Cellular processes Flashcards
What is the general structure of the membrane?
A thin, 8nm (8 x10-9 metre) flexible and sturdy barrier that surrounds the cytoplasm of a cell
What is the fluid mosaic model?
The Fluid mosaic model describes membrane structure “sea of lipids in which proteins float like icebergs”
Membrane is __% lipid and __% protein
50%, 50%
What is the membrane held by?
hydrogen bonds
what is a lipid?
lipid is barrier to entry or exit of polar substances
proteins are _______ who __________
gatekeepers, regulate traffic
what does the lipid bilayer of the cell membrane look like? (2)
- Two back-to-back layers of 3 types of lipid molecules
- Cholesterol and glycolipids scattered among a double row
of phospholipid molecules
phospholids comprise of what? (3)
- 75% of lipids
- Phospholipid bilayer = 2 parallel layers of
molecules - Each molecule is amphipathic (has both a polar & nonpolar region)
what are membranes in terms of membrane fluidity? (2)
• Membranes are fluid structures and lipids can move around within the plane of the membrane
leaflet
• Lipids rarely flip flop between membrane leaflets therefore the lipid composition of the leaflets can
be asymmetric.
What is fluidity determined by? (3)
- Lipid tail length - the longer the tail, the less fluid the membrane
- Number of double bonds (more double bonds increases fluidity)
- Amount of cholesterol (more decreases fluidity)
What are integral proteins?
extend into or completely across cell
membrane (transmembrane protein)
What are peripheral proteins?
attached to either inner or outer surface
of cell membrane and are easily removed from it
are intergral proteins amphiphilic or amphpathic?
Amphipathic
How do you describe integral proteins? (4)
• Integral proteins are amphipathic
• They have hydrophobic regions that span
the hydrophobic core of the lipid bilayer
• These regions usually consists of non polar
amino acids coiled into helices
• Hydrophilic ends of the
proteins interact with the
aqueous solution
What can membrane proteins act as? (6)
- Receptor Proteins
- Cell Identity Markers
- Linkers
- Enzymes
- Ion Channels
- Transporter Proteins
What does the molecular organisation of the membrane result in?
The molecular organisation of the membrane results in
selective permeability – the membrane allows some
substances to cross but excludes others
what is the lipid bilayer permeable and impermeable to? (5)
– Permeable to nonpolar, uncharged molecules - O2, N2 benzene
– Permeable to lipid soluble molecules – steroids, fatty acids, some
vitamins
– Permeable to small uncharged polar molecules: water, urea,
glycerol, CO2
– Impermeable to large uncharged polar molecules – glucose, amino
acids
– Impermeable to ions Na+, K+, Cl-
, Ca2+, H+
what do membrane proteins mediate?
Membrane proteins mediate the transport of substances across the
membrane that can not permeate the hydrophobic core of the lipid bilayer
more molecules move away from an area of high concentration to an area of low concentration. What affects the rate of diffusion? (5)
• the greater the difference in concentration between the 2 sides of the membrane, the faster the rate of diffusion
• the higher the temperature, the faster the rate of diffusion
• the larger the size of the diffusing substance, the slower the
rate of diffusion
• an increase in surface area, increases the rate of diffusion
• increasing diffusion distance, slows rate of diffusion
what does the rate of diffusion set a limit to?
The rate of diffusion sets a limit on the size
of cells of about 20 µm
How does a cell increase diffusion?
To increase diffusion a cell can increase the
membrane area available for exchange
(diffusion) of a substance
What is the diffusion consequences of membrane thickness?
Membrane thickness – the thicker the
membrane the slower the rate of diffusion
diffusion is very fast over _____________
small distances
what is concentration gradient?
non charged molecules will diffuse down their
concentration gradients
What is electrical gradient?
ions will be influenced by membrane potential in addition to their concentration gradient
what are movement of ions influenced by?
Movement of ions will be influenced by the electrochemical gradient
What does the selective permeability of the membrane enable?
The selective permeability of the membrane enables a difference in concentration or concentration gradient across the membrane to be established
Cells can maintain a difference in charged ions between what?
Cells can maintain a difference in charged ions between the inside &
outside of membrane establishing an electrical gradient or
membrane potential)
What do membranes mimic?
