Cell Processes Flashcards
What does it mean that the phospholipid is amphipathic?
It has both a polar & nonpolar region
How thick is the cellular membrane?
8nm
An important feature of the hydrophobic core is that it provides a highly impermeable barrier to the passage of
charged ions.
There is x% lipids and y% proteins in the cell membrane and are held together by _ bonds
There is 50% lipids and 50% proteins in the cell membrane and are held together by Hydrogen bonds
What two molecules are scattered among the double row of phospholipid molecules?
cholesterol and glycolipids
Phospholipids are x% of lipids
75%
Why do the phospholipids associate in the direction they do?
To be in the lowest energy state they orientate themselves with the polar heads facing away associating with water and the lipid tails facing inwards to associate with each other
What 3 factors determines membrane fluidity?
Lipid tail length, the longer the tail the less fluid the membrane. Number of double bonds - more double bonds increases fluidity, as you put a kink in the tail and allow more space between phospholipids Amount of cholesterol - more cholesterol DECREASES fluidity.
What are integral membrane proteins?
They extend into or completely across cell membrane (transmembrane protein) They are amphipathic
What are peripheral proteins?
attached to either inner or outer surface of cell membrane
What membrane proteins are easily removed?
peripheral proteins
Explain the protein structure of integral membrane proteins:
The hydrophobic core of the integral protein consists of amino acids that are non polar and an alpha helix coil spans the hydrophobic lipid bilayer. The ends of the integral protein interact with the aqueous solution
What are the functions of membrane proteins?
Receptor proteins Cell identity marker (involved in immune response) Linker to adjacent cells or substrates Enzymes (e.g. glucose is often broken at membrane surface) Ion channels Transporter proteins
What will the lipid bilayer allow to pass through it?
It is permeable to non polar, uncharged molecules (e.g. O2, N2, benzene) It is permeable to lipid soluble molecules (e.g. steroids, fatty acids, some vitamins) It is permeable to small uncharged polar molecules (e.g. water, urea, glycerol)
What does the lipid bilayer NOT allow through it
Impermeable to large uncharged polar molecules (e.g. glucose, amino acids) and impermeable to ions (e.g. Na+, K+, Cl-, H+)
Define diffusion
Diffusion is the random mixing of particles in a solution as a result of the particle’s kinetic energy. More molecules move away from an area of high concentration to an area of low concentration.
What affects the rate of diffusion?
The greater the difference in concentration between the two 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 the rate of diffusion; so diffusion is only very fast over small distances.
Explain the concentration gradient
A non-charged molecule will diffuse down their concentration gradient.
Explain the electrical gradient
Cells can maintain a difference in charged ions between the inside & outside of membrane establishing an electrical gradient or membrane potential.
Explain the extracellular ion concentrations at resting potential in terms of Na+, K+ and Cl-
High Na+ Low K+ High Cl-
Explain the cytoplasmic ion concentrations at resting potential in terms of Na+, K+ and Cl-
Low Na+ High K+ Low Cl-
Explain the flow of ions down their electorchemical gradient by drawing a diagram to do so.
Define osmosis
Net movement of water through a slectively permebale membrane from an area of hight water concenytration to an area of low water concentration
Define osmotic pressure
Osmotic water movement can be prevented by an opposing force. The hydrostatic pressure applied to oppose osmosis is defined as the osmotic pressure of the solution. Osmotic pressure is a colligative property. It depends only on the numbers and not the types of particles in solution.
If the solution has the same osmolarity it is
isosmotic
If the solution has a lower osmolarity it is
hyposmotic
If the solution has a higher osmolarity it is
hyperosmotic
The concentration of body fluids has an osmolarity of
280 mOsmol.
Explain tonicity
The effect a solution has on cell volume is termed tonicity. The tonicity of a solution depends on the membrane permeability of the solute.
Explain isotonic solution
no change in cell volume
Explain Hypotonic solution
cause cell swelling and eventually cell lysis (haemolysis)
Hypertonic solution
causes cell shrinkage (crenation).
What percentage of resting energy is used to maintain concentration and electrical gradients.
30%
Define pass transport
moves substances down their concentration gradient with only their kinetic energy
Define active transport
uses energy to drive substances against their concentration gradient or electrochemical gradients
Which vitamins can pass through the cell membrane without transport proteins?
A, D, E and K
Define Non-mediated tyransport
Does not directly use a transport protein
Define mediated transport
Moves materials with the help of a transport protein.
What is non-mediated transport importnat for?
excretion of wastes and absorption of nutrients
Explain the ion channel protein structure
The pore of the ion channel protein is made up of hydrophillic amino acids and the outer part of the ion channel is make of hydrophobic amino acids to embedd itself in the cell membrane. The pore of the ion channel is filled with water.
Explain ionic selectivity
If for example the ion channel has a negatively charged amino acid at its core, negatvely chraged ions will be repeled. Specific amino acids lining the pore determine the selectivity of the channel to ions.
