Module 5: Cell Processes Flashcards
What 3 lipids make up the cell membrane?
Phospholipids, glycolipids and cholesterol
What is the basic structure of the cell membrane (not including protein channels etc) ?
Made of a double layer of phospholipids with their glycerol heads facing outwards, interfacing with intra and extracellular fluids. Their fatty acid tails are hydrophobic and face the middle of the membrane. Cholesterol is attached to the glycerol heads, while glycolipids are half in-half out of the membrane, forming a carbohydrate attached to fatty acid tails.
How does the cell membrane stay together?
They are held together by H bonds.
Why is the cell membrane important?
It acts as a barrier between the cell and its environment. It regulates concentration gradients, intracellular organisation, uptake and removal or molecules and the maintenance of membrane potential
What are the six classes of membrane protein?
Receptors Cell identity markers Linkers (to cytoskeleton or other cells) Enzymes Channels Transporters
What is the fluid mosaic model?
The proteins are able to move within the membrane, making them like icebergs in the membrane sea.
How does the fluid mosaic model contribute to cell properties?
The cell can easily repair as it flows across any breakages.
The cell can be stretched or shaped- it is not rigid, making it less likely to burst
How do the phospholipids move within the membrane?
They move within the plane of their layer (leaflet), but rarely flip to the other side of the membrane.
What 3 factors determine membrane fluidity and what effect does each of them have on the membrane?
- Length of the fatty acid tail- longer is less fluid
- Number of double bonds in the tails- more than 2 means more fluid
- Amount of cholesterol- more means less fluid
Why is high cholesterol dangerous?
It makes cells rigid, and less able to repair or resist pressure
What does the plasma membrane permit through in its natural state?
- Uncharged, nonpolar, small molecules (O2, N2)
- Lipid soluble molecules (steroids, vitamens, fatty acids)
- Uncharged, polar, small molecules (H2O, CO2, Urea, glycerol)
What doesn’t the plasma membrane permit through in its natural state?
- Large, uncharged polar molecules (Glucose, amino acids)
- Charged molecules (Na+, K+, Cl-)
What is permeability?
The ability of a particular molecule to cross the cell membrane, governed by the principles of diffusion
What is diffusion?
Random mixing of particles in a solution as a result of the particle’s kinetic energy. Molecules move from a high to low gradient.
What affects the rate of diffusion and how?
Steeper gradient = faster diffusion
Higher temperature = faster diffusion
Larger SA = faster diffusion
Smaller distance = faster diffusion
How long does diffusion go for?
It continues until the inside and outside of the cell are equal, at equilibrium. However, while there is no NET particle movement, there are still movements, but in equal amounts.
How is it advantageous that the membrane is selectively permeable?
Concentration and electrical gradients can be established and maintained. (Electrochemical gradients)
What species are affected by electrical vs chemical gradients?
All are affected by chemical, only charged are affected by electrical.
Why is the electrochemical gradient useful?
It allows cells to separate and store charge and therefore energy.
How much energy does it take to maintain electrochemical gradients?
About 30% of resting energy.
What are the typical electrochemical features of the inside of a cell and how quickly would they diffuse if the cell ‘let go’ of its potentials?
Negative potential inside the cell
High in K+. Low in Na+ and Cl-
K+ would diffuse out slowly, as it’s going against its electro but with its chem gradient
Na+ would diffuse in quickly down its electrochemical gradient
Cl- would be in equilibrium due to its opposing electro and chemical gradients
What is osmosis?
The net diffusion of water across a semipermeable membrane.
Why does osmosis occur?
When the osmolarities of two solutions are different, but the solutes involved can’t cross the membrane, water flows between the two from the less to more concentrated solution, concentrating one and diluting the other until their osmolarities are equal.
What is the name of the force opposing osmosis, and what determines it?
it’s called hydrostasis and it is dependent on the number, not type of particles.
How do we know a solution’s osmolarity?
We use its molarity and the type of compound it exists as.
Eg. 1M glucoes = 0.5M NaCl = 1/3M CaCl2
What is tonicity?
It refers to effect a reference solution has on the cell volume of another
What are the three classes to describe tonicity?
Isotonic- no change in cell volume
Hypotonic- Reference sol’n causes cell swelling as it’s more dilute
Hypertonic- causes crenation as it’s more concentrated
What is Pw?
The permeability of a membrane to water
How do you calculate Pw?
Pf + Pd`
What is Pf?
The movement of water through water channels. It’s sensitive to mercury, but not temperature, and happens on a large scale.
What is Pd?
The diffusion of water through the membrane. It’s insensitive to mercury but dependent on temperature, and only happens on a small scale.
Describe passive transport
Molecules are carried down their concentration gradients
Describe active transport
Molecules are carried against their concentration gradient.
What are ion channels?
Passive transport
Integral proteins which surround a water-filled pore
Ions do not bind when travelling through it
Specific for a certain ion or class of ions
May be gated by: voltage, ligand, phosphate, mechanical, pH
Generate a current when open vs closed
What is carrier mediated transport?
- Passive or active
- Substance binds to protein, which changes shape and releases the molecule on the other side of the membrane.
