Exam 1 - Membrane Structure and Transport Processes
What are the main type of phospholipids
glycerophospholipids have glycerol backbone The phosphate connects the glycerol to the head group and the fatty acids are connected via an ester linkage be able to identify a molecule of one?
What are the four types of gap junction structure
heteromeric: connexions are made of a combination of connexins homomeric: connexions are all the same kind of connexin homotypic: the intercellular channels has all the same kind of connexin heterotypic: the intercellular channels has a combination of connexins idk if this is right also idk if I need to know this
The GLUT proteins alternate between what two conformational states:
in one, a glucose-binding site faces the outside of the membrane in the other, a glucose-binding site faces the inside. Note, uniporters are equally able to catalyze net movement in the reverse direction.
Explain protein-lipid interactions in the asymmetry of the bilayer
in vitro studies show that acidic phospholipids, particularly in PS associate with cytoskeletal proteins
What two categories are membrane proteins put in?
integral and peripheral
What is the relative diffusion rate of a substance proportional to?
its concentration gradient across the layer and its hydrophobicity
What is the hydrophobicity of a substance measured by
its partition coefficient, K, which is the relative affinity of a substance for lipid vs. water. (equilibrium constant for its partition between oil and water). K=Cm/Caq where K = partition coefficient Cm=concentration just inside the hydrophobic core (membrane) Caq=concentration in aqueous environment
What aids the movement of materials across the plasma membrane?
membrane proteins
Summarize channel proteins
move ions or water down the electrical gradient at a rapid rate the more subunits the channel proteins has, the less selective it has. The subunits make up the selectivity filter. The gate can be stimulated to open by a ligand or a change in charge (voltage)
Characteristics of pure artificial bilayer (aka protein free)
permeable to gases and small uncharged polar molecules slightly permeable to water and urea impermeable to ions and to large uncharged polar molecules
What acts as the transbilayer transport
phospholipid transporters How PC moves from the inside of the membrane to the outside
What does fick's law give you?
rate of diffusion
What state are ions in the cytosol in?
steady state
What is the concentration gradient
the difference between high and low concentration
Explain the restricted spontaneous transbilayer lipid movement
the half life of a movement of a lipid between leaflets is hours to days thus they don't move frequently?
What is equilibrium
the point of even distribution where the molecules are moving in both directions at an equal rate
How are plasmologens different from phospholipids
they have a vinyl ether linkage instead of an esther linkage connecting the FA to the glycerol
Where does ACH bind in the muscle cell
to the acetylcholine receptor
ABC Superfamily consists of what four core domains
two transmembrane (T) forming the passageway and two cytoplasmic-facing ATP-binding (A) domains.
What are the three types of transporters
uniporter, symporter, antiporter
Summary of CFTR
used in respiration and digestion The cAMP-mediated signal stimulates movement of Cl- through CFTR with Na+ Without the movement of Cl- out of the cell, you would have sticky mucus in your lungs and digestive system
What establishes the transbilayer lipid distribution
vectoral biosynthesis
Describe how ion channels work in a neuromuscular junction
-nerve terminal membrane depolarization opens voltage-gated Ca2+ channels and this triggers acetylcholine release -acetylcholine binding to the acetylcholine receptor in the muscle cell membrane opens cation channels associated with them -the resulting Na+ influx causes localized membrane depolarization, which then opens voltage-gated Na+ channels -this activates PM voltage-gated Ca2+ channels and SR Ca2+ release channels that release Ca2+ that triggers muscle contraction
What are the four structures of integral membrane proteins
1)single α helix 2)multiple α helices 3)rolled-up β sheet (β barrel) 4)anchored to the cytoplasmic surface of the membrane by an amphipathic α helix NOT ON EXAM
Na/K ATPase cycle steps
1. 3 Na ions bind to the E1 conformation 2. ATP binds to E1 conformation causing the phosphorylation of aspartate 3. There is an conformational change from E1 to E2 causing the outward transport of Na 4. Na dissociates from the E2 conformation and K bind 5. Hydrolysis of aspartyl phosphate occurs (phosphate detached) 6. There is a conformational change from E2 to E1 causing the inward transport of K 7. The K ions dissociate
In what three physiological processes is secondary active transport processes important
1. cardiac muscle contraction - Uses the Na+/Cl- antiporter 2. gas exchange, stomach acidification, bone resorption - AE1 Anion Exchangeer for gas exchange - AE1 with P Class H+/K+ ATPase for stomach acidification - AE1 with V class H+ ATPase for bone resorption 3. nutrient absorption - SGLT1
P Class Pumps Ca2+ ATPase steps of activation
1. when protein is in one conformation (E1) two Ca2+ ions bind in sequence to high-affinity sites on the cytoplasmic surface. 2. ATP binds and is hydrolyzed and the liberated Pi is transferred to a specific asparate residue in the protein, forming a high-energy acyl phosphate bond (E1~P). 3. Protein then changes conformation from E1~P to E2-P which creates two low- affinity Ca2+ binding sites on the exoplasmic surface (which faces the SR luman); this change simultaneously propels two Ca2+ ions through the protein to these sites and inactivates the high-affinity binding sites on the cytoplasmic face. 4. The Ca2+ ions then dissociate. 5. The aspartyl-phosphate bond in E2-P is hydrolysed, causing E2 to revert to E1.
