Repetition. Summary of last lecture

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1 Repetition Summary of last lecture Life at the Edge The plasma membrane is the boundary that separates the living cell from its nonliving surroundings The plasma membrane exhibits selective permeability - it allows some substances to cross it more easily than others 1

2 The Davson-Danielli sandwich model of membrane structure stated that the membrane was made up of a phospholipid bilayer sandwiched between two protein layers, and this was supported by electron microscope pictures of membranes CH2 N(CH3)3 Choline CH2 hosphate CH2 CH CH2 Glycerol C C cholesterol Fatty acids Hydrophilic head Hydrophobic tails (a) Structural formula (b) Space-filling model (c) hospholipid symbol The steroid cholesterol has different effects on membrane fluidity at different temperatures Cholesterol Cholesterol within the animal cell membrane Adding Cholesterol to a cell membrane reduces fluidity, therefore, making the cell membrane more rigid reducing phospholipid movement. Without cholesterol, cell membranes would be too fluid, not firm enough, and too permeable to some molecules. While cholesterol adds firmness and integrity to the plasma membrane and prevents it from becoming overly fluid, it also helps to maintain its fluidity. At the high concentrations as it is found in our cell's plasma membranes cholesterol helps to separate the phospholipids so that the fatty acid chains can't come together and crystallize. Therefore, cholesterol helps to prevent extremes-- whether too fluid, or too firm -- in the consistency of the cell membrane. 2

3 An overview of major functions of membrane proteins (a) (b) (c) Transport. (left) A protein that spans the membrane may provide a hydrophilic channel across the membrane that is selective for a particular solute. (right) ther transport proteins shuttle a substance from one side to the other by changing shape. Some of these proteins hydrolyze AT as an energy source to actively pump substances across the membrane. Enzymatic activity. A protein built into the membrane may be an enzyme with its active site exposed to substances in the adjacent solution. In some cases, several enzymes in a membrane are organized as a team that carries out sequential steps of a metabolic pathway. Signal transduction. A membrane protein may have a binding site with a specific shape that fits the shape of a chemical messenger, such as a hormone. The external messenger (signal) may cause a conformational change in the protein (receptor) that relays the message to the inside of the cell. Receptor Enzymes Signal AT e.g. ABCtransporter Na/K-ATase, NMDAR e.g. LC γ-secretase Receptors: e.g. TRKA p75ntr NMDR lant - Cell 3

4 Water balance in cells with walls H 2 H 2 H 2 H 2 Turgid (normal) Flaccid lasmolyzed lant cell. lant cells are turgid (firm) and generally healthiest in a hypotonic environment, where the uptake of water is eventually balanced by the elastic wall pushing back on the cell. Cellulose is a major component of the tough walls that enclose plant cells Cell walls Cellulos e microfibrils in a plant cell wall Mic rofibril About 80 cellulos e molecules associate to form a microfibril, the main architectural unit of the plant cell wall. 0.5 mm lant cells arallel cellulose molecules are held together by hydrogen bonds between hydroxyl groups attached to carbon atoms 3 and 6. CH2H H H H H CH2H CH2H H CH2H H CH2H H H H H H H CH2H H CH2H CH2H H H H H CH2H H CH2H H H bglucose mo n o mer H H CH2H H H CH2H Cellulos e molecules A cellulos e molecule is an unbranched β glucose polymer. 4

5 Water balance in cells without walls Animals and other organisms without rigid cell walls living in hypertonic or hypotonic environments must have special adaptations for osmoregulation Animal cell. An animal cell fares best in an isotonic environment unless it has special adaptations to offset the osmotic uptake or loss of water. Hypotonic solution Isotonic solution Hypertonic solution H 2 H 2 H 2 H 2 H 2 Lysed Normal Shriveled The sodium-potassium pump (Na/K-ATase is one type of active transport system Cytoplasmic Na binds to the sodium-potassium pump. [Na ] high [K ] low Na EXTRACELLULAR Na FLUID [Na ] low Na CYTL ASM [K ] high Na Na Na AD AT 2 Na binding stimulates phosphorylation by AT. K is released and Na sites are receptive again; the cycle repeats. K K Na Na Na hosphorylation causes the protein to change its conformation, expelling Na to the outside. Loss of the phosphate restores the protein s original conformation. K i K K K Extracellular K binds to the protein, triggering release of the hosphate group. 5

