Chapter 4.2 - Transport across membranes

what does diffusion require

both a concentration gradient and membrane permeability

lipid permeability is determined by

molecular size, polarity, partition coefficient

partition coefficient

ratio of solubility in nonpolar solvent to that in water

the greater the lipid solubilit, the ______ the penetration

faster

____ molecules penetrate the lipid bilayer more rapidly that _____ ones (size)

small

____ molecules have poor membrane penetration (polarity)

polar

are sugars and amino acids able to penetrate the bilayer easily

no, both polar

what types of molecules is simple diffusion relevant to

small molecules that are small enough and/or nonpolar enough to cross the membrane without aid of transport proteins, o2, co2, ethanol

relationship between diffusion rate and concentration gradient for simple diffusion

linear, non saturating

relationship between diffusion rate and concentration gradient for facilitated diffusion

hyperbolic positive

facilitated diffusion

uses protein to move solutes across a cell membrane

two main classes of membrane transport proteins

channels, transporter

channels

discriminate on size and electric charge

how do channels work

• when open, only ions (and some polar organic molecules) of the right size charge can pass through

• bidirectional

• exists only in open and closed conformation

what controls opening and closing of channels

external stimuli or conditions within the cells

transporters

undergo a series of conformational change to transfer samll solutes across the bilayer

which membrane transport protein type has a slower transfer rate

transporters

most abundant cation inside the cell and what anion balances it out

K+, balanced by a variety of negative changed anions that includ nucleic acids, proteins, and various metabolites

most abundant cation outside the cell and what anion balances it out

Na+, balanced by extracellular Cl-

what creates a membrane potential

differences in the concentration of inorganic ions across a cell membrane

is the overall charge both inside and outside completely balanced

Though overall charge might be generally balanced, tiny excesses of positive or negative chare, concentrated near the plasma membrane do occur

t or f - resting membrane potential is 0 mV

false, steady stae but not 0, anywhere between -200 to -200 mV

what is more negative, the inside or outside of the cell?

interior

passive vs active transport

• passive = down a concentration gradient – no energy is required

• active = against a concentration gradient – energy (ATP hydrolysis is required)

what types of proteins mediate passive diffusion, and what direction can it occur

• all channels and many transporters

• can go in either diection (in or out) ass long as it follows the molecules concentration gradient

what are active transporters called

pumps

what constitutes direction of neutral molecule diffusion? what about charged molecules?

• neutral - only concentration gradient

• charged - membrane potential and concentration gradient

electrochemical gradient

membrane potential and concentration gradient

is the gucose transporter active or passive

passive

what determines direction of glucose transport

concentration gradient (glucose is uncharged)

uniporter and an example

transports a single molecule ar a time down its [] gradient, glucose transporter

different conformations of transporters

• Open conformation accepts substrate

• Occluded conformation – binding sites are not accessible from either side

• Open conformation releases substrate

describe this plot

more glucose in the cell results in less glucose entering (v0 decreases)

kt equals to

½ vmax

what does a higher kt iindicate

transporter only starts to uptake its substrates when extracellular concentrations are high (low affinity)

what two GLUT’s are found in all mammalina tissues and what is their Kt

GLUT 1 and 3; 1mM

where is GLUT 2 found

liver and pancreatic beta cells

GLUT2 Kt

15-20 mM

GLUT4 Kt

5 mM

where is GLUT5 found

small intestine

what prevents glucose from leaving the cell

gets phosphorylated the second it enters the cell, no longer recognized by the transporter and cannot diffue back

what is the normal concentration of glucose in the blood stream

4-5 mM

what stimulates GLUT4 and what does that cause

insulin, increases the rate of glucose uptake into muscle and adipose tissue when glucose concentrations are high

t or f - GLUT1 is found in the same amount in all cells

false, present only in small amounts in nuscle and adipose tissue

how does insulin stimulate and adipose cells to take up cells

1. GLUT4 stored within cell in membrane vesicles (not usually on cell surface)

2. insulin binds the insulin receptor on the surface of the myocyte/adipocyte

3. when insulin binds with its receptor, vesicles move to the surface and fuse with the plasma membrane, increasing the number of glucose transporters in the plasma membrane

4. when insulin levels drop, glucose transporters are removed from the plasma membrane by endocytosis, forming small vesicles

5. smaller vesicles fuse with larger endosome

6. patches of the endosome enriched with glucose transporters bud off to become small vesicles, ready to return to the surface when insulin levels rise again

what would the consequences be if insulin were absent in an individual?

