parasitic particles that are incapable of a free living existence Invade and infect cells and redirect the synthetic machinery of the infect host cell toward the production of more virus particles Not considered to be living organisms, nor are they made of cells o Fundamental properties of living things are metabolism, irritability, and the ability tor reproduce

Lecture 3 Material Chapter 5 The Importance of Energy 





Cells need energy to drive six different kinds of changes o Synthetic work: changes in chemical bonds o Formation  Formation of new chemical bonds and the synthesis of new molecules o Mechanical work: changes in the location or orientation of a cell o Concentration work: moving molecules across a membrane against a concentration gradient o Electrical work: moving ions across a membrain against an electrochemical gradient o Heat: an increase in temperature o Bioluminescence: the production of light Organisms obtain energy either from sunlight or from the oxidation of chemical compounds o Phototrophs: light feeders o Chemotrophs: chemical feeders o Autotrophs: self-feeders o Heterotrophs other feeders Energy flows through the biosphere continuously

Bioenergetics  







The application of thermodynamic principles to reactions and processes in the biological world Systems o A closed system is sealed form its environment and can neither take in nor release energy o An open system can have energy added or removed o The change in its total energy is determined by the initial and final states of the system First law of thermodynamics tells us that energy is conserved o E represents internal energy of the system o H represents enthalpy, or heat content  If heat is released, ΔH will be negative and the reaction is exothermic  If heat energy is absorbed, ΔH will be positive and the reaction is endothermic Second law of thermodynamics tells us that reactions have directionality o Thermodynamic spontaneity is a measure of whether a reaction or process can go o In every physical or chemical change, the universe always tends toward greater disorder/entropy Free energy o ΔG=ΔH-TΔS o Every spontaneous reaction is characteriaed by a decrease in free energy of the system – ΔG (exergonic)



Opposite is endergonic

Lecture 4 Material 2 (p.23, 32-38) The Importance of Water  

Water molecules are polar Water molecules are cohesive o Associate with hydrogen bonds

The Importance of Self-Assembly 







The information required to specify the folding of macromolecules is inherent to the polymers themselves o Sometimes molecular chaperones are needed to prevent incorrect molecular interactions but do not provide additional iformation o Inherent in its amino acid sequence Molecular chaperons assist the assembly of some proteins o Reduce the probability of the formation of incorrect structures having no biological activity o Bind to specific regions that are exposed only in the early stages of assembly thereby inhibit unproductive assembly pathways o Chaperones are abundant under normal conditions and increase to higher levels in response to stresses such as increased temperature Noncovalent bonds and interactions are important in the folding of macromolecules o Hydrogen bonds o Van de Waals interactions o Hydrophobic interactions  The tendency of nonpolar groups to associate with each other  Are found in the interior of a protein molecule Self-assembly has limits o Some systems depend on information supplied by a preexisting structure

3 (p.41-54) Proteins 



The monomers are amino acids o Hydrophobic: nonpolar, hydrocarbon nature of R groups, with few or no oxygen and nitrogen atoms o Hydrophilic: distinctly polar, some uncharged, some charged The polymers are polypeptides and proteins o Linked with peptide bond, N-terminus, C=terminus





o An entire polypeptide may sometimes be a monomer unit that is part of a multimeric protein Several kinds of bonds and interactions are important in protein folding and stability o Disulfide bonds: form between the sulfur atoms of two cysteine AA residues  Become covalently linked following an oxidation reaction that removes the two H atoms from the sulfhydryl groups of the two cysteines, forming a disulfide bond  Can be broken only by reducing it again: by adding two hydrogen atoms  Intramolecular disulfide bonds stabilize the conformation of the polypeptide o Hydrogen bonds  Particularly important in stabilizing helical and sheet structures o Ionic bonds  Polypeptide folding is dictated in part by the tendency of charged groups to repel groups with the same charge and to attract groups with the opposite charge  The loss of ionic bonds accounts in part from the denaturation that most proteins undergo at high or low pH o Van der Waals interactions o Hydrophobic interactions  Tendency of hydrophobic molecules or parts of molecules to be excluded from interactions with water  Polypeptide folding is a balance between the tendency of hydrophilic groups to seek an aqueous environment near the surface of the molecule and the tendency of hydrophobic groups to minimize contact with water by associating with each other in the interior of the molecule Protein structure depends on AA sequence and interactions o Primary structure  Formal designation for the AA sequence  Three other levels are direct consequences of the primary structure o Secondary structure  Involves local interactions between amino acid residues that are close together along the chain  H-bonding between the NH and CO groups along the polypeptide backbone  Alpha helix  Every peptide bond in the helix is H-bonded through its CO group to the peptide bond immediately below it and through its NH group to the peptide bond just above it  Invariably intramolecular  Leucine, methionine, and glutamate  Beta sheet  R groups of successive amino acids jut out on alternating side s of the sheet  Maximum of H-bonding  Intramolecular or intermolecular

