1
Q
what is the function of the membrane
A
- The plasma membrane separates the cellular contents from the outside
- The internal membranes separate the contents of organelles from the rest of the cell
- Control the passage of molecules in and out of the cell
2
Q
what happens if there are no membranes
A
No membranes, no gradients, no energy
3
Q
What are the variation of the membranes
A
- Typical membrane = 50% protein, 50% lipid
- Mitochondria = 75% protein, 25% lipid
- Myelin sheath = 25% protein, 75% lipid (for insulation)
4
Q
what does the protein content part of membranes allow for
A
he protein component is what accounts for its selective permeability – the gateways into cells
5
Q
what are the different examples of protein in the body
A
• Different proteins – e.g. single/multiple alpha helices, rolled up beta sheets, glycosylated membrane lipids that do not cross membrane but are attracted to membrane because they’re lipidated - anchors that they insert into bilayer, some also associate with bona fide membrane proteins but do not themselves attach
6
Q
what are the 3 main types of lipidation
A
• 3 main types of lipidation: myristoyl, palmitoyl, farnesyl anchors.
Longer chain =more stable. Used to recruit/detach proteins from membranes
7
Q
apical and basal membranes contain….
A
different proteins,
- tight junctions enable this
8
Q
what are the different types of membrane proteins and give examples of them
A
- Channels – opens and allows flow, often very selective for particular ion (Cytic Fibrosis Transmembrane Regulator – effectively a chloride channel)
- Transporters – allow transport against the concentration gradient (ABCB1 hydrolyses ATP and pumps things out of cells e.g. drugs). Can concentrate a solute on one side of the membrane
- Integrins - involved in adhesion – attach cells to ECM
- Adhesins/connexins – attach cell to cell (connexin 26 – allows K+ ion flow between cochlear cells – mutations cause deafness)
- Receptors – transmit signals across the membrane (FGFR3 – bound to fibroblast growth factor receptor – tyrosine receptor kinase. Mutations cause achrondroplasia (short stature). Can either endocytose the ligand or the ligand will cause a conformational change in the receptor, causing a signal inside cells
- Enzymes – catalyse reactions (phospholipase C – recruited to membrane. influences cell behaviour. protein kinase C activation and stimulates Ca2+ release from the ER)
9
Q
what is passive diffusion
A
• Passive diffusion is when molecules than diffuse DIRECTLY through the phospholipid bilayer
10
Q
what is facilitated diffusion
A
- Facilitated diffusion is when a molecule moves through the phospholipid bilayer using a membrane protein but NO ATP
- Net flux depends on the electrochemical gradient
- Movement will stop will equilibrium is reached
11
Q
given an example of facilitated diffusion
A
• Moves ions such as Na+ and larger molecules such as glucose by Glut1-7
12
Q
describe Vmax and Km in facilitated diffusion
A
- Has Vmax where Km is at half Vmax and a low Km means high affinity transport
- Vmax is the maximum rate of reaction when the enzyme is saturated with substrate
- Vmax is the maximum rate of reaction when the enzyme is saturated with substrate
- Km is the concentration of substrate which permits the enzyme to achieve half Vmax. An enzyme with a high Km has a low affinity for its substrate, and requires a greater concentration of substrate to achieve Vmax
13
Q
what is active transport
A
• Active transport is when a molecule moves through the phospholipid bilayer using a membrane protein and ATP. Moves AGAINST the concentration gradient
- uses transporter proteins
14
Q
what are the type of active transport
A
primary and secondary
15
Q
what can passively diffuse
A
- Small and polar so they can penetrate the bilayer
- Small and non polar
- Polar – uncharged can cross
The larger the molecule the less likely they are to move through the bilayer
16
Q
describe the electrochemical gradient
A
- Molecules move from an area of high concentration to an area of low concentration.
- They also move according to charge.
- In this example they move from an area that is very positive to an area that is less positive (more negative).
17
Q
Describe channel proteins
A
- This is a continuous pore through the membrane
- Use facilitated diffusion to move molecules from an area of high to low concentration through a membrane protein
- Uses charge to be selective for example a channel may be negatively charged to attract a positively charged solute and repel a negatively charged solute to allow only certain molecules to enter the cell
- Move large amounts of solutes -high bulk flow
- Regulated
- Charge across the membrane influences efficiency of diffusion – e.g. negative on the inside enhances gradient
18
Q
describe the action of passive membrane transporters
A
- Solute binds to the binding sites on the outside of the membrane
- The solute binding causes transporter to change shape (conformational change)
- Solute can now move into the cell
- Movement is dependent on the electrochemical gradient, - solutes must move from a high concentration to a low concentration
- Low capacity
19
Q
describe the action of active membrane transporters
A
- Solute binds to binding sites on the outside of the membrane.
