Pumps and Transport
Describe the 5 steps of Insulin action and upregulation of GLUT transporters in the membrane
1) Glucose transporters 'stored' within cell in membrane vesicles 2) When insulin interacts with its receptor, vesicles move to surface & fuse with the plasma membrane, increasing the number of glucose transporters in the plasma membrane 3) When insulin level drops, glucose transporters are removed from the plasma membrane by endocytosis, forming small vesicles 4) The smaller vesicles fuse with larger endosome 5) Patches of the endosome enriched for glucose transporters bud off to become small vesicles, ready to return to the surface when insulin levels rise again
In the regulation of Na/K-ATPase pump activity, what 5 factors increase the activity of the pump?
1) High extracellular [K+] 2) High intracellular [Na+] 3) Insulin 4) Aldosterone 5) Thyroid hormone
In the regulation of Na/K-ATPase pump activity, what 4 factors decrease the activity of the pump?
1) Low extracellular [K+] 2) Low intracellular [Na+] 3) Dopamine 4) Ouabain (cardiac glycosides)
Name 4 Physiologically important secondary-active transporters
1) Na/Glucose transporters (take up glucose into cells) 2) Na/Ca exchangers (extrude calcium ions from cells) 3) Neurotransmitter transporters (remove neurotransmitter from the synapse) 4) Phosphate transporters (remove phosphate from renal tubules)
What are the 3 types of mechanisms of solute movement across cell membranes?
1) Simple diffusion 2) Facilitated diffusion 3) Active transport Primary-active transport Secondary-active transport
Describe the mechanism of action in simple diffusion
1) Small hydrophobic molecules or hydrophilic molecules, such as ethanol, cross the plasma membrane by traversing the phospholipid bilayer directly, without the aid of a permease protein. 2) The concentration of a solute, C, is different in the two chambers that are separated by a membrane.
What are the 2 different classes of ATP-powered pumps?
1) The P-type ATPase class 2) The F-type ATPase class
What are the Physiological functions of the Na/K-ATPase?
1) maintain sodium and potassium concentration gradients across cell membranes 2) this gradient can be used for generating the action potential and for secondary-active transport 3) prevent cells from swelling and bursting
Describe the mechanism of action for Ca+ ATPase
1) the binding of Ca+ ions occurs 2) the binding of ATP 3) during the hydrolysis of ATP, you see the translocation of Ca+ ions 4) last part is the release of the Pi
Explain the difference between simple and facilitated diffusion
1/2 Vmax is where transport rate is maxed out which allows for hormonal control you increase hormonal expression of transporter which consequently increases Vmax values
Describe an antiporter membrane protein
An Antiporter is a counter-transporter. A 2nd molecule is transported along its concentration gradient (a favorable process) and this action helps the 1st molecule go against its concentration gradient (an unfavorable process)
What does the Calcium ATPase do?
Calcium ATPase is responsible for extruding calcium ions from the cytosol. In the muscle cell, it removes Ca+ back into the scaroplasmic reticulum after muscle contraction. The hydrolysis of the ATP on the inner domain will help transport the Ca+ ions
What are the basic you need to know about simple diffusion?
Diffusion involves movement of particles from dense compartment into a less concentrated environments which eventually reachs equilibrium. It ascribes to Fick's law J=p(deltaC)
Describe the affect of Facilitated diffusion for glucose transport across membranes
Glucose movement across membranes can occur through facilitated diffusion. This diffusion is catalyzed by specific membrane proteins and is a Vmax-limited process. -the max value means that there is a finite number of channels on a given membrane
How does glucose transport happen through epithelial cells?
Glucose transport occurs through both active transport and facilitated diffusion. The sodium gradient is maintained by the Na/K pump and if you reduce Na+ concentration outside the enterocyte then you reduce the ability to pump glucose from the intestinal lumen to the bloodstream
What does Insulin do to body cells?
Insulin increases expressions of GLUT transporters. Insulin stimulates facilitated diffusion of glucose by increasing the number of GLUT transporters in the plasma membrane.
What is ouabain?
It is a ligand that competes with K+ ions for the alpha subunit of the Na/K ATPase pump. It binds and inhibits this pump.