What are three key properties of ion movement channel proteins
1.Can be highly selective for particular ions (e.g., only K+), or only cations but not anions, or they may be relatively non-selective 2.Can exist in open or closed states, transitions between these states are regulated either by ligands (ligand-gated channels; e.g. acetylcholine receptor) or by the membrane potential (voltage-gated channels; e.g., voltage-gated Ca2+channel) 3.Open channels often spontaneously close after being open for a short time
The permeability of a membrane is a function of what four factors
1.Size of the molecules 2.Solubility in lipids 3.Charge on ions 4.Presence of carrier molecules
MDR1
A type of pump in the ABC class superfamily Discovered in tumors Tumor cells often became simultaneously resistant to several chemotherapeutic drugs with unrelated chemical structures Studies showed that this resistance was due to enhanced expression of a multidrug-resistance (MDR) transport protein known as MDR1, also called P-glycoprotein. In this member of the ABC superfamily, all four domains are fused into a single 170,000-MW protein. The Mdr1 gene is frequently amplified in multidrug-resistant cells, resulting in a large overproduction of MDR1 protein. Most drugs transported by MDR1 are small hydrophobic molecules. The ATP-powered export of such drugs from the cytosol by MDR1 means much higher extracellular drug concentration is required to kill cells.
Explain how gas exchange work in systemic capillaries
AE1 (Anion Exchanger 1) is the predominant integral protein of the mammalian erythrocyte. Waste CO2 released from cells into the capillary blood diffuses across the erythrocyte membrane. In its gaseous form CO2 dissolves poorly in aqueous solutions, but the enzyme carbonic anhydrase inside the erythrocyte converts CO to the water-soluble bicarbonate (HCO -) anion. The release of O2 from hemoglobin induces a conformational change in the globin polypeptide that enables a histidine side chain to bind the proton produced. The HCO - formed is transported out of the erythrocyte in exchange for an entering Cl- via AE1.
Where does AE1 also function?
AE1 also functions in stomach acidification with theP-class H+/K+ATPase and inbone resorption withthe V-class H+ ATPase
Aquaporin structure and location
AQPisatetramerofidentical28-kDa subunits, each of which contains six transmembrane a helices that form three pairs of homologs. Thechannelthroughwhichwatermovesis thought to be lined by eight a helices, two from each subunit. AQP proteinsare expressed in abundance in erythrocytes and in other cells (e.g., the kidney cells that reabsorb water from the urine) that exhibit high permeability for water.
Explain Ca2+ Entry (Voltage- & Ca+2-Gated Channels) steps in cardiac muscle contraction
Action potential stimulates the release of Ca2+ from the SR via a voltage-gated channel (Steps 1-3). Also, Ca can induce Ca release through Ca - triggered channels (Step 4). Importantly, action potential-induced depolarization on cell surface (sarcolemma) opens Ca2+ channels (Steps 5-6), through which a strong inward current flows. Ca+2 myofiliment activation & contraction (Step 7)
What is CFTR
An ABC superfamily class pump Chloride-channel protein necessary for normal lung and digestive processes.
Aquaporin isoforms and explain AQP2
AnalogoustotheGLUTproteins,there exists several AQP isoforms For example, AQP2 is exclusively expressed in the principal cells of the connecting tubule and collecting duct and is the predominant vasopressin (AVP)- regulated water channel. Dysregulation ofaquaporins, and especially AQP2 are critically involved in many water balance disorders.
What happens to animal cells when placed in a hypotonic solution
Animal cells will swell when placed in a hypotonic solution and immersion of all animal cells in a hypertonic solution causes them to shrink.