Explain ion channel gating
a Ball protein shuts the gate which controls the opening and closing of the ion channel.
What are the different stimuli that can control ion channel opening and closing?
Voltage;
Ligandbinding;
Cell volume (stretch);
pH;
Phosphorylation.
The diffusion of ions through a channel generates a measurable current. What is this current?
About 10^-12 amps
Explain the patch clamb technique and what it is used for:
It is used for measuring the current flowing through one ionic channel.
Current fluctuations represent the opening and closing of single ion channels. The current fluctuations represent the conformational changes in channel structure that are associated with channel gating.
Are transport rates faster through channels or carriers?
Channels, bevause for a carrier protein a confromational change must occur.
Explain how carrier proteins work
Can be passive or active.
The molecule to be transported directly interacts with the carrier protein and causes a conformational change to occur to the carrier protein.
Transport proteins are very simalir to…
encymes, due to
- Specificity; (binding pocket determines this)
- Inhibition;
- Competition; (another similair molecule can act as a compeitive inhibitor)
- Saturation (transport maximum).
Explain faciliatated diffusion of glucose
- Glucose attatches to transport protein GLUT
- Transport protein changes shape. Glucose moves across cell membrane only down concentration gradient.
- Kinase enzyme reduces glcuose concentraion inside the cell by transforming glucose into glucose-6-phosphate
This conversion of glucose maintains glucose graident.
Define active transport
Active transport systems utilise metabolic energy to drive substances against their electrochemical potential gradient.
Define primary active transport
energy is directly derived from the hydrolysis of ATP.
Define secondary acive transport
the energy released by a substance diffusing down its concentration gradient is used to actively transport another substance against its concentration gradient. e.g. energy of ionic ionic diffusion
Explain the Na/K ATPase as an example of primary active transport
The Na/K pump maintains a low concentration of Na+ and a high concentration of K+ in the cytosol.
Three Na+ ions are pumped out (removed from cell) for every two K+ ions pumped into the cell.
Therefore the pump generates a net current and is electrogenic.
Explain what the difference in ion concentrations is important for:
- Maintenance of the resting membrane potential;
- Electricalexcitability;
- Contraction of muscle;
- Maintenance of steady state cell volume;
- Uptake of nutrients via secondary active transporters;
- Maintenance of intracellular pH by secondary active transporters.
What are two other examples of primary active transport used in stomach and muscles?
Ca/K ATPase in muslces
H/K ATPase in the stomach
Explain the pump-leak hypothesis.
Because there is continual leakage of Na+ ions into the cell and K+ out of the cell (down their respective gradients), the pump works continuously –
Explain the Na+ antiporter
Na+ ions rush inward, and Ca2+ or H+ are pushed out
Explain the Na+ symporters
glucose or amino acids rush inward (against their concentration gradients) together with Na+ ions.
Explain the three forms of endocytosis
phagocytosis
pinocytosis
receptor mediated endocytosis
Explain phagocytosis and to what cells this commonly occurs in
“cell eating”, carried out primarily by leukocytes, such as macrophages &
neutrophils. The foreign particle binds to a membrane receptor protein. Pseudopods extend to form a vesicle (phagosome) and engulf the particle. The phagosome fuses with a lysosome which degrades the particle.
Explain pinocytosis
“cell-drinking”. A vesicle forms around the particle and it is ingested directly without specialized structures such as pseudopods.
Explain receptor mediated endocytosis
This is a mechanism for uptake of specific substances or ligands. The desired substance binds to receptor protein in clathrin-coated pit region of cell membrane. Binding causes the membrane to fold inward forming a vesicle; vesicles become uncoated & combine with the endosome. Receptor proteins separate from ligands and return to surface. Ligands are digested by lysosomal enzymes or transported across the cell.
Explain exocytosis
substances (e.g., neurotransmitters, enzymes) are exported from the cells by fusion of the vesicle with the cell membrane.
Define epithilia
Epithelia consists of cells arranged in continuous sheets in either single of multiple layers.
What are the two basic types of epithelial tissues?
Covering and lining epithelium, e.g., epidermis of skin, lining of blood vessels and ducts;
Glandular epithelium, e.g., thyroid, adrenal, and sweat glands.
What are two membrane domains that that the tigh jnctions sperate epithelial cells into?
Apical membrane (or luminal or mucosal) that faces the lumen of the organ or body cavity;
Basolateral membrane that adheres to the adjacent basement membrane and interfaces with
the blood.
Explain paracellular transport?
Paracellular transport is governed by the laws of diffusion and the tightness of the tight junctions. The electrical resistance to ion flow through tight junctions can be measured. The higher the electrical resistance to ion flow, the greater the number of tight junction strands holding the cell together. Tight junction resistance changes in a proximal to distal direction in the GI tract and kidney.
