Term
| What types of molecules can't diffuse through the plasma membrane? |
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Definition
| charged particles (small ions), glucose, amino acids |
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Term
| How do these molecules get across plasma membranes if they can't diffuse? |
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Definition
| There are integral proteins which help them do that. |
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Term
| How do carrier proteins act like enzymes? |
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Definition
| They act to increase the rate of thermodynamically favored movements. |
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Term
| How do carrier proteins work? |
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Definition
| They bind a solute, undergo conformational change which brings the solute into the cell, and then go back to initial confirmation. |
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Term
| Are carrier proteins saturatable? |
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Definition
| Yes they have Km, Vmax, and are saturatable. |
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Term
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Definition
| These are pores through which molecules can pass. |
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Term
| What's faster in terms of moving things across the membrane, channels or carrier proteins? |
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Definition
| Channels allow free diffusion, so they are faster. |
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Term
| What determines whether things will move across a channel? |
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Definition
| Molecules move DOWN their electrochemical gradient. |
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Term
| What are the two main types of carrier proteins? |
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Definition
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Term
| How can pumps move molecules AGAINST their concentration gradients? |
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Definition
| This is only possible if they are ATP driven--pumps hydrolyze ATP for energy. (example epithelial cells of the gut absorb ALL the nutrients from food, so end up moving against gradient). |
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Term
| What does active transport mean? |
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Definition
| This basically means that ATP is used to move something across a membrane. |
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Term
| What is primary active transport? |
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Definition
| The transporter has a place where the molecule of interest binds and is taken directly across the membrane using ATP energy. |
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Term
| What is secondary active transport? |
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Definition
| These are transporters which use the energy of established ion gradients (example, Na/K) to bring molecules across membranes. |
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Term
| What is special about P-class Pumps? What is the main example of a P-Class Pump? |
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Definition
| They become phosphorylated in the course of their transport mechanism. The most important P-Class Pump is the Na+/K+ ATPase. |
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Term
| How does the Na+/K+ ATPase work? |
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Definition
| It brings in two K+ from outside the cell in exchange for three Na+ from inside the cell. SO IT IS PUMPING K+ INTO THE CELL, and NA+ OUT OF THE CELL. Basically, there are cytoplasmic Na+ binding sites, and extracellular K+ binding sites which bind these ions at different affinities. |
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Term
| How much of the cell's ATP is used by Na+/K+ ATPase? |
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Definition
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Term
| Tell me a more detailed story of the Na+/K+ transporter. |
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Definition
| 1) In initial confirmation, there are 3 high affinity cytoplasmic sites for Na+, and 2 low affinity sites for K+ extracellularly. 2)ATP binds the pump and is hydrolyzed by the pump's ATPase activity. An aspartate residue on the cytoplasmic side of the pump gets phosphorylated. 3) The high-energy phospho-D bond becomes low-energy, providing energy to move the Na+ to the outside, simultaneously making them low-affinity for Na+, so the Na+ goes away. When this happens, the K+ sites get high affinity. 4) When the K+ binds, the P-D bond is broken, and the K+ moves to the cytoplasm. The pump is then back in its initial state. |
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Term
| What is the "power stroke"? |
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Definition
| This is when the phospho-aspartate bond becomes lower energy, making the Na+ binding sites swing to the outside of the cell. |
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Term
| What are the E1 and E2 states of the Na+/K+ ATPase? |
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Definition
| E1 is initial pump conformation, with 3 high-affinity Na+ binding sites in the cytoplasmic face and 2 low-affinity K+ binding sites on the extracellular face. |
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Term
| Tell me about the relative concentrations of sodium and potassium in and outside the cell. |
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Definition
| Because of the Na+/K+ ATPase, potassium is higher in the cell and sodium is higher outside the cell. (its oK in the cell.) |
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Term
| Why is this Na+/K+ concentration gradient useful? |
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Definition
| It can be exploited for other cellular processes--such as secondary active transport |
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Term
| How is the Na+/K+ ATPase electrogenic? Is the cytoplasm negative or positive? |
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Definition
| It is electrogenic because it is pumping out 3 Na+ for every 2 K+ that it brings in. So, you get the inside of the cell being negative. |
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Term
| What's another important P-Class Pump? |
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Definition
| SERCA. (sarcoplasmic/endoplasmic reticulum Ca2+ ATPase) |
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Term
| Where is SERCA found? What percentage of the membrane proteins of that organelle is it? |
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Definition
| It is about 80% of sarcoplasmic reticulum transmembrane proteins |
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Term
| How many transmembrane helices does SERCA have? Where does Ca2+ bind in the E1 state? |
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Definition
| It has 10 transmembrane helices. Ca2+ binds initially in the cytoplasm. |
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Term
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Definition
When ATP is hydrolyzed and a high-energy phosphate
bond formed with an aspartate on the cytoplasmic side, a conformational change to E2 closes off the
pocket from the cytoplasm, with Ca2+ trapped within. A subsequent series of transitional states,
analogous to those described for the Na+/K+ ATPase, transfers the Ca2+ to a low-affinity site
that is exposed to the lumen of the sarcoplasmic reticulum. After Ca2+ diffuses from this site, the
SERCA pump returns to its basal conformation. This activity keeps the cytoplasmic concentration of
Ca2+ below 1 μM in most cells. SO IT BRINGS CA2+ FROM CYTOPLASM INTO THE SARCOPLASMIC RETICULUM |
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Term
| What are V Class Pumps? F Class Pumps? |
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Definition
| These pumps are pretty similar. Basically just pump Protons into stuff. V PUMPS ACIDIFY LYSOSOMES. and F PUMPS RUN BACKWARDS in MITOCHONDRIA. Use energy from the H+ going down their concentration gradient to synthesize ATP. |
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Term
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Definition
| They have an ATP Binding Cassette. They bind and transport a diverse group of molecules--even uncharged and hydrophobic. |
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Term
| What kind of pump are Multi-Drug Resistance (MDR) Proteins? What do they do? What kind of resistance do they confer? |
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Definition
These are ABC pumps. They are highly expressed in the epithelial cells of the intestine and kidney. They transport small, polar molecules, including some products of normal metabolism, but they can also pump a wide variety of drugs out of cells. Thus, tumors that overexpress MDR
proteins are resistant to treatment by multiple and unrelated anticancer drugs. |
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Term
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Definition
This is the cystic fibrosis transmembrane regulator. It is an ABC-Class Pump. It is expressed in lung and other organs (pancreas).