Summarize gas exchange
CO2 enters the RBC via simple diffusion from the muscle. Carbonic anhydrase combines CO2 with hydroxide to make bicarbonate. An antiporter exchange the bicarbonate (sends it out of the cell) with a Cl- ion. To keep electric neutrality it moves two negative ions. In the lungs, carbonic anhydrase breaks down bicarbonate to CO2 to be exhaled by reversing this process.
What is cardiac muscle contraction dependent on? Explain
Ca entry and exit from the muscle Ca enters the muscle through many different ways stimulated by the concentration gradient. Calcium leaves the cell through the Na/Ca antiporter. Na has a high concentration outside the cell so the antiporter moves Na into the cell down its concentration gradient. Simultaneously, one calcium is transported out of the cell. Calcium coming into the cell signals contraction of the muscle and calcium leaving the cell signals muscular relaxation.
Calmodulin in Ca2+ ATPase
Ca2+ ATPases contain the Ca2+ binding regulatory protein calmodulin which when bound to Ca2+ allosterically activates the ATPase to export Ca2+ ions from the cell. This transporter makes up more than 80% of the integral protein in SR membranes.
Two parts of secondary active transport in cardiac muscle contraction
Ca2+ Entry (Voltage- & Ca+2-Gated Channels) Ca2+ Exit (Ca2+ Pumps, Na+/Ca+2 Antiporter)
What are three key properties of channel proteins? What two states can channel proteins exist in and what regulates this? When do the channel proteins close?
Can be highly selective for particular ions (e.g., only K+), or only cations but not anions, or they may be relatively non-selective. Can exist in open or closed states, transitions between these states are regulated either by ligands (ligand-gated channels; e.g., acetylcholine receptor) or the membrane potential (voltage-gated channels; e.g., voltage-gated Ca2+ channel). Open channels often spontaneously close after being open for a short time.
What are caveole and what happens if a cell expresses calveolin?
Caveolae are a subset of lipid rafts, that form in cells that express caveolin, a protein that generates the flask-shaped lipid raft invaginations. If a cell expresses the calveolin, the lipid raft invaginate inward like a U
Describe the structure of channel proteins
Channels usually have 4, 5, or 6 subunits/domains. Typically, pore size/selectivity, correlates with the number of subunits or domains; e.g., gap junctions have 6 subunits and a large pore size-little selectivity; whereas acetylcholine receptor has 5 subunits-intermediate selectivity
Describe channel protein structure
Channels usually have 4, 5, or 6 subunits/domains. Typically, pore size/selectivity, correlates with the number of subunits or domains; e.g., gap junctions have 6 subunits and a large pore size-little selectivity; whereas acetylcholine receptor has 5 subunits-intermediate selectivity voltage gated, transmitter gated, and gap junctions
Tight junctions
Connection between cells characterized by a fusing of adjoining cell membranes. They prevent fluid movement between cells
What do F and V class pumps contain? What do they do?
Contain at least three kinds of transmembrane proteins (a, b and c) and five kinds of extrinsic polypeptides (α, β, γ, δ, ε) that form the cytoplasmic domain. They transport only protons.
GLUT 4 Protein and Diabetes
Diabetes⎯There is little doubt that we are in the midst of a worldwide epidemic of diabetes. Diabetes is defined as a state in which carbohydrates are improperly regulated by the hormone insulin. One of the major biological responses following insulin stimulation is a marked increase in the rate of glucose transport in muscle and adipose tissue, resulting from an insulin-dependent translocation of a muscle/adipose tissue-specific GLUT isoform (GLUT4) from an intracellular vesicular storage site(s) to the plasma membrane. The failure to respond to normal circulating concentrations of insulin is a common state associated with diabetes, obesity, aging and a sedentary lifestyle.
What is diffusion?
Diffusion is a process that occurs when the net movement of a substance is from a region of higher concentration to a region of lower concentration. The movement from high to low concentration continues until the molecules are evenly distributed. At this point, they move in both directions at an equal rate; there is no net diffusion.
