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1、Chapter 5Learning Objectives: 1. Principles of membrane transport;2. Passive transport and active transport;3. Two main classes of membrane transport proteins: Carriers and Channels;4. The ion transport systems;5. Endocytosis and Phagocytosis: cellular uptake of macromolecules and particles.The Move
2、ment of Substances Across Cell Membranes1. Principles of membrane transportThe plasma membrane is a selectively permeable barrier. It allows for separation and exchange of materials across the plasma membrane.B. The protein-free lipid bilayers are highly impermeable to ions.C. The energetics of solu
3、te movement:Diffusion is the spontaneous movement of material from a region of high concentration to a region of low concentration.The free-energy change during diffusion of nonelectrolytes depends on the concentration grdient.The free-energy change during diffusion of electrolytes depends on the el
4、ectrochemical gradient.D. Transport processes within an eukaryotic cell 2. Passive transport and active transportA.Ionic differentiation inside and outside cellB. Comparison of two classes of transport. Solutes cross membrane by simple diffusionDiffusion of small molecules across phospholipid bilaye
5、rsIf uncharged solutes are small enough, they can move down their concentration gradients directly across the lipid bilayer by simple diffusion. Most solutes can cross the membrane only if there is a membrane transport protein to transfer them. Passive transport, in the same direction as a concentra
6、tion gradient. Active transport, is mediated by carrier proteins, against a concentration gradient, require an input of energy.C. Two classes of membrane transport proteins Carrier proteins are responsible for both the passive and the active transport.Channel proteins are only responsible for passiv
7、e transport.Carrier proteins bind one or more solute molecules on one side of the membrane and then undergo a conformational change that transfer the solute to the other side of the membrane.The carrier protein, the Glucose transporter (GluT1 ) in the erythrocyte PM, alter conformation to facilitate
8、 the transport of glucose.Facilitate diffusion: Protein-mediated movement, movement down the gradientMost of the channel proteins are ion channels, including three types, with ion channels that they can be opened and closed The channel proteins,in contrast, interact with the solute to be transported
9、 much more weakly. The channel proteins facilitate diffusion by forming hydrophilic transmembrane channelsTransport through channel proteins occurs at a much faster rate than transport mediated by carrier proteins. 3. Active transport: Carrier protein-mediated movement up the gradientA. This process
10、 differs from facilitated diffusion in two crucial aspects:Active transport maintains the gradients for potassium, sodium, calcium, and other ions across the cell membrane. Always moves solutes up a concentration or electrochemical gradient;Active transport couples the movement of substances against
11、 gradients to ATP hydrolysis. i.e Always requires the input of energy.B. Cells carry out active transport in three main waysCouple the uphill transport of one solute across membrane to the downhill transport of another.Couple uphill transport to the hydrolysis of ATPMainly in bacteria, couple uphill
12、 transport to an input of energy from light.C. Direct active transport depends on four types of transport ATPasesThe four classes of ATP-powered transport proteins:“P” type stands for phosphorylation; ABC (ATP-binding Cassette) superfamily, bacteriahumans. Two transmembrane (T) domains and two cytos
13、olic ATP-binding (A) domainsThe Na+-K+ ATPase -A coupling active transport to ATP hydrolysis. The active transport of Na+/K+ ATPase is used to maintains electrochemical ion gradients, and thereby maintains cells excitability.The Na+/K+ pumo is required to maintain osmotic balance and stabilize cell
14、volume The biological functions of Na+/K+ pumpforming a phosphorylated protein intermediateA Model Mechanism for the Na+/K+ ATPaseOther P-type punps: including H+ and Ca+ ATPases, and H+/K+ ATPasesPlant cells have a H+-transpoting plasma membrane pump . This proton pump plays a key role in the secon
15、dary transport of solutes, in the control of cytosolic pH, and possibly in control of cell growth by means of acidification of the plant cell wall.Ca2+ pump: Ca2+-ATPase present in both the plasma membrane and the membranes of the ER. It contain 10 transmembrane helices. This Ca2+ pump functions to
16、actively transport Ca2+ out of the cytosol into either the extracellular space or the lumen of the ER. H+/K+ ATPases (epithelial lining of the stomach): which secretes a solution of concentrated acid (up to 0.16N HCl) into the stomuch chamber.The V-type pump: utilize the energy of ATP without formin
17、g a phosphorylated protein intermediate.Vacuolar(V-type) pump actively transport H+ across the walls of cytoplasmic organelles and vacuoles. They precent in lysosomes, secretory granules, and plant cell vacuoles, have also been found in the plasma membranes of a variety of cells (kidney tubules).The
18、 ABC transporters(ATP-binding cassette): Constitute the largest family of membrane transport proteins.In bacteria, ABC transporter use ATP binding and hydrolysis to transport molecules across the bilayer.The eucaryotic ABC transporter pump hydrophobic drugs out of the cytosol. MDR(multidrug resistan
19、ce) protein overexpression in human cancer cells (40%).In yeasts, ABC transporter is responsible for exporting a mating pheromone. In most vertebrate cells, ABC in ER membrane actively transports a wide variety of peptides from the cytosol into the ER. 4. Indirect active transport is driven by Ion g
20、radients - CotransportA. Sugars, amino acids, and other organic molecules into cells: The inward transport of such molecules up their concentration gradients is often coupled to, and driven by, the concomitant inward movement of these ions down their electrochemical gradients: Animal cells-Sodium io
21、ns (Na+/K+ ATPase) Plant, fungi, bacterium-Protons(H+ ATPase)Gradients created by active ion pumping store energy that can be coupled to other transport processes. The difference between animal and plant cells to absorb nutrientsB. Cotransport: Symport and antiportNa+-linked symporters import amino
22、acids and glucose into many animal cellsNa+-linked antiporter exports Ca+ from cardiac muscle cellsMedicineOubain and digoxin increase the force of heart muscle contraction by inhibiting the Na+/K+ ATPase. Fewer Ca+ ions are exportedNa+/葡萄糖協(xié)同轉(zhuǎn)運(yùn)體能逆相差20000倍的濃度梯度將葡萄糖分子轉(zhuǎn)運(yùn)至胞內(nèi) 5. Endocytosis: Large molecu
23、les enter into cellsA. Endocytosis imports extracellular molecules dissolved or suspended in fluid by forming vesicles from the plasma membraneBulk-phase endocytosis does not require surface membrane recognition.It is the nonspecific uptake of extracellular fluids. Receptor-mediated endocytosis(RME)
24、 follows the binding of substances to membrane receptors.B. Phagocytosis: The uptake of large particles Including: macromolecules, cell debris, even microorganisms and other cells.Phagocytosis is usually restricted to specialized cells called Phagocytes.Phagocytosis is initiated by cellular contact
25、with an appropriate target.Phagocytosis may be stimulated by the opsoninsPhagocytosis is driven by contractile activities of MF.C. Receptor-mediated endocytosis(高膽固醇血癥)Structure of a clathrin coated vesicleModel for the formation of a clathrin-coated pit and the selective incorporation of integral membrane proteins into clathrin-coated vesiclesD.caveolae-mediated endocytosisThe endocytic pathway is divided into the early endosomes and late endosomes pathway.Materials in the early endosomes are sorted: Integral membrane proteins are shipped back to the membrane; Other d
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