Although structurally an ABC-class pump, it has no known “pumping” function. However, it incorporates a channel that is permeable to Cl-, and that is regulated by protein kinase A. Cystic fibrosis has been linked to loss-of-function mutations in CTFR, which reduce Cl- transport across
pulmonary epithelial cells. As a result, the mucus secreted by these cells becomes abnormally thick,
compromising gas exchange and predisposing the lung to infection.
BASICALLY, you don't get enough Cl- in the lung secretions, so there is no osmotic pressure to get water in there. |
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Term
| What are transporters? How are they different from pumps? |
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Definition
| Transporters do the same thing pumps do pretty much, except they don't have ATPase activity. They get energy from existing gradients. |
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Term
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Definition
| Uniporters conduct a single species of molecule down its gradient, facilitating a process that is already thermodynamically favorable by circumventing the hydrophobic membrane barrier (facilitated diffusion). |
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Term
| what do co-transporters do? |
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Definition
Co-transporters couple the thermodynamically favorable movement of one type of molecule (down its gradient) to the unfavorable movement of
another (secondary active transport). Usually, it is the potential energy of the Na+ gradient that is tapped, with the entry of Na+ used to move some other solute against its gradient. |
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Term
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Definition
| They are secondary active transporters/co-tranporters. They use the energy of one ion moving down its gradient to bring something else with it. |
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Term
| What are antiporters? Whats another name for antiporters? |
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Definition
| They are co-transporters that do secondary active transport. Use the energy of something going down its gradient to move another particule/molecule in the OPPOSITE direction. Another name is exchanger. |
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Term
| What kind of transporter are the GLUT proteins? |
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Definition
| These are uniporters for glucose. |
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Term
| How do GLUT transporters work? What provides the energy for this? |
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Definition
bind a single molecule of glucose at a time. A conformational change exposes the glucose-binding site alternately to the extracellular and intracellular sides, and the rate of cycling is accelerated by occupation of the binding site in either conformation (Fig. 3).
The energy for this comes from the fact that glucose levels are usually much lower inside the cell. So this is a thermodynamically favorable thing. |
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Term
| Considering the relative concentrations of glucose, which binding site of the GLUT transporter is likely to become occupied? How does the cell keep this thermodynamically favorable to get more and more glucose transported? |
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Definition
| The cell phosphorylates glucose, so intracellular [Glucose] stays low. The other binding sites of GLUT get occupied, because that's where the glucose is. |
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Term
| What's an example of transcellular transport involving GLUT, and how does it work? |
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Definition
| The intestinal epithelial cells eventually get filled with glucose during feeding, and will run GLUT transporters in reverse to transport glucose into the interstitium. SO, glucose comes in from the lumen of the bowel, and gets transported out the other side of the intestinal epithelial cells. |
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Term
| What is the Na+/Ca2+ exchanger? What does it do, where is it found etc? |
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Definition
| This is an antiporter. It brings Na+ into the cell and pumps Ca2+ out. Its job is to pump calcium out of cardiac cells. It is electrogenic because it pumps in 3Na+ per 1Ca2+ out.--accumulates positive charges in the cell. |
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Term
| How is treatment of congestive heart failure related to the Na+/Ca2+ antiporter? |
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Definition
Intracellular Ca2+ is required for the contraction of heart muscle, and one
strategy for increasing cardiac output is to raise the intracellular Ca2+ concentration. Since the
operation of the Na+/Ca2+ exchanger depends on the Na+ gradient, Ca2+ removal slows if the intracellular concentration of Na+ is allowed to rise. This is the mechanism of action for drugs like DIGITALIS, which directly inhibit the Na+/K+ ATPase and therefore interfere with the secondary active transport of Ca2+ out of the cell (Fig. 4). The consequent accumulation of intracellular [Ca2+] enhances muscle contractility. |
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Term
| What are SGLT's? What do they do, where are they found? |
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Definition
| These are Na+/glucose symporters found in the loop of Henle. These guys couple Na+ influx to Glucose uptake. They prevent glucose from being excreted in the urine, because it gets filtered from the blood by the glomerus, but then gets reabsorbed by the tubule by the SGLTs. |
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Term
| What are the two different types of SGLTs? How are they different? |
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Definition
| Type 2 is in the early part of the tubule, near the glomerulus. It absorbs one Glucose at a cost of one Na+. This works well, because there is alot of glucose in the urine at the proximal tubule. Later, there are SGLT 1's expressed, which use 2 Na+s to get one glucose in. This uses more energy, but it requires more energy, because this is really going against the concentration gradient, because there is not much glucose left in the distal tubule. REMEMBER 2 is early, 1 is late. Kinda backwards, but whatevs. |
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Term
| Where are SGLTs found in renal epithelial cells? How does Glucose then get out of these cells and back to central circulation? |
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Definition
| Basically, the SGLTs are on the apical surface. There are GLUTs on the bottom that then transport glucose out. |
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