Describe Secondary Active transport
Discrete class of proteins that import or export ions and small molecules against a concentration gradient. These transporters use the energy stored in the electrochemical gradient of Na+ or H+. These transporters do not directly use metabolic energy (ATP) for transport. However, these systems ultimately depend on the proper supply of metabolic energy for transport and thus, are called secondary active transporters. the substance being actively transported utilizes energy provided by the passive movement of an ion (typically Na+) moving down its concentration gradient into the cell
Summarize nutrient absorption
Epithelials on the gut have Na+/glucose transporters. Two Na+ ions and one glucose bind to the transporter. Glucose uses the transport protein GLUT2 to transport into the blood
Describe cholesterol in the membrane. Its frequency and function.
Eucaryotic plasma membranes contain large amounts of cholesterol - up to one cholesterol molecule for every phospholipid molecule. Cholesterol enhances the permeability-barrier properties of the lipid bilayer via orienting in the bilayer with its hydroxyl group close to the polar head group of the phospholipid. In this position, cholesterol's platelike steroid rings interact with and partially immobilize regions of the hydrocarbon chain, making the membrane less deformable.
What is the function of F class pumps?
F-class pumps (found in bacteria, mitochondria and chloroplasts) function to power the synthesis of ATP from ADP and Pi by movement of protons from the exoplasmic to cytoplasmic face of the membrane (ATP Synthase). uses the movement of H+ through the pump to make ATP
What is facilitated diffusion? Is it passive or active diffusion?
Facilitated diffusion is a passive process that enables amino acids, nucleosides, sugars, and other small molecules to enter and leave cells down their concentration gradients via the assistance of membrane transport proteins.
Structure of Facilitative Diffusion of Glucose Transporters - GLUTs (uniport)
Facilitative glucose transporter (GLUT) proteins are arranged in 12 transmembrane (TM) segments to form a pore. Both the N-terminus and the C- terminus of the protein face the intracellular compartment. A large extracellular loop near the N-terminus of the transporter is glycosylated in the mature protein.
Fick's Law
Fick's law states: "the diffusion rate across the membrane (dn/dt) is directly proportional to the permeability coefficient (P), to the difference in solution concentrations (C1aq - C2aq) and to the area (A)" dn/dt=PA(C1aq -C2aq)
Describe the acetylcholine receptor ion channel structure and how it works
Five homologous subunits (α, α, β, γ, δ) combine to form a transmembrane aqueous pore. Both of the α subunits contain the acetylcholine binding sites, when acetylcholine binds to both sites, the channel undergoes a conformational change that opens the gate. The negatively charged side chains, at either end of the pore, ensure that only positively charged ions pass through the channel.
What are the three forms of transbilayer transport
Flippases: transporters that move lipids toward the cytoplasmic face of the membrane Floppases: transporters that move lipids toward the outside of the cell Scramblasses: transport lipids in either direction towards equillibrium
Describe GLUT 4 and how it functions
Following a meal, glucose signals the release of insulin from the pancreas. Insulin inhibits the release of glucose in the liver, but stimulates it in the muscles GLUT 4 goes to the membrane to allow glucose to enter the cell (movement of glucose into the cell is dependent on the number of transporters int he membrane)
Describe GLUT 2-5
GLUT 2 - Pancreas, liver, small intestine, kideny GLUT 3 - brain, placenta, kidney - has the lowest Km, which helps get glucose to the brain GLUT 4 - muscle, fat - the only glucose transporter that insulin regulates by moving glucose into muscle and fat GLUT 5 - small intestine - moves fructose
What is unique about the GLUT 2 transporter
GLUT 2 can transport glucose, galactose, AND FRUCTOSE It is the only GLUT transporter that can transport all simple sugars
What is glucose/galactose malabsorption? Explain what happens.
Glucose-Galactose Malabsorption (GGM) is characterized by neonatal onset of watery and acidic severe diarrhea, which is fatal within a few weeks unless lactose (glucose and galactose) is removed from the diet The diarrhea stops with fasting or withdrawal of the offending sugars from the diet but promptly resumes with oral feeding of diets containing lactose, glucose, or galactose. Fructose absorption is unaffected. Children with GGM thrive "normally" on fructose replacement formulas, but symptoms return even in adulthood with as little as a teaspoon of glucose (6 g). The disease is quite rare (~ 200 patients worldwide and a high proportion of cases are from consanguineous relationships). Glucose is not transferred out of the intestines. Thus, water will flow into the hypertonic environment inside of the intestines causing diarrhea
What do Ca2+ ATPase pumps do?
