Membrane Transport Of Small Molecules And The Electrical Properties Of Membrane Flashcards
The cell must contain equal quantities of positive and negative charges, must be?
Electrically Neutral
Protein-Free Lipid Bilayers are impermeable to?
Ions
The rate of diffusion, varies enormously, depending partly in the size of the molecule but mostly on its?
Relative hydrophobicity (solubility in oil)
More easily to diffuse across Lipid bilayer
Smaller molecule
More hydrophobic or nonpolar
Lipid bilayers are essentially impermeable to charged molecules (ions), bcs? _ _
The charge and high degree of hydration of such molecules prevents them from entering the hydrocarbon phase of the bilayer.
Hydrophobic molecules
02, CO2, N2, Steroid, Hormones
Small uncharged polar molecules
H2O, urea, glycerol, NH3
Large Uncharged Polar Molecules
Glucose, sucrose
Ions
H+, Na+, HCO3‐, K+, Ca²+, Cl-, Mg²+
Transfer such solutes (ions, sugars, amino acids, nucleotides, water, and many metabolites) across cell membrane
Membrane transport proteins
Specificity of membrane transport proteins
Studies in 1950s, single-gene mutation bacteria unable to transport sugars across their membrane.
Cannot transport amino acids (including cystine, the disulfide-linked dimer of cysteine) from either the urine or the intestine into the blood; resulting accumulation of casting in the urine leads to the formation of cystine stones in the kidneys
Cystinuria
Their polypeptide chains transverse the Lipid bilayer multiple times
Multi-pass transmembrane proteins
Proteins (multi-pass transmembrane proteins) enable specific hydrophilic salutes to cross the membrane without coming into direct contact with the hydrophobic interior of the Lipid bilayer,by?
Forming a protein-lined pathway across the membrane.
Major classes of membrane transport proteins
- Transporters
- Channels
Bind the specific solute to be transported and undergo series of conformational changes that alternately expose solute-binding sites on one side of the membrane and then on the other to transfer the solute across it.
Transporters
Form continues pores that extend across the Lipid bilayer. When open, it allows solutes (inorganic ions of appropriate size, charge and some cases small molecules, including water, glycerol, and amonia) to pass through them and thereby cross the membrane.
Channels
Occurs at much faster rare than transport mediated transporters
Transport through channels
●Greatly increase the permeability of the membranes to water.
●Provides corridors allowing water molecules to cross the membrane
●passive, allows faster transport
Aquaporins
Mediated by transporters coupled to an Energy source
Active Transport
All channels and many transporters allow solutes to cross the membrane only passively (downhill)
Passive transport
It forms when the concentration gradient and the electrical gradient combine to form a net driving force called?
Electrochemical gradient
Requires input of metabolic energy and is always mediated by transporters that pump to solute against the concentration or electrochemical gradient.
Active Transport
The process by which a transporters transfers a solute across the Lipid bilayer resembles an?
Enzyme-substrate reaction
The transition occurs through an _ _ in which solute is inaccessible, or occluded from either side of the membrane.
Intermediate state
When the transporter is saturated (solute-bindibf sites are occupied), the rate of transport is?
Maximal
Characteristic of the specific carrier, Measures the rate at which the carrier can flip between conformational states
Vmax (V for Velocity)
As with enzymes, the binding solutes can be blocked by either?
Competitive inhibitors or noncompetitive barriers
Compete for the same binding site and may or may not be transported
Competitive inhibitor
Binds elsewhere and alter the structure of the transporter
Noncompetitive inhibitors
Transporter is shown in three conformational states:
Outward open state
Occluded state
Inward-open state
Cells carry out such active Transport in three main ways:
- Coupled transporters
- Atp-driven
- Light-or redox_driven pumps
Harness the energy stored in concentration gradients to couple the uphill transport of one solute across the membrane to the downhill transport of another
Coupled transporters
Pumps couple uphill transport to the hydrolysis of ATP
ATP-driven pumps
Known in bacteria, archaea, mitochondria, and chloroplast, couple uphill transport to an input of energy from light, as with bacteriorhodopsin, or from a redox reaction, as with cytochrome c oxidise.
Light-or redox-driven pumps
Active Transport can be driven by?
Ion-concentration gradients
Active Transport can be driven by?
Ion-concentration gradients
Some transporters simply passively mediated the movement of a single solute from one side of the membrane to the other at a rate determined by their Vmax and Km
Uniporters
Coupled transport involves either the simultaneous transfer of a second solute in the same directions, performed by?