- This causes ATP to bind to the transporter and split to ADP and phosphate.
- The energy created is used to change the shape of the transporter (conformational change)
- The solute can move into the cell
- Movement is dependent on ATP so can move against the electrochemical gradient
20
Q
describe primary active transport
A
- ATP hydrolysis provide the energy to move the molecular against the electrochemical gradient
21
Q
what is an example of primary active transport
A
- E.g. Na+/K+ ATPase
- Na+/K+ pump maintains the resting membrane potential across the cell membrane. It moves three sodium ions out of the cell for every two potassium ions brought in meaning that the outer membrane remains mainly positive.
22
Q
what is secondary active transport
A
- The energy stored in the electrochemical gradient of a solute moving down its electrochemical gradient is used to transport another solute move actively against its concentration gradient
23
Q
describe an example of secondary active transport
A
- E.g. SGLT1
SGLT1 (Sodium glucose linked transporter) found in the intestinal epithelium. Uses the absorption of sodium down its concentration gradient to transport glucose into cells against the concentration. This means that all glucose possible is absorbed from food and none is lost in the stool - Both solute and ion bind at the same time, transporter changes conformation, free energy released as the contransported ion moves down its electrochemical gradient, can drvie the solute up its electrochical gradient- secondary active transport
24
Q
what is co transport
A
- This is a form of secondary active transport
25
what are the two types of cotransport
symport and antiport
26
what is antiport
opposite directions (so one is pumped out while one is pumped in) – Na+/K+ ATPase
27
what is symport
pumped in the same direction (they are both pumped inwards) SGLT1
28
Describe the receptor mediate endocytosis
- Particles bind to the receptor on the cell surface membrane
- The membrane bends and folds over on itself (invaginates) and forms a vesicle.
- Particles contained in that vesicle can be transported around inside the cell.
- Solute binds to the receptor on the surface and internalises the complex by endocytosis
29
what is an example of receptor mediate endocytoiss
- Ldl receptor binds through extracellular domain, internal domain changes conformation, recruits clathrin
- Causes membrane to invaginate inti liposome and close around the protein with the attached ligand
- E.g. LDL receptor taking up LDL , harvest choestrol
30
describe glucose transport
* Secondary active symport
* Glucose brought in via SGLT1 in the apical/luminal membrane with Na+
* Glucose diffuses (therefore passive) out Glut2 in the basal membrane into the extracellular fluid and enters the bloodstream down its conc gradient via facilitated difusion
* Sodium pumped out of cell and potassium pumped in by Na+K+ATPase in basal membrane which creates a lower concentration of Na+ inside the cell so drives the facilitated diffusion of sodium into the cell, bringing with it glucose
31
describe progressive familia intrahetic cholestasis
* Cholestasis: When bile cannot flow from the liver to the duodenum
* PFIC: A rare fatal disease of childhood that causes:
* Jaundice, itchy skin, failure to thrive, hepatosplenomegaly and dark urine.
* This is caused by mutation in these two transporters:
* ABCB4
* ABCB11
* ABCB4 is also known as MDR3. MDR3 transports phosphatidyl choline into the bile.
* ABCB11 also known as BSEP is a type of bile salt transport pump
32
describe familia hypercholetrolemia
* A recessively inherited disease which causes high cholesterol.
* It is caused by a deficiency in receptor mediated endocytosis.
* No low density lipoproteins are taken into cells so stay in the blood increasing blood cholesterol levels.
* This is caused by deletion of the clathrin domain on the low density lipoprotein receptor.
* Clathrin is the component of the receptor that allows it to invaginate and form a vesicle
33
what kind of mutation is cystic fibrosis
• An autosomal recessively inherited disease caused by mutations in the channel protein CFTR.
34
where is the protein channel CFTR found
• Found in the plasma membrane of epithelial cells of the lungs pancreases and intestine
35
what does the CFTR mutation cause and how do you treat it
* CFTR – Cystic fibrosis transmembrane regulator
* Type of channel protein that transports Cl- outside of the cell
* Mutation means that the channels are not brought the cell membrane.
* Treated with Lumacaftor and Ivacafor
36
what does cystic fibrosis cause and how does it cause it
• Chloride thins mucus secretions from cells. It does this by inducing the flow of Na and H20 out of cells by creating an electrochemical gradient. As a result the mucus becomes more watery and thinner. If the CFTR proteins are not there no chloride ions can enter the secretions causing them to become thick. This affects cells in the intestines, pancreas, liver kidney, sweat gland, reproductive tract and lungd.
37
how is cystic fibrosis treated
* Lumacaftor helps the mutated CFTR (ΔF508) to fold and be transported to the cell surface membrane where it can work.
* Ivacaftor is a gene therapy that acts on CFTR channel to improve transport of chloride ions.
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