Help keep the concentration of Ca2+ in the cell less than outside of the cell
Describe vectorial biosynthesis of lipids
How and where a lipid is made and packaged will determine where is is placed on the membrane PS, PE, and PC are made on the cytofacial surface of the rough ER. They are packaged on the outside of the vessicle and will end up primarily on the inside of the cell. They are carried on the outside of a lysosome and thus end up on the inside of the cell when it meets the membrane. Sphingomyelin is made on the luminal surface of the trans golgi and is carried on the inside of the vesicle, so when the vesicle meets the membrane it is pushed to the outside of the membrane
Explain the organization of membrane proteins involving lipid rafts
Hydrocarbon chains of lipids in lipid rafts are longer and straighter than they are for lipids in other parts of the bilayer and as a result these better accommodate certain membrane proteins, which tend to accumulate there. In this way, lipid rafts are thought to help organize membrane proteins - either concentrating them for transport in small vesicles or enabling proteins to function together, as when they convert extracellular signals into intracellular signals. lipid rafts organize proteins with similar function
What are the steps of activation for the Na/K ATPase
In its E1 conformation, the pump has three high-affinity binding sites for Na+ and two low-affinity binding sites for K+ on the cytoplasmic surface. E1 to E2 conversion moves the three Na+ ions out and creates two high-affinity K+ binding sites and three low-affinity Na+ binding sites on the exoplasmic face. The K+ sites fill quicklyand the Na+dissociates. Similarly, during the E2 to E1 conversion two K+ ions are transported inward. subunit has to be phosphorylated for Na to move thrugh
Describe integral membrane proteins
Integral proteins are embedded in the bilayer among the fatty acid tails. Some lie at or near the inner and outer membrane surfaces; others penetrate the membrane completely. Some integral proteins form channels through which substances can be transported into and out of the cell.
Isotonic, hypertonic and hypotonic
Isotonic: solutions that have the same osmolality as the cytoplasm Hypertonic: solutions with a greater osmality than the cytpolasm Hypotonic: solutions with lesser osmolality than the cytoplasm
How is having a low Km in the brain beneficial?
It allows the brain to get glucose out of the blood before anywhere else in the body
Lipid rafts
Lipid rafts are small, specialized areas in membranes where sphingolipids (orange) and cholesterol (yellow) are concentrated.
Lipid shells
Lipid shells are a recently proposed subset of lipid rafts that may simply be a casing of sphingomyelin and cholesterol around a single protein.
P Class Pump Ca2+ ATPase (2 types)
Most, if not all, cells have primary active pumps at the plasma membrane to extrude Ca2+ from the cell. These pumps are abbreviated PMCA (plasma membrane Ca2+ ATPases) and there are at least 4 isoforms. Ca2+ pumps also exist on the membrane surrounding the sarcoplasmic reticulum (SR) in muscle cells and the endoplasmic reticulum (ER) in other cells. These pumps are abbreviated SERCA (SR & ER Ca2+ ATPases) and there are 3 known isoforms.
Describe nutrient absorption (movement of glucose and amino acids from the intestinal lumen into the blood)
Movement of glucose (and amino acids) from the intestinal lumen into the blood is a two- stage process. Activity of the Na+/K+ ATPase in the basolateral surface membrane generates Na+ and K+ concentration gradients, and the K+ gradient generates an inside negative membrane potential. Both the Na+ concentration gradient and the membrane potential are used to drive the uptake of glucose and galactose from the intestinal lumen by the two- Na+/one- glucose symporter (SGLT1) located in the apical surface membrane. Galactose is also transported by this transporter. Fructose is transported via GLUT5. Glucose, galactose and fructose all are transported into the blood via the GLUT2 protein. SGLT1 cycles through six conformations (see .ppt for expanded detail)
What cells expend the ATP energy produced for powering these pumps?
Nerve and kidney cells expend up to 25% of the ATP produced for powering these pumps erythrocytes expend up to 50% of its ATP for this purpose.
What typically prevents desensitization that would occur in continued acetylcholine presence
Normally, acetylcholine is rapidly dehydrolyzed by acetylcholine esterase Acetylcholine doesn't last in the synapse because acetylcholine esterase breaks it down so that the muscle doesn't become desensitized to the acetylcholine and stop contracting
How does CFTR work?
Normally, via a cAMP-mediated signal, Cl- is secreted and Na+ follows to maintain electrical neutrality. The addition of Na+ and Cl- into the mucus layer lining the airway pulls water into the mucus creating an "Air Surface Liquid" that is necessary for normal pulmonary/digestive functions. CF individuals have a defective CFTR (Cystic Fibrosis Transmembrane conductance Regulator) illustrated by a red X, which results in thick, sticky mucus lining that blocks small airways and hinders normal bacterial removal (see below Figure, Right Panel). The X-Ray image shows damaged lungs of a CF patient.