Symporters / co-transporters
Transfer of a second solute in the opposite direction
Antiporters /exchangers
Allows the transporters to harvest energy stored in the electrochemical gradient if one solute, typically an inorganic ion, to transport to other
Tight coupling between the transfer of two solutes
Is used as the driving force to pump other solutes uphill, against their electrochemical gradient
Free energy released during the movement of an inorganic ion down an electrochemical gradient
Usual co-transported ion because its electrochemical gradient provides a large driving force for the active transport of a second molecule.
Na+
The Na+ that enters the cell during coupled transport is subsequently pumped by an?
ATP-driven Na+-K+ pump in the plasma membrane
Such ion-driven couple transporters is said to mediate
Secondary active transport
Such ion-driven couple transporters is said to mediate
Secondary active transport
Said to mediate primary active Transport because in these the free energy of ATP hydrolysis is used to directly drive the transport of solute against concentration gradient
ATP-driven pumps
Said to mediate primary active Transport because in these the free energy of ATP hydrolysis is used to directly drive the transport of solute against concentration gradient
ATP-driven pumps
Intestinal and kidney epithelial cells contain a variety of symporters that are driven by?
Na+ gradient across the plasma membrane
Intestinal and kidney epithelial cells contain a variety of symporters that are driven by?
Na+ gradient across the plasma membrane
Is specific for importing a small group of related sugars or amino acids into the cell
Each Na+ driven symporter
Is specific for importing a small group of related sugars or amino acids into the cell
Each Na+ driven symporter
The greater the electrochemical gradient for Na+, the _ _ it pumped into the cell
More solute
Occurs only when both Na+ and glucose are bound; their precise interactions in the solute binding sites slightly stabilise the _ _ and thereby making this transition _ _
Occluded state
Occluded state
Energetically favorable
Caused by the thermal energy drive the transporter randomly inward-open or outward-open conformation
Stochastic fluctuations.
Enhanced when Na+ is lost, bcs of cooperativity in binding of the two solutes.
Glucose dissociation
-released by nerve cells to signal at the synapses
- Are taken up again by Na+ symporters after their release
Neurotransmitters
Are important drug targets: stimulants, such as coccaine and antidepressants, inhibit them and thereby prolong signalling by the neurotransmitters, which are not cleared efficiently.
Neurotransmitter transporters
Typically built from bundles of ą helices that span the membrane.
Transporters
Are located midway through the membrane, where some helices are broken or distorted and amino acid sides chains and polypeptide backbone atoms form?
Solute-and ion binding sites
Revealed that transporters are built from inverted repeats: the packing of the transmembrane ą helices in one half of the helix bundle is structurally similar to the packing of the other half, but the two halves are inverted in the membrane relative to each other.
Crystallographic analyses
Transporters are said to be?
Pseudosymmetric
Transporters are said to be?
Pseuosymmetric
Transporters in the plasma membrane Regulates?
Cytosolic pH
Most proteins operate optimally at a particular pH. Lysosomal enzyme functions best at the?
Low pH(~5)
Functions best at the close-to-neutral pH (~7.2) found in cyctosol
Cytosolic enzymes
These transporters use the energy stored in the Na+ gradient to pump out excess H+, which either leaks in or is produced in the cell by acid-forming reactions.
Na+ - driven antiporters
Two mechanisms used to pump out excess H+
- H+ is directly transported out of the cell.
- HCO3- is brought into the cell to neutralize H+ in the cytosol.
Antipprters that uses the first mecahnism. Couples an influx of Na+ to an efflux of H+.
Na+-H+ exchanger
Uses combination of two mechanisms, that couples an influx of Na+ and HCO3- to efflux Cl- and H+ ( so that NaHCO3 comes in and HCL goes out)
Na+ driven Cl—HCO3- exchanger
Is twice as effective as the Na+-H+ exchanger: it pumpsout on H+ and neutralises another for each Na+ that enters the cell
Na+ driven Cl—HCO3- exchanger
Is the most important transporter regulating the cytosolic pH.
HCO3- antiporter
The pH inside the cell regulates both exchangers; when the pH of cytosol falls, both exchangers _ _ _
Increase their activity
Adjust the cystosolic pH in the reverse direction.
Exchangers activity increases as the cytosol becomes too alkaline
Na+ - independent Cl—HCO3- exchanger
An Na+-independent Cl—CHO3- exchanger in the plasma membrane are called
Band 3 protein
Facilitates the quick discharge of CO2 as (HCO3-) as the cell pass through capillaries in the lung.
Band 3 protein
The intracellular pH is not enteirly regulated by transporters in the plasma membrane: _ Are use to control the pH of many intracellular pH.