- Specific to certain molecule(s)
- Can have inhibitors bind to them and prevent function
- Can have 2 molecules competing for its service at the same time
- Can become saturated- max level of transport
What is the name of passive carrier mediated transport + example?
Facilitated diffusion- eg. glucose
What is involved with primary active transport?
Energy comes from ATP hydrolysis
What is secondary active transport?
Energy comes from stored ion gradients- these are used to move molecules in and out of the cell
What is the Na+/K+ATPase channel and why is it important?
Primary active transport which hydrolyses ATP to undergo a shape reconfiguration and move 2K+ into the cell and 3Na+ out. It operate continuously.
It’s important for the RMP, secondary transport, electrical excitability, cell volume and muscle/nerve function
What are other examples of primary transport carriers?
Ca2+/K+ATPase and H+/K+ATPase carriers
What are antiporters and symporters with examples?
Both are forms of secondary active transport and use the energy of ion gradients to move.
Antiporters move one thing in and one out, like the Na+ antiporter, bringing Na+ in and Ca2+ or H+ out.
Symporters bring two or more things along the same direction together, like the Na+ and glucose or amino acid symporter
What is endocytosis?
The process of bringing large molecules into the cell
What is phagocytosis?
Cell eating. It occurs mainly in leukocytes. The cell membrane binds to a receptor protein, which it flows out and around the particles, engulfing them
What is pinocytosis?
Cell drinking. A cleft appears in the cell membrane, particles flow into it and the membrane pinches off interiorly into a vesicle
What is receptor-mediated endocytosis?
This is only for the uptake of specific substances or ligands. The particles bind to a clathrin coated pit region of the membrane. This causes the membrane to fold in and forming a vesicle, which pinches off, combines with an endosome and the receptor proteins involved exit. The particles are either digested or removed.
What is exocytosis?
Substances are released from the cell when their vesicles fuse with the cell membrane.
Where are tight junctions located, and what are they made of?
They are on the apical edges of epithelial cell membranes. They are formed from the proteins occludin and claudins, and encircle the cell, fusing adjacent cell walls together.
What do tight junctions look like?
Electron microscope: Appears fused
Freeze fracture: Interlocking ridges
Why are tight junctions important?
They band cells together, preventing molecules from moving between cells. They fence off the apical vs. basolateral surfaces of the cell, preventing membrane proteins from moving between these zones. This makes the cell asymmetrical, with different ares able to function differently.
They’re important in absorption and secretion.
What are the two classes of tight junction?
Leaky (allow lots through)
Tight (allow few things through)
What are the two types of cellular transport?
Transcellular and paracellular
What is paracellular transport?
Passive, and controlled by tight junctions. The higher the electrical resistence of the tight junctions, the more there are and the less ions pass. The resistance changes proximal to distal in GI tract and kidneys. It is the movement of molecules in between cells
What is transcellular transport?
It uses primary and secondary transport alongside diffusion to absorb and secrete things from one side of the cell to another.
What must be considered when outlining the process of transcellular transport?
- Where molecules come from and exit (basolateral/apical). One step is likely active and the other passive
- Electrochemical gradient- this tells you which step is active vs passive
- Electroneutrality- when an ion is moved a counterion follows it paracellularly to maintain electroneutrality
- Osmosis- when ions move, H2O follows to maintain osmolarity
Where are Na+/K+ATPase carriers located?
Basolateral surface of most cells
What do the two different cell types in glands do?
Acinar cells form primary secretions high in molecules such as enzymes, ions etc. Duct cells modify this to ensure only waste is being secreted
What are the 6 different areas of glucose absorption?
- Tight junctions separate the cell in to apical and basolateral surface
- Na+/K+ATPase is in the basolateral membrane, accumulating K+ above its conc. gradient and removing Na+.
- Na+/Glucose symporter is in the apical membrane, which is secondary transport as it uses Na+’s low conc. gradient to accumulate glucose in a high conc. in the cell
- Due to its high conc. gradient, glucose move passively out of the cell via facilitated diffusion
- Imported Na+ is removed by the ATPase pump
- The counterion Cl- and H2O follow paracellularly to maintain electroneutrality.
What other molecules does glucose uptake transport into the blood?
Cl- and H2O
What happens if there is insufficient glucose in the blood?
Active transport slows, and eventually glucose will diffuse out of the blood and into the cells
How can we treat dehydrated people using the principles of glucose absorption?
Oral rehydration therapy: Give a sugar solution to the dehydrated. As when glucose is absorbed, water follows, this is more effective than a solution of pure water.
What is glucose/galactose malabsorption syndrome?
Results from a mutation in gene 1 which operates in Na+/glucose symporter in the small intestine. As a result, it prevents the absorption of glucose into the blood, which in turn increases the osmolarity of the lumen and encourages water to move out of the blood to the digestive tract, resulting in severe diarrhoea.
How is glucose/galactose malabsorption syndrome treated?
The glucose in the diet is substituted for fructose as a sugar source, as fructose uses a different transporter.
Where else does the Na+/glucose symporter appear?