How many glucose or galactose can bind to GLUT2 per 2 Na+ ions?
ONE
Osmotic flow
Osmotic flow is the tendency of water to move across a membrane from a solution of low solute concentration to one of high solute concentration
Differences and similarities between the classes of ATP powered pumps
P, F, and V classes transport ions only ABC superfamily class small molecules as well as ions All these classes have one or more ATP-binding sites and although these proteins are called ATPases, they normally do not hydrolyze ATP into ADP and Pi unless ions or other molecules are simultaneously transported.
What are PE, PC, PS, and PI
PE (Phosphatidylethanolamine) PC (Phosphatidylcholine; lecithin) PS (Phosphatidylserine) PI (Phosphatidylinositol) What changes is the head group. Otherwise they are all liked to a phosphate, bound to glycerol, which has a fatty acid bound by an ester linkage
What two ways can the processes involved in membrane transport be classified as?
Passive processes: substances move across the cell membrane without an expenditure of energy (the substance moves on their own down a concentration gradient, that is, from an area where its concentration is high to an area where its concentration is low.). Active Processes: the cell uses energy in moving the substance across the membrane (the substance moves against a concentration gradient, that is, from an area where its concentration is low to an area where its concentration is high.) - Unfavorable event because uses energy
Describe the effects of the transbilayer lipid distribution
Permits lipids within the plasma membrane to play essential structural and functional roles. - anchor proteins to the membrane - modify the activity of membrane bound proteins - serve as important second messengers Distinct lipid distributional patterns specifies what proteins are anchored, modified, or serve as second messengers This, in turn, sets up morphologically distinct regions, or domains!!
aquaporins
Phospholipid bilayers are somewhat permeable to water and aquaporins are channel proteins that facilitate the passage of water. The permeability to water is increased by water-channel proteins called aquaporins (AQP)
PMCA
Plasma membrane calcium ATPase
Describe the makeup of plasma membranes
Plasma membranes consist primarily of phospholipids and proteins The phospholipid molecules are arranged in two parallel rows, forming a phospholipid bilayer.
Where are plasmalogens found and what are their fuctions
Plasmalogens are found in numerous tissues, with particular enrichment in the nervous, immune, and cardiovascular system. It has been demonstrated that plasmalogens can protect cells against reactive oxygen species. In addition, they have been implicated as being signaling molecules and modulators of membrane dynamics.
what are plasmalogens
Plasmalogens are glycerophospholipids characterized by the presence of a vinyl-ether linkage at the sn-1 position and an ester-linkage at the sn-2 position.
AQP 2 and Water balance disorders
Reduced expression and/or lack of functional AQP2 are seen in conditions associated with extreme water loss (e.g. diabetes insipidus and renal failure). In contrast, increased expression and/or enhanced apical plasma membrane targeting of AQP2 are seen in conditions associated with water retention (e.g. severe congestive heart failure and pregnancy).
Summarize MDR1
Resistance of tumors to the chemotherapy drugs being given to patients was because of the enhanced expression of MDR1 MDR1 pumps drugs out of cells, so you have to give patients more of the drug to counteract this cellular protein, which will cause other cells to die (Ex: cancer patients losing hair)
SERCA
Sarcoplasmic reticulum and endoplasmic reticulum calcium ATPase
Describe how uniports work in relation to kinetics and thermodynamics
Similar to enzymes, uniporters accelerate thermodynamically favored transport. Transport is characterized by Vmax (a maximum transport rate) and Km(the substrate concentration at which half maximal transport occurs). The lower the Km, the more tightly the substrate binds to the transporter, and the greater the transport rate. The kinetics of uniporter-catalyzed transport reactions are characterized by Vmax (a maximum transport rate) and Km (the substrate concentration at which half maximal transport occurs).
GETTING TESTED ON WHEN SODIUM MOVES THROUGH THE Na/K PUMP
Sodium moves through in the E2 state when phosphate is bound to the aspartate
What is the structure of a gap junction
Structurally, the apposed lipid bilayers are penetrated by protein assemblies called connexons, each of which is formed by six connexin subunits. Two connexons join across the intercellular gap to form a continuous aqueous channel connecting the two cells. Each cell contributes a connexion made of connexion subunits
What are two kinds of secondary active transport?