Explain transcellular transport:
Epithelial cells use primary and secondary active transport often in combination with passive diffusion through ion channels to produce transport across the epithelial tissues.
This transport can either be:
Absorption: transport from lumen to blood;
Secretion: transport from blood to lumen.
Explain glndular secretion due to the structure of glands
Glands consist of two different types of epithelial cell connected in series.
Acinar cells create a primary secretion rich in organic molecules (enzymes, regulatory molecules).
Duct cells modify the composition of the primary secretion by either absorbing or secreting specific ions (e.g., HCO -, Cl-,
K+, Na+).
How is Glucose and sodium cotransported across the apical membrane?
by the SGLT transport protein
Which protein mediates the exit of Glucose across the basolateral membrane by facilitative diffusion?
GLUT transporter protein
The energy for glucose entry is provided by the _______ gradient, which is maintained by the ______ pump.
The energy for glucose entry is provided by the sodium gradient, which is maintained by the sodium pump.
What happens to water as glucose crosses the epithelium?
The movement of glucose across the epithelium creates an osmotic imbalance, which drives the absorption of water.
Label this diagram
What is oral dehydration therapy?
A simple sugar solution, when given to dehydrated babies suffering from diarrhoea, is responsible for saving millions of lives per year. The ability of glucose to enhance the absorption of Na+ and hence Cl- and water is exploited in oral rehydration therapy.
Explain Glucose/Galactose Malabsorption Syndrome
Glucose/galactose malabsorption syndrome is caused by a mutation in the Sodium-dependent Glucose (co-) Transporter (SGLT) protein. It results in accumulation of glucose and galactose in the lumen of the small intestine. This produces an osmotic imbalance, which attracts water and results in severe diarrhoea.
What is the treatment for Glucose/Galactose Malabsorption Syndrome ?
Treatment of glucose-galactose malabsorption involves the removal of glucose and galactose from the diet. Fructose is used as a source of carbohydrate. This therapy uses a facilitative transporter that is specific for fructose.
Explain how glucose is filtered in the kidney:
In the kidney, glucose in the plasma is filtered and needs to be reabsorbed or it will appear in the urine.
Explain how glucose can occur in the urine:
Glucosuria is an accumulation of glucose in the urine. It occurs if the transport maximum of the SGLT protein is exceeded. The commonest cause is diabetes mellitis because insulin activity is deficient and blood sugar is too high (over 200 mg/mL). In diabetes, the glucose symporter can not absorb glucose fast enough and glucose appears in the urine.
Explain the two step process of chloride secretion.
A cotransporter located in the basolateral membrane accumulates chloride above its electrochemical equilibrium.
This enables chloride to leave the cell via a chloride channel located in the apical membrane.
Sodium moves via the paracellular pathway to preserve electroneutrality.
Explain chlorine secretion in a diagram
What is the rate limting step of chloride secretion?
opening of Cl- channel is strictly regulated.
Even if Cl- is accumalted above electrochemical equilibrium it cannot leave the cell unless the Cl- channel is open.
What is CFTR?
Cystic Fibrosis Transmembrane conductance regulator, this is the Cl- channel
Explain secretory diarrhoea
Caused by excessive stimulation of the secretory cells in the crypts of the small intestine and colon
Excessive stimulation could be due to abnormally high concenyrations of endogenous secretagogues produced by tumours or inflammation
What mainly causes secretory diarhhoe?
Enterotoxins secreted by bacteria
enterotoxins irreversibly activate adenylate cyclase causing a maximal stimulation of CFTR, meaning there is a constant production of cAMP from ATP, meaning chloride is continuosly pumped out.
How do you treat secretory diarrhoea caused by cholera?
glucose stimulated water flux by oral rehydration therapy.
WHat are the organs affected by systic fibrosis?
a common theme is the involvement of epithelial tissue.
How do most people with CF die?
Respiratory failure
How to treat CF?
Chest percussion to improve clearance of infected secretions;
Antibiotics to treat infections;
Pancreatic enzyme replacement;
Attention to nutritional status.
Why do people with CF have 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 to produce a hypotonic solution.
The failure of epithelial cells in the ducts of sweat glands to reabsorb NaCl produces the salty sweat in CF patients
Explain on a cellular level how the mucus in lungs becomes thick in people with CF:
In a patient with cystic fibrosis, the defective Cl- channels prevent isotonic fluid secretion and enhances Na+ absorption to give a dry lung surface.
The mucus becomes thick and difficult to remove.
Bacteria proliferate and attract immune cells, which can damage healthy tissue. DNA released from bacteria and lung cells adds to the stickiness.
Airways become plugged and begin to deteriorate
How does the CFTR Cl- channel work?
Gating of the CFTR Cl- channel is associated with ATP hydrolysis at the nucleotide-binding domains (NBD1, NBD2) and requires PKA (protein kinase A) phosphorylation of the R domain.
Draw a graoh showing glucose in urine
