1-cell memb. transp. 2- 11 oct

  1. function of memb: barrier or compartmentalisation

simple passive diffu.:

Through the membrane

Through a channel/pore: proteins

solute not in contact with hydropho. part of the memb.

eg: aquaporin

carrier proteins

binding of the solute to protein, shuffling or flipping of the protein
to shuffle that molecule across memb.

passive transp. mechanis.

down conc. gradient

couple the carrier of one solute
by the mov. of other solute.

Secondary active transport processes. ⚠

harnessing the energy of one conc. gradient
to mov. another solute against conc. gradient

symport (same direction)

antiport (opposite direction)

pumps: primary active transport

Secondary active transport processes. : ⚠repeating

harnessing the energy of one conc. gradient
to mov. another solute against conc. gradient

symport (same direction)

antiport (opposite direction)

input of energy required: comes from ATP

no conc. grad. needed

important in establishing conc. grad.

fundamental for electrophysiological properties of cell

2- pores and channels

aquaporin

specialised channel:
selective diffus. of w across memb.

accelerates the rate of transport

swelling and bursting of cell as a consequence of cell volume

benefit

rapidly accelerate the transfer of solute across the memb.

types:

non gated channels= pores

gated pores=channels

always open, always there

allowing the mov. of solutes

non directional=can go in both directions

net mov. of solutes based on conc. gradient

benefit of channels: we can regulate the opening and closing under different conditions
influence the movement of solutes

gating: mechanisms by which we can open the cap
or open up the ion channel
no of gating mechanism related to ion channels

voltage gated channels

electrical charge across membrane

net electrical negativity inside the cell
and positive charge outside of the cell

charged components of that ion channel

if change in the voltage

activation of ion channel

allows the movement of ion through those channels

ligand gated channels

req. binding of a ligand

often from the extra cellular side:
extra cellular surface of the protein

causes a conformational change

oppening up the ion channel

allowing the diffusion of the solutes through the membrane

mechanically gated channels

req. mechanical stimulus

mediated through the cytoskeleton or strech of the memb.

causing the physical opening of
that ion channel

and the diffusion of that solute across the memb.

they all can regulate when they open and close

under different types of stimulus

4-eg. very selective potassium channel

3- Channel proteins
highly specific

the rate of transport high

eg. aquaporin can increase
the transfere of w molec. by 10 fold

very selective for that molec.

has 4 identical transmembrane components

provide pore through membrane

allow selective diffusion across memb.
and also maintains the very rapid transfer of solute

negatively charged amino acid: attractive to cations
non selectively attracts cations to the opening pore

only selectivly allows the trasfere of potassium across the channel

10.000 time more permeable to K than Na

different sizes of Na+ ion and K+ ion

Na+ << K+

to transfer ion needs to shed (get rid of) its water molec.

K+ can do that because it enters into selectivity filer

K+ can shed its w channels and
binds with the oxygen molecules
because of the size and proximity of those

it is energetically favourable for K+
to be able to make those connections and transfer through the selectivity filter

Na+ is too small for chemical bonding process to occur

5-rate of transport

2017-12-15 (3)

trans. rate for simple diffu. through the memb. or specific ion channels depends on 2 things:

passive process: because it is really governed by conc. gradie.

5- facilitated diffusion:
carrier mediated transport

specialised proteins embeded in the membrane
specific binding of the solute to the binding domain on the protein

cause conformational change on the structure of the protein

protein flipps around and allows the release of solute on the other side of the memb.

random flopping from configuration A to B

sometimes the solute binding triggers the conformational change

in some cases it is random fluctuation- back and forwards

end up with: net transfer of solute from region of high conc to region of low conc. net rate is always down its conc. grad. but solute might also go backwards

difu. down conc. gradient

facilitated by the carrier protein

diagram of carrier mediated transport

important feature
the carrier is only open to one side of the memb. at any one time
1-if it is open to extra cellular side, the solute can bind to the binding domain
2-get a conformational change
3-the closing of extra cellular components
4-both sides closed, then the sequential opening of the intra cellular side which allows the movement of solutes



it in never like a pore where it is open to either side of the memb. at any one time: so it is not the same as simple water filled pore

rate of transport

2017-12-19 (2)

influence of conc. grad.