Symporter: moves molecules in the same direction, one down it's concentration gradient and one up its concentration gradient Antiporter: moves two molecules in the opposite direction; one down its concentration gradient and one up its concentration gradient
What is selective permeability?
The ability of the membrane to permit certain substances to enter and exit, but to restrict the passage of others
Osmolality
The concentration of the impermeantparticles of a solution can be determined and is referred to as a solution's osmolality(osmoles solute/kg solvent).
How do the drugs Ouabain and Digitalis act as therapeutic agents for failing hearts by increasing the force of heart muscle contraction?
The drugs Ouabain and Digitalis increase the force of heart muscle contraction. The primary effect of these drugs is to inhibit the Na+/K+ ATPase, which raises intracellular Na+ and thus, decreases the Na+ concentration gradient. Subsequently, less Ca2+ ions are exported and the Ca2+ ion concentration increases. The drugs inhibit Na/K ATPase, which causes more Na to stay in the cell. This indirectly leaves calcium in the cell, causing longer heart contraction because Na is has a lower concentration gradient to leave the cell in the Ca/Na pump
What was the first GLUT protein described?
The first GLUT protein described was the erythrocyte glucose transporter, GLUT1. It is now realized that GLUT1 protein is ubiquitously expressed. In addition, several other glucose transporters have been identified (GLUT2-GLUT14) and have been shown to display specific tissue distributions
What is osmotic pressure? Why is it useful and what is it dependent on?
The hydrostatic pressure required to stop the net osmotic flow across a membrane is defined as osmotic pressure Osmotic pressure is an important force in the movement of water between various compartments of the body the osmotic pressure of a solution depends on the number of impermeant particles it contains
How are phospholipids oriented in the bilayer
The molecules are orientated in the bilayer so that the heads face outward on either side and the tails form a hydrophobic core.
How does this process differ in the pulmonary capillaries
The overall direction of this reaction is reversed in the lungs.
What is the partition coefficient a measure of?
The partition coefficient is a measure of the relative affinity of a substance for lipid versus water: the higher the substance's partition coefficient, the more lipid soluble it is.
Describe the phospholipid molecule
The phospholipid molecule consists of a polar, phosphate-containing "head" that mixes with water (hydrophilic) and nonpolar fatty acid "tails" that do not mix with water (hydrophobic).
Ca2+ Exit (Ca2+ Pumps, Na+/Ca+2 Antiporter) Steps for Cardiac Muscle Contraction
The sarcoplasmic reticulum contains a vigorous Ca2+ATPase (Step 8) In addition to a sarcolemma Ca2+ATPase, cardiac muscle cells also have a Na+/Ca2+ antiporter that plays a principal role in maintaining a low concentration of Ca2+ in the cytoplasm. The movement of three Na+ ions is required to power the export of one Ca2+ ion against the greater than 10,000-fold concentration gradient. The mitochondria of muscle are also capable of accumulating and releasing calcium (Step 12), yet this system does not appear to play a role in the normal functioning of the cell.
Describe the intracellular ion environment
The specific ionic composition of the cytosol usually differs from that of the surrounding fluid. Both passive and active transport processes are coordinated in living cells to generate and maintain these ionic gradients
Differences in the rate at which molecules simply diffuse across membranes depends largely on what? Why?
The thickness of the hydrophobic interior of all phospholipid bilayers is approximately the same 2.5 to 3 nm, and the diffusion coefficient is the same for most substances; therefore differences in the rate at which molecules simply diffuse across membranes depends largely on differences in their partition coefficient.
What does the size of gap junctions permit?
Their large pore size permits the passage of molecules up to 1000 Daltons (~1.5 nm), including amino acids and nucleoside phosphates.
Explain asymmetry in the phospholipid bilayer
There are variations in the amount of each kind of phospholipid on the inside vs. outside of the membrane The outer PM leaflet contains a higher percentage of SM and PC whereas the inner PM leaflet contains higher percentage of PE, PS, and PI.
What do ionic gradients of different ion compositions of cytosol and surrounding fluid create?
These ionic gradients create a transmembrane voltage - membrane potential (EM) approximately -70 mV. The EM is generated primarily by movement of cytosolic K+ ions through resting K+ channels.
Describe sphingolipids. What is the most prominent sphingolipid and describe its structure.