Describe the structure of the Na/K-ATPase pump
Na+/K+ ATPase is assembled from two subunits, termed a and b. --The a subunit is responsible for ATP hydrolysis and cation transport, has most binding sites. -The intracellular portion of the a subunit has a sodium binding site, a phosphorylation site, and an ATP-binding site. -The extracellular portion has a potassium-binding site and a ouabain-binding site.
Describe the basic conformational changes of Na/K-ATPase
Na/ATPase can adopt 2 distinct conformational state, termed E1 and E2, which differentially bind Na+ and K+ -ATP closes binding site and when ATP is cleaved of a Pi that action opens the channel to the outside
How does the Permeability coefficients of artificial membranes differ from real cells?
Real cells have transporters for glucose and other ions so the permeability is different and much higher than artificial membranes
Where are SGLT 1 & 2 transporters for glucose absorption found respectively in the body?
SGLT 1: small intestines and renal tubules SGLT 2: renal tubules
What is the Sodium-glucose transporter (SGLT)?
SGLT actively transports glucose into cells against its concentration gradient. 1 Glucose molecule transport is energetically driven by symport of 2 Na+ ions. The Na+ transport is the favorable process and the glucose is the unfavorable one.
What are the roles of secondary active transporters?
Secondary active transporters utilize the free energy stored in the concentration gradient of Na+ (or sometimes other ions) across the membrane to drive uphill transport of an ion or solute
What does simple diffusion require?
Simple diffusion does not require membrane proteins For simple diffusion, the rate of transport is directly proportional to the concentration gradient across the membrane.
What are 2 examples of the F-type ATPase class pumps?
The F-type ATPase class 1) Mitochondrial ATP synthase 2) Vesicular and vacuolar proton ATPase
What's the difference between the P-class and F-class ATPase pumps?
The F-type is the reserve of the P-type pump in that the proton gradient is used to synthesize ATP molecules where the P-type cleaves ATP to pump
What is the Na/K-ATPase?
The Na/K-ATPase is a primary-active ion pump that couples active Na+ and K+ transport to the hydrolysis of ATP and generates non-equilibrium distribution of Na+ and K+ in the intracellular and extracellular compartments. The pump generates a current; it is electrogenic and reverses a natural process through active transport which pushes 3Na+ out and 2K+ in.
What are 3 examples of the P-type ATPase class pumps?
The P-type ATPase class - focus on this type of class 1) Na/K ATPase 2) Ca-ATPase 3) H/K ATPase
Why does the Na/K-ATPase help with preventing a lot of swelling?
When Na+ ions come into the cell, water comes along so it is important to keep the pump working in order to get those Na+ ions out of the cytoplasmic spaces
Describe Active transport
requires coupling of transmembrane solute movement to an energy source. This coupling allows the cell to concentrate solutes on the interior or exterior. This movement of a particle from a low to high density concentration is unfavorable and thus requires some energy input.
What does the SGLT pump bring into the cell besides a lot of glucose?
water
How does the Na/K-ATPase pump change?
-When open to the outside of the cell, there is a high affinity for K+ ions and low affinity for Na+ ions. This is the point at which ouabain poison would bind to the alpha subunit -When open to the inside of the cell, there is a low affinity for K+ and high affinity for Na+ ions when exposed openings are in the cytoplasmic domains
Describe the Facilitated diffusion of solutes
-requires a carrier or a membrane protein to provide a pathway of solute movement across the membrane -What the cavity or channel provides is a nice environment for the transfer to occur and consequently the energetics of the process is reduced -think of the channel as a protein that catalyzes the transport process
What are the key learning objectives to know for membrane pumps and transport?
1) Describe the movement and transport of substance across biological membranes by passive processes. 2) Describe the movement and transport of substance across biological membranes by active processes. 3) Describe the physiological importance of two example of active and two examples of passive transport.
Sodium and glucose are transported through epithelial cell layers by a combination of pumps, channels, and transporters. Name a few along with their function.
1) ENaC: pumps Na+ ions into the enterocyte from the lumenal apical mucosal 2) SGLT: symporter that uses secondary active transport of Na+ and glucose into the enterocyte from the lumenal apical mucosal 3) Na/K pump: pumps Na+ out of enterocyte into the basal serosal and pumps K+ into the cell via ATP hydrolysis (primary active transport) 4) GLUT: pumps glucose out of enterocyte into the basal serosal via facilitated transport
