Chapter 10 Membrane Transport

Chemical potential difference

membrane transport resembles chemical equilibria: A_out = A_in 

free energy of transport corresponds to the natural log of concentration: G=RTlnA

    delta G = G(in) - G(out) = RT ln ([A]_in/[A]_out)

• calculating G helps predict whether it is thermodynamically favorable for a natural molecule to move across a membrane

Uncharged molecules move down their concentration gradient

Electrochemical potential A_out = A_in 

delta G = RT ln ([A]_in/[A]_out) = Z_AF delta mV

Z_A = charge of A        F = faraday’s constant        mV = membrane potential with respect to                                                                                         outside

Charged molecules move down their electrochemical gradient 

membrane transport = cells control their interior composition and concentrations through 2 types of transport

• passive-mediate transport/facilitated diffusion - high → low concentrations driven by concentration differences but is facilitated by pores and other transport mechanisms in membrane

• active transport - low → high concentrations that is against its concentration gradient and requires energy expended by the cell

ionophores - protein systems that help the passive mediated diffusion of ions across membranes, rapidly transports ions but are dependent on chemical potential

• carrier ionophores: proteins bind ions and help them diffuse across membranes by carrying them through the lipid bilayer

  • valinomycin - short modificed polypeptide that helps K ion travel across membranes in bacteria

• channel forming ionophores: protiens span membrane and form a port through which ions can diffuse

valinomycin

-    comprised of 3 repeats of L-valine, D-hydroxylated valine, D-valine, L-lactic acid

-    contains both amide and ester linkages

highly selective for K⁺: K+ ions coordinated by carbonyl oxygens of 6 valine resides

• replaces water molecules around the potassium center

• completely wraps around potassium iion

 rest of molecule, isopropyl and methyl face the outside of adduct providing hydrophobic interactions iwth membrane

• pore size perfect for K ion radius

• Na+ ions are too small for these interactions

porins: beta-barrel transmembrane (integral) proteins

• can only transport small molecules less than MW = 600

• can move ions across membranes

• not highly selective

• composition of B-barrel determines selectivity for nonionic substrates

Maltoporins

• facilitate transport of maltodextrins

• oligosaccharides from breakdown of starch

• maltose is disaccharide form

• has hourglass- like pore shape

• 6 hydrphobic amino acids form a greasy slide to interact with CH face of maltodextrin

• 5 glucose resides of maltodextrin and aromatic side chains lining transports channel

• solute selectivity is mainly determined by size of channel and specific interaction between side chains and solute

ion channels

• concentrations of ions differ widely inside and outside the cell

• ion channels need to be highly selective for a specific ion

• channels have transmembrane domains that allow for the rapid diffusion through a membrane

K+ channels KcsA: rrapid & highly selective

• selectivity filter

• carbony oxygens of amino acids residues are spaced to coordinate K+ ions but not other ions (like Na+)

• anionic residues at both ends of the channel help select K+ for transport

ion channels are gated/not always open, they can be closed by cell by 4 ways

• mechanosensitive channels - can close due to local deformations in lipid bilayer and can respond to direct physical stiimuli like touch, sound, and changes in osmotic pressue

• ligand-gated channels - gate in response to an extracellular chemical stimulus like neurotransmitter

• signal-gated channels - open on intracellularly binding a Ca²⁺ iion or some other signaling molecule

• Voltage-gated channels - gate in response to a change in membrane potential

  • voltage-gated in Kv channels: positively charged helix movement

    • Kv channel is transiently closed by spherical globular segment on N-terminus

proteins invovled in passive mediated transport

• carrier ionophores - binds to ions and diffuse across the bilayer

  • contain selective binding sites for specific ions (like valinomycin)

• ion channels

  • rapid passage of ions through transmembrane channels

  • selective (w/ selecitvity filter ex KcsA)

  • gated (by ligand or voltage)

• transport proteins

  • switch between 2 conformations in order to move substances across membrane

  • some transport proteins move more than one substance at a time

    • (uniport vs symport vs antiport)

active transport: endergonic process that forces transport against chemcial potential that uses energy from an exergonic process to move solutes against a gradient

• higher/lower concentrations of particular ions or molecules are desired in the cell relative to the exterior

• in order to reverse the natural chemcial potential, energy is required

• exergonic process is often ATP hydrolysis

• hydrolysis of atp is the cleaavge of the phsophate bond, it releases energy that drives the reaction

• ATP-dependent transporters: P-type ATP, F-type ATPases, V-type ATPases, A-type ATPases, ABC transporters

• P-type ATP : (Na+ - K+)-ATPase

• 3Na+ (in) + 2K+ (out) + ATP + H2O → 3Na+ (out) + 2K+ (in) + ADP + Pi

  • 3 Na+ OUT, 2 K+ IN

  • creates membrane potential (essential for excitation of nerve cells)

  • membrane proteins maintain low internal Na+ concentrations crucial for preventing cell lysis bc of osmotic pressure

  • alpha (1000 residue) & beta (300 residue) subunits

    • a is cytosol and transmembrane

    • B is extracellular

phosphorylation of aspartic acid residue on Na+/K+ ATPase is Key to activity

(aspartyl phosphate residue)

acttive transport by (Na+ - K+)-ATPase (Na+ - K+ Pump)

• ATP phosphorylates transporter (on aspartic acid residue) only in presence of sodium

• transporter only hydrolyzes aspartyl phosphate residue in presence of potassiunm