MR S2 Flashcards
Order these molecule types in order of most to least permeable to phospholipid membranes: Ions Hydrophobic molecules Small uncharged polar molecules Large uncharged polar molecules
Hydrophobic molecules
Small uncharged polar molecules
Large uncharged polar molecules
Ions
What is passive transport reliant on?
Membrane permeability
Concentration gradient
Describe active transport
Allows transport of ions against an unfavourable concentration gradient and/or electrical gradient
Energy directly or indirectly from ATP
Some cells spend 30-50% of their energy on active transport
What is the approximate free ion concentration of sodium intra and extracellularly?
Intra: ~12mM
Extra: ~145mM
How does increased concentration gradient affect rate of passive transport?
Rate of passive transport increases linearly with increasing concentration gradient
What is the approximate free ion concentration of calcium intra and extracellularly?
Intra: ~10^-7M
Extra: ~1.5mM
What is the approximate free ion concentration of chlorine intra and extracellularly?
Intra: ~4.2mM
Extra: ~123mM
What is the approximate free ion concentration of potassium intra and extracellularly?
Intra: ~4mM
Extra: ~155mM
What are the two types of transporter involved in co transport?
Symport
Antiport
What is a uniport?
A transport protein which moves one molecule per cycle
What is a co transporter?
A transport protein which simultaneously transports two molecules per cycle
What is PMCA?
A primary active transporter
Full name: plasma membrane calcium ATPase
Moves calcium ions across a membrane using ATP
Why do co transporters use secondary active transport?
They use the concentration gradients of one molecule to transport an extra molecule
Aka they don’t directly use ATP
BUT still active transport because the concentration gradients that allow co transport are set up by membrane proteins which require ATP.
What is the Na+K+ATPase (aka Na+ pump)?
Moves 2 K+ ions into the cell and 3 Na+ ions out of the cell (usually against their concentration gradients) simultaneously
Requires ATP
A P-type ATPase
~25% of BMR used for this protein
What is ATP synthetase?
Active transport in reverse mode
Uses high proton concentration gradient to produce ATP
Seen in electron transport chain/oxidative phosphorylation
What type of active transport occurs in co transporters?
Secondary
Why is the Na+ K+ pump important?
Sets up Na and K gradients
Responsible for ~-5mV of the membrane potential
Necessary for electrical excitability
Drives many secondary active transport regulatory processes eg:
-ion homeostasis
-pH
-Cell volume
-Ca concentration
-resting potential
-nutrient uptake eg glucose uptake in small intestine
Name two calcium transporters
Ca2+ Mg2+ ATPase
Na+ Ca2+ Exchanger (NCX)
What is the difference between a symport and an antiport?
Symports transport two molecules in the same direction across a membrane
Antiports transport two molecules across a membrane in different directions
Describe the Na+ Ca2+ Exchanger (NCX)
Antiport
Moves one Ca out and three Na in per cycle
Low affinity, high capacity
Transport of Na ions down concentration gradient provides energy for transport of Ca against concentration gradient.
Describe the Ca2+ Mg2+ ATPase transporter
Moves one Ca or Mg out of the cell
Active transporter
Requires ATP
High affinity, low capacity
Describe the Na H exchanger (NHE)
Antiport Exchanges one extracellular Na for one intra cellular H Electroneutral (1:1 ion exchange) Regulates pH Regulates cell volume Inhibited by amiloride Activated by growth factors
Describe the Na glucose co transporter
Symport
Entry of Na provides enough energy for entrance of glucose into cell agains concentration gradient
Important in small intestine and kidney
What can increase the passive transport of water?
Increased osmotic gradient
Water channels aka aquaporins
Where can aquaporins be found?
The proximal kidney tubules
Why are hydrophilic molecules less likely to cross a membrane?
Has to travel through hydrophobic area
So would require high free energy (ΔG) change
So thermodynamically unlikely
What are some important roles of transport systems?
Maintenance of intracellular pH
Maintenance of ionic composition
Regulation of cell volume
Concentration of metabolic fuels and building blocks
Extrusion of waste products of metabolism and toxic substances
Generation of ionic gradients necessary for electrical excitability of nerve and muscle tissue
What are the models for facilitated transport?
Protein pores (aka channels) Carrier molecules (ping-pong) Flip flop (thermodynamically unlikely)
Why is control of calcium so important?
There’s a ~20 000 fold difference between intra and extra cellular calcium so VERY tightly controlled
High intracellular calcium is highly toxic to cells
Cells signal by SMALL changes of intracellular calcium
What is SERCA?
Sarco(Endo)plasmic Reticulum Ca2+ ATPase
Transports calcium into and protons out of the endoplasmic/sacro plasmic reticulum
Uses ATP
High affinity, low capacity
What is the mitochondrial Ca uniport and when is it used?
Uses facilitated diffusion
Operates at high intracellular Ca concentrations to buffer potential damaging calcium
What are the types of gated pores?
Ligand gated channels - open or close in response to binding of ligand to receptor site
Voltage gated channels - open or close in response to change in normal membrane potential
Gap junctions - these close when intracellular calcium rises above 10μM or when cell becomes acid
Does NCX always pump ions in the same direction? What effect does this have?
No, in depolarisation NCX’s normal function is reversed
This contributes to the Ca influx during the cardiac action potential
Can also contribute to Ca toxicity ischaemian
Name some membrane proteins involved in control of pH
NHE aka Na H exchanger
NBC aka sodium bicarbonate cotransporter aka Na dependent Cl/HCO3 exchanger
AE aka Anion transporter aka Cl/HCO3 exchanger
Name the bicarbonate transporters and their actions
AE acidified the cell
NBC alkalinises the cell
Both are involved with cell volume regulation
What is facilitated diffusion?
The membrane permeability of a substance can be increased by the incorporation of certain membrane proteins into the membrane
Relies on concentration/electrical gradient for substrate movement
Outline bicarbonate reabsorption in the proximal tubule
Na/K pump sets up Na gradient
NHE pumps H out of cell
H “picks up” bicarbonate and brings it back into the cell
Describe the theory of renal hypertensive therapy
The goal is to reduce mineral ion reabsorption from urine
Therefore less water returns via osmosis
Therefore blood volume and so blood pressure falls
Describe aquaporin
Allows water to readily cross the membrane
It’s inclusion in membranes is stimulated by ADH
Describe loop diuretics
Block Na reuptake in thick descending limb of kidney
Describe amiloride
Prevents the reuptake of Na
Acts in the distal convoluted tubule on ENaC
Acts on the proximal tubule on NaH
What action does aldosterone have?
Up regulates transporters in the kidney to increase ion and water reabsorption in the kidney
Describe spironolactone
Gluticocorticoid antagonist
Used to treat high aldosterone levels
Describe the role of membrane transporters in cystic fibrosis
Na/K pump sets up gradient CFTR protein non-functional Cl builds up in cell Water moves into cell Mucus is thick and sticky
What is the role of transport proteins in diarrhoea?
CFTR protein overly active after phosphorylated by ATP
Cl transported into lumen of gut
Water follows
~diarrhoea~