 Can be parallel or antiparallel  Isoleucine, valine, phenylalanine  Motifs: certain combinates of alpha helices and beta sheets o Tertiary structure  Depends almost entirely on interactions between the various sR groups  Native conformation: most stable three dimensional structure for that particular sequence of amino acids  Fibrous proteins: highly ordered and repetitive structure  Globular proteins: polypeptide chains folded into compact structures  Domain: discrete, locally folded unit that usually has a specific function o Quaternary structure  Subunit interactions and assembly  Same bonds and forces as the tertiary structure 22 (p. 696) Protein Targeting and Sorting 

Shortly after translation begins, two main pathways for routing the newly formed polypeptide begin to diverge o First pathway: ribosomes attach to ER, transfer of polypeptides into the ER, cotranslational import o Second pathway: ribosomes remain free in the cytosol, posttranslational import: the uptake by organelles of completed polypeptides that requires the presence of special targeting signals

Lecture 5 Material 6 (p.146-151) Enzyme Regulation 







Substrate-level regulation: depends direction on the interactions of substrates and products with the enzyme o Increases in substrate concentration result in higher reaction rates o Increases in product concentration reduce the rate o By increasing or reducing the rate at which the first step functions, the whole sequence is effectively controlled Allosteric enzymes are regulated by molecules other than reactants and products o Feedback inhibition: product is a specific inhibitor of the enzyme o Allosteric regulation: enzymes can exist in two different forms  An allosteric effector is a small organic molecule that regulates the activity of an enzyme for which it is neither the substrate nor the immediate product  Binds to one of the two interconvertible forms of the enzyme, thereby stabilizing it in that state  Binds to the allosteric or ergulatory site that is distinct from the active site  Allosteric inhibitor: shifts the equilibrium between the two forms of the enzyme to favor the low affinity state  Allosteric activator: shifts equilibrium in favor of the high affinity state  These increase or decrease the likely hood of substrate binding  Catalytic subunits and regulatory subunits Allosteric enzymes exhibit cooperative interactions between subunits o Multiple catalytic sites on the enzyme bind substrate molecules, the enzyme undergoes conformation change that affect the affinity of the remaining sites for substrate  Positive cooperativity: binding of a substrate molecule increases the affinity of other catalytic subunits for substrate, rate increases  Negative cooperativity: substrate binding reduces the affinity of the other catalytic sites for substrate, activity decreases Enzymes can be regulated by the addition or removal of chemical groups o Covalent modification: enzyme’s activity is affected by the addition or removal of specific chemical groups via covalent monding o Phosphorylation/dephosphorylation  Transfer of the phosphate group from ATP to the hydroxyl group of a serine, threonine, or tyrosine residue in the protein  Enzymes that catalyze the phosphorylation are protein kinases  Protein phosphatases catalyze dephosphorylation



o Proteolytic cleavage  Involves the one-time, irreversible removal of a portion of the polypeptide chain RNA molecules as enzymes: ribozymes

23 (p.751-752) Posttranslation control 



Modifications of protein structure, function and degradation o Includes covalent modification and proteolytic cleavage o The amount of any given protein is influenced by its rate of degradation as well as its rate of production o Differences in half lives of proteins can dramatically affect the ability of different proteins to respond to changing conditions  The concentration of a protein exhibiting a short half-life (large kdeg) changes more dramatically to alterations in synthetic rate  Enzymes that are important in metabolic regulation tend to have short half-lives allowing their intracellular concentrations to rapidly be changed in response to changing conditions Ubiquitin targets proteins for degradtion by proteasomes o Ubiquitin chains serve as targeting signals that are recognized by large, protein-degrading structures called proteasomes o The proteasome binds to ubiquitylated proteins and removes their ubiquitin chains o The proteins are fed into the central channel of the proteasome and their peptide bonds are hydrolyzed in an ATP dependent process  Small peptide fragments are released from the other end of the cylinder o Some N-terminal AAs cause proteins to be rapidly ubiquitylated and degraded

