Molecular Biology of the Cell

Transcription

1 da Alberts Johnson Lewis Morgan Raff Roberts Walter Molecular Biology of the Cell Sixth Edition con integrazioni e modifiche Chapter 11 Membrane Transport of Small Molecules and the Electrical Properties of Membranes Copyright Garland Science 2015

2 MEMBRANE TRANSPORT

3 Ion concentration is different inside and outside cells

4 Synthetic lipid bilayers have different permeability to different classes of molecules

5 Permeability of lipid bilayer The gases diffuse quickly gas O2 CO2 N2 Over time, small polar uncharged molecules diffuse across a lipid bilayer Lipid soluble molecules tend to diffuse piccole molecole polari non cariche molecole lipofile glicerolo etanolo ormoni steroidei Large polar uncharged molecules, polar charged molecules and ions do not permeate grosse molecole polari cariche ioni amino acidi glucosio nucleotidi H+,Na+, HCO3-,K+ Ca2+,Cl, Mg2+ bilayer lipidico

6 Permeability coefficients of different molecules are very different

7 The two main classes of membrane transport proteins are: transporters and channels Carrier Protein They bind the solute from one side of the membranes and the other carrying side with a change in the protein conformation Channel Protein Forming hydrophilic pores in the membrane through which certain ions can passively diffuse

8 Transport across membranes can be: Passive or Active Against concentration or electrochemical gradient

9 The electrochemical gradient affects ion transport The electrical and chemical gradients can work additively to increase the drivig force on ion across membrane The electrical and chemical gradients can work against each other

10 TRANSPORTERS

11 Conformational changes of a transporter can mediate passive transport The transitions between states occur randomly if the solute concentration is higher on the outside of the bilayer there is a net transport of solute down its concentration gradient

12 Transporter-mediated diffusion reaches a maximum Binding constant of the transporter for the solute

13 Active transport is carried out in three main ways The ATP-driven pump Coupled transporters harness the couple the uphill transport energy stored to the hydrolisis of ATP in concentration gradients to couple the uphill transport of one olute across the membrane to the downhill transport of another These transporters couple uphill transport to an input of energy from light

14 Transporters can transfer one ion or two ions, in the same or in the opposite direction The tight coupling between the transfer of two solutes allows coupled transporters to harvest the energy stored in the electrochemical gradient of one solute (an inorganic ion) to transport the other

15 Glucose transport is driven by Na+ gradient Ion gradients represent an energy source

16 Glucose crosses the intestinal epithelium: transcellular transport Directed to blood

17 There are three types of ATP-driven pumps Turbine-like machines In lysosomes Work in reverse These pump can work in either direction depending on the electrochemical gradients of their solutes and the ATP/ADP ratio

18 ER calcium pump is a P-type transporter

19 Na+/K+ ATPase is also a P-type pump The conc. of K+ is times higher inside cells than outside, the reverse is true for Na+. The pump is antiporter and is also critical for maintaning ph and is electrogenic. The cell s inside being negative relative to the outside.

20 ABC transporters are the largest family of membrane transport proteins MDR pump drugs out of the cytosol REM: MDR

21 CHANNELS

22 Water crosses the membrane through channels: the aquaporins

23 Channels can have a closed or open conformation Only ions with selctive size and charge can pass and as the ion concentration increases, the flux of the ion through a channel increases proportionally but then levels off (saturates) at a meximum rate

24 Channel structure determines ion selectivity

25 Channels can be regulated by several mechanisms

26 Mechanosensitive channels open and close

27 Ion distribution determines membrane potential A membrane potential arises when there is a difference in the electrical charge on the two sides of a membrane due to a slight excess of positive ions over negative ones on one side and a slight deficit on the other.

28 Ion transport is fundamental for nerve cell function

29 Sodium channels have a key role in the generation of a membrane potential

30 Individual ion channels can be monitored by patch clamp

31 Release of neurotransmitter occurs at synapses

32 Various channels are activated in sequence at the neuromuscular junction

33 Single neurons are complex computation devices

34 THE END