BIOL2210 Memb transp and ion channels

the 4 mech of transmemb transport

simple diffusion

facilitated transp

active transp

cotransport

what molecules cross memb via simple diffusion

gases, steroid hormones, drugs (lipophilic mols)

CO2 diffuses but HCO3- is transp in RBC by cotransport

(imperm to most polar mols!!)

how do many drugs cross bilayer

simple diffusion

or look like sub for a transporter

are aquaporins pores

NO, are uniporters

what does facilitated diffusion use

pores (channels)

channel vs pores

channel is sub specific, pore only size specific

3 transporters

Channels

Transporters

ATP powered pumps

rypes of transporters

uniporter (move one direction)

symporter (move 2 mols same directon)

antiporter (move 2 mols opp direction)

beta barrel pores

some b barrels are transmemb proteins

not all memb beta barrels are pores

8-22 b-strands per barrel

TM beta barrels have hphobic external residues and hphilic internal residues

function of beta barrel pores

are passive diffusion channels

e.g. OmpF and OmpC in E.coli outer memb

do beta barrel pores have specificity

OmpF and OmpC have little selectivity

one loop folds into the barrel, prov a restriction in the middle, and acidic residues in the loop give some cation specificity

PhoE transp phosphate, has specificity but still limited

structure of gap junctions (connexin)

connexin monomers have 4 TM a-helices, typically 6 monomers per bilayer

two bilayers (cell next to eachother) next to eachother, a hexamer in each memb form the pore between 2 cells

pore size reg by diff connexin mixtures (homo hetero)

what controls opening and closing of gap junctions

phosphorylation

waht is facil diffusion dependent on

conc difference

transmembrane potential (diff in charge across memb)

osmotic pressure

(e.g. get linear increase in influx rate as increase outside conc

what transporters are involved in cotransport

symporters and antiporters

what are uniporters involved in

facilitated diffusion

(along with pores and channels)

what does it mean that co-transport via symporters and antiporters is secondary active transport

E for active transport of one mol acquired from transp one mol down its electrochemical/conc gradient

often use ATP powered pumps to maintaint the conc grad for these channels to work

uniport vs channel

are both transporters but uniport much more specific

uniport, symport and antiport overview

v substrate specific - sub binding pocket

can be carriers or channels, permeases

share common mechanism - alternating access mech

can symporters become uniporters via small mutations

yes

uniporter vs symporter and antiporter

facil diff vs co-transport/secondary active transport

role of GLUT1

fisrt glucose transporter discovered

transp gluc into RBC and across BBB

mut in GLUT1 cause De Vivo disease

GLUTs are uniporters

gluc binds halfway across memb in binding pocket

what is the largest uniport/co-transport transporter family

Mjaor facilitator superfamily

e.g. GLUT1… is in it

12 TM alpha helices

alternating access mechanism

can the diff conformations of transporters be inhibited by diff drugs

yes

do transporters have specific binding pockets for substrates

yes

diff binding sites for inward open and outward open state

what is SGLT1

sodium glucose co-transporter (symport)

can get gluc trasnp against conc grad as gluc move down its conc grad

can work with protons too if no sodium

2Na per glucose

par tof major facilitator superfamily

glucose transport in gut

GLUT2 uniporter moving gluc from ep cell into bloodstream

Ma/K ATPase (pump) pump Na out of ep cell into blood, K into cell

K channel allow K move out of ep back into blood

SGLT1 symporter move gluc into ep from intestinal lumen

what states does e.g. GLUT1 go thru

outward open conf, ligand bound occluded, inward open conf, ligand-free occuluded

(alternating access mech of all transporters)

states are in equilibrium but is a cycling process

does the transporter move around the substrate

yes

what causes glucose to detach

binding causes conf change to lowest E state, but this state has low affinity for glucose, so dissoc

what also helps maintain gluc conc grad in glut

hexokinase in cell conv some gluc to G6P

mitochondrial ATP/ADP exchanger (antiporter)

ATP has -4 charge, ADP -3 charge

cyto more positive than mito matrix (memb potential)

so get ATP move into cytosol down charge grad

plus ATP hydrolysis in cyto and ATP synth in matrix maintains conc grad