Membranes mimic capacitors and can separate and store charge.
Cells use __% of resting energy to maintain concentration and
electrical gradients
These gradients represent __________
30%, stored energy
What is osmosis?
Net movement of water through a selectively permeable membrane from an area of high water concentration to an area of lower water concentration
osmosis only occurs if membrane is..? This is the situation in?
Only occurs if membrane is permeable to water but not to certain solutes.
This is the situation in biological membranes so if an osmotic gradient exists water will move want to eliminate it.
what is osmotic pressure?
Osmotic pressure is the pressure applied by a solution to prevent
the inward flow of water across a semi-permeable membrane.
What is non-mediated transport?
does not directly use a transport protein.
what is mediated transport?
Mediated transport moves
materials with the help of a
transport protein.
what is passive transport?
Passive transport moves
substances down their
concentration or electrochemical gradients with only their kinetic
energy.
what is active transport
– Active transport uses energy to drive substances against their concentration or electrochemical gradients.
What is vesicular transport?
Vesicular transport move materials across membranes in small vesicles either by exocytosis or endocytosis – not discussed.
Why is non-mediated transport important? is it polar or non polar? hrydrophilic or hydrophobic molecules?
Important for absorption of nutrients – excretion of wastes
• Nonpolar, hydrophobic molecules
– oxygen, carbon dioxide, nitrogen, fatty acids, steroids, small
alcohols, ammonia and fat-soluble vitamins (A, E, D and K)
how does diffusion through ion channels work?
The channel forms a water filled pore that shields the ions from the hydophobic core of the lipid bilayer
ions do not bind to _______. therefore…?
Ions do not bind to channel pore. Therefore transport is very rapid.
speicific amino acids lining the pore determine?
By being selective to a particular ion the channel can?
Specific amino acids lining the pore determine the selectivity of the channel to ions.
By being selective to a particular ion the channel can harness the energy stored in the different ion gradients.
properties of channels: what is gating? (3)
• Channels contain gates that control opening and closing of
the pore
• Different stimuli can control (gate) channel opening and
closing
• Stimuli include: voltage, ligand binding, cell volume
(stretch), pH, phosphorylation
ion channels: What generates a measurable current (~10^-12 amp)?
The diffusion of over 1 million ions per second through a channel generates a measurable current (~10-12 amp)
what is the patch clamp technique?
How the current flowing through an individual channel can
be recorded
what does the current fluctuations represent? (2)
Current fluctuations represent the opening and closing of single ion channels.
It represents the conformational
changes in channel structure that are associated with
channel gating
What happens in carrier mediated transport:mode of action? (2)
•The substrate to be transported directly interacts with the
transporter protein
•Because the transporter undergoes a conformational change
transport rates are slower than those obtained for channels
carrier mediated transport proteins have proteins similar to what?
Enzymes
What do carrier mediated transport exhibit? (5)
Specificity
Inhibition
Competition
Saturation (transport maximum)
transport proteins do not…? they…?
Transport proteins do not catalyze chemical reactions they mediate transport across the cell membrane at a faster than normal rate
Mediated transport can be either?
Passive (facilitated) or active
What are the facilitated diffusion of glucose steps (3)
1) Glucose binds to transport protein (GLUT)
2) Transport protein changes shape. Glucose moves across cell
membrane (but only down
the concentration gradient)
3) Kinase enzyme reduces
glucose concentration inside the cell by transforming glucose into glucose-6-phosphate
transporters display? Glucose transport occurs until?
- Transporters display enzyme kinetics
* Glucose transport occurs until all binding sites are saturated
What is active transport?
An energy requiring process that moves molecules and
ions against their concentration or electrochemical
gradients
what are the two forms of active transport?
• Primary active transport
- energy is directly derived from the hydrolysis of ATP
- A typical cell uses 30% of its energy (ATP) on primary
active transport
• Secondary active transport
-energy stored in an ionic concentration gradient is used to
drive the active transport of a molecule against its gradient
Primary active transporters: Na/KATPase
: what is removed and brought into the cell? (2)
3 Na+ ions removed from cell as 2 K+ brought into cell.
Therefore the pump generates a nett current and is electrogenic.