The kidneys, but only in the proximal tubules. If glucose isn’t absorbed here, it will remain in the urine
What happens if there is too much glucose in the blood?
The symporters are overwhelmed, become saturated and cannot transport any more glucose. Therefore the glucose will be present in the urine, called glucosuria.
Where is glucosuria most commonly observed?
In those with diabetes
What is the renal threshold?
The point at which the symporters become saturated and the concentration of glucose in the filtered blood remains steady regardless of how much was to start with. This is also the point after which glucose begins to appear in the urine. It lieas at approx. 200mg/mL of glucose in plasma, and the transport max. is approx. 375mg/min.
What is the general overview of chloride secretion?
Cl- must be moved out of the blood and into the lumen for secretion.
What are the steps of chloride secretion?
- Tight junctions separate the cell membrane into apical and basolateral sections
- Na+/K+ATPase sets up the ion gradients (Na+ low, K+ high)
- An NaK2Cl symporter moves 1 K+, 1Na+ and 2Cl- into the cell using the Na+ conc. gradient. Cl- is accumulated above its concentration gradient.
- Cl- diffuses out its ion channel, CFTR, using passive transport, at the apical surface
- K+ diffuses out of the cell via its ion channel, and Na+ is pumped out by the ATPase
- To maintain electroneutrality, H2O and Na+ follows the Cl- ion paracellularly.
Why is it important that Cl- secretion be regulated and how is this achieved?
It moves water out of the blood, and so has the potential to cause severe dehydration. Because of this, the ion channel is gated by phosphorylation, which is the rate limiting step.
What is the underlying cause of cystic fibrosis and secretory diarrhoea?
The CFTR ion channel being too closed or too open due to a mutation or toxin.
How is CFTR activated normally?
A secretagogue binds to a G-coupled protein receptor in the membrane, stimulating adenylyl cyclase. This produces cAMP which causes a chain of reactions eventually stimulating the channel. It is the presence or absence of secretagogues which regulate Cl- secretion
How does diarrhoea arise normally?
A high number of endogenous secretagogues or inflammation
How does cholera cause secretory diarrhoea?
It produces an enterotoxin, which binds to adenylyl cyclase and holds it in the activated position, constantly producing cAMP without regulation by secretagogues. This overstimulates CFTR, overwhelming the reabsorptive capacity of the colon. If unchecked, the body may dehydrate itself and die.
How may cholera be treated? (procedure and physiology of SI)
Oral rehydration therapy.
Also, small intestine cells are produced in the crypts of the small intestine and move up to form villi as they grow older. As the crypts are responsible for Cl- secretion and the villi for glucose absorption, if the disease can be held off for a few days the purpose of the infected cells will have changed and the disease will no longer be effective.
Describe cystic fibrosis
A complex, hereditary disease inherited in autosomal recessive fashion. Heterozygotes are carriers. It is most common in Norther Eurpoeans. Median survival is 29 years. CFTR is defective, so many epithelial tissues are affected.
What organs does cystic fibrosis affect?
The liver Pancreas SI Reproductive tract Skin Lungs
How does CF affect the liver?
Small bile ducts may become plugged, impeding digestion and disrupting liver function
How does CF affect the pancreas?
Blocking of ducts prevents enzymes from entering the bowel. Due to high conc. of enzymes in the ducts the pancreas may be destroyed in itself. Diabetes is also a side effect as insulin is not able to reach the blood.
How does CF affect the SI?
Thick stool can obstruct the gut
How does CF affect the reproductive tract?
the absence of fine ducts inc. vas deferens makes 95% of males infertile. Mucous plugs blocking the uterus can make some women infertile
How does CF affect the skin?
Sweat glands malfunction, resulting in very salty weat.
Why is the sweat salty in CF patients?
Acinar cells produce the 1my secretion, with a high conc. of ions etc. Duct cells are supposed to reabsorb these. However, if the CFTR is not working, Cl- is not reabsorbed and the gradient is more positive, impeding Na+ from being reabsorbed, too. Therefore both are expressed in the sweat as NaCl, making the sweat salty.
What is a normal lung environment?
Normally, the lungs are covered in a thin layer of mucus due to Cl- secretion and Na+ reabsorption. This mucus can be pushed up the airway for removal, keeping the airways clear
How does CF affect the lungs?
It clogs the airway and damages them, impairing breathing. It is the leading cause of death for CF patients.
How does CF damage the lungs?
Cl- is not secreted, which in turn makes Na+ absorbed more. This results in a very dry lung surface, making the mucus thick and sticky. This is also an ideal environment for bacteria, which attract immune cells digesting them but also damaging healthy lung tissue. The destroyed bacteria and lung cells also release DNA, making the mucus even sticker, and hard to remove, plugging the airways and deteriorating lung tissue.
How can CF be managed?
- Chest percussion to clear infected secretions
- Antibiotics for infections
- Pancreatic enzyme replacement
- Diet
What is the gating process of CFTR?
- Protein kinase A is activated by cAMP, signalling phosphate to bind to CFTR’s regulatory domain
- ATP binds to the nucleotide bonding sites, causing the channel to open.
- As the ATP is converted to ADP, the channel closes again, preventing Cl- movement