ATP-driven H+ pumps
An _ _ of transporter in epithelial cells underlies the Transcellualr Transport of Solutes
Asymmetric Distribution
In _ _ , such those that absorb nutrients in the gut, transporters are distributed ___ in the plasma membrane and thereby contribute to the transcellular transport of absorbed nutrients.
Epithelial cells
Nonuniformly
Located in the apical (absorptive) domain of the plasma membrane actively transport nutrients in the cell, building up substantial concentration gradients for these solutes across the plasma membrane
Na+–linked symporters
In the basal and lateral (badolateral) domains allow the nutrients to leave the cell passively down these concentration gradients.
Uniporters
Extend as thin, fingerlikd projections from the apical surface of each cell. Such ___ can increase the total absorption area of cell as much as 25-fold, thereby enhancing its transport capabilities.
Microvilli
Depends on the nonuniform distribution of transporters in cells plasma membrane
Trancellular transport of glucose across an intestine epithelial cell
Pumped into the cell through the apical domain of membrane by Na+-powered glucose transporter
Glucose
The Na+ gradient driving the glucose symport is maintained by the ___ ___ in the basal and lateral plasma membrane domains, which keeps the internal concentration of Na+ low.
Na+-K+ pump
Adjacent cells are connected by impermeable tight junctions, which have a dual function in the trasport process:
- They prevent solutes from crossing the epithelium between cells, allowing a gradient of glucose to be maintained across the cell sheet.
- They also serve as a diffusion barrier (fences) within the plasma membrane, which help confine the various transporters to their respective membrane domains.
3 Classes of ATP-driven Pumps
- P-Type pumps
- ABC Transporters (ATP-binding Cassette transporters)
- V-type pumps
Often called transport ATPases because they hydrolyzed ATP to ADP and phosphate and use the energy released to pump ions on other solutes across a membrane
ATP-driven pumps
Are structurally and functionally related to multipass transmembrane proteins.
P-Type pumps
They are called “P-type” because?
They phosphorylate themselves during the pumping cycle.
This class is cludes many of the ion pumps that are are responsible for setting up and maintaining of ,,, across cell membranes
P-type pumps
Na+, K+, H+, and Ca2+
Differ structurally from P-type ATPases and primarily pump small molecules across cell membranes.
ABC transporters (ATP -binding Cassette Transporters)
Are turbine-like protein machines, constructed from multiple different subunit.
V-type pumps
Transfers H+ into organelles such as lysosomes, synaptic vesicles, and plant or yeast vacuole (V = vacuolar), to acidity the interior of these organelles.
V-type proton pump
When the ATP/ADP ratio is high, they _____,
When the ATP/ADP ratio is low, they can ___
Hydrolyzed ATP; Synthesize ATP
In mitochondria normally works in this “reverse” mode to make most of the cells ATP
F-type ATPase
Structurally related to the V-type pumps is a distinct family of?
F-type ATPases / ATP synthases
Called ATP synthases because they normally work in ___,
Reverse
Instead of using ATP hydrolysis to drive H+ transport, they use the H+ gradient across the membrane to drive the synthesis of ATP from ADP and phosphate
ATP synthases
Are found in the plasma membrane of bacteria, the inner membrane of mitochondria, and the thylakoid membrane of chloroplasts.
ATP synthases
Is generated either during the electron-transport steps of oxidative phosphorylation (aerobic bacteria and mitochondria), during photosynthesis (in choloroplasts), or by the light driven H+ pump (bacteriorhodopsin) in Halobacterium.
H+ gradient
A P-type ATPase pumps Ca2+ into the?
Sarcoplasmic Reticulum in Muscle cell
Specialised type of endoplasmic reticulum that forms a network of tubular scas in the muscle cell cytoplasm, and it serves as an intracellular store of Ca2+
Sarcoplasmic reticulum (SR)
When an action potential depolarizes the muscle cell plasma membrane, __ is released in the cytosol from SR through Ca2+ release channels, stimulating the ____ ______
Ca2+
Muscle to contract
Accounts for about 90% of the membrane protein of the SR, moves Ca2+ from the cytosol back into the SR.
Ca2+ pumps
SR Ca2+ pump and related pump have revealed the molecular mechanism of P-type transport ATPase in grat detail
● they all have similar structures containing 10 transmembrane ą helices connected to three cytosolic domains
● in Ca2+ pump, amino acid sides chains protruding from the transmembrane helices form two centrally positioned binding sites for Ca2+
● In the pumps of ATP-bound nonphosphorylated state, these binding sites are accessible only from the cytosolic side of the SR membrane
Triggered a series of conformational changes that close the passageway to the cytosol and activate a phosphotransfer reaction in which the terminal phosphate of the ATP is transferred to an aspartate that is highly conserved among all P-type ATPases.