They have the same structure as the phospholipids but they have a sphingosine backbone instead of a glycerol SM (Sphingomyelin), which contains a phosphocholine head group, is a phospholipid. It is the most prominent with the phosphotidyl head group Other sphingolipids are glycolipids in which a single sugar residue or branched oligosaccharide is attached to the sphingosine backbone; e.g., GlcCer (Glucosylcerebroside).
What is the ABC superfamily specific for?
This class includes more than 100 different transport proteins specific for a single substrate or a group of substrates including ions, sugars, peptides, polysaccharides and even proteins.
P-Class Pump (Na+/K+ ATPase)
This ion pump is a tetramer of subunit composition α2β2. The β-subunit is required for newly synthesized α-subunits for correct folding but apparently is not involved directly in ion pumping. The overall process of transport moves three Na+ ions out of and two K+ ions into the cell per ATP.
How is transbilayer lipid asymmetry maintained?
Transbilayer lipid asymmetry is maintained by vectorial biosynthesis, restricted spontaneous movement, protein-lipid interactions and phospholipid transporters.
What are channel proteins
Transport specific types of ions or water down their concentration or electrical gradients. Form pores in the membrane by association of homologous subunits or domains of a single polypeptide.
Describe channel proteins
Transport specific types of ions or water down their concentration or electrical gradients. Form pores in the membrane by association of homologous subunits or domains of a single polypeptide. They form a protein-lined passageway across the membrane through which multiple ions or water molecules move simultaneously, single file at a very rapid rate.
What ist he function of V class pumps
V-class pumps generally function to maintain the low pH of acidic vesicles by pumping protons from the cytoplasm into the acidic vesicles (H+ ATPase). the moving of H+ through the pump maintains a low pH
Summarize ACH in ion channels of muscle
When ACH binds to a subunit the gate opens allowing cations (Ca2+) to flow through causing depolarization. Ca2+ enters the muscle and causes contraction
How is cholesterol helpful in high concentrations
While cholesterol tends to make membranes less fluid (i.e., rigid), at high concentrations (as is the case in most eucaryotic cells) it also prevents hydrocarbon chains from coming together and crystallizing.
Tonicity
With regards to cell volume regulation, the term tonicity is used to describe the osmolality of a solution relative to the cytoplasm.
What controls the opening of the gap junction channel
[Ca2+]i and pH control opening of the channel; e.g., an increase in [Ca2+]i and/or a decrease in pH cause channel closing, so that dead and dying cells are isolated from their neighbors.
Myasthenia Gravis (MG)
a long-term neuromuscular disease that leads to varying degrees of muscle weakness. MG is an autoimmune disease that results from acetylcholine receptor antibodies. Generally treated with acetylcholine esterase inhibitors, such as neostigmine and pyridostigmine.
What is the rate of diffusion (dn/dt) across the lipid bilayer given by?
a modification of Fick's law In the modification P (permeability coefficient) = K So, dn/dt=KA(C1aq -C2aq) The permeability coefficient accounts for the membrane thickness (x), diffusion coefficient (D) and the solubility of solute in membrane and is given by: P=KD/x.
P Class Pumps
a) Consists of a transmembrane catalytic α-subunit, which contains an ATP-binding site, and usually a smaller β-subunit, which may have regulatory functions. b) Many of these pumps are tetramers composed of 2 α- and 2 β-subunits. c) During the transport process, at least one of the α-subunits is phosphorylated and the ions are thought to move through the phosphorylated subunit. d) This class includes the Na+/K+ ATPase, H+/K+ ATPase and several Ca+ ATPases.
There are four principal classes of ATP-powered pumps designated as what?
a) P-Class b) F-Class c) V-Class d) ABC Superfamily-Class
What are gap junctions
channels that communicate directly between cells.
What are lipid rafts made of
cholesterol and sphingomyelins
Summarize cholesterol in membranes
cholesterol enhances the permeability of the membrane by putting its hydroxyl group under the polar head group This causes rigidity and prevents hydrocarbon chains (FA) from crystalizing together. This in effect actually gives the membrane fluidity This also allows proteins to move through the membrane
what three things determine the rate of diffusion through fick's law
concentration gradient area it crosses partition coeficient (how much it likes lipids)
What are the three structures of the peripheral proteins, which are loosely bound to the membrane surface?
covalently attached lipid chain - either a fatty acid or prenyl group - in the cytosolic monolayer oligosaccharide linker to PI in the noncytosolic monolayer noncovalent interaction with other membrane proteins NOT ON EXAM