Lecture 6 Material Chapter 6 Activation Energy and the Metastable State 





Before a chemical reaction can occur, the activation energy barrier must be overcome o Activation energy: minimum amount of energy that reacts must have before collisions between them will be successful in giving rise to products  Reactants need to reach an intermediate chemical stage called the transition state o The actual rate of a reaction is always proportional to the fraction of molecules that have an energy content equal to or greater than EA The metastable state is a result of the activation barrier o Molecules are thermodynamically unstable but they do not have enough energy to exceed the activation energy barrier—they are seemingly stable in a metastable state o If it were not for the metastable state, all reactions would proceed quickly to equilibrium Catalysts overcome the activation energy barrier o If the reactants can be bound on some sort of surface in an arrangement that brings potentially reactive portions of adjacent molecules into close juxtaposition, their interaction will be greatly favored and the activation energy effective reduced o The primary feature of a catalyst is that it is not permanently changed or consumed as the reaction proceeds

Enzymes as biological catalysts 



All catalysts share three basic properties o Increases the rate of a reaction by lowering the activation energy requirement o A catalyst acts by forming transient, reversible complexes with substrate molecules, binding in a manner that facilitates their interaction and stabilizes the intermediate transition state o A catalyst changes only the rate at which equilibrium is achieved, it has no effect on the position of the equilibrium o Enzymes are much more specific than inorganic catalysts, and their activities can be regulated much more carefully Most enzymes are proteins o The active site: usually an actual groove or pocket with chemical and structural properites that accommodate the intended substrate or substrates with high specificity  Only a few AAs are involved in the active sites of the many proteins that have been studied



 Cysteine, histidine, serine, aspartate, glutamate, lysine o Enzymes display a very high degree of substrate specificity  Some accept a number of closely related soubstrates and others accept any of a whole group of substrates as long as they possess some common structural feature —group specificity o Enzymes are sensitive to temperature  At low temperatures, the rate of an enzyme-catalyzed reaction increases with temperature  Greater kinetic energy  Further increases in temperature result in denaturation of the enzyme molecule  Temperature range over which an enzyme denatures varies from enzyme to enzyme o Enzymes are also sensitive to pH  Most are activity only within a pH range of 3-4 pH units  Activity is usually dependent on having such groups present in a specific either charged or uncharged form  Extreme changes in pH also disrupt ionic and hydrogen bonds Substrate binding, activation, and catalysis occur at the active site o Induced fit model for substrate binding  Substrate binding at the active site distorts both the enzyme and the substrate, thereby stabilizing the substrate molecules in their transition state and rendering certain substrate bonds more susceptible to catalytic attack o The role of the active site is also to activate the substrate by subjecting it to the right chemical environment for catalysis  Bond distortion: distorts one or more of its bonds, thereby weakening the ond and making it more susceptible to catalytic attack  Proton transfer: the enzyme may also accept or donate protons, thereby increasing the chemical reactivity of the substrate  Electro transfer: enzymes may also accept or donate electrons, thereby forming temporary covalent bonds between the enzyme and its substrate o The catalytic event:  Initial random collision of a substrate molecule with the active site results in its binding to amino acid residues that are strategically positioned there  Substrate binding induces a change in enzyme conformation that tightens the fit between the substrate molecule and the active site and lowers the free energy of the transition state. This facilitates the conversion of substrate into products  The products are then released from the active site enabling the enzyme to return to its original conformation

Enzyme Kinetics 

Enzyme kinetics concerns reaction rats and the manner in which reaction rates are influenced by factors including the concentrations of substrates, products, and inhibitors











o Focus on initial reaction rates Most enzymes display Michaelis-Menten kinetics o Consider how the initial reaction velocity changes depending on the substrate concentration  Hyperbolic relationship  As [S] tends toward infinity, v approaches an upper limiting value known as the maximum velocity  Value depends on the number of enzyme molecules and can therefore be increased only by adding more enzyme  At saturation, all available enzyme molecules are operating at maximum capacity o Enzyme E first reacts with substrate S, forming the transient enzyme-substrate complex ES, which then undergoes the actual catalytic reaction to form free enzme and product P o V=Vmax*[S]/ (Km+ [S]  Km is the concentration of substrate that gives exactly half the maximum value Vmax and Km? o At very low substrate concentration, the initial reaction velocity is roughly proportional to the substrate concentration  Increases linearly with substrate concentration o At very high substrate concentrations, the velocity of an enzyme-catalyzed reaction is essentially independ...