Ca2+ binding
Returns the pump to the initial conformation, and the cycle starts again.
Hydrolysis of the labile phosphoryl-aspartate bond
The concentration of K+ is typically ___ higher inside cells than outside
10-30 times
Belongs to the family of P-type ATPases and operates as an ATP-driven antiporter, actively pumping Na+ out of the cell against its steep electrochemical gradient and pumping K+ in.
Na+-K+ pump
It drives a net electric current across the membrane, tending to create an electrical potential, with the cells inside being negative relative to the outside
Electrogenic
Constitute to the largest family of Membrane Transport Proteins
ABC transporter
ABC transporter so named because?
Each member contains two highly conserved ATPase domains or ATP-Binding “Cassettes” on the cytosolic side of the membrane
_____ brings together the two ATPase domains and _____ leads to their dissociation
ATP binding;ATP hydrolysis
Harvest the energy released upon ATP binding and hydrolysis to dive the transport of solutes across the bilayer
ABC Transporters
The transport (in ABC transporters) is directional toward the inside or toward outside, depending on the particular conformational change in the solute binding site that is linked to _______ ___
ATP hydrolysis
In bacteria such as E. Coli that have doubled membranes, the ABC transporters are located in the ______ ______, and ____ ____ operates to capture the nutrients and deliver them to the transporters
Inner membrane
Auxiliary mechanism
ABC transporters consists of multiple domains. Typicall..
Two hydrophobic domains, each built of six membrane-spanning ą helices, together fork the translocation pathway and provide substrate specificity.
Two ATPase domains protrude in cytosol.
Bacteria with double membrane are called ____ because?
Gram negative; they don’t retain the dark blue dye used in Gram staining.
Bacteria with single membrane (but thicker peptidoglycan cell walls), such as staphylococci and streptococci, retain the blue dye and therefore called?
Gram-positive; their single membrane is analogous to the inner (plasma) membrane of Gram-negative bacteria
The first eukaryotic ABC transporters identified were discovered because of their ability to_____. One of these transporters is the ____
Pump hydrophobic drugs out of the cytosol
Multidrug resistance (MDR) protein also called P-glycoprotein
These cells pump drugs put of the cell very efficiently and are therefore relatively resistant to the drugs toxic effects
Cancer cells
Causes malaria
Protis Plasmodium falciparum
The development of resistance to the antimalarial drug _____ has hampered the control of malaria
Chloroquine
Family of P-type transport ATPase, which includes?
Ca2+ and Na+-K+ pumps
Largest family of membrane transport proteins and is especially important clinically.
Superfamily of ABC transporters
The channels are “___” and usually open transiently in response to a specific perturbation in the membrane.
Gated
Response to specific perturbation such as a change in membrane potential (____) or the binding of neurotransmitter to the channel (______)
Voltage-gated channels
Transmitter-gated channels
Have important role in determining the resting membrane potential across the plasma membrane in most animal cell
K+-selective leak channels
Responsible for the amplification and propagation of action potentials in electrically excitable cells, such as neurons and skeletal cells
Voltage-gated ion channels
Convert chemical signals to electrical signals at chemical synapses
Transmitter-gated ion channels
Executors neurotransmitters such as ___ and _____, open transmitter-gated cation channels and thereby ________…
Acetylcholine and glutamate
Depolarize the postsynaptic membrane toward the threshold level for firing an action potential.
Inhibitory neurotransmitters, such as ____ and ____, open transmitter-gated Cl - or K+ channels and thereby…
GABA and Glycine
Suppress firing by keeping the postunaptic membrane polarized.
A subclass of glutamate-gated ion channels called ____ is highly permeable to __, which can trigger the long-term changes in synapse efficacy
(synapse plasticity) such as __ and __ that are thought to be involved in some forms of learning and memory
NMDa receptor channel
Ca2+
LTP and LDP
A typical neuron receives thousands of exciting and inhibitory inputs, which combine by spatial and temporal summation to produce a?
Combined postsynaptic potential (PSP) at the initial segment of of its axon.
Is translated into the rate of firing action potentials by a mixture of cation channels in the initial segment membrane
Magnitude of the PSP
Two important properties distinguish ion channels from aqueous pores.
First, they show ion selectivity, permitting some inorganic ions to pass, but not others.
second, ion channels are not continuously open. Instead, they are gated, which allows them to open briefly and then close again.
The permeating ions have to shed most or all of their associated water molecules to pass, often in single file, through the narrowest part of the channel, which is called the? That limits their passage
Selectivity filter