6 An electrogenic pump is a transport protein that generates the voltage across a membrane Cotransport: active transport driven by a concentration gradient See also F-class H -pump: Mitochondria: AT generation Chloroplasts: hotosynthesis compare with: Na/K ATase AT H H H roton pump Sucrose-H cotransporter H H Sucrose Diffusion of H H gradient is either created by AT or H gradient is used to make/synthesize AT (as in choroplasts or mitochondria) H H e.g.: V-class proton pumps at vacuolar membranes in plants, yeast, other fungi; at endosomal and lysomal membranes in animal cells; at plasma membrane of osteoclasts and some kidney tubule cells. AT-synthesis: F-class H -pump electromotive force (emf) F-class pumps do not form phosphoprotein intermediates and transport only protons. V/F-class structures are similar and contain similar proteins, but none of their subunits are related to the -class pumps. F-class pumps operate in the reverse directions (compared to V-class) to utilize energy in a proton concentration or electrochemical gradient to synthesize AT. 6

7 Exergonic and Endergonic Reactions in Metabolism An exergonic reaction proceeds with a net release of free energy and is spontaneous Reactants Free energy Energy roducts Amount of energy released ( G <0) rogress of the reaction Exergonic reaction: energy released Enzymes Act as Catalysts and Lower the Reaction Activation Energy (E A ) Barrier An enzyme catalyzes reactions by lowering the E A barrier The effect of enzymes on reaction rate Course of reaction without enzyme E A without enzyme EA with enzyme is lower Free energy Reactants Course of reaction with enzyme G is unaffected by enzyme roducts rogress of the reaction 7

8 The Structure and Hydrolysis of AT AT (adenosine triphosphate) is the cellʼs energy shuttle ( currency ) provides energy for cellular functions Adenine NH2 N C C N - CH H HC N H C N CH hosphate groups H H Ribose H H The Regeneration of AT Catabolic pathways drive the regeneration of AT from AD and phosphate AT synthesis from AD i requires energy AT hydrolysis to AD i yields energy Cell Respiration: - Glycolysis - Krebs Cycle - xidative hosphorylation AT Energy from catabolism (exergonic, energy yielding processes) Energy for cellular work (endergonic, energyconsuming processes) AD i 8

9 The three types of cellular work are powered by the hydrolysis of AT i Mechanical Motor protein rotein moved (a) Mechanical work: AT phosphorylates motor proteins Transport AT Membrane protein i AD i Solute Solute trans ported (b) Transport work: AT phosphorylates transport proteins Chemical NH2 NH3 Glu Glu i Reactants: Glutamic acid and ammonia roduct (glutamine) made (c) Chemical work: AT phosphorylates key reactants Induced Fit Model In the induced-fit model of enzyme action: - the active site is flexible, not rigid - the shapes of the enzyme, active site, and substrate adjust to maximize the fit, which improves catalysis - there is a greater range of substrate specificity This model is more consistent with a wider range of enzymes 9

10 The catalytic cycle of an enzyme (conformation changes during the cycle) 1 Substrates enter active site; enzyme changes shape so its active site embraces the substrates (induced fit). 2 Substrates held in active site by weak interactions, such as hydrogen bonds and ionic bonds. Substrates 6 Active site Is available for two new substrate Mole. Enzyme Enzyme-substrate complex 3 Active site (and R groups of its amino acids) can lower E A and speed up a reaction by acting as a template for substrate orientation, stressing the substrates and stabilizing the transition state, providing a favorable microenvironment, participating directly in the catalytic reaction. 5 roducts are Released. roducts 4 Substrates are Converted into roducts. Competitive inhibitors Enzyme Inhibitors Bind to the active site of an enzyme, competing with the substrate A substrate can bind normally to the active site of an enzyme. Substrate Active site Enzyme (a) Normal binding A competitive inhibitor mimics the substrate, competing for the active site. Competitive inhibitor (b) Competitive inhibition 10

11 Noncompetitive inhibitors bind to another part of an enzyme, changing the function A noncompetitive inhibitor binds to the enzyme away from the active site, altering the conformation of the enzyme so that its active site no longer functions. Noncompetitive inhibitor (c) Noncompetitive inhibition 11