What does the Primary active transporters: Na pump maintain?
The Na pump maintains a low concentration of Na+ and a high concentration of K+ in the cytosol
The difference in ion concentration is important for? (6)
- Maintain resting membrane potential
- Electrical excitability
- Contraction of muscle
- Maintenance of steady state cell volume
- Uptake of nutrients via secondary active transporters
- Maintenance of intracellular pH by secondary active transporters
Why does the Na pump work continuously?
Because Na and K are continually leaking back into the cell down their respective gradients the pump works continuously – known as the pump-leak hypothesis
What does secondary active transport use? Thus these transporters indirectly use?..
Uses energy stored in an ion gradients created by
primary active transporters to move other substances
against their own concentration gradient
Thus these transporters indirectly use the energy
obtained by hydrolysis of ATP
Cells have many secondary transporters that are powered by?
Cells have many secondary active transporters that are powered by the Na+ gradient initially established by the Na pump
epithelial tissues (5)
• consist of cells arranged in continuous sheets in
either single of multiple layers
• cells sit on a basement membrane
• form the boundary between the body’s organs or
between the body and the external environment
• are subject to physical breakdown and injury –
therefore undergo constant and rapid renewal
process
• Refer to course notes on epithelial structure and
function
tight junction structure (3)
• Tight junctions are composed of thin bands that encircle
the cell and make contact with thin bands from adjacent cells
• In EM it appears that the membranes are fused together
• In freeze fracture tight junctions appear as an interlocking
network of ridges in the plasma membrane
Tight junctions act as what?
• A barrier – they restrict the movement of substances
through the intercellular space between cells
• A fence – they prevent membrane proteins from
diffusing in the plane of the lipid bilayer
what are the two distinct membrane domains of epithelial cells?
• Apical (or luminal or mucosal) membrane that faces the lumen of the organ or body cavity
• Basolateral membrane that adheres to the adjacent
basement membrane and interfaces with the blood
The distinct membrane domains means what?
• The distinct membrane domains means that different transport proteins can be inserted into either the apical or basolateral membrane
Transport can occur via the ________ or _________
pathway or via _____
Transport can occur via the paracellular or transcellular
pathway or via both
What is paracellular transport governed by?
Paracellular transport is governed by the laws of
diffusion and the tightness of the junctions
The higher the _________ to ion flow the greater the number of ______________
The higher the electrical resistance to ion flow the
greater the number of tight junction strands holding the
cell together
What are two functional classifications of epithelial tissue?
- Leaky epithelium – paracellular transport dominates
* Tight epithelium – transcellular transport dominates
what type of transport does epithelial use? the transport can either be…?
Epithelilal cells use primary and secondary active
transport often in combination with passive diffusion through ion channels to produce transport across the epithelial tissues
- Absorption: transport from lumen to blood
- Secretion: transport from blood to lumen
Transepithelial transport can be broken down into which
following areas?
1) Entry and exit steps: the entry step for absorption is the apical but for secretion is the basolateral membrane
2) Electrochemical gradient: is the entry or exit step
passive or active
3) Electroneutrality: movement of a positive or negative ion will attract a counter ion
4) Osmosis: nett movement of ions will establish a
difference in osmolarity that will cause water to flow
by osmosis
What is transepithelial transport?
Epithelial cells use different collections of transporters and channels to mediate either secretion or absorption
What happens in glucose absorption in the small intestine? (6)
- Tight junctions divide cells
into apical and basolateral membrane
domains - Na-pump sets up ion gradients
- The sodium glucose symporter (SGLT) uses the energy of the Na gradient to to actively accumulate glucose above its concentration
gradient - Facilitative glucose transporter (GLUT) mediates glucose exit across the basolateral membrane via passive diffusion down its gradient.
- Na taken up via the glucose exits via the basolateral Na-pump.
- The transport of Na and glucose across the epithelium induces
paracellular Cl and water fluxes
what is oral rehydration therapy?
The ability of glucose to
enhance the absorption of Na+ and hence Cl- and water is exploited in oral rehydration therapy
A simple sugar solution when
given to dehydrated babies
suffering from diarrhea is
responsible for saving millions of lives per year
What is glucose-galactose malabsorption syndrome? (3)
• A mutation to the glucose symporter in the small intestine means that sugar is retained in the intestine lumen.