flux 🚩 conc. grad 🚩

but we reach a point that called saturation
=maximum transfer rate
=maximum flux for the solute

if we increase the conc. grad. we cant get greater rate of transport ax=cross the membrane

saturation is an important feature

relates to the:

no. of binding sites

the no. of carrier proteins that are present in relation to conc. gard.

another important feature:

how well those solutes can
actually bind to the carrier protein

similar to enzyme substrate reaction

the transport of the solute across the memb. not result in any change in that solute characteristics

just a physical transfer of one side of the memb. to another

quantify that by Km=affinity constant : concentration of the solute required to achieve half the maximum transfer rate

relates to the binding affinity

solutes that bind with
higher affinity to that carrier protein 🚩 lower Km 🏴 means better binding

more quickly to saturate

limitation of transport rate
by carrier protein: all of these factors
will slow down the rate of the transport of the molec.
and limit the transfer rate or the flux through carrier mediated transport

how many binding sites?

how strong is the binding affinity between the
solute and carrier protein

binding process takes certain amount of time
to bind and release of the other site

how quickly this protein can change its configuration

the sequence: binding to the solute- conformational change- release of the solute across the other side

final points:

read the slide:
Points about carriers (facilitated diffusion)

work bidirectional:
depending on the conc. grad.

get saturated at high conc.

transfere rate can be reduced by compatitive binding
bind molecules with similar structure
limits the rate of transport of particular solute

they are temperature dependent

can be blocked by some pharmacological agents and toxins

difference between transfer mediated by pores and those mediated by carrier proteins
Carriers/transporters are NOT water-filled pores/channels

6- sofar uniport process: uniporter
Transport a single solute
across the memb. down its conc. gradient

7-coupled transport: Co-transporters
Transfer of one solute depends
on the simultaneous transport of
a second solute

utilising the conc. grad. of one solute to pump or cotransport the other solute against its conc. gradient

symport:
both solutes transfere in the same direction
might be from extra cellular site to the intracellular site

antiport:
the transfer of one solute into the cell is coupled
to the transfer of another solute out of the cell

example of cotransport mechanism: process is referred to as
secondary active transport ⚠

sodium - Glucose transporter SGLT1

Na is one of the most utilised ions in the body
in terms of the co-transport process -

part of the reason:

we have very high extracellular conc. gradient for Na

but very low inside of the cell

so very strong conc. gradient and strong electrical gradient

combined electrochemical gradient is very favourable
for the diffusion of sodium ions into the cell

very strong potential energy we have there

utilise and harness that to transport other solutes to the cell against their concentration gradient

diagram

blue=sodium

electrochemical gradient for Na going into the cell

specific transporter protein

cotransport mechanism=symporter

binding of one solute
increases the affinity of other solute to bind to that molecule

by Na binding to the carrier protein:
increases the affinity for glucose binding to that carrier protein

both of those bind to the perspective binding sites

then we get the conformational change of those proteins

Na moving down conc. grad. into the cell
allows the pumping or transport of Glucose against its conc. grad to accumulate inside the cell

transport solutes in the same direction

other example

hydrogen ions based transported processes

very impo for maintaining the PH in cells and
different organelles within the cell as well

relies on the presence of conc. grad:
need to have that to trans. other solute against its conc. grad

an active transport

because we need energy of one conc. gradien to
drive the transfer of another solute against its conc. grad.

NOT establish a conc. grad. itself

inorder to do that we have the process of the active transport

Water filled pores and channels increase permeability

Pores and channels can be selective:

eg aquaporin for water.

JX = Flux of X across the membrane (moles/cm2.s)

Permeability of membrane to X: depend on the permeability of the memb. to that particular solute
Px: proportional relationship

[x] concentration grad. across the memb. for that particular solute: proportional relationship ([X]o - [X]i)

carriers are gated by 2 doors : never open at the same time