L3940_memtrans_462A_2013sm

Transport stops when equilibrium is reached what

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Unformatted text preview: the channel “Paddles” include a voltage ­sensing domain that undergoes a conformaGonal change upon membrane depolarizaGon that in turn opens the channel Voltage ­gated channels: transiently inacGvated by a ball and chain within ms of opening mechanism inacGvaGon domain Flexible polypepGde that tethers ball to channel Similar mechanism works for both voltage ­ gated Na+ and voltage ­gated K+ channels Ball is a globular water ­soluble domain that binds specifically to the open channel Carriers allow solutes to flow in and out of cells according to their electrochemical gradient •  Facilitates the unidirecGonal movement of molecules across the membrane •  Carrier assisted transport of solutes occur much faster than simple diffusion of the same molecule (but slower than channels). •  Transport stops when equilibrium is reached What determines the direcGon the molecule flows through the carrier? Model of carrier proteins: the erythrocyte glucose transporter (GLUT1) •  Facilitated diffusion •  Transports glucose down its concentraGon gradient •  Uniport (GLUT1) •  Under normal physiological condiGons most GLUT1 molecules are always imporGng glucose •  This is NOT the only way glucose gets into cells (other GLUTs pp. 393). GLUT1: Structure has not been determined What can we say from the hydropathy plot? Predicted Structure Model 12 transmembrane α ­helices Four of the α ­helices have polar groups along one side that may form a hydrophilic channel at the center through which the glucose may travel Proposed mechanism •  T1 state recognizes the substrate and open to another side. – Filtering mechanism Transport Rate of Passive diffusion •  Molecules undergoing random moGon tend naturally to diffuse from an area of high concentraGon to an area of low concentraGon. The rate of transport is proporGonal to the concentraGon difference. C1 C2 High concentraGon difference, higher rate of transport Rate of transport = D (C1  ­ C2) (D is the diffusion coefficient of the diffusing molecules) Rate of transport Low concentraGon difference, low rate of transport C1  ­ C2 Rate of transport by passive transporters V is the iniGal velocity of accumulaGon is limited of solute when its concentraGon is [S] 0 out saturaGon Kt (Ktransport) is a combinaGon of rate constants characterisGc for a transport system disGnguishes a facilitated diffusion mechanism from passive diffusion Rate depends on glucose concentraGon What would this graph look like if you ploZed passive diffusion of a membrane permeable molecule? Specificity of GLUT1 Substrate Kt (mM) D ­glucose 1.5 D ­mannose (posiGon of one hydroxyl group differs 20 from D ­glucose) D ­galactose (posiGon of one hydroxyl group differs 30 from D ­glucose) L ­glucose Highest specificity for? 3000 Double reciprocal p...
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