• The associated increase in lumen osmolarity induces
a water efflux
• The increased water flow produces a pronounced diarrhea
What is the treatment for glucose-galactose malabsorption? (3)
• Therapy is to remove glucose and galactose from the diet • To use fructose as a source of carbohydrate • This therapy utilises a facilitative transporter (GLUT5) that is specific for fructose
what is glucose reabsorption in the kidney?
In the kidney glucose in the plasma is filtered and
needs to be reabsorbed or it will appear in the
urine
In diabetes what happens in the glucose symporter?
In diabetes the glucose symporter can not absorb
glucose fast enough and glucose appears in the
urine
what happens if glucose absorption is impaired?
If glucose absorption is impaired or the transporter is saturated glucose will appear in the urine
Chloride secretion steps (6)
- Tight junctions divide cells into apical and basolateral membrane
domains - Na pump a sets up ion gradients
- The NaK2Cl symporter
uses the energy of the Na gradient to actively accumulate chloride
above its electrochemical gradient - Cl leaves the cell by passive diffusion through an ion channel
- Na exits via the basolateral Na-pump and K+ via channel
- The transport of Cl across the epithelium induces paracellular Na and water fluxes
The rate limiting step
• Although Cl- is accumulated above electrochemical equilibrium it can not leave the cell unless the Cl- channel
is open
• The opening of the Cl- channel is strictly regulated (gated)
• Thus the opening of the Cl- channel is the rate-limiting step
in Cl- secretion
• The Cl- channel has been identified at the molecular level as the Cystic Fibrosis Transmembrane conductance Regulator (CFTR)
• CFTR over stimulation has been implicated in secretory
diarrhea and its dysfunction causes cystic fibrosis
what is secretory diarrhoea caused by?
Caused by excessive stimulation of the secretory cells in the crypts
of the small intestine and colon
what can be used to treat secretory diarhoea?
Oral rehydration therapy can be used to treat secretory diarrhoea
caused by cholera
What is cystic fibrosis?
A complex inherited disorder that affects children and young adults
How is cystic fibrosis inherited?
It is inherited in an autosomal recessive fashion
– Heterozygotes have no symptoms but are carriers
– The child of two carriers have a 1 in 4 chance of getting cystic fibrosis (CF)
Cystic fibrosis disease frequency among ethnic groups
Disease frequency varies among ethnic groups:
– In Northern Europeans 1 in 2500 newborns are affected
and 1 in 25 are carriers
– Less common in other ethnic groups
organs affected by cystic fibrosis? (3)
Patients affected with cystic fibrosis have a diverse range of symptoms •A common theme is the involvement of epithelial tissues •Most cases of mortality are due to respiratory failure
what are clinical management of cystic fibrosis includes?
• Chest percussion to improve clearance of infected secretions • Antibiotics to treat infections • Pancreatic enzyme replacement • Attention to nutritional status
Cystic fibrosis a defect in Cl- secretion (normal lung epithelial cells):
A balance between secretion
and absorption keeps the lung surface moist but prevents excessive fluid build up
Cystic fibrosis a defect in Cl- secretion (lung epithelial cells in CF):
The defective Cl- channel prevents isotonic fluid secretion and
enhances Na+ absorption to give a dry lung surface
Cysric fibrosis and sweat formation
• People with CF have a very salty sweat
• Formation of sweat is a two stage process:
– a primary isotonic secretion of fluid by acinar cells
– a secondary reabsorption of NaCl but NOT water
produces a hypotonic solution
What produces the salty sweat in CF patients?
The failure of epithelial cells in the ducts of sweat glands to reabsorb
NaCl produces the salty sweat in CF patients
In the duct cells the membrane potential is ________ and Cl wants to enter the cell down its _________________
In CF patients _____is ______and Cl- accumulates in the ______ producing _________
In the duct cells the membrane potential is depolarised and Clwants to enter the cell down its electrochemical gradient
In CF patients CFTR is defective and Cl- accumulates in the duct
lumen producing salty sweat