• glucose can bind non enzymatically to proteins

• messes protein function up

• causes various problems through out the body

idirect/secondary transport

where direct active ttransport set up one of the gradients

coupled transport

another way to describe indirect active transport - links the uphill transport (against its gradient) of one solute across a membrane to the downhill (with its gradient) of another

what types of proteins participate in coupled transport

antiporters and symporters

direct active transport

requires “pumps” that selectively bind and move the solute across a membrane driven by changes in the proteins conformation

what must the movement against a []gradient be linked to in direct active transport

an exergonic reaction liike ATP hydrolysis

what type of ATP driven pump do we focus on this class and why is it ccalled that

p-class pumps, directly phophorylated

4 types of ATP driven driven pumps

• p-class pumps

• v-class proton pumps

• f-class proton pumps

• ABC superfamily

example of a p-class pump in out body, v important, think of the brain

Na+/K+ ATPase

what does the Na+/K+ ATPase do

maintains the membrane potential

how does the Na+/K+ ATPase work (steps)

1. 3 Na+ bind

2. pump phosphorylates itself, hydrolyzing ATP

3. phosphorylation triggers a conformational change and 3 Na+ is ejected

4. 2 K+ binds

5. pump dephosphorylates itself

6. oumo returns to original conformation and 2 K+ are ejected

what do Ca 2+ pumps do

keep intracellular Ca2+ concentrations low, p class pumps, unidirectional

sarcoplasmic reticulum

specialized type of ER that forms a network of tubular sacs in the cytosol of muscle cells and serves as an intracellular store of calcium (involved in muscle contraction)

what direction does the Ca2+ pump pump

unidirectional - from cytosol to lumen of SR

what else is intracellular calcium important for

signal transduction

antiporter vs symporter

• both transport 2 (/2 types of) molecules, one against its gradient and the other with its gradient

• both rely on direct active transport to establish a gradient that can be used

• symporter

  • transports both molecules in the same direction

• antiporter

  • transports the two molecules in opposite directions

are intestinal lumen concentrations of glucose higher or lower than the blood stream

in blood the glucose levels are lower because the blood contains a lot more water, thus waters the glucose down

could glucose get into intestinal cells via a glucose uniporter

no, the glucose concentration is higher in the intestinal cells due to the action of the symporter on the apical membrane, so glucose would diffuse down its gradient (from the intestinal cell to te bloodstream or gut lumen)

is extracellular concentration of Na+ or lower than intracellular and why?

it is higher due to the action of the Na+/K+ ATPases that are present on the apical and basal membranes

how does glucose get transported from the gut lumen to the bloodstream

1. Na+/K+ ATPases on the apical membrane establish a Na+ gradient

2. symporter transports a glucose and Na+ into the intestinal cell (energy derived from the Na+ gradient)

3. glucose diffuses passively into the blood stream through a uniporter in the basal membrane

4. excess Na+ ions are removed via Na+/K+ ATPases to maintain the gradient

role of tight junctions in the process of glucose uptake from the intestine?

stopping the glucose from directly diffusing into the bloodstream which allows for tighter control on blood glucose levels

ion chennels selectivity and directionality, what do they allow

• selective

• bidirectional

• allow diffusion in the direction of the electrochemical gradient

different types of stimuli that influence the opening and closing of ion channels

• mechanically gated

• ligand gated

• voltage gated

mechanically gated ion channel definition and example

• conformational state depends on mechanical forces (like stretch tension) that are apllied to the membrane

• ex. auditory hair cells in the ear

ligand gated ion channel definition and example

• conformational state depends on the binding of specific molecules (ligand) and can be open or closed upon ligand binding

• ex. acetylcholine receptor

voltage gated ion channel definition and example

• conformational state deoends on the difference in ionic charge on the two sides of the membrane

• ex. sodium and potassium channels that depolarize and repolarize membranes

what happens when K+ enters its ion chennel

loses it water if hydration (bound water) in the selectivity filter section of the channel and become coordinated to channel carbonyl oxygens

Na+ vs K+ in ion channels and how that effects selectivity

Na+ is smaller than K+ and thus cannot coordinate as well as K+ can with the oxygen atoms in the channel, this means K+ passes through the channel more

how does water move across membranes (2)

• simple diffusion - takes a long time

• aquaporins (faster)

aquaporins

specialized channels for water transport

describ ethe structure of aquaporins

one face includes a series of hydrophobic amino acids that transiently form hydrogen bonds with individuals water molecules as they move single file through the channe;, so narrow that ions that are hydrated cannot pass through, only singluar water molecules

direction of water diffusion through aquaporins

from outside (high [water]/low [solute]) to inside (low [water]/ high [solute])

RBC examples of transport

• simple diffusion - oxygen and carbon dioxide

• passive diffusion - glucose uniporter

• indirect actove transport - anion exchange antiporter

• promary active transport - Na+/K+ ATPase

• aquaporins - water channels