L3940_memtrans_462A_2013sm

G digitalsis block the dephosphorylagon of the atpase

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Unformatted text preview: lot saturaGng velocity Vmax The iniGal velocity of transport can be described with the Michaelis ­Menten equaGon characterisGc concentraGon Kt at which the transport system funcGons effecGvely Vo = Vmax[Sout] Kt + [Sout] Double reciprocal plot with 6 ­benzyl ­D ­galactose glucose Effect of 6 ­benzyl ­D ­galactose, ??? inhibi4on AcGve transport is transport against a concentraGon gradient using energy . couples transport of a substrate directly to a chemical reacGon (usually ATP hydrolysis.) couples transport of a substrate to a concentraGon gradient (usually of H+ or Na+) created by acGve transport The Na+K+ ATPase establishes the concentraGon gradient of Na+ and K+ across the membrane of neurons. Passive ion channels in the membrane open when the neuron fires, allowing propagaGon of nerve impulses. The Na+K+ ATPase reestablishes the resGng potenGal Nature Reviews Molecular Cell Biology 12, 60 ­70 (January 2011) Proposed Mechanism •  AnGport •  Rate: 1000 slower than ions channels •  Cotransport creates a net separaGon of charge => membrane potenGal •  Central role, energy invested in a single reacGon ~ 25% of total consumpGon of a human at rest DephosphorylaGon step can be inhibited by certain drugs or poisons Cardiotonic steroids (e.g. digitalsis) block the dephosphorylaGon of the ATPase which inhibits transport Why does blocking dephosphosrylaGon inhibit transport? Proposed Mechanism •  AnGport •  Rate: 1000 slower than ions channels •  Cotransport creates a net separaGon of charge => membrane potenGal •  Central role, energy invested in a single reacGon ≈25% of total consumpGon of a human at rest Secondary acGve transport •  Couple the movement of an ion or molecule against its electrochemical gradient to the movement of a different ion or molecule down its electrochemical gradient Cotransport Why is this o^en called “secondary ac4ve transport?” Lactose permease •  Most well ­studied secondary acGve transporter (bacterium E. coli) •  Single chain of 417 residues. •  member of a large group of related transporters called the Major Facilitator Superfamily (MFS) Transports the sugar lactose into the cell across the plasma membrane. Lactose permease MFS proteins typically contain 12 transmembrane helices divided into two similar domains (each of which consists of 6 helices) with the substrate binding site in between the two •  Symport: both H+ and lactose move into the cell from the extracellular fluid •  Ac4ve transport: movement of lactose against its concentraGon gradient – coupled with – movement of H+ down its electrochemical gradient ConformaGonal changes allow lactose and H+ to be cotransported into the cell Lecture 40 Membrane Tran...
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